| 1. |
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| 2. |
- Allard, Anna, et al.
(author)
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Småbiotopsuppföljning i NILS år 2008
- 2009
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Reports (other academic/artistic)abstract
- Denna rapport presenterar resultat för mängden av småbiotoper vid åkermark i det svenska landskapet. Analyserna görs på uppdrag av Jordbruksverket, som underlag för bl.a. utvärderingen av miljökvalitetsmålet Ett rikt odlingslandskap. Särskilda rutiner har tagits fram för att aggregera olika variabler för att välja ut de småbiotoper som uppfyller de krav som Jordbruksverket har ställt upp, ur den befintliga databasen. Urvalet av småbiotoper är anpassat för att överensstämma med det urval av objekt som ingår i det s.k. KULT-stödet (miljöersättning till lantbrukare för skötsel av värdefulla natur- och kulturmiljöer) inom Jordbruksverkets Landsbygdsprogram. Arbetet har utförts vid institutionen för skoglig resurshushållning, Sveriges lantbruks-universitet, Umeå. Resultaten baseras på data från flygbildsinventeringen inom det nationella miljöövervakningsprogrammet NILS (Nationell Inventering av Landskapet i Sverige) vilket följer tillstånd och förändringar i det svenska landskapet och hur dessa påverkar förutsättningarna för den biologiska mångfalden. NILS finansieras av Naturvårdsverket, och ingår där i programområde Landskap. Ett viktigt syfte med programmet är att följa upp de nationella miljökvalitetsmålen för olika naturtyper och fungera som underlag för att se om genomförda policybeslut och miljövårdsåtgärder leder till önskade förbättringar
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| 3. |
- Andersen, Grethe Neumann, et al.
(author)
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Bronchoalveolar matrix metalloproteinase 9 relates to restrictive lung function impairment in systemic sclerosis.
- 2007
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In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 101:10, s. 2199-2206
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Journal article (peer-reviewed)abstract
- Systemic sclerosis (SSc) is frequently associated with interstitial lung disease (ILD) often leading to lung fibrosis. In this study we investigated whether matrix metalloproteinase 9 (MMP-9) and its natural inhibitor; the tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), would be associated with remodelling in ILD in SSc. Levels of total MMP-9, pro-MMP-9 and TIMP-1 were measured in bronchoalveolar lavage (BAL) fluid from nine SSc patients with ILD, seven SSc patients without ILD and 16 age- and sex-matched healthy controls. Total MMP-9 and pro-MMP-9 levels were significantly elevated in SSc patients with ILD, compared to levels in SSc patients without ILD and healthy controls. In SSc patients with ILD calculated active MMP-9 levels were significantly higher than in SSc patients without ILD and tended to be higher than in healthy controls. TIMP-1 levels were elevated in both patient groups compared to healthy controls. Total-, pro- and active MMP-9 levels as well as pro-MMP-TIMP-1 and active MMP-9/TIMP-1 ratios were inversely associated with total lung capacity. The present study suggests that MMP-9 plays a pathophysiological role in the remodelling in ILD and lung fibrosis associated with SSc, and may represent a new therapeutic target in this condition.
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| 4. |
- Andersen, Grethe N., et al.
(author)
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Cytokine mRNA profile of alveolar T lymphocytes and macrophages in patients with systemic sclerosis suggests a local Tr1 response
- 2011
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In: Scandinavian Journal of Immunology. - Oslo : Univ.forl.. - 0300-9475 .- 1365-3083. ; 74:3, s. 272-81
-
Journal article (peer-reviewed)abstract
- The development of an autoimmune disease like systemic sclerosis (SSc) is suspected to be driven by an activated T lymphocyte subset, expressing a cytokine profile specific to the disease. To further characterize the type of immune reaction in SSc, we searched for a broad panel of cytokine messenger ribonucleic acids (mRNAs) in T lymphocytes and monocytes/macrophages from paired samples of bronchoalveolar lavage fluid and peripheral blood in 18 patients and 16 age- and sex-matched controls. RNA from CD3(+) T lymphocytes and CD14(+) monocytes/macrophages was examined by means of the reverse transcriptase polymerase chain reaction. SSc alveolar T lymphocytes expressed a cytokine profile suggestive of a mixed Th1/Th2 reaction, showing an increased frequency of mRNA for interleukin (IL)-10, IL-6 and interferon (IFN)γ, while IL-1β, IFNγ and tumour necrosis factor β were expressed in blood T lymphocytes in a higher percentage of patients with SSc than controls. SSc alveolar T cells expressed IL-10 mRNA more often than peripheral T cells, a phenomenon not found in controls and which may point at local IL-10 activation/response in SSc lung. Transforming growth factor β mRNA was present in all alveolar as well as peripheral blood T cell samples in patients and controls. The cytokine mRNA profile in SSc with interstitial lung disease (ILD) was similar to the profile found in SSc without ILD. Our findings point at a mixed Th1/Th2 reaction in SSc and may indicate regulatory T 1 cell activation/response in the lungs of patients with SSc.
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| 5. |
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| 6. |
- Ebenhag, Sven-Christian, 1976, et al.
(author)
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Time transfer using an asynchronous computer network: Results from three weeks of measurements
- 2007
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In: European Frequency and Time Forum, 29/5 - 1/6, Geneva, CH.
-
Conference paper (peer-reviewed)abstract
- We have performed a time transfer experimentbetween two atomic clocks, over a distance of approximately 75km using an 10 Gbit/s asynchronous fiber-optic computernetwork. The time transfer was accomplished through passivelistening on existing data traffic and a pilot sequence in the SDHbit stream. In order to assess the fiber-link clock comparison, wesimultaneously compared the clocks using a GPS carrier phaselink. The standard deviation of the difference between the twotime transfer links over the three-week time period was 243 ps.
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| 7. |
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| 8. |
- Ekström, Magnus Pär, et al.
(author)
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The association of body mass index, weight gain and central obesity with activity-related breathlessness : the Swedish Cardiopulmonary Bioimage Study
- 2019
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In: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 74:10, s. 958-964
-
Journal article (peer-reviewed)abstract
- Introduction: Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m(2)) is rapidly increasing globally and its impact on breathlessness is unclear.Methods: This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score >= 1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex.Results: We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m(2); and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness.Conclusion: Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Garvanska, Dimitriya H., et al.
(author)
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The NSP3 protein of SARS-CoV-2 binds fragile X mental retardation proteins to disrupt UBAP2L interactions
- 2024
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In: EMBO Reports. - : Springer Nature. - 1469-221X .- 1469-3178. ; 25:2, s. 902-926
-
Journal article (peer-reviewed)abstract
- Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1, FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have attenuated replication in vitro and reduced levels of viral antigen in lungs during the early stages of infection. We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins and provides molecular insight into the possible underlying molecular defects in fragile X syndrome.
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| 14. |
- Hedekvist, Per Olof E, 1967, et al.
(author)
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Accurate time transfer utilizing the synchronization in an SDH-network
- 2006
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In: 2006 Optical Fiber Communication Conference, and the 2006 National Fiber Optic Engineers Conference; Anaheim, CA; United States; 5 March 2006 through 10 March 2006. - 9781557528032 ; 2006
-
Conference paper (peer-reviewed)abstract
- A nationwide system for accurate time distribution is being developed, utilizing synchronization in an SDH-network. The first experimental results based on this technique are presented, performed on, but not limited to, STM-64.
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| 15. |
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| 16. |
- Huang, Ranyang, et al.
(author)
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Expression of a Mast Cell Tryptase in the Human Monocytic Cell Lines U-937 and Mono Mac 6
- 1993
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In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 38:4, s. 359-367
-
Journal article (peer-reviewed)abstract
- Expression of a mast cell tryptase mRNA was detected in two human monocytic cell lines, the U-937 and the Mono Mac 6, and in normal human peripheral blood(PB) monocytes. In the U-937 cell line but not in normal PB monocytes, the tryptase expression was upregulated 3-50 fold following phorbol ester (PMA)-induced differentiation, but no such induction was seen after retinoic acid, interferon-gamma or vitamin D3 exposure. The tryptases expressed in PMA-induced and non-induced U-937 and in Mono Mac 6 were characterized by PCR amplification and nucleotide sequence analysis. The U-937 cell line was found to express a tryptase identical to one of the previously cloned mast-cell beta tryptases (Tryptase I), and the tryptase expressed in Mono Mac 6 was found to be nearly identical to the previously cloned alpha tryptase. By northern blot analysis with oligonucleotide probes specific for the alpha and beta tryptases both cell lines were found to express only one type of tryptase. Densitometric quantifications of tryptase mRNA levels, in the two cell lines, showed approximately 80 times higher mRNA levels in Mono Mac 6 compared to non-induced U-937. Immunohistochemical staining for tryptase showed a marked heterogeneity in the Mono Mac 6 cell line. Only one out of 10 cells were positive for the protein but the levels in these cells were very high, equivalent, or even higher than the levels seen in the human mast cell line HMC-1. This shows that the expression of a single tryptase, in this case the alpha tryptase, is sufficient for the production of a stable protein and probably also a stable proteolytically active tetramer. The family of human mast-cell tryptases has been considered to represent a class of proteases specifically expressed in mast cells and basophilic leucocytes. The expression of tryptases in two monocytic cell lines and in normal PB monocytes indicate that in humans, the lineage specificity of these serine proteases is less restricted than earlier expected. The cloning of a full length cDNA for the murine counterpart to the human mast cell tryptases, the MMCP-6, is presented. No expression of the MMCP-6 was detected in a panel of mouse monocyte or macrophage cell lines indicating a species difference in the lineage specificity of the 'mast cell tryptases'.
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| 17. |
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| 18. |
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| 19. |
- Marsell, Richard, et al.
(author)
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GSK-3 inhibition by an orally active small molecule increases bone mass in rats
- 2012
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In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 50:3, s. 619-627
-
Journal article (peer-reviewed)abstract
- Glycogen synthase kinase 3β (GSK-3β) actions are central in the canonical Wnt pathway, important in many biological processes and a potential drug target for treating several diseases. It is appreciated that a balanced Wnt canonical signaling is crucial for the maintenance of normal bone mass. In this study we investigated the effects of a potent orally active GSK-3 inhibitor, AZD2858, on bone mass in rats. Treatment (1μM) of human osteoblast cells with AZD2858 in vitro increased β-catenin levels after a short period of time. In rats, oral AZD2858 treatment caused a dose-dependent increase in trabecular bone mass compared to control after a two-week treatment with a maximum effect at a dose of 20mg/kg once daily (total BMC: 172% of control; p<0.001). A small but significant effect was also seen at cortical sites (total BMC: 111% of control; p<0.001). Biomechanical testing demonstrated an increase in both vertebral compression strength at a dose of 20mg/kg once daily (Load at failure: 370% of control, p<0.001) and diaphyseal strength of femora subjected to a three point bending test (Load at failure: 115% of control; p<0.01). Furthermore, histomorphometry showed a dramatic increase in bone formation indices, and serum markers of both bone formation (Osteocalcin, 146% of control; p<0.001) and resorption (CTX, 189% of control; p<0.001) were elevated. Our conclusion is that a GSK-3 inhibitor drug may prove effective as an anabolic strategy in the treatment of diseases characterized by low bone mass, since AZD2858 has extensive bone building effects at predominantly trabecular sites.
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| 20. |
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| 21. |
- Molin, Daniel, et al.
(author)
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Mast cells express functional CD30 ligand and are the predominant CD30L-positive cells in Hodgkin's disease
- 2001
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In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 114:3, s. 616-623
-
Journal article (peer-reviewed)abstract
- Hodgkin's disease (HD) tumours are characterized by the presence of few tumour cells, the Hodgkin and Reed-Sternberg (HRS) cells, surrounded by a large amount of non-neoplastic cells. The role of this cell infiltrate for the development of HD is not known. CD30, belonging to the tumour necrosis factor receptor superfamily, is highly expressed on HRS cells and believed to be involved in tumourigenesis and tumour progression. Tumour samples from 42 patients were immunohistochemically double-stained for tryptase, a mast cell-specific proteinase and CD30 ligand (CD30L). Tryptase-positive mast cells were present in all tumours. Of these cells, 50% expressed CD30L and 66% of the CD30L-positive cells were mast cells. CD30L mRNA in in vitro developed normal mast cells and malignant human and murine mast cell lines was detected using reverse transcription polymerase chain reaction. CD30L protein expressed on human mast cells was detected using flow cytometry. In a co-culture assay, the human mast cell line HMC-1 stimulated thymidine uptake in HRS cell lines, and the stimulation could be blocked using CD30L-specific monoclonal antibodies. In conclusion, mast cells are present in HD tumours and are the predominant CD30L-expressing cells. CD30L-CD30 interaction is a pathway by which mast cells may stimulate DNA synthesis in HRS cells.
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| 22. |
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| 23. |
- Nilsson, Gunnar, et al.
(author)
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C3a and C5a are chemotaxins for human mast cells and act through distinct receptors via a pertussis toxin-sensitive signal transduction pathway
- 1996
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In: Journal of Immunology. - 0022-1767 .- 1550-6606. ; 157:4, s. 1693-1698
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Journal article (peer-reviewed)abstract
- Mast cells are known to accumulate at sites of inflammation, however, the chemotaxins involved are undefined. Since most natural leukocyte secretagogues also induce cell migration, and since the anaphylatoxins C3a and C5a are mast cell secretagogues, we hypothesized that both C3a and C5a are also mast cell chemotaxins. Here we report that C3a and C5a are, in fact, potent chemotaxins for the human mast cell line HMC-1. The optimal concentrations, half-maximal effective concentrations (a measure of agonist potency) and the efficacy (response at the optimal concentration) compared with medium control were, for C3a: 10 nM, 0.5 nM, and 256%, respectively; for C5a: 1 nM, 10 pM and 145%. Chemotaxis of HMC-1 cells to both C3a and C5a was blocked by pertussis toxin, suggesting that Gi-coupled receptors are involved in signal transduction. C3a and C5a also induced transient pertussis toxin-inhibitable increases in [Ca2+]i (ED50 = 1 nM for both) that could be homologously but not heterologously desensitized, suggesting that the receptors for C3a and C5a are distinct. These results make C3a the most effective mast cell chemotaxin identified to date. The chemotactic potency described here for C3a is also 100- to 1000-fold greater than for all of its previously described cellular actions. Direct chemoattraction of mast cells by C3a and C5a may help explain the rapid accumulation of mast cells at sites of inflammation.
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| 24. |
- Nilsson, Joacim, et al.
(author)
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Differentiation-associated redox-regulation in human B cell lines from stem cell/pro-B to plasma cell
- 2004
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In: Immunology Letters. - : Elsevier BV. - 0165-2478 .- 1879-0542. ; 94:1-2, s. 83-89
-
Journal article (peer-reviewed)abstract
- Redox-regulation of receptors and transcription factors are important for lymphocyte activation, differentiation and apoptosis. Thioredoxin (Trx) is a key redox-regulating protein and oxidative stress sensor operating in synergy with Trx-reductase and protein disulfide isomerase (PDI). The expression of Trx, PDI, and the Trx-regulated transcription-factor Pax5 were analyzed in a panel of human B cell lines and were compared with that of the Bcl-2 family proteins, also redox-controlled. The panel included representative cells from various stages: FLEB14-4 (pro-B), REH and NALM-6 (pre-B), Rael and Daudi (small mature B), U-698 and NC0467.3 (B-blasts), LP-1, U-1996, and U-266 (plasma cells). We found a significant congruence and co-variation of Trx and Bcl-2 levels in the B-lineage, with high expression levels in early stages (pro-B and pre-B) and in the late stage representing terminally-differentiated plasma cells, whereas mid-stage small resting B cells showed a very low expression. PDI increased significantly in plasma-blasts and plasma cells, indicating its importance in the highly specialized immunoglobulin assembly-machinery, including disulfide-bond isomerization. Pax5 was expressed in early and mid-stages, but was silenced in terminal stages. We conclude that the high Trx and Bcl-2-expression early and late in the B cell maturation pathway reflects a redox-strategy favoring an increased survival potential of the B cells at those stages. © 2004 Elsevier B.V. All rights reserved.
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| 25. |
- Nilsson, J, et al.
(author)
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Thioredoxin prolongs survival of B-type chronic lymphocytic leukemia cells
- 2000
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In: Blood. - 0006-4971 .- 1528-0020. ; 95:4, s. 1420-1426
-
Journal article (peer-reviewed)abstract
- Thioredoxin (Trx) is a ubiquitous protein disulfide oxidoreductase with antioxidant, cytokine, and chemotactic properties. Previously, we showed that Trx, in synergy with interleukin 1 (IL-1), IL-2, IL-4, tumor necrosis factor alpha (TNF-alpha), and CD40-ligation induced S-phase entry and mitosis in normal B cells and B-type chronic lymphocytic leukemia (B-CLL) cells. The viability of B-CLL cells stimulated by these protocols is high, and it has been hypothesized that the overexpression of Bcl-2 found in B-CLL protects the cells from apoptosis in vitro and in vivo. In this study, we have analyzed the response of cells derived from 12 samples of patients with B-CLL to recombinant human Trx in spontaneous apoptosis, with special reference to the Bcl-2 expression. Long-term cultures of B-CLL clones showed significantly higher viability when supplemented with human Trx (P =.031), also exemplified with clones surviving more than 2 months. Short-term cultures of B-CLL cells exposed to 1 microg/mL of Trx for 1, 5, or 12 days maintained expression or delayed down-regulation of Bcl-2 compared with control cultures containing RPMI 1640 medium and 10% fetal calf serum only (P =.032,. 002,.026, respectively). All B-CLL cells expressed constitutive Trx at varying but low levels, in contrast to adult T-cell leukemias, which overexpress Trx, as previously reported. We found that Trx added to B-CLL cells increased in a dose-dependent fashion the release of TNF-alpha, which has been suggested to be an autocrine growth factor for these cells. In conclusion, we have found that human recombinant Trx induced TNF-alpha secretion, maintained Bcl-2, and reduced apoptosis in B-CLL cells.
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| 26. |
- Sehlstedt, Maria, 1979-, et al.
(author)
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Suppressed signal transduction in the bronchial epithelium of patients with systemic sclerosis
- 2009
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In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 103:2, s. 301-308
-
Journal article (peer-reviewed)abstract
- INTRODUCTION: Systemic sclerosis (SSc) is an autoimmune disorder, which frequently affects the lungs, with manifestations of interstitial lung disease (ILD) with lung fibrosis and of pulmonary hypertension. The pathogenesis remains largely unrecognised. OBJECTIVE: The aim of this study was to elucidate the inflammation in the bronchial mucosa in patients with SSc. SUBJECTS AND METHODS: Twenty-three subjects diagnosed with SSc participated. Twelve of the SSc patients showed signs of ILD, four were smokers and seven were treated with oral corticosteroids. Seventeen non-smoking, age- and sex-matched healthy subjects served as controls. Bronchoscopy was performed to sample endobronchial mucosal biopsies, which were immunohistochemically stained using a panel of antibodies against inflammatory markers. RESULTS: The number of neutrophils was significantly elevated in the submucosa of SSc patients, regardless of ILD, or whether the subject was smoking or using oral corticosteroids. No up-regulation of neutrophil chemoattractants or cytokines was seen in the bronchial epithelium. The signal transduction pathways and adhesion molecule expression tended to be suppressed or unchanged in SSc patients compared with controls. CONCLUSION: It is concluded that SSc is associated with a chronic neutrophilic inflammation in the bronchial mucosal, with signs of suppressed signal transduction, regardless of the presence of interstitial lung disease.
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| 27. |
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| 28. |
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| 29. |
- Abelev, Betty, et al.
(author)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
-
Journal article (peer-reviewed)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 30. |
- Abelev, Betty, et al.
(author)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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In: Journal of High Energy Physics. - 1029-8479. ; :11
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Journal article (peer-reviewed)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 31. |
- Abelev, Betty, et al.
(author)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
-
In: Journal of High Energy Physics. - 1029-8479. ; :7
-
Journal article (peer-reviewed)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 32. |
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| 33. |
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| 34. |
- Agarwal, Prasoon, et al.
(author)
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Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as a potential therapeutic target.
- 2016
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:6, s. 6809-6923
-
Journal article (peer-reviewed)abstract
- Multiple myeloma (MM) is a malignancy of the antibody-producing plasma cells. MM is a highly heterogeneous disease, which has hampered the identification of a common underlying mechanism for disease establishment as well as the development of targeted therapy. Here we present the first genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in MM patient samples, defining a common set of active H3K4me3-enriched genes and silent genes marked by H3K27me3 (H3K27me3 alone or bivalent) unique to primary MM cells, when compared to normal bone marrow plasma cells. Using this epigenome profile, we found increased silencing of H3K27me3 targets in MM patients at advanced stages of the disease, and the expression pattern of H3K27me3-marked genes correlated with poor patient survival. We also demonstrated that pharmacological inhibition of EZH2 had anti-myeloma effects in both MM cell lines and CD138+ MM patient cells. In addition, EZH2 inhibition decreased the global H3K27 methylation and induced apoptosis. Taken together, these data suggest an important role for the Polycomb repressive complex 2 (PRC2) in MM, and highlights the PRC2 component EZH2 as a potential therapeutic target in MM.
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| 35. |
- Agarwal, Prasoon, et al.
(author)
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The epigenomic map of multiple myeloma reveals the importance of Polycomb gene silencing for the malignancy
-
Other publication (other academic/artistic)abstract
- Multiple myeloma (MM) is characterized by accumulation of post-germinal center, isotype switched, long-living plasma cells with retained proliferation capacity within the bone marrow. MM is highly heterogeneous and remains fatal. This heterogeneity has hampered identification of a common underlying mechanism for disease establishment and the development of targeted therapy. We recently provided proof-of-principle that gene silencing associated with H3K27me3 contributes to the malignancy of MM. Here we present the first epigenomic map of MM for H3K27me3 and H3K4me3 derived by ChIP- and RNA sequencing from freshly-isolated bone marrow plasma cells from four patients. We compile lists of targets common among the patients as well as unique to MM when compared with PBMCs. Indicating the clinical relevance of our findings, we find increased silencing of H3K27me3 targets with disease progression and in patients presenting with a poor prognosis. Bivalent genes further significantly correlated to under-expressed genes in MM and were unique to MM when compared to PBMCs. Furthermore, bivalent genes, unlike H3K27me3 targets, significantly associated with transcriptional activation upon Polycomb inhibition indicating a potential for drug targeting. Thus, we suggest that gene silencing by Polycomb plays an important role in the development of the malignant phenotype of the MM cell during tumor progression.
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| 36. |
- Ajore, Ram, et al.
(author)
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Functional dissection of inherited non-coding variation influencing multiple myeloma risk
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
-
Journal article (peer-reviewed)abstract
- Thousands of non-coding variants have been associated with increased risk of human diseases, yet the causal variants and their mechanisms-of-action remain obscure. In an integrative study combining massively parallel reporter assays (MPRA), expression analyses (eQTL, meQTL, PCHiC) and chromatin accessibility analyses in primary cells (caQTL), we investigate 1,039 variants associated with multiple myeloma (MM). We demonstrate that MM susceptibility is mediated by gene-regulatory changes in plasma cells and B-cells, and identify putative causal variants at six risk loci (SMARCD3, WAC, ELL2, CDCA7L, CEP120, and PREX1). Notably, three of these variants co-localize with significant plasma cell caQTLs, signaling the presence of causal activity at these precise genomic positions in an endogenous chromosomal context in vivo. Our results provide a systematic functional dissection of risk loci for a hematologic malignancy.
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| 37. |
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| 38. |
- Alzrigat, Mohammad, et al.
(author)
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EZH2 inhibition in multiple myeloma downregulates myeloma associated oncogenes and upregulates microRNAs with potential tumor suppressor functions.
- 2017
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:6, s. 10213-10224
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Journal article (peer-reviewed)abstract
- Multiple Myeloma (MM) is a plasma cell tumor localized to the bone marrow (BM). Despite the fact that current treatment strategies have improved patients' median survival time, MM remains incurable. Epigenetic aberrations are emerging as important players in tumorigenesis making them attractive targets for therapy in cancer including MM. Recently, we suggested the polycomb repressive complex 2 (PRC2) as a common denominator of gene silencing in MM and presented the PRC2 enzymatic subunit enhancer of zeste homolog 2 (EZH2) as a potential therapeutic target in MM. Here we further dissect the anti-myeloma mechanisms mediated by EZH2 inhibition and show that pharmacological inhibition of EZH2 reduces the expression of MM-associated oncogenes; IRF-4, XBP-1, PRDM1/BLIMP-1 and c-MYC. We show that EZH2 inhibition reactivates the expression of microRNAs with tumor suppressor functions predicted to target MM-associated oncogenes; primarily miR-125a-3p and miR-320c. ChIP analysis reveals that miR-125a-3p and miR-320c are targets of EZH2 and H3K27me3 in MM cell lines and primary cells. Our results further highlight that polycomb-mediated silencing in MM includes microRNAs with tumor suppressor activity. This novel role strengthens the oncogenic features of EZH2 and its potential as a therapeutic target in MM.
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| 39. |
- Alzrigat, Mohammad, et al.
(author)
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The polycomb group protein BMI-1 inhibitor PTC-209 is a potent anti-myeloma agent alone or in combination with epigenetic inhibitors targeting EZH2 and the BET bromodomain
- 2017
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:61, s. 103731-103743
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Journal article (peer-reviewed)abstract
- Multiple myeloma (MM) is a tumor of plasmablasts/plasma cells (PCs) characterized by the expansion of malignant PCs with complex genetic aberrations in the bone marrow (BM). Recent reports, by us and others, have highlighted the polycomb group (PcG) proteins as potential targets for therapy in MM. The PcG protein BMI-1 of the polycomb repressive complex 1 (PRC1) has been reported to be overexpressed and to possess oncogenic functions in MM. Herein, we report on the anti-myeloma effects of the BMI-1 inhibitor PTC-209 and demonstrate that PTC-209 is a potent anti-myeloma agent in vitro using MM cell lines and primary MM cells. We show that PTC-209 reduces the viability of MM cells via induction of apoptosis and reveal that the anti-MM actions of PTC-209 are mediated by on-target effects i.e. downregulation of BMI-1 protein and the associated repressive histone mark H2AK119ub, leaving other PRC1 subunits such as CBX-7 and the catalytic subunit RING1B unaffected. Importantly, we demonstrate that PTC-209 exhibits synergistic and additive anti-myeloma activity when combined with other epigenetic inhibitors targeting EZH2 and BET bromodomains. Collectively, these data qualify BMI-1 as a candidate for targeted therapy in MM alone or in combinations with epigenetic inhibitors directed to PRC2/EZH2 or BET bromodomains.
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| 40. |
- Andersen, Grethe Neumann, et al.
(author)
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Assessment of vascular function in systemic sclerosis : indications of the development of nitrate tolerance as a result of enhanced endothelial nitric oxide production
- 2002
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In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 46:5, s. 1324-1332
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate the relationship between endothelium-dependent and endothelium-independent functions and the stiffness of conduit arteries as well as levels of endothelial activation markers in patients with systemic sclerosis (SSc). METHODS: Endothelium-dependent (i.e., flow-mediated) and endothelium-independent (i.e., nitroglycerin-induced) dilation of the brachial artery was measured as the percentage of change from baseline (FMD% and NTG%, respectively) in 24 SSc patients and 24 age- and sex-matched healthy controls by high-resolution ultrasound imaging. The maximum increase in systolic pressure per unit of time (dP/dt(max)), as a measure of arterial wall stiffness, was assessed in the radial artery by pulse applanation tonometry. Plasma nitrate, the most important metabolite of nitric oxide, and 24-hour urinary excretion of nitrate were measured by gas chromatography mass spectrometry. Soluble E-selectin and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured by enzyme-linked immunosorbent assay. RESULTS: Brachial artery FMD% and NTG% did not differ between SSc patients and controls. Radial artery dP/dt(max) was significantly increased in the patients and correlated significantly with elevated levels of plasma nitrate and sVCAM-1. Twenty-four-hour urinary nitrate excretion tended to be elevated. Brachial artery NTG% was significantly inversely correlated with levels of plasma nitrate and soluble endothelial adhesion molecules. CONCLUSION: The ability of the brachial arteries to dilate in response to hyperemia and nitroglycerin challenge is preserved in SSc. Stiffness of the radial artery is increased, however. Endothelial activation seems to determine the extent of the brachial artery NTG% and the radial artery dP/dt(max). The data are compatible with the hypothesis that nitrate tolerance is present in the vascular smooth muscle cells of the brachial artery wall in SSc.
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| 41. |
- Andersen, Grethe Neumann, et al.
(author)
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Correlation between increased nitric oxide production and markers of endothelial activation in systemic sclerosis : findings with the soluble adhesion molecules E-selectin, intercellular adhesion molecule 1, and vascular adhesion molecule 1
- 2000
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In: Arthritis and Rheumatism. - 0004-3591 .- 1529-0131. ; 43:5, s. 1085-1093
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Journal article (peer-reviewed)abstract
- Objective To determine the relationship between vascular function and the inflammatory response in systemic sclerosis (SSc), and to investigate whether production of endothelial-derived nitric oxide (NO) is disturbed in this disease. Methods We measured plasma nitrate, urinary excretion of both nitrate and cGMP, and soluble adhesion molecules of endothelial origin in patients with SSc and in age- and sex-matched controls and compared these levels between groups. Additionally, we performed correlation analysis to determine how these variables were related to one another. Plasma nitrate and 24-hour-urinary excretion of nitrate in patients and controls were measured after a 72-hour nitrate-free-diet, using a gas chromatography/mass spectrometric method. Soluble adhesion molecules intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1), and E-selectin and cytokines were measured by enzyme-linked immunosorbent assay. The expression of E-selectin was further investigated in skin biopsy specimens by immunoperoxidase staining, and the presence of inducible NO synthase by immunoblotting. Results Plasma nitrate and 24-hour-urinary-excretion of cGMP were significantly elevated in patients compared with controls, while 24-hour-urinary-excretion of nitrate tended to be elevated in SSc patients. Levels of sICAM-1, sVCAM-1, and sE-selectin were significantly elevated in the patients. Levels of plasma nitrate in the patients correlated significantly with levels of sVCAM-1 (P = 0.020) and sE-selectin (P = 0.018) and approached a significant correlation with sICAM-1 (P = 0.055), suggesting that activated endothelial cells may produce plasma nitrate. Conclusion NO synthesis is elevated in SSc patients, and the activated endothelial cell is a likely site of its production.
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| 42. |
- Andersson, Sandra, et al.
(author)
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The Transcriptomic and Proteomic Landscapes of Bone Marrow and Secondary Lymphoid Tissues
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12, s. e115911-
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Journal article (peer-reviewed)abstract
- Background: The sequencing of the human genome has opened doors for global gene expression profiling, and the immense amount of data will lay an important ground for future studies of normal and diseased tissues. The Human Protein Atlas project aims to systematically map the human gene and protein expression landscape in a multitude of normal healthy tissues as well as cancers, enabling the characterization of both housekeeping genes and genes that display a tissue-specific expression pattern. This article focuses on identifying and describing genes with an elevated expression in four lymphohematopoietic tissue types (bone marrow, lymph node, spleen and appendix), based on the Human Protein Atlas-strategy that combines high throughput transcriptomics with affinity-based proteomics. Results: An enriched or enhanced expression in one or more of the lymphohematopoietic tissues, compared to other tissue-types, was seen for 693 out of 20,050 genes, and the highest levels of expression were found in bone marrow for neutrophilic and erythrocytic genes. A majority of these genes were found to constitute well-characterized genes with known functions in lymphatic or hematopoietic cells, while others are not previously studied, as exemplified by C19ORF59. Conclusions: In this paper we present a strategy of combining next generation RNA-sequencing with in situ affinity-based proteomics in order to identify and describe new gene targets for further research on lymphatic or hematopoietic cells and tissues. The results constitute lists of genes with enriched or enhanced expression in the four lymphohematopoietic tissues, exemplified also on protein level with immunohistochemical images.
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| 43. |
- Appiah Mensah, Alex, et al.
(author)
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Modelling potential yield capacity in conifers using Swedish long-term experiments
- 2022
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In: Forest Ecology and Management. - : Elsevier BV. - 0378-1127 .- 1872-7042. ; 512
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Journal article (peer-reviewed)abstract
- Information on forest site productivity is a key component to assess the carbon sequestration potential of boreal forests. While site index (SI) is commonly used to indicate forest site productivity, expressions of SI in the form of yield capacity (potential maximum mean annual volume increment) is desirable since volume yield is central to the economic and ecological analyses of a given species and site. This paper assessed the functional relationship between SI and yield capacity on the basis of yield plot data from long-term experiments measured over several decades for Norway spruce (Picea abies), Scots pine (Pinus sylvestris), Lodgepole pine (Pinus contorta) and Larch (Larix decidua and Larix sibirica) in Sweden. Component models of total basal area and volume yield were also developed. SI was determined by existing height development functions using top height and age, whereas functions for stand-level (m2 ha- 1) basal area development were constructed based on age, SI and initial stand density using difference equations and nonlinear mixed-effects models. The relation between volume yield (m3 ha- 1) and top height was adjusted with total basal area production through nonlinear mixed-effects models. Species-specific parametric regression models were used to construct functional relationships between SI and yield capacity. The root mean square errors of the species-specific models ranged from 2 to 6% and 10-18% of the average values for the basal area and volume equations, respectively. For the yield capacity functions, the explained variations (R2) were within 80-96%. We compared our yield capacity functions to earlier functions of the species and significant differences were observed in both lower and higher SI classes, especially, for Scots pine and Norway spruce. The new functions give better prediction of yield capacity in current growing conditions; hence, they could later be used for comparing tree species' production under similar site and management regimes in Sweden.
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| 44. |
- Artacho Ruiz, Josep, et al.
(author)
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The synthesis and characterization of all diastereomers of a linear symmetrically fused tris-Troger's base analogue: New chiral cleft compounds
- 2006
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In: Chemistry: A European Journal. - : Wiley. - 1521-3765 .- 0947-6539. ; 12:10, s. 2692-2701
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Journal article (peer-reviewed)abstract
- The synthesis and characterization of all diastereomers of a linear symmetrically fused tris-Troger's base analogue are described. The diastereomers are unambiguously assigned as syn-anti 1a, anti-anti 1b, and syn-syn 1c isomers, by using X-ray diffraction analysis and NMR spectroscopy. For the first time, the anti-anti and the syn-syn diastereomers of a linear symmetrically fused tris-Troger's base analogue have been synthesized. Molecules 1a and 1c are new cleft compounds and analysis of compound 1a in the solid state shows inclusion of one molecule of CH2Cl2 in the larger aromatic cleft, whereas in isomer 1c disordered solvent molecules are trapped in the extended aromatic cleft. Furthermore, in the solid state, isomer 1c forms infinite open channels along one of the crystallographic axes and perpendicular to this axis there are infinitely extending "wedged-ravines". Importantly, each of the diastereomers 1a-c is resistant to inversion at the stereogenic nitrogen atoms under strongly and weakly acidic conditions in the range from room temperature (RT) to 95 degrees C. This observed configurational stability at the stereogenic nitrogens of 1a-c is unique for analogues of Troger's base in general to date. Finally, the ratio of cleft compounds 1a and 1c significantly increased relative to cavity compound 1b when ammonium chloride was used as an additive in the Troger's base condensation to 1a-c suggesting a templating effect of the ammonium ion.
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| 45. |
- Bagerius, Henric, 1974, et al.
(author)
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Vad vill vi med historielärarutbildningen?
- 2022
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In: Historisk tidskrift. - 0345-469X. ; 142:4, s. 607-618
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Journal article (other academic/artistic)abstract
- En central del av verksamheten vid nästan alla institutioner som bedriver undervisning och forskning i historia är att utbilda historielärare. Historiker av facket diskuterar emellertid sällan frågor om lärarutbildningens innehåll och uppläggning, utöver de som knyter an till specifika historievetenskapliga sakområden. Vad behöver framtida historielärare kunna, och hur skiljer det sig eventuellt från vad framtida historiker bör kunna? Hur förhåller sig ämnesstudier till ämnesdidaktik och utbildningsvetenskap? Svaren på den typen av frågor har stor betydelse inte bara för lärarutbildningen utan för universitetsämnet historia och dess utövare i stort. Hur ska vi som historiker förhålla oss till det? Som en utgångspunkt för en sådan diskussion har en grupp historiker verksamma inom lärarutbildningen vid Göteborgs och Örebro universitet genomfört en inventering av historiedidaktiken i ämneslärarutbildningen vid tio av totalt sjutton svenska lärosäten där sådan utbildning med inriktning mot historia inom gymnasieskolan bedrivs idag. Med hjälp av publikt tillgänglig information och en enkät via epost till de ansvariga för utbildningarna har gruppen kartlagt historiedidaktiska kursmål och kurslitteratur, examensarbetenas inriktning och vem som undervisar i historiedidaktik. Medan det finns vissa gemensamma drag i hur målen för utbildningarna formuleras, visar genomgången på betydande variationer mellan lärosätena avseende kurslitteratur, examensarbeten och bemanning. Mot den bakgrunden diskuteras i denna idé- och debattartikel vad likheter och skillnader kan bero på samt om, och i så fall hur, det är ett problem att historielärarutbildningarna är så olika.
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| 46. |
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| 47. |
- Baumgart, Juliane, et al.
(author)
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Urogenital disorders in women with adjuvant endocrine therapy after early breast cancer
- 2011
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In: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 204:1, s. 26.e1-7
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate the prevalence of urogenital symptoms and vaginal atrophy in postmenopausal breast cancer patients on adjuvant endocrine therapy. STUDY DESIGN: A population-based, cross-sectional study on postmenopausal breast cancer patients on adjuvant endocrine treatment and age-matched control subjects. Vaginal atrophy was assessed by gynecologic examination and atrophy-related symptoms by validated questionnaires. RESULTS: In all, 57.6% of aromatase inhibitor-treated and 32.4% of tamoxifen-treated breast cancer patients rated at least 1 vaginal atrophy symptom as moderate/severe, which was significantly more common than in control subjects (P < .01). Aromatase inhibitor-treated patients more often had moderate or severe vaginal atrophy (P < .05), a more atrophic cytohormonal evaluation, and significantly higher vaginal pH (P < .05) than all control subjects, irrespective of hormonal use. CONCLUSION: Our findings indicate that the frequency of vaginal atrophy symptoms, particularly in aromatase inhibitor-treated women, might have been underestimated in previous clinical trials.
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| 48. |
- Bengtsson, Kenneth, et al.
(author)
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Så kan Sverige bli ledande nation i resurseffektivitet
- 2016
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In: Dagens Nyheter. - 1101-2447. ; :2016-04-30
-
Journal article (pop. science, debate, etc.)abstract
- Ny rapport. Det svenska näringslivet kan bli mer hållbart, resurssmart och därmed internationellt konkurrenskraftigt. Men för det behövs en tydlig politisk avsiktsförklaring och riktlinjer. Vi har listat sex områden där policyutveckling brådskar, skriver företrädare för näringsliv, forskning och myndigheter i en gemensam uppmaning.
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| 49. |
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| 50. |
- Bengtsson, Lars, 1958-, et al.
(author)
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A high-performance embedded massively parallel processing system
- 1994
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In: Proceedings of the First International Conference on Massively Parallel Computing Systems (MPCS) The Challenges of General-Purpose and Special-Purpose Computing. - Piscataway, N.J. : IEEE. - 0818663227 - 9780818663222 ; , s. 201-206
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Conference paper (peer-reviewed)abstract
- A need to apply the massively parallel computing paradigm in embedded real-time systems is foreseen. Such applications put new demands on massively parallel systems, different from those of general purpose computing. For example, time determinism is more important than maximal throughput, physical distribution is often required, size, power, and I/O are important, and interactive development tools are needed. The paper describes an architecture for high-performance, embedded, massively parallel processing, featuring a large number of nodes physically distributed over a large area. A typical node has thousands of processing elements (PEs) organized in SIMD mode and is the size of the palm of a hand, Intermodule communication over a scalable optical network is described. A combination of wavelength division multiplexing (WDM) and time division multiplexing (TDM) is used. © 1994 IEEE.
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