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| 4. |
- Wasserman, D, et al.
(författare)
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Compulsory admissions of patients with mental disorders: State of the art on ethical and legislative aspects in 40 European countries
- 2020
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Ingår i: European psychiatry : the journal of the Association of European Psychiatrists. - : Royal College of Psychiatrists. - 1778-3585. ; 63:1, s. e82-
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Tidskriftsartikel (refereegranskat)abstract
- Background.Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care.Methods.The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions.Results.We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures.Conclusions.We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.
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| 5. |
- Fritzell, Peter, et al.
(författare)
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Cost-effectiveness of lumbar fusion and nonsurgical treatment for chronic low back pain in the Swedish lumbar spine study : A multicenter, randomized, controlled trial from the Swedish Lumbar Spine Study Group
- 2004
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Ingår i: Spine. - : Lippincott Williams & Wilkins. - 0362-2436 .- 1528-1159. ; 29:4, s. 421-434
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Tidskriftsartikel (refereegranskat)abstract
- Study Design. A cost-effectiveness study was performed from the societal and health care perspectives. Objective. To evaluate the costs-effectiveness of lumbar fusion for chronic low back pain (CLBP) during a 2-year follow-up. Summary of Background Data. A full economic evaluation comparing costs related to treatment effects in patients with CLBP is lacking. Patients and Methods. A total of 284 of 294 patients with CLBP for at least 2 years were randomized to either lumbar fusion or a nonsurgical control group. Costs for the health care sector ( direct costs), and costs associated with production losses ( indirect costs) were calculated. Societal total costs were identified as the sum of direct and indirect costs. Treatment effects were measured using patient global assessment of improvement, back pain ( VAS), functional disability (Owestry), and return to work. Results. The societal total cost per patient ( standard deviations) in the surgical group was significantly higher than in the nonsurgical group: Swedish kroner (SEK) 704,000 ( 254,000) vs. SEK 636,000 ( 208,000). The cost per patient for the health care sector was significantly higher for the surgical group, SEK 123,000 ( 60,100) vs. 65,200 ( 38,400) for the control group. All treatment effects were significantly better after surgery. The incremental cost-effectiveness ratio ( ICER), illustrating the extra cost per extra effect unit gained by using fusion instead of nonsurgical treatment, were for improvement: SEK 2,600 ( 600 - 5,900), for back pain: SEK 5,200 ( 1,100 - 11,500), for Oswestry: SEK 11,300 ( 1,200 - 48,000), and for return to work: SEK 4,100 ( 100 21,400). Conclusion. For both the society and the health care sectors, the 2-year costs for lumbar fusion was significantly higher compared with nonsurgical treatment but all treatment effects were significantly in favor of surgery. The probability of lumbar fusion being cost-effective increased with the value put on extra effect units gained by using surgery.
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| 7. |
- Murray, Alison E., et al.
(författare)
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Roadmap for naming uncultivated Archaea and Bacteria
- 2020
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Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 5:8, s. 987-994
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Tidskriftsartikel (refereegranskat)abstract
- The assembly of single-amplified genomes (SAGs) and metagenome-assembled genomes (MAGs) has led to a surge in genome-based discoveries of members affiliated with Archaea and Bacteria, bringing with it a need to develop guidelines for nomenclature of uncultivated microorganisms. The International Code of Nomenclature of Prokaryotes (ICNP) only recognizes cultures as 'type material', thereby preventing the naming of uncultivated organisms. In this Consensus Statement, we propose two potential paths to solve this nomenclatural conundrum. One option is the adoption of previously proposed modifications to the ICNP to recognize DNA sequences as acceptable type material; the other option creates a nomenclatural code for uncultivated Archaea and Bacteria that could eventually be merged with the ICNP in the future. Regardless of the path taken, we believe that action is needed now within the scientific community to develop consistent rules for nomenclature of uncultivated taxa in order to provide clarity and stability, and to effectively communicate microbial diversity. In this Consensus Statement, the authors discuss the issue of naming uncultivated prokaryotic microorganisms, which currently do not have a formal nomenclature system due to a lack of type material or cultured representatives, and propose two recommendations including the recognition of DNA sequences as type material.
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| 8. |
- Gagic, Vesna, et al.
(författare)
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Combined effects of agrochemicals and ecosystem services on crop yield across Europe
- 2017
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 20:11, s. 1427-1436
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Tidskriftsartikel (refereegranskat)abstract
- Simultaneously enhancing ecosystem services provided by biodiversity below and above ground is recommended to reduce dependence on chemical pesticides and mineral fertilisers in agriculture. However, consequences for crop yield have been poorly evaluated. Above ground, increased landscape complexity is assumed to enhance biological pest control, whereas below ground, soil organic carbon is a proxy for several yield-supporting services. In a field experiment replicated in 114 fields across Europe, we found that fertilisation had the strongest positive effect on yield, but hindered simultaneous harnessing of below- and above-ground ecosystem services. We furthermore show that enhancing natural enemies and pest control through increasing landscape complexity can prove disappointing in fields with low soil services or in intensively cropped regions. Thus, understanding ecological interdependences between land use, ecosystem services and yield is necessary to promote more environmentally friendly farming by identifying situations where ecosystem services are maximised and agrochemical inputs can be reduced.
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| 9. |
- Hedlund, J., et al.
(författare)
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Management of patients with community-acquired pneumonia treated in hospital in Sweden
- 2002
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Ingår i: Scandinavian Journal of Infectious Diseases. - 0036-5548. ; 34:12, s. 887-92
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the management of patients with community-acquired pneumonia (CAP) treated in hospital in Sweden, a multicentre retrospective cohort study was performed with medical record review of 982 patients (mean age 63 y) at 17 departments of infectious diseases at hospitals in Sweden. Information on antimicrobial therapy, demographic characteristics, comorbid conditions, physical examination findings, and laboratory and microbiological test results were recorded. Outcome measures were in-hospital mortality and length of hospital stay (LOS). Cultures were obtained from blood in 80% and from sputum in 22% of the patients. A microbiological aetiology was determined for 23% of the patients, with Streptococcus pneumoniae as the dominating agent (9%). The initial antibiotic treatment was mostly given intravenously (78%). Penicillin (50%) or a cephalosporin (30%) was the most common choice. Both of these drugs were usually given as a single agent. The overall mortality was 3.5% and the mean LOS was 6.4 d. Thus, the outcome was favourable despite the empirical antibiotic treatment having a narrow spectrum compared with the broader approach recommended in most recent guidelines on the management of CAP. These findings suggest that a majority of patients who are hospitalized with moderately severe pneumonia can be treated initially with penicillin alone.
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| 11. |
- Bowers, Robert M., et al.
(författare)
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Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea
- 2017
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Ingår i: Nature Biotechnology. - : NATURE PUBLISHING GROUP. - 1087-0156 .- 1546-1696. ; 35:8, s. 725-731
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Tidskriftsartikel (refereegranskat)abstract
- We present two standards developed by the Genomic Standards Consortium (GSC) for reporting bacterial and archaeal genome sequences. Both are extensions of the Minimum Information about Any (x) Sequence (MIxS). The standards are the Minimum Information about a Single Amplified Genome (MISAG) and the Minimum Information about a Metagenome-Assembled Genome (MIMAG), including, but not limited to, assembly quality, and estimates of genome completeness and contamination. These standards can be used in combination with other GSC checklists, including the Minimum Information about a Genome Sequence (MIGS), Minimum Information about a Metagenomic Sequence (MIMS), and Minimum Information about a Marker Gene Sequence (MIMARKS). Community-wide adoption of MISAG and MIMAG will facilitate more robust comparative genomic analyses of bacterial and archaeal diversity.
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| 12. |
- Gandaglia, G., et al.
(författare)
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The fatty acid amide hydrolase inhibitor oleoyl ethyl amide counteracts bladder overactivity in female rats
- 2014
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Ingår i: Neurourology and Urodynamics. - : John Wiley & Sons. - 0733-2467 .- 1520-6777. ; 33:8, s. 1251-1258
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Tidskriftsartikel (refereegranskat)abstract
- AIMS:To study micturition and bladder overactivity in female rats after chronic treatment with the fatty acid amide hydrolase (FAAH) inhibitor oleoyl ethyl amide (OEtA).METHODS:Sprague-Dawley rats received daily subcutaneous injections of OEtA (0.3 mg/kg), or vehicle for 2 weeks. Cystometries, organ bath studies, Western blot, and immunofluorescence were then used. Expressions of FAAH, cannabinoid 1 and 2 receptors (CB1 and CB2), mitogen-activated protein kinase (MAPK), vesicular acetyl choline-transporter protein (VAChT), and calcitonin gene-related peptide (CGRP) were evaluated.RESULTS:At baseline, OEtA-treated rats had higher values (P < 0.05) of micturition intervals (MI) and volumes (MV), bladder capacity (BC), threshold pressure, and flow pressure than vehicle controls. Intravesical PGE2 reduced MI, MV, and BC, and increased basal pressure and the area under the curve in all rats. However, these urodynamic parameters were altered less by intravesical PGE2 in OEtA-treated rats (P < 0.05 vs. vehicle controls). Compared to vehicle controls, detrusor from OEtA-treated rats had larger contractions to carbachol at 10-0.1 µM, but no difference in Emax was recorded. FAAH, CB1, CB2, VAChT, or CGRP was similarly expressed in bladders from all rats. In separate experiments, intravesical OEtA increased mucosal expression of phosphorylated MAPK.CONCLUSIONS:Chronic FAAH inhibition altered sensory urodynamic parameters and reduced bladder overactivity. Even if it cannot be excluded that OEtA may act on central nervous sensory pathways to contribute to these effects, the presence of FAAH and CB receptors in the bladder and activation of intracellular signals for CB receptors by intravesical OEtA suggest a local role for FAAH in micturition control. Neurourol. Urodynam
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| 14. |
- Holmfeldt, Linda, et al.
(författare)
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The genomic landscape of hypodiploid acute lymphoblastic leukemia
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:3, s. 242-252
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Tidskriftsartikel (refereegranskat)abstract
- The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32-39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.
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| 15. |
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| 16. |
- Liu, Qing, et al.
(författare)
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Linomide and antibody-targeted superantigen therapy abolishes formation of liver metastases in mice.
- 2003
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Ingår i: European Surgical Research. - : S. Karger AG. - 0014-312X .- 1421-9921. ; 35:6, s. 457-463
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Tidskriftsartikel (refereegranskat)abstract
- Hematogenous spread of tumor cells and metastasis formation in the liver are insidious aspects of cancer progression and are not frequently amenable to curative treatment. We examined the effect of Linomide and antibody-targeted therapy against the formation of hepatic metastases in vivo. For this purpose, syngenic B16 melanoma cells transfected with GA733-2 (a human colon cancer cell surface antigen) were injected into a mesenteric vein of C57/Bl6 mice. To test bacterial superantigen (Sag) targeting for immunotherapy of liver metastases, we used genetically fused proteins consisting of SEA and a Fab moiety of a GA733-2 tumor-reactive antibody (C215Fab-SEA). Linomide dose-dependently reduced hepatic metastases, and at 300 mg/kg this reduction was more than 80%. Treatment with C215Fab-SEA decreased metastases formation by 49% and the combination of Linomide and C215Fab-SEA was found to completely abolish liver metastases (>99% reduction). Taken together, our novel data suggest that Linomide and antibody-targeted superantigen therapy individually markedly reduce and together abolish liver metastases. Considering that current therapy of hepatic metastases is mainly limited to surgical resection in a subgroup of patients, these findings indicate that Linomide alone or in combination with antibody-targeted superantigen may provide a novel approach against liver metastases.
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| 17. |
- Liu, Qing, et al.
(författare)
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Roquinimex inhibits dextran sodium sulfate-induced murine colitis
- 2003
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Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 52:2, s. 64-68
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Roquinimex is a modulator of the immune system and has been shown to attenuate induction of several inflammatory and autoimmune diseases. The objective of the present study was to determine the efficacy of roquinimex in a model of murine colitis. Materials and methods: For this purpose, Balb/c mice were exposed to 5% dextran sodium sulfate (DSS) in the drinking water for five to six days. Roquinimex (300 mg kg(-1) day(-1)) was administered by subcutaneous (s.c.) injection 3 days prior to and throughout the treatment period with DSS. In separate experiments, 300 mg kg(-1) day(-1) of roquinimex was given therapeutically after initiation of DSS challenge. Results: DSS provoked clinical signs of colitis, reduced crypt height (CH) and increased mucosal damage score (MDS) as analyzed by histology. In addition, challenge with DSS increased the colonic content of myeloperoxidase (MPO). Prophylactic administration of DSS-treated mice with roquinimex significantly reduced clinical signs of colitis, MDS and the CH-reduction. Moreover, in roquinimex treated animals, the MPO activity was significantly reduced by more than 50% compared to DSS control mice. Notably, therapeutic administration of roquinimex in DSS-treated mice also significantly inhibited the MDS, CH-reduction and MPO activity. Conclusions: These findings suggest that roquinimex strongly inhibits murine colitis and may provide a novel pharmacological approach to treat inflammatory bowel disease.
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| 18. |
- Mei, Zulin, et al.
(författare)
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Inconsistent responses of carabid beetles and spiders to land-use intensity and landscape complexity in north-western Europe
- 2023
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Ingår i: Biological Conservation. - 0006-3207 .- 1873-2917. ; 283
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Tidskriftsartikel (refereegranskat)abstract
- Reconciling biodiversity conservation with agricultural production requires a better understanding of how key ecosystem service providing species respond to agricultural intensification. Carabid beetles and spiders represent two widespread guilds providing biocontrol services. Here we surveyed carabid beetles and spiders in 66 winter wheat fields in four northwestern European countries and analyzed how the activity density and diversity of carabid beetles and spiders were related to crop yield (proxy for land-use intensity), percentage cropland (proxy for landscape complexity) and soil organic carbon content, and whether these patterns differed between dominant and non-dominant species. <17 % of carabid or spider species were classified as dominant, which accounted for >90 % of individuals respectively. We found that carabids and spiders were generally related to different aspects of agricultural intensification. Carabid species richness was positively related with crop yield and evenness was negatively related to crop cover. The activity density of non-dominant carabids was positively related with soil organic carbon content. Meanwhile, spider species richness and non-dominant spider species richness and activity density were all negatively related to percentage cropland. Our results show that practices targeted to enhance one functionally important guild may not promote another key guild, which helps explain why conservation measures to enhance natural enemies generally do not ultimately enhance pest regulation. Dominant and non-dominant species of both guilds showed mostly similar responses suggesting that management practices to enhance service provisioning by a certain guild can also enhance the overall diversity of that particular guild.
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| 19. |
- Narahashi, T, et al.
(författare)
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Mechanisms of alcohol-nicotine interactions: alcoholics versus smokers.
- 2001
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Ingår i: Alcoholism, clinical and experimental research. - 0145-6008. ; 25:5 Suppl ISBRA
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Forskningsöversikt (refereegranskat)abstract
- This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Toshio Narahashi and Bo Söderpalm. The presentations were (1) Nicotinic mechanisms and ethanol reinforcement: Behavioral and neurochemical studies, by Bo Söderpalm, M. Ericson, P. Olausson, and J. A. Engel; (2) Chronic nicotine and ethanol: Differential regulation in gene expression of nicotinic acetylcholine receptor subunits, by X. Zhang and A. Nordberg; (3) Nicotine-ethanol interactions at neuronal nicotinic acetylcholine receptors, by Toshio Narahashi, William Marszalec, and Gary L. Aistrup; (4) Relapse prevention in alcoholics by cigarette smoking? Treatment outcome in an observational study with acamprosate, by L.G. Schmidt, U. Kalouti, M. Smolka, and M. Soyka; and (5) Effect of nicotine on voluntary ethanol intake and development of alcohol dependence in male rats, by L. Hedlund and G. Wahlström.
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| 22. |
- Strittmatter, F., et al.
(författare)
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Expression of fatty acid amide hydrolase (FAAH) in human, mouse, and rat urinary bladder and effects of FAAH inhibition on bladder function in awake rats
- 2012
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 61:1, s. 98-106
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Cannabinoid receptor (CB)-mediated functions may be involved in the regulation of bladder function, but information on endocannabinoid signals during micturition is scarce.OBJECTIVE:Investigate the expression of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) in human, rat, and mouse bladders and study the effects of inhibition of FAAH during urodynamics in awake rats.DESIGN, SETTING, AND PARTICIPANTS:Bladder tissue from humans, mice, and rats was used for measurements. Female Sprague-Dawley rats were administered the FAAH inhibitor oleoyl ethyl amide (OEtA) or vehicle intravenously (IV) or intravesically (IVES) with or without rimonabant (CB1 antagonist) or SR144528 (CB2 antagonist).MEASUREMENTS:Real-time transcriptase-polymerase chain reaction, Western blot, immunohistochemistry, and cystometry in awake rats.RESULTS AND LIMITATIONS:Messenger RNA and protein for FAAH was expressed in the mucosa of human, mouse, and rat urinary bladders. Immunoreactivities for FAAH and CB2 were codistributed in rat and human urothelium. IV OEtA (0.3mg/kg) to rats increased intercontraction intervals (ICIs), micturition volume (MV), bladder capacity (BC), and threshold pressure (TP) by 17±1%, 16±1%, 17±1%, and 19±5%, respectively (all p<0.05 vs baseline). IVES OEtA (1 and 10mg/l) in rats dose-dependently increased (p<0.05 vs baseline) ICI (19±2% and 35±5%), MV (15±3% and 32±4%), BC (16±2% and 34±4%), and TP (15±1%, 21±3%). SR144528 (IVES 5mg/l) abolished all effects of OEtA, whereas rimonabant only counteracted effects of OEtA on TP.CONCLUSIONS:Bladder mucosa of all species expressed FAAH. Rat and human urothelium coexpressed FAAH and CB2. The FAAH inhibitor OEtA altered urodynamic parameters that reflect sensory functions of micturition in rats. Suggesting a role for the endocannabinoid system in bladder mechanoafferent functions of rats, effects of IVES OEtA were abolished by an IVES CB2 antagonist and partly counteracted by an IVES CB1 antagonist.
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| 30. |
- Bauer, Ricarda M., et al.
(författare)
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Coupling of α1-adrenoceptors to ERK1/2 in the human prostate
- 2011
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Ingår i: Urologia internationalis. - : S. Karger AG. - 0042-1138 .- 1423-0399. ; 86:4, s. 427-433
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: α1-Adrenoceptors are considered critical for the regulation of prostatic smooth muscle tone. However, previous studies suggested further α1-adrenoceptor functions besides contraction. Here, we investigated whether α1-adrenoceptors in the human prostate may activate extracellular signal-regulated kinases (ERK1/2). METHODS: Prostate tissues from patients undergoing radical prostatectomy were stimulated in vitro. Activation of ERK1/2 was assessed by Western blot analysis. Expression of ERK1/2 was studied by immunohistochemistry. The effect of ERK1/2 inhibition by U0126 on phenylephrine-induced contraction was studied in organ-bath experiments. RESULTS: Stimulation of human prostate tissue with noradrenaline (30 μM) or phenylephrine (10 μM) resulted in ERK activation. This was reflected by increased levels of phosphorylated ERK1/2. Expression of ERK1/2 in the prostate was observed in smooth muscle cells. Incubation of prostate tissue with U0126 (30 μM) resulted in ERK1/2 inhibition. Dose-dependent phenylephrine-induced contraction of prostate tissue was not modulated by U0126. CONCLUSIONS: α1-Adrenoceptors in the human prostate are coupled to ERK1/2. This may partially explain previous observations suggesting a role of α1-adrenoceptors in the regulation of prostate growth.
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| 31. |
- Belfrage, Hans, et al.
(författare)
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Combined activation of murine lymphocytes with staphylococcal enterotoxin and interleukin-2 results in additive cytotoxic activity
- 1994
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Ingår i: Cancer Immunology and Immunotherapy. - 1432-0851. ; 38:4, s. 71-265
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Tidskriftsartikel (refereegranskat)abstract
- This report demonstrates that in vitro activation of murine spleen cells with interleukin-2 (IL-2) or the bacterial superantigen staphylococcal enterotoxin A (SEA) results in different patterns of activation and function of cytotoxic cells. Lymphokine-activated killer activity and antibody-dependent cellular cytotoxicity (ADCC) are mainly mediated by IL-2 activated natural killer (NK) cells. SEA is the most powerful T cell mitogen known so far and retargets cytotoxic T lymphocytes (CTL) to tumors expressing major histocompatibility complex (MHC) class II in staphylococcal-enterotoxin-dependent cellular cytotoxicity (SDCC). Culture of mouse spleen cells with SEA led to expansion and activation of T cells, which demonstrated strong SDCC activity and some NK-like cytotoxicity after 5 days in culture. Cell sorting revealed that both CD8+ and CD4+ T cells mediated SDCC but the former were more effective. Phenotypic analysis showed that SEA preferentially stimulated and expanded T cells expressing T cell receptor V beta 11, in particular CD8+ T cells. Combined activation with SEA and IL-2 resulted in simultaneous induction of T and NK cell cytotoxicity. Moreover, IL-2 had additive effects on SEA-induced SDCC. Combined treatment with SEA and IL-2 might therefore be an approach to induce maximal cytotoxicity against tumors and to recruit both T and NK cells in tumor therapy.
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| 32. |
- Belfrage, Hans, et al.
(författare)
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Enhanced and prolonged efficacy of superantigen-induced cytotoxic T lymphocyte activity by interleukin-2 in vivo
- 1995
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Ingår i: Cancer Immunology and Immunotherapy. - 1432-0851. ; 41:2, s. 87-94
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Tidskriftsartikel (refereegranskat)abstract
- The bacterial superantigen, staphylococcal enterotoxin A (SEA) activates T cells with high frequency and directs them to lyse MHC-class-II-expressing cells in superantigen-dependent cell-mediated cytotoxicity (SDCC). Treatment of mice with SEA induced strong CD8+ T-cell(CTL)-mediated SDCC, as well as abundant cytokine production from CD4+ and CD8+ T cells. However, both cytotoxicity and cytokine release were transient. In contrast, combined treatment with SEA and recombinant interleukin-2 (rIL-2) increased peak levels and maintained CTL activity. These effects were concomitant with an increased number of SEA-reactive V beta 11+ T cells. Both the CD4+ and CD8+ populations contained higher frequencies of cells expressing IL-2 receptor (IL-2R) alpha beta, which suggests that continuous IL-2R signaling preserves its high expression and subsequently prevents loss of growth factor signals necessary for expansion of T cells. Although IL-2R expression was increased among both CD4+ and CD8+ cells, only the cytotoxic function of CTL, but not cytokine production from either CD4 or CD8, was augmented. These findings demonstrate that treatment with rIL-2 potentiates superantigen-induced cytotoxicity and maintains high CTL activity. rIL-2 might therefore be useful in improving superantigen-based tumor therapy.
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| 33. |
- Belfrage, Hans, et al.
(författare)
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Prevention of superantigen induced down-regulation of T cell mediated cytotoxic activity by IL-2 in vivo. 1996 Accepted for publication in Immunology
- 1997
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Ingår i: Immunology. - 0019-2805. ; 90:2, s. 8-183
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Tidskriftsartikel (refereegranskat)abstract
- Administration of staphylococcal enterotoxin A (SEA) to mice induces profound activation, cytokine production and cytotoxic activity of both CD4+ and CD8+ T cells, but subsequently activated cells are deleted or become anergic. This study demonstrates that administration of interleukin-2 (IL-2) can prevent sea-induced hyporesponsiveness in CD8+ cytotoxic T lymphocytes (CTL). Repeated injections with sea every fourth day resulted in severely reduced cytotoxic activity in the spleen, which correlated with a reduced number of sea-responsive T-cell receptor (TCR)-V beta 11+ CD8+ cells. Studies of purified TCR-V beta 11+ CD8+ cells showed that they possessed intact cytotoxic activity per cell compared with cells from mice given a single injection of SEA, indicating that deletion was the main mechanism for the reduced cytotoxic activity. Combined treatment with SEA and IL-2 increased the number of cytotoxic cells in the spleen after each SEA injection and prevented the down-regulation of cytotoxic activity. Increased cytotoxic activity could be related to increased number and proliferation of CD8+ IL-2R alpha + cells, suggesting that administration of IL-2 maintained IL-2 responsiveness among CD8+ cells. Studies of sorted TCR-V beta 11+ CD8+ cells demonstrated that combined treatment with SEA and IL-2 also increased cytotoxic activity per cell compared with treatment with SEA alone. Taken together, IL-2 administration in vivo augmented SEA-induced expansion of T cells as well as the cytotoxic activity per CTL, and prevented SEA-induced cell deletion.
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| 34. |
- Belfrage, Hans, et al.
(författare)
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Prevention of superantigen-induced tolerance in vivo by interleukin-2 treatment. 1996 Submitted
- 1997
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Ingår i: Cancer Immunology and Immunotherapy. - 1432-0851. ; 44:2, s. 77-82
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Tidskriftsartikel (refereegranskat)abstract
- Injection of the superantigen staphylococcal enterotoxin A (SEA) activates both CD4+ and CD8+ T cells expressing certain families of T cell receptor (TCR) variable-region beta (V beta) chain. T cells respond with profound cytokine production and induction of cytotoxicity. Repeated injections, however, cause deletion and anergy of both CD4+ and CD8+ T cells, resulting in reduced frequency of SEA-responsive cells TCR-V beta11+ as well as reduced cytokine levels in serum upon challenge with SEA. Exogenous interleukin-2 (IL-2) in vivo rescued SEA-responsive CD4+ and CD8+ cells from SEA-induced deletion and/or increase expansion of SEA-primed cells as well as preventing downregulation of endogenous IL-2 production in vivo. Combined treatment with SEA and IL-2 also superinduced production of important cytokines for the cytotoxic function of T cells, tumour necrosis factor alpha, interferon gamma and IL-6, on a cellular level. These studies show that continuous stimulation with IL-2 in vivo could be useful for superantigen-based immunotherapy by induction of excessive T cell activation and by prevention of the development of T cell deletion and anergy.
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| 35. |
- Bengtsson, G., et al.
(författare)
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Food- and density-dependent dispersal : Evidence from a soil collembolan
- 1994
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Ingår i: Journal of Animal Ecology. - : JSTOR. - 0021-8790. ; 63:3, s. 513-520
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Tidskriftsartikel (refereegranskat)abstract
- 1. Dispersal in a fungivore species of Collembola, Onychiurus armatus, in a homo- geneous soil was theoretically approached as a deterministic compartmental process, in which the movement of animals between discrete patches could be described by a series of differential equations or by the discrete geometric probability distribution, assuming a constant probability to move from one patch to the next. 2. Experiments were designed for a release of collembolans in two types of soil in a physical arrangement of distinct patches represented by vials connected by tubings to cover a distance of 40 cm. Dispersal distances of individuals were determined, and theoretical and observed distributions compared. 3. Dispersal rates, estimated from transfer rate constants, ranged from 0 020 to 1 42 day-1, suggesting that an average 0. armatus moved less than 10 cm day -1. The probability to leave a patch varied between 0 10 and 0 50. 4. Dispersal was dependent on population density, soil type and length of fungal mycelium; it was almost twice as high at a high than at a low density (90 000 and 30000 individuals m-2) in a mor soil and four times as high in a sandy compared with a mor soil. Dispersal rate decreased as the mycelial length increased, especially in a sandy soil. 5. Collembolans in a feeding phase had a higher tendency to disperse than those that were moulting. 6. Enriching the soil patch at 40 cm distance from the release point with a favoured food item, the fungal species Mortierella isabellina, increased dispersal rate by more than four times in a mor soil, suggesting that fungal odour can attract collembolans from a large distance and enhance their rate of movement more than a three-fold increase of their population density does.
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| 36. |
- Bezemer, T. M., et al.
(författare)
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Divergent composition but similar function of soil food webs of individual plants: plant species and community effects
- 2010
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Ingår i: Ecology. - 0012-9658. ; 91:10, s. 3027-3036
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Tidskriftsartikel (refereegranskat)abstract
- Soils are extremely rich in biodiversity, and soil organisms play pivotal roles in supporting terrestrial life, but the role that individual plants and plant communities play in influencing the diversity and functioning of soil food webs remains highly debated. Plants, as primary producers and providers of resources to the soil food web, are of vital importance for the composition, structure, and functioning of soil communities. However, whether natural soil food webs that are completely open to immigration and emigration differ underneath individual plants remains unknown. In a biodiversity restoration experiment we first compared the soil nematode communities of 228 individual plants belonging to eight herbaceous species. We included grass, leguminous, and non-leguminous species. Each individual plant grew intermingled with other species, but all plant species had a different nematode community. Moreover, nematode communities were more similar when plant individuals were growing in the same as compared to different plant communities, and these effects were most apparent for the groups of bacterivorous, carnivorous, and omnivorous nematodes. Subsequently, we analyzed the composition, structure, and functioning of the complete soil food webs of 58 individual plants, belonging to two of the plant species, Lotus corniculatus (Fabaceae) and Plantago lanceolata (Plantaginaceae). We isolated and identified more than 150 taxa/groups of soil organisms. The soil community composition and structure of the entire food webs were influenced both by the species identity of the plant individual and the surrounding plant community. Unexpectedly, plant identity had the strongest effects on decomposing soil organisms, widely believed to be generalist feeders. In contrast, quantitative food web modeling showed that the composition of the plant community influenced nitrogen mineralization under individual plants, but that plant species identity did not affect nitrogen or carbon mineralization or food web stability. Hence, the composition and structure of entire soil food webs vary at the scale of individual plants and are strongly influenced by the species identity of the plant. However, the ecosystem functions these food webs provide are determined by the identity of the entire plant community.
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| 37. |
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| 38. |
- Birkhofer, Klaus, et al.
(författare)
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A framework to identify indicator species for ecosystem services in agricultural landscapes
- 2018
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Ingår i: Ecological Indicators. - : Elsevier BV. - 1470-160X .- 1872-7034. ; 91, s. 278-286
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Tidskriftsartikel (refereegranskat)abstract
- Improving our understanding of the relationships between biodiversity and the delivery of ecosystem services is crucial for the development of sustainable agriculture. We introduce a novel framework that is based on the identification of indicator species for single or multiple ecosystem services across taxonomic groups based on indicator species analyses. We utilize multi-species community data (unlike previous single species approaches) without giving up information about the identity of species in our framework (unlike previous species richness approaches). We compiled a comprehensive community dataset including abundances of 683 invertebrate, vertebrate and plant species to identify indicator species that were either positively or negatively related to biological control, diversity of red-listed species or crop yield in agricultural landscapes in southern Sweden. Our results demonstrate that some taxonomic groups include significantly higher percentages of indicator species for these ecosystem services. Spider communities for example included a higher percentage of significant positive indicator species for biological control than ground or rove beetle communities. Bundles of indicator species for the analysed ecosystem service potentials usually included species that could be linked to the respective ecosystem service based on their functional role in local communities. Several of these species are conspicuous enough to be monitored by trained amateurs and could be used in bundles that are either crucial for the provision of individual ecosystem services or indicate agricultural landscapes with high value for red-listed species or crop yields. The use of bundles of characteristic indicator species for the simultaneous assessment of ecosystem services may reduce the amount of labour, time and cost in future assessments. In addition, future analysis using our framework in other ecosystems or with other subsets of ecosystem services and taxonomic groups will improve our understanding of service-providing species in local communities. In any case, expert knowledge is needed to select species from the identified subsets of significant indicator species and these species should be validated by existing data or additional sampling prior to being used for ecosystem service monitoring.
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| 39. |
- Birkhofer, Klaus, et al.
(författare)
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Relationships between multiple biodiversity components and ecosystem services along a landscape complexity gradient
- 2018
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Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 218, s. 247-253
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Tidskriftsartikel (refereegranskat)abstract
- The assessment of effects of anthropogenic disturbance on biodiversity (BD) and ecosystem services (ES) and their relationships are key priorities of the Intergovernmental Panel for Biodiversity and Ecosystem Services. Agricultural landscapes and their associated BD provide multiple ES and it is crucial to understand how relationships between ES and BD components change along gradients of landscape complexity. In this study, we related eight ES potentials to the species richness of five invertebrate, vertebrate and plant taxonomic groups in cereal farming systems. The landscape complexity gradient ranged from areas dominated by annually tilled arable land to areas with high proportions of unfertilized, non-rotational pastures and uncultivated field borders. We show that after accounting for landscape complexity relationships between yield and bird richness or biological control became more positive, but relationships between bird richness and biological control became less positive. The relationship between bird and plant richness turned from positive to negative. Multidiversity (overall biodiversity), was positively related to landscape complexity, whereas multifunctionality (overall ES provision), was not significantly related to either one of these. Our results suggest that multidiversity can be promoted by increasing landscape complexity; however; we found no support for a simultaneous increase of several individual ES, BD components or multifunctionality. These results challenge the assumption that bio-diversity-friendly landscape management will always simultaneously promote multiple ES in agricultural landscapes. Future studies need to verify this pattern by using multi-year data, larger sets of ES and BD components and a study design that is appropriate to address larger spatial scales and relationships in several regions.
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| 40. |
- Bivalacqua, Trinity J., et al.
(författare)
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Dysregulation of cGMP-dependent protein kinase 1 (PKG-1) impairs erectile function in diabetic rats: influence of in vivo gene therapy of PKG1 alpha
- 2007
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 99:6, s. 1488-1494
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the expression of cGMP-dependent protein kinase 1 (PKG1)alpha and PKG1 beta in the corpus cavernosum, and to evaluate the effect of adenoviral gene transfer of PKG1 alpha to the erectile compartment on erectile function in a rat model of diabetes. Diabetic (DM; induced by streptozotocin) male Sprague Dawley rats were transfected with adenoviruses (AdCMV beta gal or AdCMVPKG1 alpha, in 10 rats each) 2 months after the induction of DM. Intracavernosal pressure (ICP) during stimulation of the cavernosal nerve (CN) was assessed, and compared with mean arterial pressure (MAP). Erectile tissue was harvested for Western blot analysis, immunohistochemistry and total PKG activity. Ten age-matched rats without DM served as the control. Compared to controls, AdCMV beta gal-transfected DM rats had significantly lower peak ICP responses, ICP/MAP ratios, and filling rates during CN stimulation. In DM rats transfected with AdCMVPKG1 alpha, peak ICP, ICP/MAP ratios and filling rates were significantly better than in DM rats transfected with the reporter gene. As assessed by Western blot and immunohistochemistry, expression of PKG1 alpha and PKG1 beta was lower in corporal tissue from DM AdCMV beta gal-transfected rats than in controls. PKG1 alpha expression was improved after AdCMVPKG1 alpha gene therapy. Total PKG activity was lower in DM rat corporal tissue than in controls, and PKG1 alpha gene transfer significantly improved DM corporal PKG activity to a value greater than in the control. PKG1 alpha and PKG1 beta activities are reduced in the erectile tissue of the diabetic rat, and gene transfer of PKG1 alpha to the penis restored PKG activity and erectile function in vivo in diabetic rats. Gene therapy procedures targeting PKG1 alpha might be an interesting future therapeutic approach to overcome diabetic erectile dysfunction resistant to oral pharmacotherapy.
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| 41. |
- Björck, Matts, et al.
(författare)
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Segregation and interdiffusion in (Fe,Co)/Pt superlattices
- 2009
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 79:8, s. 085428-
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Tidskriftsartikel (refereegranskat)abstract
- We report on the chemical structure of (Fe,Co)/Pt superlattices, which recently have shown high uniaxial magnetocrystalline anisotropy combined with high saturation magnetic moments. In particular, the homogeneity of the (Fe,Co) alloy is studied with a combination of x-ray and neutron reflectometry-the latter in a configuration where magnetic scattering is negligible. It is deduced, with support from off-specular x-ray reflectivity patterns and corresponding simulations, that the lower (Fe,Co)-on-Pt interface contains more Co than the upper Pt-on-(Fe,Co) interface. This can occur as Co interdiffuses into Pt more easily than Fe, as shown by density-functional calculations. The effect of this interdiffusion and segregation on the uniaxial anisotropy is discussed, and it is found that the previously observed discrepancy between experimental and theoretical anisotropy values can be quantitatively accounted for.
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| 42. |
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| 43. |
- Carvalho, Lara, et al.
(författare)
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Alkali enhanced biomass gasification with in situ S capture and a novel syngas cleaning : Part 2: Techno-economic analysis
- 2018
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Ingår i: Energy. - : Elsevier. - 0360-5442 .- 1873-6785. ; 165:Part B, s. 471-482
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Tidskriftsartikel (refereegranskat)abstract
- Previous research has shown that alkali addition has operational advantages in entrained flow biomass gasification and allows for capture of up to 90% of the biomass sulfur in the slag phase. The resultant low-sulfur content syngas can create new possibilities for syngas cleaning processes. The aim was to assess the techno-economic performance of biofuel production via gasification of alkali impregnated biomass using a novel gas cleaning systemcomprised of (i) entrained flow catalytic gasification with in situ sulfur removal, (ii) further sulfur removal using a zinc bed, (iii) tar removal using a carbon filter, and (iv) CO2 reductionwith zeolite membranes, in comparison to the expensive acid gas removal system (Rectisol technology). The results show that alkali impregnation increases methanol productionallowing for selling prices similar to biofuel production from non-impregnated biomass. It was concluded that the methanol production using the novel cleaning system is comparable to the Rectisol technology in terms of energy efficiency, while showing an economic advantagederived from a methanol selling price reduction of 2–6 €/MWh. The results showed a high level of robustness to changes related to prices and operation. Methanol selling prices could be further reduced by choosing low sulfur content feedstocks.
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| 44. |
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| 45. |
- Chen, G, et al.
(författare)
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Single-cell analyses of X Chromosome inactivation dynamics and pluripotency during differentiation
- 2016
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 26:10, s. 1342-1354
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Tidskriftsartikel (refereegranskat)abstract
- Pluripotency, differentiation, and X Chromosome inactivation (XCI) are key aspects of embryonic development. However, the underlying relationship and mechanisms among these processes remain unclear. Here, we systematically dissected these features along developmental progression using mouse embryonic stem cells (mESCs) and single-cell RNA sequencing with allelic resolution. We found that mESCs grown in a ground state 2i condition displayed transcriptomic profiles diffused from preimplantation mouse embryonic cells, whereas EpiStem cells closely resembled the post-implantation epiblast. Sex-related gene expression varied greatly across distinct developmental states. We also identified novel markers that were highly enriched in each developmental state. Moreover, we revealed that several novel pathways, including PluriNetWork and Focal Adhesion, were responsible for the delayed progression of female EpiStem cells. Importantly, we “digitalized” XCI progression using allelic expression of active and inactive X Chromosomes and surprisingly found that XCI states exhibited profound variability in each developmental state, including the 2i condition. XCI progression was not tightly synchronized with loss of pluripotency and increase of differentiation at the single-cell level, although these processes were globally correlated. In addition, highly expressed genes, including core pluripotency factors, were in general biallelically expressed. Taken together, our study sheds light on the dynamics of XCI progression and the asynchronicity between pluripotency, differentiation, and XCI.
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| 46. |
- Costantini, E. A.C., et al.
(författare)
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Local adaptation strategies to increase or maintain soil organic carbon content under arable farming in Europe : Inspirational ideas for setting operational groups within the European innovation partnership
- 2020
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Ingår i: Journal of Rural Studies. - : Elsevier BV. - 0743-0167. ; 79, s. 102-115
-
Tidskriftsartikel (refereegranskat)abstract
- In the European Union, the setting of Operational Groups (OG) is supported by the European Innovation Partnership to tackle specific problems and favor innovation in agriculture. They constitute an important aspect of the current Common Agricultural Policy. Increasing or maintaining soil organic carbon (SOC) content under arable farming has been acknowledged as a primary target of European agriculture. SOC-preserving agriculture needs its techniques to be tailored to local conditions, namely, the combination of factors related to the environment (climate and soil characteristics), to the farming system (land use type, farm specialization, crop management), but also to the social and cultural context (market and availability of production means, subsidies, farmers’ education, propensity for innovation and change). In this paper we present inspirational ideas and show success examples of local adaptations strategies to increase or maintain SOC content in soils under arable farming in Europe. They include: · Adoption of soil management strategies to improve SOC storage in irrigated systems. · Precision farming and other high-tech solutions able to generate local diagnosis and adaptive strategies for increasing SOC and reducing greenhouse gasses emissions. · Innovative strategies for extending soil cover periods and introducing cover crops in rotations in areas with limited water availability or prone to harsh weather conditions. · Management of rainfed and low input crops to maintain and increase SOC in dry climates and erosive prone soils. These case studies could facilitate the setting up of OGs and the application of innovative practices in different European countries.
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| 47. |
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| 48. |
- Dohlsten, M, et al.
(författare)
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Lymphocyte subpopulations and lymphokine production in children with constitutional aplastic anemia
- 1988
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Ingår i: Pediatric Hematology & Oncology. - : Informa UK Limited. - 1521-0669 .- 0888-0018. ; 5:2, s. 143-151
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Tidskriftsartikel (refereegranskat)abstract
- The expression of lymphocyte surface markers as well as the production of interleukin-2 (IL-2) and interferon-gamma (IFN) by mitogen-stimulated peripheral blood mononuclear cells (MNC) have been studied in five children with constitutional aplastic anemia. A significantly reduced T4/T8 ratio was found and two of five patients also had a reduced percentage of B cells. One patient had a high percentage of HLA-DR positive T8+ cells, very suggestive of a high degree of circulating activated T suppressor/cytotoxic cells. IL-2 production was reduced in two patients, whereas IFN production was only reduced in one of these. The abnormalities found correlate with the duration of the bone marrow failure. The patients with the longest duration of bone marrow failure also exhibited the lowest T4/T8 ratio. No spontaneous IFN production was detected in any of the patients. There was no clinical benefit or reversal of the immune abnormalities during and following treatment with cimetidine and cyclosporine A in two patients.
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| 49. |
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| 50. |
- Faber, Zachary J, et al.
(författare)
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The genomic landscape of core-binding factor acute myeloid leukemias
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 48, s. 1551-1556
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Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving the core-binding factor (CBF) transcriptional complex. To better understand the genomic landscape of CBF-AMLs, we analyzed both pediatric (n = 87) and adult (n = 78) samples, including cases with RUNX1-RUNX1T1 (n = 85) or CBFB-MYH11 (n = 80) rearrangements, by whole-genome or whole-exome sequencing. In addition to known mutations in the Ras pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a previously unappreciated cooperating pathway in CBF-AML. Outside of signaling alterations, RUNX1-RUNX1T1 and CBFB-MYH11 AMLs demonstrated remarkably different spectra of cooperating mutations, as RUNX1-RUNX1T1 cases harbored recurrent mutations in DHX15 and ZBTB7A, as well as an enrichment of mutations in epigenetic regulators, including ASXL2 and the cohesin complex. This detailed analysis provides insights into the pathogenesis and development of CBF-AML, while highlighting dramatic differences in the landscapes of cooperating mutations for these related AML subtypes.
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