| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
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| 3. |
- Rich, Rebecca L., et al.
(författare)
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A global benchmark study using affinity-based biosensors
- 2009
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 386:2, s. 194-216
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Tidskriftsartikel (refereegranskat)abstract
- To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.
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| 4. |
- Aragam, Krishna G., et al.
(författare)
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Phenotypic Refinement of Heart Failure in a National Biobank Facilitates Genetic Discovery
- 2019
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Ingår i: Circulation. - 0009-7322. ; 139:4, s. 489-501
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure (HF) is a morbid and heritable disorder for which the biological mechanisms are incompletely understood. We therefore examined genetic associations with HF in a large national biobank, and assessed whether refined phenotypic classification would facilitate genetic discovery. Methods: We defined all-cause HF among 488 010 participants from the UK Biobank and performed a genome-wide association analysis. We refined the HF phenotype by classifying individuals with left ventricular dysfunction and without coronary artery disease as having nonischemic cardiomyopathy (NICM), and repeated a genetic association analysis. We then pursued replication of lead HF and NICM variants in independent cohorts, and performed adjusted association analyses to assess whether identified genetic associations were mediated through clinical HF risk factors. In addition, we tested rare, loss-of-function mutations in 24 known dilated cardiomyopathy genes for association with HF and NICM. Finally, we examined associations between lead variants and left ventricular structure and function among individuals without HF using cardiac magnetic resonance imaging (n=4158) and echocardiographic data (n=30 201). Results: We identified 7382 participants with all-cause HF in the UK Biobank. Genome-wide association analysis of all-cause HF identified several suggestive loci (P<1×10 -6 ), the majority linked to upstream HF risk factors, ie, coronary artery disease (CDKN2B-AS1 and MAP3K7CL) and atrial fibrillation (PITX2). Refining the HF phenotype yielded a subset of 2038 NICM cases. In contrast to all-cause HF, genetic analysis of NICM revealed suggestive loci that have been implicated in dilated cardiomyopathy (BAG3, CLCNKA-ZBTB17). Dilated cardiomyopathy signals arising from our NICM analysis replicated in independent cohorts, persisted after HF risk factor adjustment, and were associated with indices of left ventricular dysfunction in individuals without clinical HF. In addition, analyses of loss-of-function variants implicated BAG3 as a disease susceptibility gene for NICM (loss-of-function variant carrier frequency=0.01%; odds ratio,12.03; P=3.62×10 -5 ). Conclusions: We found several distinct genetic mechanisms of all-cause HF in a national biobank that reflect well-known HF risk factors. Phenotypic refinement to a NICM subtype appeared to facilitate the discovery of genetic signals that act independently of clinical HF risk facto rs and that are associated with subclinical left ventricular dysfunction.
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| 5. |
- Schepetkin, Igor A, et al.
(författare)
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Molecular docking of 2-(benzimidazol-2-ylthio)-N-phenylacetamide-derived small-molecule agonists of human formyl peptide receptor 1.
- 2012
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Ingår i: Journal of molecular modeling. - : Springer Science and Business Media LLC. - 0948-5023 .- 1610-2940. ; 18:6, s. 2831-2843
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Tidskriftsartikel (refereegranskat)abstract
- Human N-formyl peptide receptor 1 (FPR1) is a G protein-coupled receptor (GPCR) involved in host defense and sensing cellular damage. Since structure-based ligand design for many GPCRs, including FPR1, is restricted by the lack of experimental three dimensional structures, homology modeling has been widely used to study GPCR-ligand binding. Indeed, receptor-ligand binding mode predictions can be derived from homology modeling with supporting ligand information. In the present work, we report comparative docking studies of 2-(benzimidazol-2-ylthio)-N-phenylacetamide derived FPR1 agonists, identified here and previously, with several known FPR1 peptide agonists in a FPR1 homology model that is based on the crystal structure of bovine rhodopsin. We found that the binding pocket of the most active molecules shares some common features with high affinity FPR1 peptide agonists, suggesting that they may bind to similar binding sites. Classification tree analysis led to the derivation of a good recognition model based on four amino acid descriptors for distinguishing FPR1 ligands from inactive analogs. Hence, the corresponding residues (Thr199, Arg201, Gly202, and Ala261) can be considered as markers of important areas in the ligand binding site. Concurrently, we identified several unique binding features of benzimidazole derivatives and showed that alkoxy-substituents of the benzimidazole ring are located within a FPR1 hole bounded by Thr199, Thr265, Ile268, and Leu271 or in a groove in the vicinity of Leu198, Arg201, Gly202, and Arg205. The understanding of these molecular features will likely prove beneficial in future design of novel FPR1 agonists based on the benzimidazole scaffold.
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| 6. |
- Ahmed, Hamad, et al.
(författare)
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Experimental Observation of Thin-shell Instability in a Collisionless Plasma
- 2017
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Ingår i: Astrophysical Journal Letters. - : Institute of Physics Publishing (IOPP). - 2041-8205 .- 2041-8213. ; 834:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on the experimental observation of the instability of a plasma shell, which formed during the expansion of a laser-ablated plasma into a rarefied ambient medium. By means of a proton radiography technique, the evolution of the instability is temporally and spatially resolved on a timescale much shorter than the hydrodynamic one. The density of the thin shell exceeds that of the surrounding plasma, which lets electrons diffuse outward. An ambipolar electric field grows on both sides of the thin shell that is antiparallel to the density gradient. Ripples in the thin shell result in a spatially varying balance between the thermal pressure force mediated by this field and the ram pressure force that is exerted on it by the inflowing plasma. This mismatch amplifies the ripples by the same mechanism that drives the hydrodynamic nonlinear thin-shell instability (NTSI). Our results thus constitute the first experimental verification that the NTSI can develop in colliding flows.
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| 7. |
- Ahmed, Hamad, et al.
(författare)
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Time-Resolved Characterization of the Formation of a Collisionless Shock
- 2013
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 110:20
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Tidskriftsartikel (refereegranskat)abstract
- We report on the temporally and spatially resolved detection of the precursory stages that lead to the formation of an unmagnetized, supercritical collisionless shock in a laser-driven laboratory experiment. The measured evolution of the electrostatic potential associated with the shock unveils the transition from a current free double layer into a symmetric shock structure, stabilized by ion reflection at the shock front. Supported by a matching particle-in-cell simulation and theoretical considerations, we suggest that this process is analogous to ion reflection at supercritical collisionless shocks in supernova remnants.
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| 8. |
- Alexander, Stephen P. H., et al.
(författare)
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The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors
- 2023
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Ingår i: BRITISH JOURNAL OF PHARMACOLOGY. - : British pharmacological society. - 0007-1188 .- 1476-5381. ; 180
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Tidskriftsartikel (refereegranskat)abstract
- The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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| 9. |
- Benatar, Michael, et al.
(författare)
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Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01) : a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
- 2024
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 23:7, s. 687-699
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Tidskriftsartikel (refereegranskat)abstract
- Background: Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder leading to muscle weakness and respiratory failure. Arimoclomol, a heat-shock protein-70 (HSP70) co-inducer, is neuroprotective in animal models of amyotrophic lateral sclerosis, with multiple mechanisms of action, including clearance of protein aggregates, a pathological hallmark of sporadic and familial amyotrophic lateral sclerosis. We aimed to evaluate the safety and efficacy of arimoclomol in patients with amyotrophic lateral sclerosis.Methods: ORARIALS-01 was a multinational, randomised, double-blind, placebo-controlled, parallel-group trial done at 29 centres in 12 countries in Europe and North America. Patients were eligible if they were aged 18 years or older and met El Escorial criteria for clinically possible, probable, probable laboratory-supported, definite, or familial amyotrophic lateral sclerosis; had an ALS Functional Rating Scale-Revised score of 35 or more; and had slow vital capacity at 70% or more of the value predicted on the basis of the participant's age, height, and sex. Patients were randomly assigned (2:1) in blocks of 6, stratified by use of a stable dose of riluzole or no riluzole use, to receive oral arimoclomol citrate 1200 mg/day (400 mg three times per day) or placebo. The Randomisation sequence was computer generated centrally. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was the Combined Assessment of Function and Survival (CAFS) rank score over 76 weeks of treatment. The primary outcome and safety were analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03491462, and is completed.Findings: Between July 31, 2018, and July 17, 2019, 287 patients were screened, 245 of whom were enrolled in the trial and randomly assigned. The modified intention-to-treat population comprised 239 patients (160 in the arimoclomol group and 79 in the placebo group): 151 (63%) were male and 88 (37%) were female; mean age was 57·6 years (SD 10·9). CAFS score over 76 weeks did not differ between groups (mean 0·51 [SD 0·29] in the arimoclomol group vs 0·49 [0·28] in the placebo group; p=0·62). Cliff's delta comparing the two groups was 0·039 (95% CI –0·116 to 0·194). Proportions of participants who died were similar between the treatment groups: 29 (18%) of 160 patients in the arimoclomol group and 18 (23%) of 79 patients in the placebo group. Most deaths were due to disease progression. The most common adverse events were gastrointestinal. Adverse events were more often deemed treatment-related in the arimoclomol group (104 [65%]) than in the placebo group (41 [52%]) and more often led to treatment discontinuation in the arimoclomol group (26 [16%]) than in the placebo group (four [5%]).Interpretation: Arimoclomol did not improve efficacy outcomes compared with placebo. Although available biomarker data are insufficient to preclude future strategies that target the HSP response, safety data suggest that a higher dose of arimoclomol would not have been tolerated.Funding: Orphazyme.
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| 10. |
- Bremer, Kåre, et al.
(författare)
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An ordinal classification for the families of flowering plants
- 1998
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Ingår i: ANNALS OF THE MISSOURI BOTANICAL GARDEN. - : MISSOURI BOTANICAL GARDEN. - 0026-6493. ; 85:4, s. 531-553
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Recent cladistic analyses are revealing the phylogeny of flowering plants in increasing detail, and there is support for the monophyly of many major groups above the family level. With many elements of the major branching sequence of phylogeny established
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| 11. |
- Carroll, David C., et al.
(författare)
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Dynamic control and enhancement of laser-accelerated protons using multiple laser pulses
- 2009
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Ingår i: Comptes Rendus. Physique. - : Elsevier BV. - 1631-0705. ; 10:2-3, s. 188-196
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Tidskriftsartikel (refereegranskat)abstract
- The use of schemes involving multiple laser pulses to enhance and control the properties of beams of protons accelerated in ultra-intense laser irradiation of planar foil targets is discussed. Specifically, the schemes include the use of a second laser pulse to produce and control preplasma expansion of the target to enhance energy coupling to the proton beam; the use of a second laser pulse to drive shock deformation of the target to change the direction of the proton beam; and a scheme involving dual high intensity laser pulses to change the properties of the sheath field, with the aim of modifying the proton energy spectrum. An overview of our recent experimental and theoretical results is given. The overall aim of this work is to determine the extent to which the properties of the sheath-accelerated proton beam can be optically controlled, to enable beam delivery at high repetition rates. To cite this article: D.C. Carroll et al., C. R. Physique 10 (2009). (C) 2009 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
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| 12. |
- Chen, Hao Yu, et al.
(författare)
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Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids With Aortic Stenosis
- 2020
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Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 5:6, s. 694-702
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets.Objective: To identify novel genetic loci and pathways associated with AS.Design, Setting, and Participants: This genome-wide association study used a case-control design to evaluate 44 703 participants (3469 cases of AS) of self-reported European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (from January 1, 1996, to December 31, 2015). Replication was performed in 7 other cohorts totaling 256 926 participants (5926 cases of AS), with additional analyses performed in 6942 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Follow-up biomarker analyses with aortic valve calcium (AVC) were also performed. Data were analyzed from May 1, 2017, to December 5, 2019.Exposures: Genetic variants (615 643 variants) and polyunsaturated fatty acids (ω-6 and ω-3) measured in blood samples.Main Outcomes and Measures: Aortic stenosis and aortic valve replacement defined by electronic health records, surgical records, or echocardiography and the presence of AVC measured by computed tomography.Results: The mean (SD) age of the 44 703 GERA participants was 69.7 (8.4) years, and 22 019 (49.3%) were men. The rs174547 variant at the FADS1/2 locus was associated with AS (odds ratio [OR] per C allele, 0.88; 95% CI, 0.83-0.93; P = 3.0 × 10-6), with genome-wide significance after meta-analysis with 7 replication cohorts totaling 312 118 individuals (9395 cases of AS) (OR, 0.91; 95% CI, 0.88-0.94; P = 2.5 × 10-8). A consistent association with AVC was also observed (OR, 0.91; 95% CI, 0.83-0.99; P = .03). A higher ratio of arachidonic acid to linoleic acid was associated with AVC (OR per SD of the natural logarithm, 1.19; 95% CI, 1.09-1.30; P = 6.6 × 10-5). In mendelian randomization, increased FADS1 liver expression and arachidonic acid were associated with AS (OR per unit of normalized expression, 1.31 [95% CI, 1.17-1.48; P = 7.4 × 10-6]; OR per 5-percentage point increase in arachidonic acid for AVC, 1.23 [95% CI, 1.01-1.49; P = .04]; OR per 5-percentage point increase in arachidonic acid for AS, 1.08 [95% CI, 1.04-1.13; P = 4.1 × 10-4]).Conclusions and Relevance: Variation at the FADS1/2 locus was associated with AS and AVC. Findings from biomarker measurements and mendelian randomization appear to link ω-6 fatty acid biosynthesis to AS, which may represent a therapeutic target.
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| 13. |
- Chen, H.Y., et al.
(författare)
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Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study
- 2023
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:21, s. 1927-1939
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Tidskriftsartikel (refereegranskat)abstract
- Aims Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. Methods and results A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10−8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2–SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26–1.35; P = 2.7 × 10−51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08–1.37; P = 1.4 × 10−3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90–5.12; P = 2.1 × 10−20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17–1.23; P = 4.8 × 10−73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05–1.9; P = 1.9 × 10−12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. Conclusion Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies. © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
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| 14. |
- Christopoulos, Arthur, et al.
(författare)
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THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.
- 2021
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Ingår i: British journal of pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 178 Suppl 1
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Forskningsöversikt (refereegranskat)abstract
- The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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| 15. |
- Culina, Antica, et al.
(författare)
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Connecting the data landscape of long-term ecological studies : The SPI-Birds data hub
- 2021
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Ingår i: Journal of Animal Ecology. - : John Wiley & Sons. - 0021-8790 .- 1365-2656. ; 90:9, s. 2147-2160
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Tidskriftsartikel (refereegranskat)abstract
- The integration and synthesis of the data in different areas of science is drastically slowed and hindered by a lack of standards and networking programmes. Long-term studies of individually marked animals are not an exception. These studies are especially important as instrumental for understanding evolutionary and ecological processes in the wild. Furthermore, their number and global distribution provides a unique opportunity to assess the generality of patterns and to address broad-scale global issues (e.g. climate change). To solve data integration issues and enable a new scale of ecological and evolutionary research based on long-term studies of birds, we have created the SPI-Birds Network and Database ()-a large-scale initiative that connects data from, and researchers working on, studies of wild populations of individually recognizable (usually ringed) birds. Within year and a half since the establishment, SPI-Birds has recruited over 120 members, and currently hosts data on almost 1.5 million individual birds collected in 80 populations over 2,000 cumulative years, and counting. SPI-Birds acts as a data hub and a catalogue of studied populations. It prevents data loss, secures easy data finding, use and integration and thus facilitates collaboration and synthesis. We provide community-derived data and meta-data standards and improve data integrity guided by the principles of Findable, Accessible, Interoperable and Reusable (FAIR), and aligned with the existing metadata languages (e.g. ecological meta-data language). The encouraging community involvement stems from SPI-Bird's decentralized approach: research groups retain full control over data use and their way of data management, while SPI-Birds creates tailored pipelines to convert each unique data format into a standard format. We outline the lessons learned, so that other communities (e.g. those working on other taxa) can adapt our successful model. Creating community-specific hubs (such as ours, COMADRE for animal demography, etc.) will aid much-needed large-scale ecological data integration.
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| 16. |
- Dieckmann, Mark Eric, et al.
(författare)
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The Weibel instability in a circular rarefaction wave
- 2012
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Ingår i: Proceedings of the 39th European Physical Society Conference & 16th Int. Congress on Plasma Physics. ; , s. P1.176-1-P1.176-4
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Konferensbidrag (refereegranskat)abstract
- Instabilities behind the front of a cylindrically expanding plasma have been investigated experimentally and with a particle-in-cell simulation. Tubelike filamentary structures form behind the front of a plasma created by irradiating wire targets with a ps-duration and intense ( 1019 W cm-2) laser pulse. These filaments exhibit coherent magnetic fields with a remarkable stability ( 103 / wp: plasma frequency). PIC simulations indicate that an instability driven by a thermal anisotropy of the electron population is the cause. This instability requires a plasma density gradient and hot electrons. It can thus contribute to the generation of strongsustained magnetic fields in astrophysical jets.
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| 17. |
- Englund, Oskar, et al.
(författare)
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Multifunctional perennial production systems for bioenergy: performance and progress
- 2020
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Ingår i: Wiley Interdisciplinary Reviews. - : Wiley. - 2041-8396 .- 2041-840X.
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Tidskriftsartikel (refereegranskat)abstract
- As the global population increases and becomes more affluent, biomass demands for food and biomaterials will increase. Demand growth is further accelerated by the implementation of climate policies and strategies to replace fossil resources with biomass. There are, however, concerns about the size of the prospective biomass demand and the environmental and social consequences of the corresponding resource mobilization, especially concerning impacts from the associated land-use change. Strategically integrating perennials into landscapes dominated by intensive agriculture can, for example, improve biodiversity, reduce soil erosion and nutrient emissions to water, increase soil carbon, enhance pollination, and avoid or mitigate flooding events. Such ?multifunctional perennial production systems? can thus contribute to improving overall land-use sustainability, while maintaining or increasing overall biomass productivity in the landscape. Seven different cases in different world regions are here reviewed to exemplify and evaluate (a) multifunctional production systems that have been established to meet emerging bioenergy demands, and (b) efforts to identify locations where the establishment of perennial crops will be particularly beneficial. An important barrier towards wider implementation of multifunctional systems is the lack of markets, or policies, compensating producers for enhanced ecosystem services and other environmental benefits. This deficiency is particularly important since prices for fossil-based fuels are low relative to bioenergy production costs. Without such compensation, multifunctional perennial production systems will be unlikely to contribute to the development of a sustainable bioeconomy.
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| 18. |
- Giovannoni, Maria Paola, et al.
(författare)
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Further studies on 2-arylacetamide pyridazin-3(2H)-ones: Design, synthesis and evaluation of 4,6-disubstituted analogs as formyl peptide receptors (FPRs) agonists.
- 2013
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Ingår i: European journal of medicinal chemistry. - : Elsevier BV. - 1768-3254 .- 0223-5234. ; 64C, s. 512-528
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Tidskriftsartikel (refereegranskat)abstract
- Formyl peptide receptors (FPRs) play an essential role in the regulation of endogenous inflammation and immunity. In the present studies, a large series of pyridazin-3(2H)-one derivatives bearing an arylacetamide chain at position 2 was synthesized and tested for FPR agonist activity. The pyridazin-3(2H)-one ring was confirmed to be an appropriate scaffold to support FPR agonist activity, and its modification at the 4 and 6 positions led to the identification of additional active agonists, which induced intracellular Ca(2+) flux in HL-60 cells transfected with either FPR1, FPR2, or FPR3. Seven formyl peptide receptor 1 (FPR1)-specific and several mixed FPR1/FPR2 dual agonists were identified with low micromolar EC50 values. Furthermore, these agonists also activated human neutrophils, inducing intracellular Ca(2+) flux and chemotaxis. Finally, molecular docking studies indicated that the most potent pyridazin-3(2H)-ones overlapped in their best docking poses with fMLF and WKYMVM peptides in the FPR1 and FPR2 ligand binding sites, respectively. Thus, pyridazinone-based compounds represent potential lead compounds for further development of selective and/or potent FPR agonists.
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| 19. |
- Huang, Chelsea X., et al.
(författare)
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TESS Spots a Hot Jupiter with an Inner Transiting Neptune
- 2020
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 892:1
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Tidskriftsartikel (refereegranskat)abstract
- Hot Jupiters are rarely accompanied by other planets within a factor of a few in orbital distance. Previously, only two such systems have been found. Here, we report the discovery of a third system using data from the Transiting Exoplanet Survey Satellite (TESS). The host star, TOI-1130, is an eleventh magnitude K-dwarf in Gaia G-band. It has two transiting planets: a Neptune-sized planet (3.65 ± 0.10 R\oplus) with a 4.1 days period, and a hot Jupiter (1.50-0.22+0.27 RJ) with an 8.4 days period. Precise radial-velocity observations show that the mass of the hot Jupiter is 0.974-0.044+0.043 MJ. For the inner Neptune, the data provide only an upper limit on the mass of 0.17 MJ (3σ). Nevertheless, we are confident that the inner planet is real, based on follow-up ground-based photometry and adaptive-optics imaging that rule out other plausible sources of the TESS transit signal. The unusual planetary architecture of and the brightness of the host star make TOI-1130 a good test case for planet formation theories, and an attractive target for future spectroscopic observations.
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| 20. |
- Lai, En Yin, et al.
(författare)
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Effects of the antioxidant drug tempol on renal oxygenation in mice with reduced renal mass
- 2012
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Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 0363-6127 .- 1522-1466 .- 1931-857X. ; 303:1, s. F64-74
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Tidskriftsartikel (refereegranskat)abstract
- We tested the hypothesis that reactive oxygen species (ROS) contributed to renal hypoxia in C57BL/6 mice with ⅚ surgical reduction of renal mass (RRM). ROS can activate the mitochondrial uncoupling protein 2 (UCP-2) and increase O(2) usage. However, UCP-2 can be inactivated by glutathionylation. Mice were fed normal (NS)- or high-salt (HS) diets, and HS mice received the antioxidant drug tempol or vehicle for 3 mo. Since salt intake did not affect the tubular Na(+) transport per O(2) consumed (T(Na/)Q(O2)), further studies were confined to HS mice. RRM mice had increased excretion of 8-isoprostane F(2α) and H(2)O(2), renal expression of UCP-2 and renal O(2) extraction, and reduced T(Na/)Q(O2) (sham: 20 ± 2 vs. RRM: 10 ± 1 μmol/μmol; P < 0.05) and cortical Po(2) (sham: 43 ± 2, RRM: 29 ± 2 mmHg; P < 0.02). Tempol normalized all these parameters while further increasing compensatory renal growth and glomerular volume. RRM mice had preserved blood pressure, glomeruli, and patchy tubulointerstitial fibrosis. The patterns of protein expression in the renal cortex suggested that RRM kidneys had increased ROS from upregulated p22(phox), NOX-2, and -4 and that ROS-dependent increases in UCP-2 led to hypoxia that activated transforming growth factor-β whereas erythroid-related factor 2 (Nrf-2), glutathione peroxidase-1, and glutathione-S-transferase mu-1 were upregulated independently of ROS. We conclude that RRM activated distinct processes: a ROS-dependent activation of UCP-2 leading to inefficient renal O(2) usage and cortical hypoxia that was offset by Nrf-2-dependent glutathionylation. Thus hypoxia in RRM may be the outcome of NADPH oxidase-initiated ROS generation, leading to mitochondrial uncoupling counteracted by defense pathways coordinated by Nrf-2.
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| 21. |
- Lakens, Daniel, et al.
(författare)
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Justify your alpha
- 2018
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Ingår i: Nature Human Behaviour. - : Nature Publishing Group. - 2397-3374. ; 2:3, s. 168-171
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Tidskriftsartikel (refereegranskat)abstract
- In response to recommendations to redefine statistical significance to P ≤ 0.005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level.
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| 22. |
- Lönnbro, Per, et al.
(författare)
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Analysis of neutrophil membrane traffic during phagocytosis
- 2007
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Ingår i: Neutrophil Methods and Protocols (Methods in Molecular Biology). - 1588297888 - 9781588297884
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Bokkapitel (populärvet., debatt m.m.)abstract
- In this chapter, we describe methods to study membrane traffic during phagosome formation and maturation.
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| 23. |
- Mariani, Raffaello, et al.
(författare)
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A Note on the Generation of a Compressible Vortex Rings Using Helium as Driver Gas.
- 2012
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Ingår i: Proceedings of the Institution of Mechanical Engineers. Part G, Journal of Aerospace Engineering. - : Sage Publications. - 0954-4100 .- 2041-3025. ; 227:10, s. 1637-1645
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Tidskriftsartikel (refereegranskat)abstract
- An experimental study has been conducted on the generation and propagation of compressible vortex rings using helium as a driver gas, with the aim of evaluating the effects of multi-gas operations for real-life applications. The advantage of such system, when compared to a constant gas system based on ambient air, is to effectively increase the Mach number while keeping the pressure ratio constant. Three pressure ratios of ~4, 8 and 12 were set, corresponding to experimental Mach numbers of approximately 1.50, 1.81 and 2.05. The increase in incident Mach number resulted in the variation of the vortex ring and trailing jet structure, and an increase in both the velocity magnitude and vorticity field. Results showed a transition from the regular-reflection shock-cell system at the experimental Mach number approximately 1.50 to the presence of a Mach reflection with a central Mach disc, which grew in size with further increase in incident Mach number. The presence of the Mach disc resulted in the formation of a subsonic jet, internal to the main trailing jet. Its velocity was measured to be in the order of magnitude of 550 m/s, with the speed of sound of helium at 1005 m/s. Results also demonstrated that shear layers formed between the subsonic and main trailing jet have opposing vorticity, with that of the subsonic jet being approximately half in magnitude. Secondary counter-rotating vortex rings were generated ahead of the main vortex and orbited around it. The analysis of the vorticity field has shown that these secondary vortices have a magnitude approximately half of that of the vorticity of the main vortex, and has confirmed that they have an opposite direction of rotation.
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| 24. |
- Mariani, Raffaello, et al.
(författare)
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Shock-Free Compressible Vortex Rings Impinging on a Stationary Surface: Effects of Surface Angle Variation.
- 2013
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Ingår i: Experimental Thermal and Fluid Science. - : Elsevier BV. - 0894-1777 .- 1879-2286. ; 47, s. 126-142
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Tidskriftsartikel (refereegranskat)abstract
- An experimental study has been conducted on the impingement of compressible vortex rings on stationary, inclined, smooth surfaces. Four surface angle inclinations were evaluated: 90° (perpendicular to theflow longitudinal axis), 75°, 60°, and 45°. The flow was assumed axisymmetric for the 90° benchmark case. A single pressure ratio of ~4 was used, corresponding to an experimental incident shock wave Mach number of ~1.31, generating a shock-free compressible vortex ring.Results showed two main flow processes: the interaction of the reflected shock wave with the approaching vortical structure, and the impingement of the vortex ring on the surface. At surface inclinationangles other than 90, these processes are asymmetrical and the shape of the reflected shock ismodified by the approaching vortex ring. The lower outer section of the reflected shock wave is initiallydiffracted by the lower core of the vortex ring, its central section is then captured by the central section ofthe torus, and ultimately the upper outer section is diffracted by the upper core. The vortex ring subsequently impinges on the surface with the lower core impacting first, undergoing an asymmetrical stretching and deformation.Flow field studies showed an initial decrease in velocity magnitude and vorticity field as the flow transitionedfrom a symmetrical to an asymmetrical impingement, possibly due to the uneven formation of the boundary layer. The velocity magnitude and vorticity field of the upper core subsequently increase again, as a result of the upwards deflection of the flow. Oppositely, the lower core is seen to dissipate. Surface pressure measurements confirmed the asymmetry in the flow development. As the surface angle is varied, the pressure at the central measurement location is seen to decrease as the position ofthe stagnation point is altered. An interesting feature within the surface measurements is a strong lateral acceleration due to the formation of vortex lines which roll around the main vortex core.
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| 25. |
- Melin, Beatrice S., et al.
(författare)
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Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:5, s. 789-794
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 x 10(-9), odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 x 10(-10), OR = 1.24), 16p13.3 (rs2562152; P = 1.93 x 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 x 10(-11), OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 x 10(-10), OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 x 10(-9), OR = 1.19), 1q44 (rs12076373; P = 2.63 x 10(-10), OR = 1.23), 2q33.3 (rs7572263; P = 2.18 x 10(-10), OR = 1.20), 3p14.1 (rs11706832; P = 7.66 x 10(-9), OR = 1.15), 10q24.33 (rs11598018; P = 3.39 x 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 x 10(-10), OR = 1.16), 14q12 (rs10131032; P = 5.07 x 10(-11), OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 x 10(-9), OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.
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