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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Devos, David, et al.
(författare)
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Trial of Deferiprone in Parkinson’s Disease
- 2022
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 387:22, s. 2045-2055
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDIron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear.METHODSWe conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome.RESULTSA total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants.CONCLUSIONSIn participants with early Parkinson's disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks.
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- Householder, John Ethan, et al.
(författare)
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One sixth of Amazonian tree diversity is dependent on river floodplains
- 2024
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Ingår i: NATURE ECOLOGY & EVOLUTION. - 2397-334X.
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Tidskriftsartikel (refereegranskat)abstract
- Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function.
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| 5. |
- Luize, Bruno Garcia, et al.
(författare)
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Geography and ecology shape the phylogenetic composition of Amazonian tree communities
- 2024
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Ingår i: JOURNAL OF BIOGEOGRAPHY. - 0305-0270 .- 1365-2699.
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Amazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types. Location: Amazonia. Taxon: Angiosperms (Magnoliids; Monocots; Eudicots). Methods: Data for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny. Results: In the terra firme and v & aacute;rzea forest types, the phylogenetic composition varies by geographic region, but the igap & oacute; and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R-2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R-2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types. Main Conclusion: Numerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions.
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- Pacheco, Gonçalo P., et al.
(författare)
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Experimental and Kinetic Investigation of Stoichiometric to Rich NH3/H2/Air Flames in a Swirl and Bluff-Body Stabilized Burner
- 2021
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Ingår i: Energy and Fuels. - : American Chemical Society (ACS). - 0887-0624 .- 1520-5029. ; 35:9, s. 7201-7216
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Tidskriftsartikel (refereegranskat)abstract
- Ammonia (NH3) is an inorganic substance considered as a promising fuel for power sector decarbonization. As a result of the absence of carbon in its structure, ammonia is capable of producing energy with zero CO2 emissions when burned. However, the combustion of NH3 presents several challenges as a result of its low reactivity and low flame speed as well as the formation of large quantities of nitrogen oxides (NOx) and frequent ammonia slip. A suggested solution for gas turbines is the use of rich-to-lean approaches, with a fuel-rich first-stage combustion, which mitigates NOx formation, followed by a lean phase for the oxidation of the remaining reactants, improving combustion efficiency. To help assess this concept, the present work investigates experimentally and computationally the combustion of ammonia/air mixtures, enriched by hydrogen (H2) for enhanced burning characteristics, in a swirl and bluff-body stabilized burner, at stoichiometric to fuel-rich conditions. Stability tests were performed for a fixed thermal input (2.8 kW), and flames of fuel/air equivalence ratios of 1.0, 1.1, and 1.2, with molar fractions of ammonia in fuel of 0.7 and 0.8, were studied. Temperature profiles along the combustor axis were measured, and flue gas measurements for NOx emissions and unburned NH3 and H2 concentrations were performed for the six studied flames. Computational simulations were performed using a chemical reactor network coupled with recent kinetic mechanisms to compare species trends and further understand the NOx formation and NH3 conversion into hydrogen, through rate of production analyses. It was found that the present laboratory combustor performed well in terms of flame stability, also generating low levels of NOx emissions in all fuel-rich conditions. H2 was detected in high concentrations in the flue gas, partially originated from ammonia dissociation, and is followed by high unburned ammonia emissions. Both H2 and NH3 emissions increase with the equivalence ratio. A secondary, spontaneous diffusion flame was observed above the combustor, proving that the flue gas may subsequently be burned. Higher fractions of hydrogen in the fuel generate more unburned ammonia but also higher H2 concentrations in the flue gas. The predictions based on a reactor network model coupled with the evaluated kinetic mechanisms presented good agreement with the experimentally observed species trends and fair agreement with species values.
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| 7. |
- ter Steege, Hans, et al.
(författare)
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Mapping density, diversity and species-richness of the Amazon tree flora
- 2023
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Ingår i: COMMUNICATIONS BIOLOGY. - 2399-3642. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution. A study mapping the tree species richness in Amazonian forests shows that soil type exerts a strong effect on species richness, probably caused by the areas of these forest types. Cumulative water deficit, tree density and temperature seasonality affect species richness at a regional scale.
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| 8. |
- Camargo, Samia M., et al.
(författare)
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Structure and Genetic Variability of the Oceanic Whitetip Shark, Carcharhinus longimanus, Determined Using Mitochondrial DNA
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Information regarding population structure and genetic connectivity is an important contribution when establishing conservation strategies to manage threatened species. The oceanic whitetip shark, Carcharhinus longimanus, is a highly migratory, large-bodied, pelagic shark listed by the IUCN (International Union for Conservation of Nature) Red List as "vulnerable" throughout its range and "critically endangered" in the western north Atlantic. In 2014, the species was protected globally under Appendix II of CITES (Convention on International Trade in Endangered Species), limiting and regulating trade. This study used partial sequences of mitochondrial DNA (mtDNA) control region to determine the population genetic structure of oceanic whitetip sharks across the Atlantic and Indian Oceans. 724 base pairs were obtained from 215 individuals that identifed nine polymorphic sites and defined 12 distinct haplotypes. Total nucleotide diversity (pi) was 0.0013 and haplotype diversity (h) was 0.5953. The Analysis of Molecular Variance (AMOVA) evidenced moderate levels of population structure (phi(ST) = 0.1039) with restricted gene flow between the western and eastern Atlantic Ocean, and a strong relationship between the latter region and the Indian Ocean. Even though the oceanic whitetip is a highly migratory animal the results presented here show that their genetic variability is slightly below average of other pelagic sharks. Additionally, this study recommends that at least two populations in the Atlantic Ocean should be considered distinct (eastern and western Atlantic) and conservation efforts should be focused in areas with the greatest genetic diversity by environmental managers.
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| 9. |
- Carbajales, Carlos, et al.
(författare)
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Structure-Based Design of New KSP-Eg5 Inhibitors Assisted by a Targeted Multicomponent Reaction
- 2014
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Ingår i: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 15:10, s. 1471-1480
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Tidskriftsartikel (refereegranskat)abstract
- An integrated multidisciplinary approach that combined structure-based drug design, multicomponent reaction synthetic approaches and functional characterization in enzymatic and cell assays led to the discovery of new kinesin spindle protein (KSP) inhibitors with antiproliferative activity. A focused library of new benzimidazoles obtained by a Ugi + Boc removal/cyclization reaction sequence generated low-micromolar-range KSP inhibitors as promising anticancer prototypes. The design and functional studies of the new chemotypes were assessed by computational modeling and molecular biology techniques. The most active compounds-20 (IC50=1.49 mu m, EC50=3.63 mu m) and 22 (IC50=1.37 mu m, EC50=6.90 mu m)-were synthesized with high efficiency by taking advantage of the multicomponent reactions.
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| 10. |
- Coelho, Denis A., 1971-, et al.
(författare)
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A tentative efficiency index for pointing device use in computer aided design : A pilot study
- 2018
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Ingår i: Work. - : IOS Press. - 1051-9815 .- 1875-9270. ; 61:1, s. 157-170
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Focusing on the efficiency aspect of computer pointing devices’ usability, this paper reports on a novel and tentative empirically derived efficiency index for 3D CAD.OBJECTIVE: Three commercially available computer pointing devices were compared: a standard horizontal computer mouse, a vertical device (supporting neutral pronation of the forearm) and a slanted device.METHODS: Pilot structured observations of 10 subjects’ activity were carried out to estimate the proportion of each unique computer mouse operation during CAD modelling with a 3D parametric software. Pointing, dragging and steering standardized tasks were implemented by software and performed by 20 users. Effectiveness and efficiency were calculated and discomfort, effort and ease of use were subjectively assessed.RESULTS: The mean efficiency index value was lower for the vertical device. Assessments of discomfort, effort and ease of use also supported considering preference for the horizontal and slanted devices, providing limited internal validation.CONCLUSION: Results suggest the tentative index may offer a valid means of ranking performance of alternative pointing devices regarding operation efficiency.
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