| 1. |
- George, Julie, et al.
(author)
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Comprehensive genomic profiles of small cell lung cancer
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
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Journal article (peer-reviewed)abstract
- We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
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| 2. |
- Löwemark, Ludvig, et al.
(author)
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Practical guidelines and recent advances in the Itrax XRF core-scanning procedure
- 2019
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In: Quaternary International. - : Elsevier BV. - 1040-6182 .- 1873-4553. ; 514, s. 16-29
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Journal article (peer-reviewed)abstract
- XRF core scanning has evolved to become a standard analytical technique for the rapid assessment of elemental, density and textural variations in a wide range of sediments and other materials, with applications ranging from palaeoceanography, paleoclimatology, geology, and environmental forensics to environmental protection. In general, scanning provides rapid, non-destructive acquisition of elemental and textural variations at sub-millimetre resolution for a wide range of materials. Numerous procedural adaptations have been developed for the growing number of applications, such as analyses of unconsolidated, water-rich sediments, powdered soil samples, or resin bags. Here, practical expertise and guidance from the Itrax community, gained over 15 years, is presented that should provide insights for new and experienced users.
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| 3. |
- Vieceli, Nathalia Cristine, 1989, et al.
(author)
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Recycling of Li-Ion Batteries from Industrial Processing: Upscaled Hydrometallurgical Treatment and Recovery of High Purity Manganese by Solvent Extraction
- 2023
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In: Solvent Extraction and Ion Exchange. - : Informa UK Limited. - 0736-6299 .- 1532-2262. ; 41:2, s. 205-220
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Journal article (peer-reviewed)abstract
- Manganese plays a central role in lithium-ion batteries (LIBs) but its recycling is rarely addressed when compared to other valuable metals present in LIBs, such as Co and Ni. Thus, the main goal of this work was to study and achieve the separation of Mn from Co and Ni by solvent extraction from a leachate obtained from LIBs using hydrochloric acid in an upscaled reactor, which is an innovative aspect of this work. The results confirmed the high selectivity of D2EHPA towards Mn, which could be completely extracted in two stages (0.5 M D2EHPA at pH 2.5). The main co-extracted metals were Al, Cu and Co, but with lower concentrations than Mn. The behavior of minor impurities such as Zn and Mg was also monitored. Scrubbing using manganese chloride was crucial to remove impurities from the loaded organic and prevent their presence in the stripping product, and high O:A ratios negatively affected the scrubbing efficiency. Keeping the concentration of HCl up to 0.5 M in the stripping stage helped to limit the stripping of impurities. Manganese oxide was precipitated as a product with 99.5% purity (with traces of Zn, Cu and Co), which could be reused in the battery value chain.
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| 4. |
- Vieceli, Nathalia Cristine, 1989, et al.
(author)
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Solvent extraction of cobalt from spent lithium-ion batteries: Dynamic optimization of the number of extraction stages using factorial design of experiments and response surface methodology
- 2023
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In: Separation and Purification Technology. - : Elsevier BV. - 1873-3794 .- 1383-5866. ; 307
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Journal article (peer-reviewed)abstract
- The optimization of lithium-ion batteries (LiBs) recycling is crucial not only from a waste management perspective but also to decrease the dependence on imports of critical raw materials. In addition, the diversification of the recycling technologies is very important for better flexibility of the market. This study aims at investigating the recovery of Co from spent LiBs using solvent extraction from a real chloride-based solution obtained after the removal of Mn, which is very rarely reported. Cyanex 272 was used as the extractant and the effect of several variables on the extraction efficiency was considered to model and optimize the separation of Co and Ni. The number of extraction stages directly affects not only the process efficiency but also its cost. Thus, in this work, a novel approach was developed to assist in the selection of the number of extraction stages using a dynamic method based on the factorial design of experiments and response surface methodology combined with the Kremseŕs Equation. This method can assist the process design, decrease the overall cost of the operation, and optimize the separation of Co and Ni in a reduced number of extraction stages. The concentration of Co and Ni in the feed solutions is ∼ 8.3 g/L and 1.9 g/L, respectively. Based on the results, 98% extraction efficiency for Co can be achieved in 1 to 2 extraction stages with low co-extraction of Ni (<5%) when using 0.6–0.8 M Cyanex 272, O:A ratio below 1 and pH ∼ 5, but several combinations of conditions could provide similar results.
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| 5. |
- Abdallah, J., et al.
(author)
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Masses, lifetimes and production rates of Xi(-) and Xi(+) at LEP 1
- 2006
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In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 639:3-4, s. 179-191
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Journal article (peer-reviewed)abstract
- Measurements of the Xi(-) and (Xi) over bar (+) masses, mass differences, lifetimes and lifetime differences are presented. The (Xi) over bar (+) sample used is much larger than those used previously for such measurements. In addition, the S production rates in Z -> b (b) over bar and Z -> q (q) over bar events are compared and the position xi* of the maximum of the distribution in Z -> q (q) over bar events is measured.
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| 6. |
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| 7. |
- Bug, Gesine, et al.
(author)
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Fludarabine/TBI 8 Gy versus fludarabine/treosulfan conditioning in patients with AML in first complete remission : a study from the Acute Leukemia Working Party of the EBMT
- 2023
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In: Bone Marrow Transplantation. - : Springer Nature. - 0268-3369 .- 1476-5365. ; 58:6, s. 710-716
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Journal article (peer-reviewed)abstract
- The optimal reduced intensity conditioning (RIC) regimen is a matter of debate. We retrospectively compared conditioning with fludarabine plus fractionated total body irradiation of 8 Gy (FluTBI) and fludarabine plus treosulfan 30, 36 or 42 g/m2 (FluTreo) in 754 patients with AML above the age of 40 years undergoing an allogeneic hematopoietic stem cell transplant (HSCT) in first complete remission (CR). After balancing patient characteristics by propensity score matching of 115 patients in each group, FluTBI was associated with a significantly lower probability of relapse compared to FluTreo (18.3% vs. 34.7%, p = 0.018) which was counteracted by a higher non-relapse mortality (NRM, 16.8% vs. 5.3%, p = 0.02). Thus, overall survival and graft-versus-host disease-free and relapse-free survival at 2 years were similar between groups (OS 66.9% vs. 67.8%, GRFS 50.3% vs. 45.6%). Univariate analysis by age group demonstrated a higher NRM exclusively in patients ≥55 years of age treated with FluTBI compared to FluTreo (27.6% vs. 5.8%, p = 0.02), while a similarly low NRM was observed in patients <55 years in both groups (6.0% vs. 4.7%, p = ns). We conclude that both conditioning regimens are effective and safe, but FluTBI may better be reserved for younger patients below the age of 55 years.
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| 8. |
- Cheng, Qin-Bo, et al.
(author)
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Improvement and comparison of likelihood functions for model calibration and parameter uncertainty analysis within a Markov chain Monte Carlo scheme
- 2014
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In: Journal of Hydrology. - : Elsevier BV. - 0022-1694 .- 1879-2707. ; 519:Part B, s. 2202-2214
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Journal article (peer-reviewed)abstract
- Summary In this study, the likelihood functions for uncertainty analysis of hydrological models are compared and improved through the following steps: (1) the equivalent relationship between the Nash–Sutcliffe Efficiency coefficient (NSE) and the likelihood function with Gaussian independent and identically distributed residuals is proved; (2) a new estimation method of the Box–Cox transformation (BC) parameter is developed to improve the effective elimination of the heteroscedasticity of model residuals; and (3) three likelihood functions—NSE, Generalized Error Distribution with BC (BC-GED) and Skew Generalized Error Distribution with BC (BC-SGED)—are applied for SWAT-WB-VSA (Soil and Water Assessment Tool – Water Balance – Variable Source Area) model calibration in the Baocun watershed, Eastern China. Performances of calibrated models are compared using the observed river discharges and groundwater levels. The result shows that the minimum variance constraint can effectively estimate the BC parameter. The form of the likelihood function significantly impacts on the calibrated parameters and the simulated results of high and low flow components. SWAT-WB-VSA with the NSE approach simulates flood well, but baseflow badly owing to the assumption of Gaussian error distribution, where the probability of the large error is low, but the small error around zero approximates equiprobability. By contrast, SWAT-WB-VSA with the BC-GED or BC-SGED approach mimics baseflow well, which is proved in the groundwater level simulation. The assumption of skewness of the error distribution may be unnecessary, because all the results of the BC-SGED approach are nearly the same as those of the BC-GED approach.
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| 9. |
- Gustafsen, Camilla, et al.
(author)
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Heparan sulfate proteoglycans present PCSK9 to the LDL receptor
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- Coronary artery disease is the main cause of death worldwide and accelerated by increased plasma levels of cholesterol-rich low-density lipoprotein particles (LDL). Circulating PCSK9 contributes to coronary artery disease by inducing lysosomal degradation of the LDL receptor (LDLR) in the liver and thereby reducing LDL clearance. Here, we show that liver heparan sulfate proteoglycans are PCSK9 receptors and essential for PCSK9-induced LDLR degradation. The heparan sulfate-binding site is located in the PCSK9 prodomain and formed by surface-exposed basic residues interacting with trisulfated heparan sulfate disaccharide repeats. Accordingly, heparan sulfate mimetics and monoclonal antibodies directed against the heparan sulfate-binding site are potent PCSK9 inhibitors. We propose that heparan sulfate proteoglycans lining the hepatocyte surface capture PCSK9 and facilitates subsequent PCSK9: LDLR complex formation. Our findings provide new insights into LDL biology and show that targeting PCSK9 using heparan sulfate mimetics is a potential therapeutic strategy in coronary artery disease.
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| 10. |
- Jenninger, Berthold, et al.
(author)
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Development of a design for an ionisation vacuum gauge suitable as a reference standard
- 2021
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In: Vacuum. - : Elsevier Ltd. - 0042-207X .- 1879-2715. ; 183
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Journal article (peer-reviewed)abstract
- The EURAMET EMPIR project “16NRM05 - Ion gauge” aims to develop an ionisation vacuum gauge suitable as a reference vacuum standard. In such a gauge the electron trajectories and their kinetic energy inside the ionisation volume should be well defined and stable. In the search for a suitable design, a series of simulations on different ionisation gauge concepts that have the potential to meet stringent stability requirements have been carried out. Different software packages were used for this purpose. This paper focuses on the design aspects and the performance of the different ionisation gauge concepts that have been investigated by simulation. Parameters such as ionisation gauge sensitivity, ion collection efficiency and electron transmission efficiency, have been determined as a function of emission current, pressure and electron source alignment.
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| 11. |
- Jiang, Hai, et al.
(author)
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The combined status of ATM and p53 link tumor development with therapeutic response
- 2009
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In: Genes & Development. - : Cold Spring Harbor Laboratory. - 0890-9369 .- 1549-5477. ; 23:16, s. 1895-1909
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Journal article (peer-reviewed)abstract
- While the contribution of specific tumor suppressor networks to cancer development has been the subject of considerable recent study, it remains unclear how alterations in these networks are integrated to influence the response of tumors to anti-cancer treatments. Here, we show that mechanisms commonly used by tumors to bypass early neoplastic checkpoints ultimately determine chemotherapeutic response and generate tumor-specific vulnerabilities that can be exploited with targeted therapies. Specifically, evaluation of the combined status of ATM and p53, two commonly mutated tumor suppressor genes, can help to predict the clinical response to genotoxic chemotherapies. We show that in p53-deficient settings, suppression of ATM dramatically sensitizes tumors to DNA-damaging chemotherapy, whereas, conversely, in the presence of functional p53, suppression of ATM or its downstream target Chk2 actually protects tumors from being killed by genotoxic agents. Furthermore, ATM-deficient cancer cells display strong nononcogene addiction to DNA-PKcs for survival after DNA damage, such that suppression of DNA-PKcs in vivo resensitizes inherently chemoresistant ATM-deficient tumors to genotoxic chemotherapy. Thus, the specific set of alterations induced during tumor development plays a dominant role in determining both the tumor response to conventional chemotherapy and specific susceptibilities to targeted therapies in a given malignancy.
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| 12. |
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| 13. |
- Lenoir, Jonathan, et al.
(author)
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Local temperatures inferred from plant communities suggest strong spatial buffering of climate warming across Northern Europe
- 2013
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In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 19:5, s. 1470-1481
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Journal article (peer-reviewed)abstract
- Recent studies from mountainous areas of small spatial extent (<2500km2) suggest that fine-grained thermal variability over tens or hundreds of metres exceeds much of the climate warming expected for the coming decades. Such variability in temperature provides buffering to mitigate climate-change impacts. Is this local spatial buffering restricted to topographically complex terrains? To answer this, we here study fine-grained thermal variability across a 2500-km wide latitudinal gradient in Northern Europe encompassing a large array of topographic complexities. We first combined plant community data, Ellenberg temperature indicator values, locally measured temperatures (LmT) and globally interpolated temperatures (GiT) in a modelling framework to infer biologically relevant temperature conditions from plant assemblages within <1000-m2 units (community-inferred temperatures: CiT). We then assessed: (1) CiT range (thermal variability) within 1-km2 units; (2) the relationship between CiT range and topographically and geographically derived predictors at 1-km resolution; and (3) whether spatial turnover in CiT is greater than spatial turnover in GiT within 100-km2 units. Ellenberg temperature indicator values in combination with plant assemblages explained 4672% of variation in LmT and 9296% of variation in GiT during the growing season (June, July, August). Growing-season CiT range within 1-km2 units peaked at 6065 degrees N and increased with terrain roughness, averaging 1.97 degrees C (SD=0.84 degrees C) and 2.68 degrees C (SD=1.26 degrees C) within the flattest and roughest units respectively. Complex interactions between topography-related variables and latitude explained 35% of variation in growing-season CiT range when accounting for sampling effort and residual spatial autocorrelation. Spatial turnover in growing-season CiT within 100-km2 units was, on average, 1.8 times greater (0.32 degrees Ckm1) than spatial turnover in growing-season GiT (0.18 degrees Ckm1). We conclude that thermal variability within 1-km2 units strongly increases local spatial buffering of future climate warming across Northern Europe, even in the flattest terrains.
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| 14. |
- Schiffer, Christian, et al.
(author)
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Vp/Vs ratios in the Parnaíba Basin from joint active-passive seismic analysis : Implications for continental amalgamation and basin formation
- 2021
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In: Tectonophysics. - : Elsevier. - 0040-1951 .- 1879-3266. ; 801
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Journal article (peer-reviewed)abstract
- The Phanerozoic intracontinental Parnaíba Basin in northeast Brazil lies atop crust composed of Archaean to Mesoproterozoic cratonic blocks and Neoproterozoic mobile belts. Recently, active and passive source geophysical surveys characterised the crustal structure beneath the basin. We use information from published active-source seismic and new, coincident receiver function (RF) data to obtain Vp/Vs ratios for sedimentary and crustal structure and make inferences about crustal compositions and tectonic evolution. In our approach, sedimentary and crustal Vp/Vs ratios are adjusted to match common conversion point (CCP) images of RFs and known Moho and basement geometry. We use a P-wave model from published wide-angle reflection/refraction (WARR) seismics, and structural features from a deep seismic reflection (DSR) profile. CCP images of the primary RF conversions were used to model the crust, whilst conversions of multiples were used for the sediment-basement interface. The maximum uncertainties in Vp/Vs are estimated to be 0.15 for the basin and 0.03 for the crust. Vp/Vs ratios in the basin were estimated between 1.7 and 2.2. Lower values correlate with the exposure of older units primarily in the east of the basin, whilst higher values coincide with exposed younger units of the Parnaíba Basin. The obtained crustal Vp/Vs ratios between 1.73 and 1.81 support the previously published segmentation of the crust. In particular, we identified three regions of elevated Vp/Vs ratios, which can be related to proposed Neoproterozoic suture zones underlying the Parnaíba Basin, as well as high velocity lower crust beneath. The high Vp/Vs ratios can be explained by mafic compositions, for example metamorphosed or intruded crust, or fluids and sedimentary rocks entrained into highly deformed crust, typical for modifications related to suture zones. These new deep geophysical models provide important and complementary evidence for crustal amalgamation and the formation of the Parnaíba Basin.
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| 15. |
- Schroer, Christian G, et al.
(author)
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Hard x-ray nanofocusing with refractive x-ray optics : full beam characterization by ptychographic imaging
- 2013
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In: Proceedings of SPIE. - : SPIE. - 9780819496980 ; , s. 884807-
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Conference paper (peer-reviewed)abstract
- Hard x-ray scanning microscopy relies on small and intensive nanobeams. Refractive x-ray lenses are well suited to generate hard x-ray beams with lateral dimensions of 100 nm and below. The diffraction limited beam size of refractive x-ray lenses mainly depends on the focal length and the attenuation inside the lens material. The numerical aperture of refractive lenses scales with the inverse square root of the focal length until it reaches the critical angle of total reflection. We have used nanofocusing refractive x-ray lenses made of silicon to focus hard x-rays at 8 and 20 keV to (sub-)100 nm dimensions. Using ptychographic scanning coherent diffraction imaging we have characterized these nanobeams with high accuracy and sensitivity, measuring the full complex wave field in the focus. This gives access to the full caustic and aberrations of the x-ray optics.
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| 16. |
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| 17. |
- Vieceli, Nathalia Cristine, 1989, et al.
(author)
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Optimization of manganese recovery from a solution based on lithium-ion batteries by solvent extraction with d2ehpa
- 2021
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In: Metals. - : MDPI AG. - 2075-4701. ; 11:1, s. 1-20
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Journal article (peer-reviewed)abstract
- Manganese is a critical metal for the steelmaking industry, and it is expected that its world demand will be increasingly affected by the growing market of lithium-ion batteries. In addition to the increasing importance of manganese, its recycling is mainly determined by trends in the recycling of iron and steel. The recovery of manganese by solvent extraction has been widely investigated; however, the interaction of different variables affecting the process is generally not assessed. In this study, the solvent extraction of manganese from a solution based on lithium-ion batteries was modeled and optimized using factorial designs of experiments and the response surface methodology. Under optimized conditions (O:A of 1.25:1, pH 3.25, and 0.5 M bis(2-ethylhexyl) phosphoric acid (D2EHPA)), extractions above 70% Mn were reached in a single extraction stage with a coextraction of less than 5% Co, which was mostly removed in two scrubbing stages. A stripping product containing around 23 g/L Mn and around 0.3 g/L Co can be obtained under optimized conditions (O:A of 8:1, 1 M H2SO4 and around 13 min of contact time) in one stripping stage.
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| 18. |
- Wasof, Safaa, et al.
(author)
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Disjunct populations of European vascular plant species keep the same climatic niches
- 2015
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In: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 24:12, s. 1401-1412
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Journal article (peer-reviewed)abstract
- Aim Previous research on how climatic niches vary across species ranges has focused on a limited number of species, mostly invasive, and has not, to date, been very conclusive. Here we assess the degree of niche conservatism between distant populations of native alpine plant species that have been separated for thousands of years. Location European Alps and Fennoscandia. Methods Of the studied pool of 888 terrestrial vascular plant species occurring in both the Alps and Fennoscandia, we used two complementary approaches to test and quantify climatic-niche shifts for 31 species having strictly disjunct populations and 358 species having either a contiguous or a patchy distribution with distant populations. First, we used species distribution modelling to test for a region effect on each species' climatic niche. Second, we quantified niche overlap and shifts in niche width (i.e. ecological amplitude) and position (i.e. ecological optimum) within a bi-dimensional climatic space. Results Only one species (3%) of the 31 species with strictly disjunct populations and 58 species (16%) of the 358 species with distant populations showed a region effect on their climatic niche. Niche overlap was higher for species with strictly disjunct populations than for species with distant populations and highest for arctic-alpine species. Climatic niches were, on average, wider and located towards warmer and wetter conditions in the Alps. Main conclusion Climatic niches seem to be generally conserved between populations that are separated between the Alps and Fennoscandia and have probably been so for 10,000-15,000 years. Therefore, the basic assumption of species distribution models that a species' climatic niche is constant in space and time-at least on time scales 104 years or less-seems to be largely valid for arctic-alpine plants.
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| 19. |
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