| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Loza, M. J., et al.
(författare)
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Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study
- 2016
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Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration:NCT01274507(ADEPT), registered October 28, 2010 and NCT01982162(U-BIOPRED), registered October 30, 2013.
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| 3. |
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| 4. |
- Chatron, N., et al.
(författare)
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Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy
- 2020
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:5, s. 1447-1461
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Tidskriftsartikel (refereegranskat)abstract
- Developmental and epileptic encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathy caused by bi-allelic loss-of-function variants in GAD1, as presented by 11 patients from six independent consanguineous families. Seizure onset occurred in the first 2 months of life in all patients. All 10 patients, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1(-/-) mouse model. Four patients died before 4 years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the c-aminobutyric acid (GABA) metabolism as it catalyses the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele.
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| 5. |
- Prigge, Justin R., et al.
(författare)
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Hepatocyte Hyperproliferation upon Liver-Specific Co-disruption of Thioredoxin-1, Thioredoxin Reductase-1, and Glutathione Reductase
- 2017
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Ingår i: Cell Reports. - : Cell Press. - 2211-1247. ; 19:13, s. 2771-2781
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Tidskriftsartikel (refereegranskat)abstract
- Energetic nutrients are oxidized to sustain high intracellular NADPH/NADP(+) ratios. NADPH-dependent reduction of thioredoxin-1 (Trx1) disulfide and glutathione disulfide by thioredoxin reductase-1 (TrxR1) and glutathione reductase (Gsr), respectively, fuels antioxidant systems and deoxyribonucleotide synthesis. Mouse livers lacking both TrxR1 and Gsr sustain these essential activities using an NADPH-independent methionine-consuming pathway; however, it remains unclear how this reducing power is distributed. Here, we show that liver-specific co-disruption of the genes encoding Trx1, TrxR1, and Gsr (triplenull) causes dramatic hepatocyte hyperproliferation. Thus, even in the absence of Trx1, methionine-fueled glutathione production supports hepatocyte S phase deoxyribonucleotide production. Also, Trx1 in the absence of TrxR1 provides a survival advantage to cells under hyperglycemic stress, suggesting that glutathione, likely via glutaredoxins, can reduce Trx1 disulfide in vivo. In triple-null livers like in many cancers, deoxyribonucleotide synthesis places a critical yet relatively low-volume demand on these reductase systems, thereby favoring high hepatocyte turnover over sustained hepatocyte integrity.
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| 6. |
- Abreu, Soraia Carvalho, et al.
(författare)
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Differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells
- 2020
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Ingår i: American Journal of Physiology: Lung Cellular and Molecular Physiology. - : American Physiological Society. - 1040-0605 .- 1522-1504.
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Tidskriftsartikel (refereegranskat)abstract
- Growing evidence demonstrates that human mesenchymal stromal cells (MSCs) modify their in vivo anti-inflammatory actions depending on the specific inflammatory environment encountered. Understanding this better is crucial to refine MSC-based cell therapies for lung and other diseases. Using acute exacerbations of cystic fibrosis (CF) lung disease as a model, the effects of ex vivo MSC exposure to clinical bronchoalveolar lavage fluid (BALF) samples, as a surrogate for the in vivo clinical lung environment, on MSC viability, gene expression, secreted cytokines, and mitochondrial function was compared to effects of BALF collected from healthy volunteers. CF BALF samples which cultured positive for Aspergillus sp. (Asp) induced rapid MSC death, usually within several hours of exposure. Further analyses suggested the fungal toxin gliotoxin as a potential mediator contributing to CF BALF-induced MSC death. RNA sequencing analyses of MSCs exposed to either Asp+ or Asp- CF BALF samples identified a number of differentially expressed transcripts, including those involved in interferon-signaling, anti-microbial gene expression, and cell death. Toxicity did not correlate with bacterial lung infections. These results suggest that the potential use of MSC-based cell therapies for CF or other lung diseases may not be warranted in the presence of Aspergillus.
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| 7. |
- Alix, James J. P., et al.
(författare)
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Assessment of the reliability of the motor unit size index (MUSIX) in single subject "round-robin" and multi-centre settings
- 2019
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Ingår i: Clinical Neurophysiology. - : ELSEVIER IRELAND LTD. - 1388-2457 .- 1872-8952. ; 130:5, s. 666-674
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The motor unit size index (MUSIX) is incorporated into the motor unit number index (MUNIX). Our objective was to assess the intra-/inter-rater reliability of MUSIX in healthy volunteers across single subject "round robin" and multi-centre settings.Methods: Data were obtained from (i) a round-robin assessment in which 12 raters (6 with prior experience and 6 without) assessed six muscles (abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, extensor digitorum brevis and abductor hallucis) and (ii) a multi-centre study with 6 centres studying the same muscles in 66 healthy volunteers. Intrafinter-rater data were provided by 5 centres, 1 centre provided only intra-rater data. Intrafinter-rater variability was assessed using the coefficient of variation (COV), Bland-Altman plots, bias and 95% limits of agreement.Results: In the round-robin assessment intra-rater COVs for MUSIX ranged from 7.8% to 28.4%. Inter-rater variability was between 7.8% and 16.2%. Prior experience did not impact on MUSIX values. In the multi-centre study MUSIX was more consistent than the MUNIX. Abductor hallucis was the least reliable muscle.Conclusions: The MUSIX is a reliable neurophysiological biomarker of reinnervation.Significance: MUSIX could provide insights into the pathophysiology of a range of neuromuscular disorders, providing a quantitative biomarker of reinnervation.
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| 8. |
- Cage, Alix G., et al.
(författare)
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Identification of the Icelandic Landnam tephra (AD 871 +/- 2) in Scottish fjordic sediment
- 2011
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Ingår i: Quaternary International. - : Elsevier BV. - 1040-6182 .- 1873-4553. ; 246, s. 168-176
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Tidskriftsartikel (refereegranskat)abstract
- Certain marginal marine environments, such as the Scottish fjord systems, contain high-resolution records of palaeoclimatic change in which decadal to centennial climatic events can be resolved. This paper explores the possibilities of using tephrochronology to stratigraphically constrain the timing of such events in the Loch Sunart record (MD04-2831) on the NW coast of Scotland (UK). One tephra horizon (containing both silicic and basaltic shards) is identified within Late Holocene sediment with geochemical analyses of the basaltic shards suggesting an origin in the Veidiviitn-Baroarbunga volcanic system. Radiocarbon age estimates and stratigraphic information suggests that the AD 871 Landnam tephra is the most likely candidate. The shards identified within this horizon appear hydrated and indicate the operation of post-depositional weathering processes possibly influenced by the saline conditions of the fjord environment.
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| 9. |
- Calogiuri, Tullia, et al.
(författare)
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Design and Construction of an Experimental Setup to Enhance Mineral Weathering through the Activity of Soil Organisms
- 2023
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Ingår i: Journal of Visualized Experiments. - : Journal of Visualized Experiments. - 1940-087X. ; :201
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Tidskriftsartikel (refereegranskat)abstract
- Enhanced weathering (EW) is an emerging carbon dioxide (CO2) removal technology that can contribute to climate change mitigation. This technology relies on accelerating the natural process of mineral weathering in soils by manipulating the abiotic variables that govern this process, in particular mineral grain size and exposure to acids dissolved in water. EW mainly aims at reducing atmospheric CO2 concentrations by enhancing inorganic carbon sequestration. Until now, knowledge of EW has been mainly gained through experiments that focused on the abiotic variables known for stimulating mineral weathering, thereby neglecting the potential influence of biotic components. While bacteria, fungi, and earthworms are known to increase mineral weathering rates, the use of soil organisms in the context of EW remains underexplored. This protocol describes the design and construction of an experimental setup developed to enhance mineral weathering rates through soil organisms while concurrently controlling abiotic conditions. The setup is designed to maximize weathering rates while maintaining soil organisms' activity. It consists of a large number of columns filled with rock powder and organic material, located in a climate chamber and with water applied via a downflow irrigation system. Columns are placed above a fridge containing jerrycans to collect the leachate. Representative results demonstrate that this setup is suitable to ensure the activity of soil organisms and quantify their effect on inorganic carbon sequestration. Challenges remain in minimizing leachate losses, ensuring homogeneous ventilation through the climate chamber, and avoiding flooding of the columns. With this setup, an innovative and promising approach is proposed to enhance mineral weathering rates through the activity of soil biota and disentangle the effect of biotic and abiotic factors as drivers of EW.
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| 10. |
- Chan, Young, et al.
(författare)
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Reinnervation as measured by the motor unit size index is associated with preservation of muscle strength in amyotrophic lateral sclerosis, but not all muscles reinnervate
- 2022
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Ingår i: Muscle and Nerve. - : John Wiley & Sons. - 0148-639X .- 1097-4598. ; 65:2, s. 203-210
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Tidskriftsartikel (refereegranskat)abstract
- Introduction/Aims: The motor unit size index (MUSIX) may provide insight into reinnervation patterns in diseases such as amyotrophic lateral sclerosis (ALS). However, it is not known whether MUSIX detects clinically relevant changes in reinnervation, or if all muscles manifest changes in MUSIX in response to reinnervation after motor unit loss.Methods: Fifty-seven patients with ALS were assessed at 3-month intervals for 12 months in four centers. Muscles examined were abductor pollicis brevis, abductor digiti minimi, biceps brachii, and tibialis anterior. Results were split into two groups: muscles with increases in MUSIX and those without increases. Longitudinal changes in MUSIX, motor unit number index (MUNIX), compound muscle action potential amplitude, and Medical Research Council strength score were investigated.Results: One hundred thirty-three muscles were examined. Fifty-nine percent of the muscles exhibited an increase in MUSIX during the study. Muscles with MUSIX increases lost more motor units (58% decline in MUNIX at 12 months, P <.001) than muscles that did not increase MUSIX (34.6% decline in MUNIX at 12 months, P <.001). However, longitudinal changes in muscle strength were similar. When motor unit loss was similar, the absence of a MUSIX increase was associated with a significantly greater loss of muscle strength (P =.002).Discussion: MUSIX increases are associated with greater motor unit loss but relative preservation of muscle strength. Thus, MUSIX appears to be measuring a clinically relevant response that can provide a quantitative outcome measure of reinnervation in clinical trials. Furthermore, MUSIX suggests that reinnervation may play a major role in determining the progression of weakness.
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| 11. |
- Corbett, Thomas, et al.
(författare)
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Organic carbon source controlled microbial olivine dissolution in small-scale flow-through bioreactors, for CO2 removal
- 2024
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Ingår i: NPJ MATERIALS DEGRADATION. - : Nature Publishing Group. - 2397-2106. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- The development of carbon dioxide removal methods, coupled with decreased CO2 emissions, is fundamental to achieving the targets outlined in the Paris Agreement limiting global warming to 1.5 degrees C. Here we are investigating the importance of the organic carbon feedstock to support silicate mineral weathering in small-scale flow through bioreactors and subsequent CO2 sequestration. Here, we combine two bacteria and two fungi, widely reported for their weathering potential, in simple flow through bioreactors (columns) consisting of forsterite and widely available, cheap organic carbon sources (wheat straw, bio-waste digestate of pig manure and biowaste, and manure compost), over six weeks. Compared to their corresponding abiotic controls, the inoculated straw and digestate columns release more total alkalinity (similar to 2 times more) and produce greater dissolved and solid inorganic carbon (29% for straw and 13% for digestate), suggesting an increase in CO2 sequestration because of bio-enhanced silicate weathering. Microbial biomass is higher in the straw columns compared to the digestate and manure compost columns, with a phospholipid fatty acid derived total microbial biomass 10 x greater than the other biotic columns. Scanning Electron Microscopy imaging shows the most extensive colonisation and biofilm formation on the mineral surfaces in the straw columns. The biotic straw and digestate columns sequester 50 and 14 mg C more than their abiotic controls respectively, while there is no difference in the manure columns. The selection of organic carbon sources to support microbial communities in the flow through bioreactors controlls the silicate weathering rates and CO2 sequestration.
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| 12. |
- Howe, John A., et al.
(författare)
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Fjord systems and archives: a review
- 2010
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Ingår i: Geological Society, London, Special Publications. - 0305-8719. ; 344, s. 5-15
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Forskningsöversikt (refereegranskat)abstract
- Fjords are glacially over-deepened semi-enclosed marine basins, typically with entrance sills separating their deep waters from the adjacent coastal waters which restrict water circulation and thus oxygen renewal. The location of fjords is principally controlled by the occurrence of ice sheets, either modern or ancestral. Fjords are therefore geomorphological features that represent the transition from the terrestrial to the marine environment and, as such, have the potential to preserve evidence of environmental change. Typically, most fjords have been glaciated a number of times and some high-latitude fjords still possess a resident glacier. In most cases, glacial erosion through successive glacial/interglacial cycles has ensured the removal of sediment sequences within the fjord. Hence the stratigraphic record in fjords largely preserves a glacial-deglacial cycle of deposition over the last 18 ka or so. Sheltered water and high sedimentation rates have the potential to make fjords ideal depositional environments for preserving continuous records of climate and environmental change with high temporal resolution. In addition to acting as high-resolution environmental archives, fjords can also be thought of as mini-ocean sedimentary basin laboratories. Fjords remain an understudied and often neglected sedimentary realm. With predictions of warming climates, changing ocean circulation and rising sea levels, this volume is a timely look at these environmentally sensitive coastlines.
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| 13. |
- Merle, Renaud E., 1976-, et al.
(författare)
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Occurrence of inherited supra-subduction zone mantle in the oceanic lithosphere as inferred from mantle xenoliths from Dragon Seamount (southern Tore–Madeira Rise)
- 2012
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Ingår i: Journal of the Geological Society. - : Geological Society of London. - 0016-7649 .- 2041-479X. ; 169:3
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Tidskriftsartikel (refereegranskat)abstract
- Spinel-bearing peridotite and pyroxenite xenoliths dredged from the Dragon Seamount (southern Tore–Madeira Rise, West Iberia and Morocco margin) give an insight into the composition of the underlying lithosphere. These xenoliths are devoid of evidence of strong host lava–peridotite interaction and re-equilibration or late impregnation in the plagioclase facies. The spinels and pyroxenes from the Dragon peridotites have compositions distinct from those of both lherzolites and harzburgites from the Iberia margin and the Mid-Atlantic Ridge. They display a highly depleted composition, in particular, high Cr-number, up to 0.63 in the spinels, consistent with a melting degree between 12 and 19%. Because of the strong chemical similarities between the Tore–Madeira Rise, Newfoundland peridotites, and peridotites from supra-subduction zones, we propose that the Dragon peridotites formed in a similar context. The pyroxenites display a cumulate texture and are probably a high-temperature–high-pressure cumulate formed by fractional crystallization from a melt. The Tore–Madeira Rise peridotites may represent a former mantle wedge in an oceanic arc, later included into the continental lithosphere and finally tectonically disseminated within the lithosphere during the rifting of the Newfoundland–Iberia continental lithosphere. As a consequence, rifting processes may produce heterogeneities in the oceanic lithosphere and influence isotopic compositions of ocean island basalt-type lavas during plume–lithosphere interactions, as inferred for the southern Tore–Madeira Rise.Supplementary material: Further information on the analytical results is available at http://www.geolsoc.org.uk/SUP18512.
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| 14. |
- Nicklin, Richard E. J., et al.
(författare)
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Surface Chemistry of Alanine on Ni{111}
- 2015
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 119:47, s. 26566-26574
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Tidskriftsartikel (refereegranskat)abstract
- The adsorption of l-alanine on Ni{111} has been studied as a model of enantioselective heterogeneous catalysts. Synchrotron-based X-ray photoelectron spectroscopy and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy were used to determine the chemical state, bond coordination, and out-of-plane orientation of the molecule on the surface. Alanine adsorbs in anionic and zwitterionic forms between 250 and approximate to 320 K. NEXAFS spectra exhibit a strong angular dependence of the pi* resonance associated with the carboxylate group, which is compatible with two distinct orientations with respect to the surface corresponding to the bidentate and tridentate binding modes. Desorption and decomposition begin together at approximate to 300 K, with decomposition occurring in a multistep process up to approximate to 450 K. Comparison with previous studies of amino acid adsorption on metal surfaces shows that this is among the lowest decomposition temperatures found so far and lower than typical temperatures used for hydrogenation reactions where modified Ni catalysts are used.
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| 15. |
- Ortar, Nathalie, et al.
(författare)
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Powering ‘smart’ futures : data centres and the energy politics of digitalisation
- 2023
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Ingår i: Energy Futures: Anthropocene Challenges, Emerging Technologies and Everyday Life. - Berlin : Walter de Gruyter. - 9783110745627 ; , s. 125-168
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Bokkapitel (refereegranskat)abstract
- Everyday life as we knew it is increasingly challenged in a world of climate, social, health and political crisis. Emerging technologies, data analytics and automation open up new possibilities which have implications for energy generation, storage and energy demand. To support these changes we urgently need to rethink how energy will be sourced, shared and used. Yet existing approaches to this problem, driven by engineering, data analytics and capital, are dangerously conservative and entrenched.Energy Futures critically evaluates this context, and the energy infrastructures, stakeholders, and politics that participate in it, to propose plausible, responsible and ethical modes of encountering possible energy futures. Imagining anthropocene challenges, emerging technologies and everyday life otherwise through empirically grounded studies, opens up possible energy futures.Energy Futures proposes and demonstrates a new critical and interventional futures-oriented energy anthropology. Combining the theories and methods of futures anthropology with the critical expertise and perspectives of energy anthropology creates a powerful mode of engagement, which this book argues is needed to disrupt the dominant narratives about our energy futures. Its contributors collectively reveal and evidence through innovative ethnographic practice how new knowledge about imagined and possible energy futures can be mobilised in engagements with emerging technologies, anthropocene challenges and everyday realities.
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