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| 233. |
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| 234. |
- di Bari, R., et al.
(författare)
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Buildings LCA and digitalization: Designers' toolbox based on a survey
- 2022
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Ingår i: IOP Conference Series: Earth and Environmental Science. - : IOP Publishing. - 1755-1307 .- 1755-1315. ; 1078:1
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Konferensbidrag (refereegranskat)abstract
- In a context of digitalization and increasing quality requirements, the building sector is facing an increasing level of complexity regarding its design process. This results in a growing number of involved actors from different domains, a multitude of tasks to be completed and a higher degree of needed expertise. New buildings are also required to reach higher performances in terms of environmental quality. To that regard, the exploitation of the full potential of digital tools can facilitate the integration of environmental aspects in the planning process, limit productivity shortcomings and reduce environmental impacts, which can result from an unaware decision making. Building environmental assessment can be performed through several Life Cycle Assessment (LCA)-based tools. “Pure calculation” tools quantify final buildings' environmental potential, while “complex tools” additionally support decision making during the planning process. It is often difficult to choose the best suitable tool, which strongly depends on the user's needs. Within the IEA EBC Annex 72, a survey was realized with the main objective of creating a comprehensive overview of the existing tools dedicated to buildings LCA. The questionnaire included the usability, functionality, compliance, data reliability and interoperability of the analysed tools. Lastly, based on the survey outcomes and their critical assessment, a procedure for the identification and selection of a tool has been proposed based on user's needs. As a result, this work outlines main features of currently available building LCA tools, for which there is a harmonized status in terms of usability and overall applied LCA methodology. Despite the need for more automatized workflows, tools' embedding is mostly not yet applicable in system chains or limited to a restricted number of tools.
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| 235. |
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| 236. |
- Horn, M. R., et al.
(författare)
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Polyoxometalates (POMs) : From electroactive clusters to energy materials
- 2021
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Ingår i: Energy & Environmental Science. - : Royal Society of Chemistry. - 1754-5692 .- 1754-5706. ; 14:4, s. 1652-1700
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Tidskriftsartikel (refereegranskat)abstract
- Polyoxometalates (POMs) represent a class of nanomaterials, which hold enormous promise for a range of energy-related applications. Their promise is owing to their "special"structure that gives POMs a truly unique ability to control redox reactions in energy conversion and storage. One such amazing capability is their large number of redox active sites that arises from the complex three-dimensional cluster of metal-oxide ions linked together by oxygen atoms. Here, a critical review on how POMs emerged from being molecular clusters for fundamental studies, to next-generation materials for energy applications is provided. We highlight how exploiting the versatility and activity of these molecules can lead to improved performance in energy devices such as supercapacitors and batteries, and in energy catalyst applications. The potential of POMs across numerous fields is systematically outlined by investigating structure-property-performance relationships and the determinant factors for energy systems. Finally, the challenges and opportunities for this class of materials with respect to addressing our pressing energy-related concerns are identified. This journal is © The Royal Society of Chemistry.
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| 237. |
- Kennedy, S. A., et al.
(författare)
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Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Protein-protein-interaction networks (PPINs) organize fundamental biological processes, but how oncogenic mutations impact these interactions and their functions at a network-level scale is poorly understood. Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. Mapping >6000 PPIs shows that this network is extensively rewired in cells expressing transforming levels of KRASG13D (mtKRAS). The factors driving PPIN rewiring are multifactorial including changes in protein expression and phosphorylation. Mathematical modelling also suggests that the binding dynamics of low and high affinity KRAS interactors contribute to rewiring. PPIN rewiring substantially alters the composition of protein complexes, signal flow, transcriptional regulation, and cellular phenotype. These changes are validated by targeted and global experimental analysis. Importantly, genetic alterations in the most extensively rewired PPIN nodes occur frequently in CRC and are prognostic of poor patient outcomes.
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| 238. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 239. |
- Bonekamp, N. A., et al.
(författare)
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Small-molecule inhibitors of human mitochondrial DNA transcription
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 588, s. 712-716
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Tidskriftsartikel (refereegranskat)abstract
- Altered expression of mitochondrial DNA (mtDNA) occurs in ageing and a range of human pathologies (for example, inborn errors of metabolism, neurodegeneration and cancer). Here we describe first-in-class specific inhibitors of mitochondrial transcription (IMTs) that target the human mitochondrial RNA polymerase (POLRMT), which is essential for biogenesis of the oxidative phosphorylation (OXPHOS) system(1-6). The IMTs efficiently impair mtDNA transcription in a reconstituted recombinant system and cause a dose-dependent inhibition of mtDNA expression and OXPHOS in cell lines. To verify the cellular target, we performed exome sequencing of mutagenized cells and identified a cluster of amino acid substitutions in POLRMT that cause resistance to IMTs. We obtained a cryo-electron microscopy (cryo-EM) structure of POLRMT bound to an IMT, which further defined the allosteric binding site near the active centre cleft of POLRMT. The growth of cancer cells and the persistence of therapy-resistant cancer stem cells has previously been reported to depend on OXPHOS7-17, and we therefore investigated whether IMTs have anti-tumour effects. Four weeks of oral treatment with an IMT is well-tolerated in mice and does not cause OXPHOS dysfunction or toxicity in normal tissues, despite inducing a strong anti-tumour response in xenografts of human cancer cells. In summary, IMTs provide a potent and specific chemical biology tool to study the role of mtDNA expression in physiology and disease. Inhibitors of mitochondrial transcription that target human mitochondrial RNA polymerase provide a chemical biology tool for studying the role of mitochondrial DNA expression in a wide range of pathologies.
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| 240. |
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