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- Galetin, Aleksandra, et al.
(författare)
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Membrane transporters in drug development and as determinants of precision medicine
- 2024
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Ingår i: NATURE REVIEWS DRUG DISCOVERY. - 1474-1776 .- 1474-1784. ; 255–280, s. 255-280
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Forskningsöversikt (refereegranskat)abstract
- The effect of membrane transporters on drug disposition, efficacy and safety is now well recognized. Since the initial publication from the International Transporter Consortium, significant progress has been made in understanding the roles and functions of transporters, as well as in the development of tools and models to assess and predict transporter-mediated activity, toxicity and drug-drug interactions (DDIs). Notable advances include an increased understanding of the effects of intrinsic and extrinsic factors on transporter activity, the application of physiologically based pharmacokinetic modelling in predicting transporter-mediated drug disposition, the identification of endogenous biomarkers to assess transporter-mediated DDIs and the determination of the cryogenic electron microscopy structures of SLC and ABC transporters. This article provides an overview of these key developments, highlighting unanswered questions, regulatory considerations and future directions. Significant progress has been made in understanding the influence of membrane transporters in drug disposition and response. Here, the International Transporter Consortium provides an update on the current status of membrane transporters in drug development and regulatory requirements, discusses recent scientific advances in the field and highlights future directions and unanswered questions.
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- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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- Yap, Jane Yee, et al.
(författare)
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A graphical method for carbon dioxide emissions reduction in multi–product plants
- 2020
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Ingår i: Process Safety and Environmental Protection: Transactions of the Institution of Chemical Engineers, Part B. - : Elsevier BV. - 1744-3598 .- 0957-5820. ; 133, s. 51-63
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Tidskriftsartikel (refereegranskat)abstract
- Carbon dioxide emissions reduction has been a common trend for many industrial processes in recent years. However, few analytical tools have been developed for visualising CO2 emissions reduction and supporting decisions at the enterprise level. A graphical technique known as Carbon Emission Composite Curves was developed previously, but was limited to the production of single product. In this work, the CO2 emissions reduction procedure is focused and extended to multi-product plants, in which CO2 emissions of shared and dedicated facilities of the production line are analysed. For cases where the carbon intensity of shared facilities is higher than that of the dedicated facilities, CO2 emissions reduction should focus on the shared facilities, before efforts are put forward for the dedicated facilities. In contrast, when the carbon intensity of dedicated facilities is higher than that of the shared facilities, it is necessary to explore ways to reduce CO2 emissions of the dedicated facilities. Two case studies are used to illustrate the procedure.
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- Yap, Jane Yee, et al.
(författare)
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A heuristic-based technique for carbon footprint reduction for the production of multiple products
- 2018
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Ingår i: Chemical Engineering Transactions. - 2283-9216 .- 2283-9216. ; 70, s. 943-948
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Tidskriftsartikel (refereegranskat)abstract
- Carbon footprint (CF) reduction is a common trend for many industrial processes in recent years. However, not many analytical tools have been developed for visualising CF reduction at enterprise level. A graphical technique known as the CF Composite Curves to aid decision making in CF reduction at enterprise level has been developed in previous work. However, the method was limited to the production of a single product. In this paper, the CF reduction procedure is extended to the more general case of multiple products. The CF of shared and independent facilities are analysed. An illustrative example shows that for cases when the CF intensity of shared facilities is higher than that of the independent facilities, CF reduction should focus on the shared facilities, before efforts are put forward for the independent facilities. In contrast, when the CF intensity of independent facilities is higher than that of the shared facilities, it is necessary to explore ways to reduce CF of the independent facilities.
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