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- Folkersen, Lasse, et al.
(author)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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In: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Journal article (peer-reviewed)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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| 2. |
- Maroju, Praveen Kumar, et al.
(author)
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Attosecond coherent control of electronic wave packets in two-colour photoionization using a novel timing tool for seeded free-electron laser
- 2023
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In: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 17, s. 200-207
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Journal article (peer-reviewed)abstract
- In ultrafast spectroscopy, the temporal resolution of time-resolved experiments depends on the duration of the pump and probe pulses, and on the control and characterization of their relative synchronization. Free-electron lasers operating in the extreme ultraviolet and X-ray spectral regions deliver pulses with femtosecond and attosecond duration in a broad array of pump-probe configurations to study a wide range of physical processes. However, this flexibility, together with the large dimensions and high complexity of the experimental set-ups, limits control of the temporal delay to the femtosecond domain, thus precluding a time resolution below the optical cycle. Here we demonstrate a novel single-shot technique able to determine the relative synchronization between an attosecond pulse train-generated by a seeded free-electron laser-and the optical oscillations of a near-infrared field, with a resolution of one atomic unit (24 as). Using this attosecond timing tool, we report the first example of attosecond coherent control of photoionization in a two-colour field by manipulating the phase of high-order near-infrared transitions.
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| 3. |
- O'Callaghan-Gordo, Cristina, et al.
(author)
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Prevalence of and risk factors for chronic kidney disease of unknown aetiology in India : Secondary data analysis of three population-based cross-sectional studies
- 2019
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In: BMJ Open. - : BMJ. - 2044-6055. ; 9:3
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Journal article (peer-reviewed)abstract
- Objectives To assess whether chronic kidney disease of unknown aetiology (CKDu) is present in India and to identify risk factors for it using population-based data and standardised methods. Design Secondary data analysis of three population-based cross-sectional studies conducted between 2010 and 2014. Setting Urban and rural areas of Northern India (states of Delhi and Haryana) and Southern India (states of Tamil Nadu and Andhra Pradesh). Participants 12 500 individuals without diabetes, hypertension or heavy proteinuria. Outcome measures Mean estimated glomerular filtration rate (eGFR) and prevalence of eGFR below 60 mL/min per 1.73 m 2 (eGFR <60) in individuals without diabetes, hypertension or heavy proteinuria (proxy definition of CKDu). Results The mean eGFR was 105.0±17.8 mL/min per 1.73 m 2. The prevalence of eGFR <60 was 1.6% (95% CI=1.4 to 1.7), but this figure varied markedly between areas, being highest in rural areas of Southern Indian (4.8% (3.8 to 5.8)). In Northern India, older age was the only risk factor associated with lower mean eGFR and eGFR <60 (regression coefficient (95% CI)=a '0.94 (0.97 to 0.91); OR (95% CI)=1.10 (1.08 to 1.11)). In Southern India, risk factors for lower mean eGFR and eGFR <60, respectively, were residence in a rural area (a '7.78 (-8.69 to -6.86); 4.95 (2.61 to 9.39)), older age (a '0.90 (-0.93 to -0.86); 1.06 (1.04 to 1.08)) and less education (a '0.94 (-1.32 to -0.56); 0.67 (0.50 to 0.90) for each 5 years at school). Conclusions CKDu is present in India and is not confined to Central America and Sri Lanka. Identified risk factors are consistent with risk factors previously reported for CKDu in Central America and Sri Lanka.
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