| 1511. |
- van de Vegte, Yordi, et al.
(författare)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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| 1512. |
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| 1513. |
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| 1514. |
- Wain, Louise V., et al.
(författare)
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Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
- 2017
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
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| 1515. |
- Walker, Anthony P, et al.
(författare)
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Horizon 2020 EuPRAXIA design study
- 2017
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 874:1
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Tidskriftsartikel (refereegranskat)abstract
- The Horizon 2020 Project EuPRAXIA ("European Plasma Research Accelerator with eXcellence In Applications") is preparing a conceptual design report of a highly compact and cost-effective European facility with multi-GeV electron beams using plasma as the acceleration medium. The accelerator facility will be based on a laser and/or a beam driven plasma acceleration approach and will be used for photon science, high-energy physics (HEP) detector tests, and other applications such as compact X-ray sources for medical imaging or material processing. EuPRAXIA started in November 2015 and will deliver the design report in October 2019. EuPRAXIA aims to be included on the ESFRI roadmap in 2020.
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| 1516. |
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| 1517. |
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| 1518. |
- Wang, J., et al.
(författare)
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A thermal balance oriented task mapping for CMPs
- 2018
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Ingår i: ACM International Conference Proceeding Series. - New York, NY, USA : Association for Computing Machinery. - 9781450365024 ; , s. 12-16
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Konferensbidrag (refereegranskat)abstract
- CMP (Chip Multi Processors) has been concerned and applied in more and more fields. With the technical progress in semiconductor manufacturing, the focus/research on on-chip power density and heat generation of the chips are increasing. The heat distribution of the chip heavily affects its reliability. In this article a heat-balancing task mapping algorithm is proposed to optimize the heat distribution and ensure the reliability of CMP. First, the thermal distribution of CMP is analyzed by what. Then, based on above analysis, a cost function based on usage and location of on-chip processors is proposed. Finally, a mapping algorithm based on above cost function is .developed to assign threads to cores while running applications with the min-cost principle dynamically. The simulation results revel that the heat-balancing algorithm proposed effectively optimizes heat distribution and ensures computational performance either.
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| 1519. |
- Wang, J. M., et al.
(författare)
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Melatonin receptor activation provides cerebral protection after traumatic brain injury by mitigating oxidative stress and inflammation via the Nrf2 signaling pathway
- 2019
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Ingår i: Free Radical Biology and Medicine. - : Elsevier BV. - 0891-5849. ; 131, s. 345-355
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is a principal cause of death and disability worldwide. Melatonin, a hormone made by the pineal gland, is known to have anti-inflammatory and antioxidant properties. In this study, using a weight-drop model of TBI, we investigated the protective effects of ramelteon, a melatonin MT1/MT2 receptor agonist, and its underlying mechanisms of action. Administration of ramelteon (10 mg/kg) daily at 10:00 a.m. alleviated TBI-induced early brain damage on day 3 and long-term neurobehavioral deficits on day 28 in C57BL/6 mice. Ramelteon also increased the protein levels of interleukin (IL)-10, IL-4, superoxide dismutase (SOD), glutathione, and glutathione peroxidase and reduced the protein levels of IL-1 beta, tumor necrosis factor, and malondialdehyde in brain tissue and serum on days 1, 3, and 7 post-TBI. Similarly, ramelteon attenuated microglial and astrocyte activation in the perilesional cortex on day 3. Furthermore, ramelteon decreased Keap 1 expression, promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear accumulation, and increased levels of downstream proteins, including SOD-1, heme oxygenase-1, and NQO1 on day 3 post-TBI. However, in Nrf2 knockout mice with TBI, ramelteon did not decrease the lesion volume, neuronal degeneration, or myelin loss on day 3; nor did it mitigate depression-like behavior or most motor behavior deficits on day 28. Thus, timed ramelteon treatment appears to prevent inflammation and oxidative stress via the Nrf2-antioxidant response element pathway and might represent a potential chronotherapeutic strategy for treating TBI.
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| 1520. |
- Wang, J., et al.
(författare)
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Optimal Sprinting Pattern in Thermal Constrained CMPs
- 2021
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Ingår i: IEEE Transactions on Emerging Topics in Computing. - : IEEE Computer Society. - 2168-6750.
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Tidskriftsartikel (refereegranskat)abstract
- CS (Computational Sprinting) is a promising technique to tackle the thermal challenge in CMPs (Chip Multi-Processors). Sprinting pattern, the boosted chip and voltage during the sprinting time, greatly impacts the CMP performance. In the paper, we address how to find out the optimal sprinting pattern which maximizes the performance of CMPs within thermal limitation. First, we conduce a mathematical proof to show that any thermal-constrained CMP, when it executes an application, has a specialized, sustainable configuration (vo; fo), under which the CMP can keep sprinting without resting and meanwhile its performance is maximized. Then, we design a self-adaptive algorithm automatically altering the chip frequency with adjustable step size and voltage in runtime to reach the optimal value. Finally, our extensive experimental results reveal that our Optimal Sprinting Pattern (OSP) outperforms state-of-the-art sprinting techniques, Full Sprinting Policy (FSP) and Adaptive Sprinting Pacing (ASP). Specifically, our OSP improves the computational efficiency in MIPS by up to 59% against FSP and 40% against ASP. It also achieves higher energy efficiency in MIPJ, by up to 41% and 25% over FSP and ASP, respectively. Moreover, we demonstrate that our method is effective for various CMPs with different scales, CPU architectures and chip nano-technologies.
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