| 1. |
- Chen, Zhishan, et al.
(författare)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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| 2. |
- Huerta, E. A., et al.
(författare)
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Enabling real-time multi-messenger astrophysics discoveries with deep learning
- 2019
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Ingår i: Nature reviews physics. - : Springer Science and Business Media LLC. - 2522-5820. ; 1:10, s. 600-608
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Forskningsöversikt (refereegranskat)abstract
- Multi-messenger astrophysics is a fast-growing, interdisciplinary field that combines data, which vary in volume and speed of data processing, from many different instruments that probe the Universe using different cosmic messengers: electromagnetic waves, cosmic rays, gravitational waves and neutrinos. In this Expert Recommendation, we review the key challenges of real-time observations of gravitational wave sources and their electromagnetic and astroparticle counterparts, and make a number of recommendations to maximize their potential for scientific discovery. These recommendations refer to the design of scalable and computationally efficient machine learning algorithms; the cyber-infrastructure to numerically simulate astrophysical sources, and to process and interpret multi-messenger astrophysics data; the management of gravitational wave detections to trigger real-time alerts for electromagnetic and astroparticle follow-ups; a vision to harness future developments of machine learning and cyber-infrastructure resources to cope with the big-data requirements; and the need to build a community of experts to realize the goals of multi-messenger astrophysics. A group of experts suggests ways in which deep learning can be used to enhance the potential for discovery in multi-messenger astrophysics.
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| 3. |
- Mao, Jiwei, 1990, et al.
(författare)
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Relieving metabolic burden to improve robustness and bioproduction by industrial microorganisms
- 2024
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Ingår i: Biotechnology Advances. - 0734-9750. ; 74
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Forskningsöversikt (refereegranskat)abstract
- Metabolic burden is defined by the influence of genetic manipulation and environmental perturbations on the distribution of cellular resources. The rewiring of microbial metabolism for bio-based chemical production often leads to a metabolic burden, followed by adverse physiological effects, such as impaired cell growth and low product yields. Alleviating the burden imposed by undesirable metabolic changes has become an increasingly attractive approach for constructing robust microbial cell factories. In this review, we provide a brief overview of metabolic burden engineering, focusing specifically on recent developments and strategies for diminishing the burden while improving robustness and yield. A variety of examples are presented to showcase the promise of metabolic burden engineering in facilitating the design and construction of robust microbial cell factories. Finally, challenges and limitations encountered in metabolic burden engineering are discussed.
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| 4. |
- Ni, Bao Yu, et al.
(författare)
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Numerical Simulation of an Air-Bubble System for Ice Resistance Reduction
- 2022
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Ingår i: Journal of Marine Science and Engineering. - : MDPI AG. - 2077-1312. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- Ships sailing through cold regions frequently encounter floe ice fields. An air-bubble system that reduces friction between the hull and ice floes is thus considered useful for the reduction of ice-induced resistance. In this study, a numerical analysis procedure based on coupled finite volume method (FVM) and discrete element method (DEM) is proposed to simulate complicated hull-water-gas-ice interactions for ice-going ships installed with air-bubble systems. The simulations reveal that after turning on the air-bubble system ice floes in contact with the hull side wall are pushed away from the hull by the gas-water mixture, resulting in an ice-free zone close to the side hull. It is found that the drag reduction rate increases with the increase of ventilation, while the bow ventilation plays a deciding role in the overall ice-resistance reduction. The proposed procedure is expected to facilitate design of new generations of ice-going ships.
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| 5. |
- Zhang, Yuan, et al.
(författare)
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Healthy lifestyle counteracts the risk effect of genetic factors on incident gout : a large population-based longitudinal study
- 2022
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Risk genes linked to the development of gout have been identified, and lifestyle factors are related to gout risk. It remains unclear whether healthy lifestyle factors can mitigate the genetic risk of gout. Therefore, we aimed to explore whether and to what extent a healthy lifestyle can mitigate the risk of gout related to genetic factors.Methods: Within the UK Biobank, 416,481 gout-free participants (aged 37–74) were identified at baseline. Polygenic risk for gout was assessed and categorized as low (lowest tertile), middle (tertile 2), and high (highest tertile). Healthy lifestyle factors included no/moderate alcohol consumption, no smoking, physical activity, and a healthy diet. Participants were categorized into three groups according to their number of healthy lifestyle factors: unfavorable (0 or 1), intermediate (any 2), and favorable (3 or 4). Data were analyzed using Cox proportional hazard models.Results: Over the follow-up (median: 12.1 years), 6206 participants developed gout. Compared to low genetic risk, the hazard ratios (HRs) and 95% confidence intervals (CIs) of gout was 1.44 (1.35–1.54) for middle and 1.77 (1.66–1.89) for high genetic risk. The HRs (95% CIs) of gout were 0.63 (0.59–0.67) for a favorable lifestyle and 0.79 (0.75–0.85) for an intermediate lifestyle, compared to an unfavorable lifestyle. In joint effect analysis, compared to participants with low genetic predisposition and a favorable lifestyle, the HRs (95% CIs) of gout were 2.39 (2.12–2.70)/3.12 (2.79–3.52) in those with middle and high genetic predisposition plus unfavorable lifestyle profiles, and 1.53 (1.35–1.74)/1.98 (1.75–2.24) for those with middle and high genetic predisposition plus favorable lifestyle profiles, respectively. Moreover, compared to an unfavorable lifestyle, the HRs of gout related to a favorable lifestyle was 0.64 (95% CI, 0.56–0.73) for low genetic risk, 0.65 (95% CI, 0.58–0.72) for middle genetic risk, and 0.62 (95% CI, 0.57–0.69) for high genetic risk. There was a significant additive interaction between unfavorable lifestyle and high genetic risk on gout.Conclusions: Healthy lifestyle was associated with a lower risk of gout and may attenuate the risk of gout related to genetic factors by almost a third.
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| 6. |
- Zhong, Kai, et al.
(författare)
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Direct measurements and CFD simulations on ice-induced hull pressure of a ship in floe ice fields
- 2023
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Ingår i: Ocean Engineering. - : Elsevier BV. - 0029-8018. ; 272
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Tidskriftsartikel (refereegranskat)abstract
- Floe ice fields are expected to replace level ice to be the most common environment for future polar sea transportation under the long-term trend of global warming. In this study, the authors aim to develop a viable analysis procedure to predict the ice-induced hull pressure characteristics for ships navigating in floe ice fields. A novel ice model test procedure is established, which is characterized by making use of non-refrigerated synthetic model ice and tactile pressure sensors to measure the hull pressure. The numerical tool is based on a state-of-the-art CFD-DEM numerical framework; a novel method to monitor the hull pressure during the interaction between the hull and ice floes during the CFD-DEM simulations. Statistical analysis indicates the probability distributions of the ice pressure from the experiment and the numerical results are comparable. Besides, the impacts of ship speed and ice floe concentration on the hull pressure distribution are also examined. Increasing speed and ice concentration will make the probability distribution of ice pressure shift towards the high-pressure going interval, resulting in an increased mean of ice pressure. It is also found that increased speed leads to a smaller variance, while increased ice concentration results in a larger variance.
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