| 1. |
- Cremades, Andrés, et al.
(författare)
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Identifying regions of importance in wall-bounded turbulence through explainable deep learning
- 2024
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Ingår i: Nature Communications. - : Nature Research. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite its great scientific and technological importance, wall-bounded turbulence is an unresolved problem in classical physics that requires new perspectives to be tackled. One of the key strategies has been to study interactions among the energy-containing coherent structures in the flow. Such interactions are explored in this study using an explainable deep-learning method. The instantaneous velocity field obtained from a turbulent channel flow simulation is used to predict the velocity field in time through a U-net architecture. Based on the predicted flow, we assess the importance of each structure for this prediction using the game-theoretic algorithm of SHapley Additive exPlanations (SHAP). This work provides results in agreement with previous observations in the literature and extends them by revealing that the most important structures in the flow are not necessarily the ones with the highest contribution to the Reynolds shear stress. We also apply the method to an experimental database, where we can identify structures based on their importance score. This framework has the potential to shed light on numerous fundamental phenomena of wall-bounded turbulence, including novel strategies for flow control.
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| 2. |
- Deshpande, Rahul, et al.
(författare)
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Reynolds-number effects on the outer region of adverse-pressure-gradient turbulent boundary layers
- 2023
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Ingår i: Physical Review Fluids. - : American Physical Society (APS). - 2469-990X. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- We study the Reynolds-number effects on the outer region of moderate adverse-pressure-gradient (APG) turbulent boundary layers (TBLs) and find that their small-scale (viscous) energy reduces with increasing friction Reynolds number (Reτ). The trend is based on analyzing APG TBL data across 600≲Reτ≲7000 and contrasts with the negligible variation in small viscous-scaled energy noted for canonical wall flows. The data sets considered include those from a well-resolved numerical simulation [Pozuelo, J. Fluid Mech. 939, A34 (2022)0022-112010.1017/jfm.2022.221], which provides access to an APG TBL maintained at near-equilibrium conditions across 1000≲Reτ≲ 2000, with a well-defined flow history, and a new high-Reτ (∼7000) experimental study from the large Melbourne wind tunnel, with its long test section modified to permit development of an APG TBL from a "canonical"upstream condition. The decrease in small-scale energy with Reτ is revealed via decomposing the streamwise normal stresses into small- and large-scale contributions, based on a sharp spectral cutoff. The origin for this trend is traced back to the production of turbulent kinetic energy in an APG TBL, the small-scale contribution to which is also found to decrease with Reτ in the outer region. The conclusion is reaffirmed by investigating attenuation of streamwise normal stresses due to changing spatial resolutions of the numerical grid or hotwire sensors, which reduces with increasing Reτ and is found to be negligible at Reτ∼7000 in this study. The results emphasize that new scaling arguments and spatial-resolution corrections should be tested rigorously across a broad Reτ range, particularly for pressure gradient TBLs.
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| 3. |
- Stanaway, Jeffrey D., et al.
(författare)
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Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
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Tidskriftsartikel (refereegranskat)abstract
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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| 4. |
- Upadhayaya, RamShankar, et al.
(författare)
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Carba-LNA-5MeC/A/G/T Modified Oligos Show Nucleobase-Specific Modulation of 3′-Exonuclease Activity, Thermodynamic Stability, RNA Selectivity, and RNase H Elicitation : Synthesis and Biochemistry
- 2011
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Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 76:11, s. 4408-4431
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Tidskriftsartikel (refereegranskat)abstract
- Using the intramolecular 5-exo-5-hexenyl radical as a key cyclization step, we previously reported an unambiguous synthesis of carba-LNA thymine (cLNA-T), which we subsequently incorporated in antisense oligonudeotides (AON) and investigated their biochemical properties [J. Am. Chem. Soc. 2007, 129 (26), 8362-8379]. These cLNA-T incorporated oligos showed specific RNA affinity of +3.5-5 degrees C/modification for AON:RNA heteroduplexes, which is comparable to what is found for those of LNAs (Locked Nucleic Acids). These modified oligos however showed significantly enhanced nuclease stability (ca. 100 times more) in the blood serum compared to those of the LNA modified counterparts without compromising any RNase H recruitment capability. We herein report the synthesis of 5-methylcytosine-1-yl (C-Me), 9-adeninyl (A), and 9-guaninyl (G) derivatives of cLNA and their oligonucleotides and report their biochemical properties as potential RNA-directed inhibitors. In a series of isosequential carba-LNA modified AONs, we herein show that all the cLNA modified AONs are found to be RNA-selective, but the magnitude of RNA-selectivity of 7'-R-Me-cLNA-G (cLNA-G) (Delta T-m = 2.9 degrees C/modification) and intractable isomeric mixtures of 7'-(S/R)-Me-cLNA-T (cLNA-T, Delta T-m = 2.2 degrees C/modification) was found to be better than diastereomeric mixtures of 7'-(S/R)-Me-cLNA-C-Me with trace of cENA-C-Me (cLNA-C-Me, Delta T-m = 1.8 degrees C/modification) and 7'-R-Me-cLNA-A (cLNA-A, Delta T-m = 0.9 degrees C/modification). cLNA-C-Me modified AONs however exhibited the best nuclease stability, which is 4-, 7-, and 20-fold better, respectively, than cLNA-T, cLNA-A, and cLNA-G modified counterparts, which in turn was more than 100 times stable than that of the native. When the modification sites are appropriately chosen in the AONs, the cLNA-A, -G, and -C-Me modified sites in the AON:RNA hybrids can be easily recognized by RNase H, and the RNA strand of the hybrid is degraded in a specific manner, which is important for the design of oligos for therapeutic purposes. The cLNA-C-Me modified AON/RNA, however, has been found to be degraded 4 times faster than cLNA-A and G modified counterparts. By appropriately choosing the carba-LNA modification sites in AON strands, the digestion of AON:RNA can be either totally repressed or be limited to cleavage at specific sites or at a single site only (similar to that of catalytic RNAzyme or DNAzyme). Considering all physico- and biochemical aspects of cLNA modified oligos, the work suggests that the cLNA modified antisense oligos have the potential of being a promising therapeutic candidate due to their (i) higher nucleobase-specific RNA affinity and RNA selectivity, (ii) greatly improved nuclease stability, and (iii) efficient RNase H recruitment capability, which can induce target RNA cleavage in a very specific manner at multiple or at a single site, in a designed manner.
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