| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- Butler-Laporte, Guillaume, et al.
(författare)
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HLA allele-calling using whole-exome sequencing identifies 129 novel associations in 11 autoimmune diseases: a multi-ancestry analysis in the UK Biobank
- 2023
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Ingår i: Communicaitons Biology. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) region on chromosome 6 is strongly associated with many immune-mediated and infection-related diseases. Due to its highly polymorphic nature and complex linkage disequilibrium patterns, traditional genetic association studies of single nucleotide polymorphisms (SNPs) do not perform well in this region. Instead, the field has adopted the assessment of the association of HLA alleles (i.e., entire HLA gene haplotypes) with disease. Often based on genotyping arrays, these association studies impute HLA alleles, decreasing accuracy and thus statistical power for rare alleles and in non-European ancestries. Here, we use whole-exome sequencing (WES) from 454,824 UK Biobank participants to directly call HLA alleles using the HLA- HD algorithm. We show this method is more accurate than imputing HLA alleles and harness the improved statistical power to identify 360 associations for 11 auto-immune phenotypes (at least 129 likely novel), leading to better insights into the specific coding polymorphisms that underlie these diseases. We show that HLA alleles with synonymous variants, often overlooked in HLA studies, can significantly influence these phenotypes. Lastly, we show that HLA sequencing may improve polygenic risk scores accuracy across ancestries. These findings allow better characterization of the role of the HLA region in human disease.
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| 3. |
- Butler-Laporte, Guillaume, et al.
(författare)
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Increasing serum iron levels and their role in the risk of infectious diseases : a Mendelian randomization approach
- 2023
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 52:4, s. 1163-1174
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Increased iron stores have been associated with elevated risks of different infectious diseases, suggesting that iron supplementation may increase the risk of infections. However, these associations may be biased by confounding or reverse causation. This is important, since up to 19% of the population takes iron supplementation. We used Mendelian randomization (MR) to bypass these biases and estimate the causal effect of iron on infections. Methods As instrumental variables, we used genetic variants associated with iron biomarkers in two genome-wide association studies (GWASs) of European ancestry participants. For outcomes, we used GWAS results from the UK Biobank, FinnGen, the COVID-19 Host Genetics Initiative or 23andMe, for seven infection phenotypes: 'any infections', combined, COVID-19 hospitalization, candidiasis, pneumonia, sepsis, skin and soft tissue infection (SSTI) and urinary tract infection (UTI). Results Most of our analyses showed increasing iron (measured by its biomarkers) was associated with only modest changes in the odds of infectious outcomes, with all 95% odds ratios confidence intervals within the 0.88 to 1.26 range. However, for the three predominantly bacterial infections (sepsis, SSTI, UTI), at least one analysis showed a nominally elevated risk with increased iron stores (P <0.05). Conclusion Using MR, we did not observe an increase in risk of most infectious diseases with increases in iron stores. However for bacterial infections, higher iron stores may increase odds of infections. Hence, using genetic variation in iron pathways as a proxy for iron supplementation, iron supplements are likely safe on a population level, but we should continue the current practice of conservative iron supplementation during bacterial infections or in those at high risk of developing them.
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| 4. |
- Yoshiji, Satoshi, et al.
(författare)
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Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity
- 2023
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Ingår i: Nature Metabolism. - : Springer Nature. - 2522-5812. ; 5, s. 248-264
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Tidskriftsartikel (refereegranskat)abstract
- How obesity contributes to COVID-19 severity is not fully understood. In this study, Yoshiji et al. found that the plasma protein nephronectin partially mediates the effect of obesity on the risk of COVID-19 severity using a two-step Mendelian randomization approach and omics analyses. Obesity is a major risk factor for Coronavirus disease (COVID-19) severity; however, the mechanisms underlying this relationship are not fully understood. As obesity influences the plasma proteome, we sought to identify circulating proteins mediating the effects of obesity on COVID-19 severity in humans. Here, we screened 4,907 plasma proteins to identify proteins influenced by body mass index using Mendelian randomization. This yielded 1,216 proteins, whose effect on COVID-19 severity was assessed, again using Mendelian randomization. We found that an s.d. increase in nephronectin (NPNT) was associated with increased odds of critically ill COVID-19 (OR = 1.71, P = 1.63 x 10(-10)). The effect was driven by an NPNT splice isoform. Mediation analyses supported NPNT as a mediator. In single-cell RNA-sequencing, NPNT was expressed in alveolar cells and fibroblasts of the lung in individuals who died of COVID-19. Finally, decreasing body fat mass and increasing fat-free mass were found to lower NPNT levels. These findings provide actionable insights into how obesity influences COVID-19 severity.
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| 5. |
- Fu, Yifeng, 1984, et al.
(författare)
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Ultrafast Transfer of Metal Enhanced Carbon Nanotubes at Low Temperature for Large Scale Electronics Assembly
- 2010
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Ingår i: Advanced Materials. - : Wiley. - 0935-9648 .- 1521-4095. ; 22:44, s. 5039-5042
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Tidskriftsartikel (refereegranskat)abstract
- An indium-assisted ultrafast carbon nanotube (CNT) transfer method with a yield rate over 90% is described. Metal-coated as-transferred CNT structures exhibit excellent electrical performance that is at least one order of magnitude better than the previously published results. Shear test results show that the adhesion between CNTs and the substrate is greatly improved and excellent flexibility is obtained after the transfer process.
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| 6. |
- Hultström, Michael, 1978-, et al.
(författare)
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Dehydration is associated with production of organic osmolytes and predicts physical long-term symptoms after COVID-19 : a multicenter cohort study
- 2022
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Ingår i: Critical Care. - : Springer Nature. - 1364-8535 .- 1466-609X. ; 26
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We have previously shown that iatrogenic dehydration is associated with a shift to organic osmolyte production in the general ICU population. The aim of the present investigation was to determine the validity of the physiological response to dehydration known as aestivation and its relevance for long-term disease outcome in COVID-19.METHODS: The study includes 374 COVID-19 patients from the Pronmed cohort admitted to the ICU at Uppsala University Hospital. Dehydration data was available for 165 of these patients and used for the primary analysis. Validation was performed in Biobanque Québécoise de la COVID-19 (BQC19) using 1052 patients with dehydration data. Dehydration was assessed through estimated osmolality (eOSM = 2Na + 2 K + glucose + urea), and correlated to important endpoints including death, invasive mechanical ventilation, acute kidney injury, and long COVID-19 symptom score grouped by physical or mental.RESULTS: Increasing eOSM was correlated with increasing role of organic osmolytes for eOSM, while the proportion of sodium and potassium of eOSM were inversely correlated to eOSM. Acute outcomes were associated with pronounced dehydration, and physical long-COVID was more strongly associated with dehydration than mental long-COVID after adjustment for age, sex, and disease severity. Metabolomic analysis showed enrichment of amino acids among metabolites that showed an aestivating pattern.CONCLUSIONS: Dehydration during acute COVID-19 infection causes an aestivation response that is associated with protein degradation and physical long-COVID.TRIAL REGISTRATION: The study was registered à priori (clinicaltrials.gov: NCT04316884 registered on 2020-03-13 and NCT04474249 registered on 2020-06-29).
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| 7. |
- Tong, Yiheng, et al.
(författare)
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Effects of the position of a bluff-body on the diffusion flames : A combined experimental and numerical study
- 2018
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Ingår i: Applied Thermal Engineering. - : Elsevier BV. - 1359-4311. ; 131, s. 507-521
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Tidskriftsartikel (refereegranskat)abstract
- The effects of the position of a bluff-body on diffusion flame structures and flame instability characteristics were investigated both experimentally and numerically. The flame pattern diagram and the stability limits of the methane-air diffusion flame were investigated to evaluate the effects caused by the alternation of the position of a bluff-body. A disk-shape bluff-body was mounted 10 mm above or at the same height with the annular channel exit. The bulk velocity of the annular air flow varied between Ua = 0 to 8 m/s; while the fuel jet velocity being ranged from Uj = 0 to 30 m/s. Various flame patterns, including the recirculation zone flame, the stable diffusion flame, the split flame and the lifted flame till flame blowoff, were observed and recorded by the high-speed camera. High-speed Particle Image Velocimetry (PIV) was also adopted to give deeper insight into the characteristics of the flow fields and the flame patterns. The hybrid RANS/LES model was utilized to simulate the mixing characters of the reactants, the scalar dissipation rates, the flow fields and their interactions with the flame structures. The size and strength of the recirculation zones downstream of the bluff-body altered with the change in the position of the bluff-body. It is found that flames in burners with two different bluff-body positions behave similarly with each other, except those under conditions with high annular air velocities (Ua > 6.8 m/s). Mounting the bluff-body 10 mm above the annular channel exit could better stabilize the flame. A recirculation vortex was found adjacent to the outer wall of the bluff-body. It played an important role in the flame stabilization. Combustion affected the flow fields significantly by accelerating the central jet and enlarging the outer recirculation zone.
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| 8. |
- Tong, Yiheng, et al.
(författare)
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Experimental Investigation on Effects of Central Air Jet on the Bluff-body Stabilized Premixed Methane-air Flame
- 2017
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Ingår i: Energy Procedia. - : Elsevier BV. - 1876-6102. ; 107, s. 23-32
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Tidskriftsartikel (refereegranskat)abstract
- Flame stabilized by a bluff-body is a common scene in many engineering applications due to the enhanced mixing characteristics, improved flame stability, and ease of combustion control. We recently designed a burner which has a conical bluff body with a central air injector. In the current work, effects of the central air jet on the heat load of the bluff body, the flame structures and the flame blowoff limits were investigated. It was found that the central air jet can significantly reduce the heat load to the bluff body. It is a considerable solution to the problem caused by the high heat load in practical applications. The flame structures and blowout limits were altered with the addition of central air jet as well. Different blowout behaviors caused by the air jet were observed and reported. The bluff-body could be cooled down by the center air injection but then it seems not to stabilize the flame any more.
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| 9. |
- Tong, Yiheng, et al.
(författare)
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Experimental investigation on the influences of bluff-body's position on diffusion flame structures
- 2017
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Ingår i: Boilers and Heat Recovery Steam Generator; Combustion Turbines; Energy Water Sustainability; Fuels, Combustion and Material Handling; Heat Exchangers, Condensers, Cooling Systems, and Balance-of-Plant. - 9780791857601 ; 1
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Konferensbidrag (refereegranskat)abstract
- Effects of the bluff-body's position on diffusion flame structures and flame instability characteristics were investigated experimentally. A flame regime diagram together with the corresponding flow fields were proposed to evaluate the influences caused by the alternation of bluff-body's position. The disk shape bluff-body was placed 10 mm downstream or at the same height with the annular channel exit. The bulk velocity of the annular air flow varied from 0 to 8.6m/s while the central jet fuel velocity ranged from 0 to 30m/s. Various flame patterns including the recirculation zone flame, the stable diffusion jet flame, split-flashing flame and lifted flame were observed and recorded with a high speed camera. It is found that the flame has approximately the same patterns with different bluff-body's positions, except for cases with high air flow rate (Ua > 6.8m/s) and low fuel flow rate (Uj < 5m/s). Under that operating conditions, placing the disk bluff-body 10 mm above the annular channel could better stabilize the flame. High speed Particle Image Velocimetry (PIV) was also used to get deeper insight into the characteristics of the flow fields and flame stabilization. The size and strength of the recirculation zone downstream of the bluff-body altered with the changing of bluff-body's position and other operating conditions. The recirculation zone, in the burner with the bluff-body placed 10 mm above the air channel exit, was found larger and stronger than that in the other burner geometry. In the reacting case, a recirculation bubble was formed besides the bluff-body's outer wall which enhanced the flame stabilization. It is also found that the combustion changed the flow fields by enlarging the recirculation bubbles downstream of the bluff-body.
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| 10. |
- Tong, Yiheng, et al.
(författare)
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Experimental study on bluff-body stabilized premixed flame with a central air/fuel jet
- 2017
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Ingår i: Energies. - : MDPI AG. - 1996-1073. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- Bluff-body flame holders are commonly employed in many industrial applications. A bluff-body is usually adopted to enhance the downstream mixing of the combustion products and the fresh fuel-air mixtures, thus to improve the flame stability and to control the combustion process. In the present paper, flames stabilized by a conical-shape bluff-body flame holder with a central air/fuel jet were studied. Effects of both a central air jet and a central fuel jet on the structures and lean blowout limits of the premixed annular flames, and on the temperature on the upper surface of the bluff-body were investigated and presented. It was revealed that a central jet led to a considerable reduction of the temperature on the upper surface of the bluff-body. It was proposed to be caused by the alternation of flow structures (in the case with a central air jet) altogether with the flame lifting from the burner (in the case with a central fuel jet). Thus, it might be used to solve the problem of the bluff-body with high heat loads in practical applications. The flame stability characteristics, for example the unstable flame dynamics and the lean blowout limits, varied with the injection of an air or fuel jet through the central pipe. Different blowout behaviors, being with or without the occurrence of flame split and flashing, caused by a central air jet were presented in the paper. In addition, when a small amount of central fuel jet (i.e., Uf/Ua = 0.045) was injected into the flow fields, an unsteady circular motion of the flame tip along the outer edge of the bluff-body was observed as well. Whereas, with an increase in the amount of the central fuel jet, the flame detached from the outer edge of the bluff-body and then became much more unstable. With a central air or fuel jet injecting into the flow field, premixed flames stabilized by the bluff-body became more unstable and easier to blowout.
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