| 1. |
- Akbari, Parsa, et al.
(författare)
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Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 373:6550
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale human exome sequencing can identify rare protein-coding variants with a large impact on complex traits such as body adiposity. We sequenced the exomes of 645,626 individuals from the United Kingdom, the United States, and Mexico and estimated associations of rare coding variants with body mass index (BMI). We identified 16 genes with an exome-wide significant association with BMI, including those encoding five brain-expressed G protein-coupled receptors (CALCR, MC4R, GIPR, GPR151, and GPR75). Protein-truncating variants in GPR75 were observed in ∼4/10,000 sequenced individuals and were associated with 1.8 kilograms per square meter lower BMI and 54% lower odds of obesity in the heterozygous state. Knock out of Gpr75 in mice resulted in resistance to weight gain and improved glycemic control in a high-fat diet model. Inhibition of GPR75 may provide a therapeutic strategy for obesity.
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| 2. |
- Dong, Jingran, et al.
(författare)
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Kinetics and mechanism of oxidation of the anti-tubercular prodrug isoniazid and its analog by iridium(IV) as models for biological redox systems
- 2017
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Ingår i: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9234 .- 1477-9226. ; 46:26, s. 8377-8386
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Tidskriftsartikel (refereegranskat)abstract
- A complex reaction mechanism of oxidation of the anti-tubercular prodrug isoniazid (isonicotinic hydrazide, INH) by [IrCl6]2− as a model for redox processes of such drugs in biological systems has been studied in aqueous solution as a function of pH between 0 and 8.5. Similar experiments have been performed with its isomer nicotinic hydrazide (NH). All reactions are overall second-order, first-order in [IrCl6]2− and hydrazide, and the observed second-order rate constants k′ have been determined as a function of pH. Spectrophotometric titrations indicate a stoichiometry of [Ir(IV)]:[hydrazide] = 4:1. HPLC analysis shows that the oxidation product of INH is isonicotinic acid. The derived reaction mechanism, based on rate law, time-resolved spectra and stoichiometry, involves parallel attacks by [IrCl6]2− on all four protolytic species of INH and NH as rate-determining steps, depending on pH. These steps are proposed to generate two types of hydrazyl free radicals. These radicals react further in three rapid consecutive processes, leading to the final oxidation products. Rate constants for the rate-determining steps have been determined for all protolytic species I–IV of INH and NH. They are used to calculate reactivity–pH diagrams. These diagrams demonstrate that for both systems, species IV is ca. 105 times more reactive in the redox process than the predominant species III at the physiological pH of 7.4. Thus, species IV will be the main reactant, in spite of the fact that its concentration at this pH is extremely low, a fact that has not been considered in previous work. The results indicate that pH changes might be an important factor in the activation process of INH in biological systems also, and that in such systems this process most likely is more complicated than previously assumed
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| 3. |
- Ning, Zhongrui, et al.
(författare)
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Wetter trend in source region of Yangtze River by runoff simulating based on Grid-RCCC-WBM
- 2024
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Ingår i: Journal of Hydrology. - 0022-1694. ; 631
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Tidskriftsartikel (refereegranskat)abstract
- Exploring the future hydroclimatic conditions of source region of Yangtze River (SRYaR), an alpine affected by climate change significantly, is essential for basin water resources management and development ss global climate change intensifies and the process of climate warming and humidification in Northwest China. This study proposed a practical framework for assessing water resource response to the context of climate changes in alpine catchments from the respective of both runoff and hydroclimatic conditions. Utilizing Grid-RCCC-WBM driven by corrected climatic forcing from the global climate models, this study estimate the prospective overall warmer and wetter pattern in the source region of Yangtze River. The key results indicated that: (1) Under all future scenarios, both temperature and precipitation within the catchment exhibit a significant upward trend. Projections from multi-model ensembles (MME) suggest that during the mid-term period (2041–2060, MT), temperatures are expected to rise by [0.74 °C, 3.08 °C] compared to the baseline period (1995–2014), with precipitation changes ranging from [4.8%, 21.4%]. (2) Future runoff within the catchment exhibits a consistent increase, with a linear trend rate of 1.1 mm/decade. runoff changes in MT compared to the baseline period vary from [−5.1%, 33.7%]. Runoff decreases in the northern part of the catchment, while notable increases occur in the southeastern and western regions. (3) In the future, the ratio of catchment evaporation capacity to precipitation decreases in comparison to the baseline period with an augmentation in soil moisture, enhancing its capacity for water retention and reducing the conversion of precipitation to evaporation, resulting a wetting trend of the catchment. (4) The future snowpack in the catchment continues to decrease, with a significant reduction in both the proportion of snowfall relative to total precipitation and the proportion of snowmelt runoff relative to total runoff, the risk of water resources crisis in the watershed is escalating.
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| 4. |
- Piao, Shilong, et al.
(författare)
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Evaluation of terrestrial carbon cycle models for their response to climate variability and to CO2 trends
- 2013
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013. ; 19:7, s. 2117-2132
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate 10 process-based terrestrial biosphere models that were used for the IPCC fifth Assessment Report. The simulated gross primary productivity (GPP) is compared with flux-tower-based estimates by Jung etal. [Journal of Geophysical Research 116 (2011) G00J07] (JU11). The net primary productivity (NPP) apparent sensitivity to climate variability and atmospheric CO2 trends is diagnosed from each model output, using statistical functions. The temperature sensitivity is compared against ecosystem field warming experiments results. The CO2 sensitivity of NPP is compared to the results from four Free-Air CO2 Enrichment (FACE) experiments. The simulated global net biome productivity (NBP) is compared with the residual land sink (RLS) of the global carbon budget from Friedlingstein etal. [Nature Geoscience 3 (2010) 811] (FR10). We found that models produce a higher GPP (133 +/- 15Pg Cyr-1) than JU11 (118 +/- 6Pg Cyr-1). In response to rising atmospheric CO2 concentration, modeled NPP increases on average by 16% (5-20%) per 100ppm, a slightly larger apparent sensitivity of NPP to CO2 than that measured at the FACE experiment locations (13% per 100ppm). Global NBP differs markedly among individual models, although the mean value of 2.0 +/- 0.8Pg Cyr-1 is remarkably close to the mean value of RLS (2.1 +/- 1.2 Pg Cyr-1). The interannual variability in modeled NBP is significantly correlated with that of RLS for the period 1980-2009. Both model-to-model and interannual variation in model GPP is larger than that in model NBP due to the strong coupling causing a positive correlation between ecosystem respiration and GPP in the model. The average linear regression slope of global NBP vs. temperature across the 10 models is -3.0 +/- 1.5Pg Cyr-1 degrees C-1, within the uncertainty of what derived from RLS (-3.9 +/- 1.1Pg Cyr-1 degrees C-1). However, 9 of 10 models overestimate the regression slope of NBP vs. precipitation, compared with the slope of the observed RLS vs. precipitation. With most models lacking processes that control GPP and NBP in addition to CO2 and climate, the agreement between modeled and observation-based GPP and NBP can be fortuitous. Carbon-nitrogen interactions (only separable in one model) significantly influence the simulated response of carbon cycle to temperature and atmospheric CO2 concentration, suggesting that nutrients limitations should be included in the next generation of terrestrial biosphere models.
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| 5. |
- Sun, Ning, et al.
(författare)
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Design guidelines for fluid-elastic instability of tube bundles subjected to two-phase cross flow
- 2019
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Ingår i: Journal of Zhejiang University: Science A. - 1673-565X. ; 20:8, s. 577-589
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Tidskriftsartikel (refereegranskat)abstract
- Fluid-elastic instability of tube bundles is the main cause of vibration failure of heat exchangers. To establish more reasonable and reliable design guidelines for fluid-elastic instability of tube bundles subjected to two-phase cross flow, we investigated experimentally the effects of the flow conditions of the two-phase flow and the geometrical characteristics of the tube bundles on damping, vibration, and fluid-elastic instability. Moreover, we proposed recommended values of the instability constant based on the conductivity difference measurement (CDM) model and the classification of tube bundle arrangements. The reliability of these values was also verified. The results indicated that the damping ratio in the lift direction was smaller than that in the drag direction and fluid-elastic instability was more prone to occur. The order of stability of the four tube bundle arrangements from high to low was normal triangular, normal square, rotated square, and rotated triangular. Thus, to avoid fluid-elastic instability, the normal triangular tube bundle is recommended for large shell-and-tube heat exchangers subjected to two-phase cross flow. In addition, for normal square and normal triangular tube bundles, the recommended instability constant is 4.0. For rotated square and rotated triangular tube bundles, the recommended instability constant is 1.1 when the mass damping parameter is less than or equal to 0.54, otherwise the value is 1.5.
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| 6. |
- Sun, Xiaohong, et al.
(författare)
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In-situ electrochemical synthesis of heteroatoms-doped reduced graphene oxide toward nonradical degradation of tetracycline
- 2023
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Ingår i: Chemical Engineering Journal. - 1385-8947. ; 471
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Tidskriftsartikel (refereegranskat)abstract
- Nonradical-based advanced oxidation processes (AOPs) catalyzed by defective carbonaceous materials have exhibited great superiorities in trace antibiotics removal from natural water matrices. However, the complicated, extensive and highly-energy consumed synthesis methods are seriously hindering its development and application. Herein an in-situ electrochemical synthesis technology was developed and N/B/F-codoped RGO was assembled on the Ti foam effectively by using ionic liquid (IL) as the heteroatoms parents. Other benefits of the IL including anti-RGO agglomeration, suppressing hydrolysis side reaction and reducing internal resistance were also demonstrated. Based on the diverse substrates exploration and comprehensive characterizations, adsorption and desolvation of the water molecules around IL-GO was found the two critical procedures for GO reduction and heteroatoms-doping. Hydrophilicity and porosity are the two essential properties for substrate selection. The solvent substitute experiments indicated electrochemical reduction of GO is a proton-mediated electron transfer reaction and the protons come from the solvent. Remarkable heteroatoms content was obtained from −1.0 V ∼ -1.2 V within 30 min under normal temperature and pressure. The degradation performance of N/B/F-codoped RGO was examined in an electrochemical system without any chemical additive. 93.0 % of trace tetracycline (5 mg L-1) was removed at −0.6 V within 60 min and the corresponding TOC removal efficiency was 40 %. Electron transfer efficiency can be even improved in the natural water matrices. The degradation mechanism investigation suggested that N/B/F-codoped RGO is able to simultaneously catalyze two nonradical pathways including electron transfer and singlet-dominated AOP. This work provides a highly effective, green and low-cost nonradical-based AOP technology for controlling antibiotics pollution in the environmental water matrices.
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