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1.
Viktoria M. S. Kjær Loukas Ieremias Dr. Viktorija Daugvilaite Dr. Michael Lückmann Prof. Thomas M. Frimurer Prof. Trond Ulven Prof. Mette M. Rosenkilde Dr. Jon Våbenø 《ChemMedChem》2021,16(17):2623-2627
The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca2+ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch. 相似文献
2.
Patricia Seoane-Collazo Amparo Romero-Pic Eva Rial-Pensado Laura Liares-Pose nxela Estvez-Salguero Johan Fern Rubn Nogueiras Carlos Diguez Miguel Lpez 《International journal of molecular sciences》2021,22(4)
Several studies have reported that nicotine, the main bioactive component of tobacco, exerts a marked negative energy balance. Apart from its anorectic action, nicotine also modulates energy expenditure, by regulating brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. These effects are mainly controlled at the central level by modulation of hypothalamic neuropeptide systems and energy sensors, such as AMP-activated protein kinase (AMPK). In this study, we aimed to investigate the kappa opioid receptor (κOR)/dynorphin signaling in the modulation of nicotine’s effects on energy balance. We found that body weight loss after nicotine treatment is associated with a down-regulation of the κOR endogenous ligand dynorphin precursor and with a marked reduction in κOR signaling and the p70 S6 kinase/ribosomal protein S6 (S6K/rpS6) pathway in the lateral hypothalamic area (LHA). The inhibition of these pathways by nicotine was completely blunted in κOR deficient mice, after central pharmacological blockade of κOR, and in rodents where κOR was genetically knocked down specifically in the LHA. Moreover, κOR-mediated nicotine effects on body weight do not depend on orexin. These data unravel a new central regulatory pathway modulating nicotine’s effects on energy balance. 相似文献
3.
Single-metal high-temperature solid sorbents for syngas cleaning using Mn, Ca, Fe, Cu, or Mo supported on γ-Al2O3 were synthesized, characterized, and tested in a fixed-bed reactor. H2S and SO2 concentrations in the gas after treatment at T = 400 to 700 °C were compared with thermodynamic calculations. The Mn-based sorbent showed the best ability to achieve a low sulfur residual in the gas, especially at temperatures above 600 °C. Sorbents with Fe, Cu, and Mo gave SO2 formation in the initial phase, but this could be avoided by a pre-reduction treatment of the sorbent material. 相似文献
4.
《Journal of dairy science》2022,105(3):2439-2452
Bias in dairy genetic evaluations, when it exists, has to be understood and properly addressed. The origin of biases is not always clear. We analyzed 40 yr of records from the Lacaune dairy sheep breeding program to evaluate the extent of bias, assess possible corrections, and emit hypotheses on its origin. The data set included 7 traits (milk yield, fat and protein contents, somatic cell score, teat angle, udder cleft, and udder depth) with records from 600,000 to 5 million depending on the trait, ~1,900,000 animals, and ~5,900 genotyped elite artificial insemination rams. For the ~8% animals with missing sire, we fit 25 unknown parent groups. We used the linear regression method to compare “partial” and “whole” predictions of young rams before and after progeny testing, with 7 cut-off points, and we obtained estimates of their bias, (over)dispersion, and accuracy in early proofs. We tried (1) several scenarios as follows: multiple or single trait, the “official” (routine) evaluation, which is a mixture of both single and multiple trait, and “deletion” of data before 1990; and (2) several models as follows: BLUP and single-step genomic (SSG)BLUP with fixed unknown parent groups or metafounders, where, for metafounders, their relationship matrix gamma was estimated using either a model for inbreeding trend, or base allele frequencies estimated by peeling. The estimate of gamma obtained by modeling the inbreeding trend resulted in an estimated increase of inbreeding, based on markers, faster than the pedigree-based one. The estimated genetic trends were similar for most models and scenarios across all traits, but were shrunken when gamma was estimated by peeling. This was due to shrinking of the estimates of metafounders in the latter case. Across scenarios, all traits showed bias, generally as an overestimate of genetic trend for milk yield and an underestimate for the other traits. As for the slope, it showed overdispersion of estimated breeding values for all traits. Using multiple-trait models slightly reduced the overestimate of genetic trend and the overdispersion, as did including genomic information (i.e., SSGBLUP) when the gamma matrix was estimated by the model for inbreeding trend. However, only deletion of historical data before 1990 resulted in elimination of both kind of biases. The SSGBLUP resulted in more accurate early proofs than BLUP for all traits. We considered that a snowball effect of small errors in each genetic evaluation, combined with selection, may have resulted in biased evaluations. Improving statistical methods reduced some bias but not all, and a simple solution for this data set was to remove historical records. 相似文献
5.
Marthe Jordbrekk Blikra Sigrun Henjum Inger Aakre 《Comprehensive Reviews in Food Science and Food Safety》2022,21(2):1517-1536
Brown algae are becoming increasingly popular as a food source and dietary supplement in Europe and other Western countries. As they are highly rich in iodine, they represent a potential new dietary iodine source. Iodine deficiency has been re-emerging in Europe, and it is important to ensure adequate intake through one's diet. However, macroalgae, and especially brown algae, may contain very high amounts of iodine, and both iodine deficiency and excessive iodine may increase the risk of negative health effects. The iodine content of algae or foods containing algae is currently not regulated in the European Union. The aim of this paper is to review the literature to determine the chemical species of iodine in brown algae, the loss of iodine during processing, and the bioavailability and bioaccessibility of iodine. A systematic search of the literature was performed in April 2021, via the databases Web of Science and PubMed. The review includes studies of iodine in brown macroalgae in relation to bioavailability, bioaccessibility, processing and speciation. A meta-analysis was conducted in relation to the following topics: (i) the correlation between total iodine and iodide (I–) content in brown algae; (ii) the correlation between the loss of iodine during processing and the I– content; and (iii) the correlation between bioavailability and the I– content. The bioavailability of iodine from brown algae was generally high, with in vivo bioavailability ranging from 31% to 90%. The in vitro bioavailability of iodine (2%–28%) was systematically lower than in vivo bioavailability (31%–90%), indicating an inadequate in vitro methodology. Processing may reduce the iodine content of brown algae, and a higher I– content was positively correlated with increased iodine loss during processing. Although processing strategies may reduce the iodine content of brown algae significantly, the iodine content may still be high after processing. These findings may be used in food safety evaluations of brown algae as well as in the development of macroalgae-containing foods with iodine contents suitable for human consumption. Further research on processing techniques to reduce the iodine content in brown macroalgae are warranted. 相似文献
6.
《International Journal of Hydrogen Energy》2022,47(48):20705-20717
Water electrolysis technologies aim to provide a significant increase in green hydrogen production efficiency. In this work, a framework was developed to explore the use of supercritical water for alkaline electrolysis. This framework was used to perform Arrhenius analysis as a function of potential, and to explore activation energies for sub- and supercritical water electrolysis. An analysis of the conductivity of solution unveiled a discontinuity in the trends between sub- and supercritical potassium hydroxide solution conductivity. Unlike prior work on supercritical water electrolysis, this work investigates trends in electrochemical parameters, the sources of these trends, and how they change between the sub- and supercritical regimes. 相似文献
7.
《International Journal of Hydrogen Energy》2022,47(88):37171-37182
In this work, copper sulfide particles are synthesized with different Co doping concentrations such as 0, 1 and 5% at 80 °C by optimizing synthesis times from 1 to 3 h. Copper sulfide particles possess two structural phases of covellite CuS and digenite Cu9S5. The increase in synthesis time from 1 to 3 h increases the Cu9S5 phase growth and changes the morphology from flower to microsphere. The CuS synthesized with 0, 1 and 5% Co dopant concentrations demonstrate flower consisting of agglomerated nanosheets, microsphere and flower like microsphere. The elemental investigation substantiates Co ions presence in CuS microspheres. The A1g (LO) mode intensity is decreased with increase in Co dopant concentration confirming Co incorporation into CuS microsphere. The CuS synthesized with 0, 1, 5% Co dopants exhibit 322 mV, 305 mV and 289 mV to attain 100 mA/cm2 in 1 M KOH seawater. The CuS synthesized with 5% Co dopant demonstrates higher double layer capacitance (Cdl) of 173.9 mFcm?2 and lower charge transfer resistance (Rct) of 6.07 Ω with 78.84% retention after 10 h continuous stability than that of the other pristine (118.3 mFcm?2, 13.72 Ω) and 1% Co doped CuS microsphere (165.7 mFcm?2, 8.55 Ω) indicating more surface active site and rapid charge carrier transport, respectively. 相似文献
8.
9.
《Mechatronics》2021
Currently, the Electric Power Steering (EPS) system is an essential component of the vehicle because it provides assistive steering torque to the driver. To ensure a faster steering response, the position of the EPS in some vehicles is moved closer to the tire rather than the steering wheel. The steering torque, which is provided by the EPS in the steering system, mainly affects the driver’s feel while steering. Therefore, the driver often feels uncomfortable owing to such positioning of the EPS in the steering system. In particular, the nonlinearity of the Universal Joint (UJ), which is one of parts of the steering system, can be felt at the steering wheel side.In this paper, we proposed an algorithm based on the mathematical model of the steering torque in the steering system to improve the steering feel. The mathematical model is structured using parameters that can be obtained from the information of the steering system. Moreover, the formulation of the steering torque consists of the two parts, namely the deformation part, which describes the propagation inside the steering system, and the friction part that describes the inherent friction in the UJ.Simulation and experiments were conducted to verify the proposed mathematical model with similar conditions to the real tire load during the steering motion. Furthermore, to improve the driver’s feel during steering, a torque compensation algorithm is proposed and verified through experiments. 相似文献
10.
A novel method of hydrofluidisation food freezing is numerically investigated in this paper. This technique is based on freezing small food products in a liquid medium under highly turbulent flow conditions when the heat transfer coefficient is higher than 1 000 W⋅m−2⋅K−1, which depends on the operating and flow conditions. A numerical model was developed to characterise the freezing process in terms of the heat transfer and diffusion of liquid solution components into the food product. The study investigates the freezing process of spherical samples in binary solutions of ethanol (30%) and glycerol (40%) and ternary solution of ethanol and glucose (15%/25%). The developed model was employed to determine the concentration of the liquid solution in food samples and to quantify the effect of sample size, heat transfer coefficient, solution temperature and concentration on the process. The food sample size varied from 5 to 30 mm, and the heat transfer coefficients varied from 1 000 to 4 000 W⋅ m−2⋅ K−1. The results confirm that a freezing time of 15 min for 30 mm diameter samples or less than 1 min for 5 mm diameter samples can be achieved with the hydrofluidisation method. The solution uptake was influenced by the solution type, sample size and process parameters and varied from 8.9 to 35 g of solute per kg of product for ethanol-glucose and glycerol solutions, respectively. This paper quantifies the advantages and possible limitations of hydrofluidisation, which has not yet been entirely studied, especially in terms of the mass absorption of different solutes. 相似文献