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Mathew J. Jones Dr. Alice Dawson Prof. Tim G. Hales Prof. William N. Hunter 《Chembiochem : a European journal of chemical biology》2020,21(10):1526-1533
Bicuculline, a valued chemical tool in neurosciences research, is a competitive antagonist of specific GABAA receptors and affects other pentameric ligand-gated ion channels including the glycine, nicotinic acetylcholine and 5-hydroxytryptamine type 3 receptors. We used a fluorescence-quenching assay and isothermal titration calorimetry to record low-micromolar dissociation constants for N-methylbicuculline interacting with acetylcholine-binding protein and an engineered version called glycine-binding protein (GBP), which provides a surrogate for the heteromeric interface of the extracellular domain of the glycine receptor (GlyR). The 2.4 Å resolution crystal structure of the GBP:N-methylbicuculline complex, sequence and structural alignments reveal similarities and differences between GlyR and the GABAA receptor–bicuculline interactions. N-methylbicuculline displays a similar conformation in different structures, but adopts distinct orientations enforced by interactions and steric blocks with key residues and plasticity in the binding sites. These features explain the promiscuous activity of bicuculline against the principal inhibitory pentameric ligand-gated ion channels in the CNS. 相似文献
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Martia Shahsavan Mohammadrasool Morovatiyan J.Hunter Mack 《International Journal of Hydrogen Energy》2018,43(29):13575-13582
The thermodynamic efficiency of internal combustion engines is primarily dependent on the compression ratio and specific heat ratio of the working fluid. Due to a higher specific heat ratio, using a noble gas and oxygen instead of air can increase the thermal efficiency. The lack of nitrogen in the working fluid also eliminates NOx formation. In this study, the three-dimensional turbulent injection of hydrogen into a constant volume combustion chamber has been modeled and compared to mixtures of oxygen with nitrogen, argon, and xenon at different injection velocities. The results indicate that the hydrogen jet has a longer penetration length in nitrogen compared to argon and xenon. However, smaller penetration lengths lead to more complex jet shapes and larger cone angles. Combustion in a noble gas environment results in higher temperatures and OH radical concentrations, due in part to lower specific heats and the jet characteristics. Furthermore, mixedness is investigated using mean spatial variation and mean scalar dissipation. Hydrogen in argon shows a better mixing rate compared to nitrogen and xenon due to the higher diffusivity. The results indicate that reduction in mean spatial variation can lead to a shorter ignition delay. 相似文献
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J. Tranter BSc C. Hunter BSc PhD J. Gunn BSc PhD J. Perkins BSc PhD 《Water and Environment Journal》1996,10(4):273-279
Faecal coliform concentrations were determined at stream and water inflow sampling sites within an upland catchment in North Derbyshire containing rough, semiimproved and improved pastures. The results indicated that, during its passage through the catchment, the faecal indicators of the stream increased, and this may constitute a health risk to cavers using a popular recreational cave into which the stream drains. The decline in streamwater quality suggests that a semipermanent store of bacteria existed in catchment soils, and hydrological processes operated to transfer bacteria from the land to the stream channel. Contrary to expectations, intra-catchment differences in the bacterial quality of water at inflow and stream sampling sites could not be related to the intensity of agricultural land use in adjacent areas. This is explained with reference to changes in the nature of hydrological transport pathways associated with the improvement of pastures. 相似文献
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“… … …. but that there turtle is an insect.” 相似文献
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Emmanouil D. Protonotarios Buzz Baum Alan Johnston Ginger L. Hunter Lewis D. Griffin 《Journal of the Royal Society Interface》2014,11(99)
Human observers readily make judgements about the degree of order in planar arrangements of points (point patterns). Here, based on pairwise ranking of 20 point patterns by degree of order, we have been able to show that judgements of order are highly consistent across individuals and the dimension of order has an interval scale structure spanning roughly 10 just-notable-differences (jnd) between disorder and order. We describe a geometric algorithm that estimates order to an accuracy of half a jnd by quantifying the variability of the size and shape of spaces between points. The algorithm is 70% more accurate than the best available measures. By anchoring the output of the algorithm so that Poisson point processes score on average 0, perfect lattices score 10 and unit steps correspond closely to jnds, we construct an absolute interval scale of order. We demonstrate its utility in biology by using this scale to quantify order during the development of the pattern of bristles on the dorsal thorax of the fruit fly. 相似文献
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Increasingly, evidence-based treatments are being implemented by community treatment providers, and it is important to understand whether they can be implemented with similar quality and equivalent effectiveness across gender and racial groups. This study examined whether initiation, engagement, dosage, treatment satisfaction, or outcomes for adolescents who received the Adolescent Community Reinforcement Approach (A-CRA) in a large implementation effort were equivalent by gender or racial group. Analyses of data from 2,141 adolescents representing 33 sites across the United States revealed no significant differences for initiation, engagement, or retention by gender or race. Ninety-six percent of the sample reported being satisfied with treatment; however, male adolescents had significantly higher rates of treatment satisfaction than female adolescents, and African American adolescents had significantly higher rates of treatment satisfaction than Caucasian adolescents. A subset of the initial sample (n = 1,819) was used to investigate outcomes. All racial groups had significant increases in days abstinent from alcohol and other drugs and in the percentage in recovery across the measurement period but did not differ from one another at the six-month follow-up. Female adolescents had a higher percentage of days abstinent from alcohol and other drugs and were more likely to be in recovery at the six-month follow-up than male adolescents. Overall, process indicators suggest the intervention was well implemented across gender and racial groups and equally effective across racial groups, with males having equivalent gains in abstinence and recovery compared with females despite males having greater intake severity and differential outcomes at six months. (PsycINFO Database Record (c) 2011 APA, all rights reserved) 相似文献
10.
Hunter Patrick G.; Schellenberg E. Glenn; Griffith Andrew T. 《Canadian Metallurgical Quarterly》2011,11(5):1068
We examined emotional responding to music after mood induction. On each trial, listeners heard a 30-s music excerpt and rated how much they liked it, whether it sounded happy or sad, and how familiar it was. When the excerpts sounded unambiguously happy or sad (Experiment 1), the typical preference for happy-sounding music was eliminated after inducing a sad mood. When the excerpts sounded ambiguous with respect to happiness and sadness (Experiment 2), listeners perceived more sadness after inducing a sad mood. Sad moods had no influence on familiarity ratings (Experiments 1 and 2). These findings imply that “misery loves company.” Listeners in a sad mood fail to show the typical preference for happy-sounding music, and they perceive more sadness in music that is ambiguous with respect to mood. (PsycINFO Database Record (c) 2011 APA, all rights reserved) 相似文献