139 research outputs found
Optimization model of conventional missile maneuvering route based on improved Floyd algorithm
No full textMechanistic Insight into Subunit Stoichiometry for KIR Channel Gating: Ligand Binding, Gating, Binding-Gating Coupling, Coordination, and Cooperativity
No full textLigand-gated ion channels couple intra- and extracellular chemical signals to cellular excitability. In response to a specific ligand, these channels change their permeability to certain ions by opening or closing their ion conductive pathway, a controlling mechanism known as channel gating. Although recent studies with X-ray crystallography and site-directed mutagenesis have revealed several structures potentially important for channel gating, the gating mechanism is still elusive. Ligand-dependent channel gating involves a series of transient events and asymmetric movements of individual subunits. Understanding of these events appears to be a challenge to current approaches in gating studies by using the homomeric wild-type or mutant channels. I therefore took an alternative approach by constructing heteromeric channels. Subunit stoichiometric studies of the Kir1.1 channel showed that a minimum of one functional subunit was required for the pH-dependent gating of the channel. Four subunits in this channel were coordinated as dynamic functional dimers. In Kir6.2 channel, stoichiometry for proton-binding was almost identical to that for channel gating in the M2 helix, suggesting a one-to-one direct coupling of proton binding in C-terminus to channel gating in M2 helix. Positive cooperativity was suggested among subunits in both the proton binding and channel gating. Ligand binding can be differentiated from channel gating by studying the ATP-dependent gating of Kir6.2 channel. Disruptions in ATP binding were found to change both the potency and efficacy of the concentration-dependent curves, while the baseline activity instead of maximum inhibition was affected by disruptions of channel gating. Four subunits in the Kir6.2 channel undergo negative cooperativity in ATP binding and positive cooperativity in channel gating. The ligand binding was coupled to the gating mechanism in the same subunit and neighboring subunits, although the intrasubunit coupling was more effective. These results are well described with the operational model which we have applied to ion channel studies for the first time. By manipulating the relative distance and the interaction of two transmembrane helices, the inner helix bundle of crossing was found to not only serve as a gate but also determine the consequence of ligand binding.Doctor of Philosophy (PhD)Biolog
Mechanistic Insight into Subunit Stoichiometry for KIR Channel Gating: Ligand Binding, Gating, Binding-Gating Coupling, Coordination, and Cooperativity
No full textLigand-gated ion channels couple intra- and extracellular chemical signals to cellular excitability. In response to a specific ligand, these channels change their permeability to certain ions by opening or closing their ion conductive pathway, a controlling mechanism known as channel gating. Although recent studies with X-ray crystallography and site-directed mutagenesis have revealed several structures potentially important for channel gating, the gating mechanism is still elusive. Ligand-dependent channel gating involves a series of transient events and asymmetric movements of individual subunits. Understanding of these events appears to be a challenge to current approaches in gating studies by using the homomeric wild-type or mutant channels. I therefore took an alternative approach by constructing heteromeric channels. Subunit stoichiometric studies of the Kir1.1 channel showed that a minimum of one functional subunit was required for the pH-dependent gating of the channel. Four subunits in this channel were coordinated as dynamic functional dimers. In Kir6.2 channel, stoichiometry for proton-binding was almost identical to that for channel gating in the M2 helix, suggesting a one-to-one direct coupling of proton binding in C-terminus to channel gating in M2 helix. Positive cooperativity was suggested among subunits in both the proton binding and channel gating. Ligand binding can be differentiated from channel gating by studying the ATP-dependent gating of Kir6.2 channel. Disruptions in ATP binding were found to change both the potency and efficacy of the concentration-dependent curves, while the baseline activity instead of maximum inhibition was affected by disruptions of channel gating. Four subunits in the Kir6.2 channel undergo negative cooperativity in ATP binding and positive cooperativity in channel gating. The ligand binding was coupled to the gating mechanism in the same subunit and neighboring subunits, although the intrasubunit coupling was more effective. These results are well described with the operational model which we have applied to ion channel studies for the first time. By manipulating the relative distance and the interaction of two transmembrane helices, the inner helix bundle of crossing was found to not only serve as a gate but also determine the consequence of ligand binding
Femtosecond laser induced ultrafast interface dynamics between single layer graphene and quartz substrate: A theoretical study
No full textSiO2 is the most widely used dielectric substrate for graphene devices. Theoretically investigating the interaction between graphene and SiO2 is vitally important for understanding graphene properties and improving device performance. In recent years, density functional theory (DFT) has been used to investigate the graphene–SiO2 interaction in ground states. However, the strong interface dynamics for an excited graphene–SiO2 system in ultrafast nonequilibrium processes was rarely researched. In this work, a real-time time-dependent density functional theory (rt-TDDFT) method was adopted to study the femtosecond laser induced ultrafast structure evolution and the underlying dynamics mechanism of the interface between a single layer graphene and a Si-terminated quartz substrate. This work indicates that rt-TDDFT is a promising method to study the strong electron dynamics and the coupled nuclear dynamics for graphene-SiO2 interfaces under ultrafast optical excitation, which benefits graphene device designs and mechanism analysis
Formulation, development, and optimization of a novel octyldodecanol-based nanoemulsion for transdermal delivery of ceramide IIIB
No full textRunping Su,1 Li Yang,2 Yue Wang,1 Shanshan Yu,1 Yu Guo,1 Jiayu Deng,1 Qianqian Zhao,1 Xiangqun Jin1 1Department of Pharmaceutics, School of Pharmacy, 2Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China Abstract: This research aimed to develop and optimize a nanoemulsion-based formulation containing ceramide IIIB using phase-inversion composition for transdermal delivery. The effects of ethanol, propylene glycol (PG), and glycerol in octyldodecanol and Tween 80 systems on the size of the nanoemulsion region in the phase diagrams were investigated using water titration. Subsequently, ceramide IIIB loading was kept constant (0.05 wt%), and the proposed formulation and conditions were optimized via preliminary screening and experimental design. Factors such as octyldodecanol/(Tween 80:glycerol) weight ratio, water content, temperature, addition rate, and mixing rate were investigated in the preliminary screening experiment. Response surface methodology was employed to study the effect of water content (30%–70%, w/w), mixing rate (400–720 rpm), temperature (20°C–60°C), and addition rate (0.3–1.8 mL/min) on droplet size and polydispersity index. The mathematical model showed that the optimum formulation and conditions for preparation of ceramide IIIB nanoemulsion with desirable criteria were a temperature of 41.49°C, addition rate of 1.74 mL/min, water content of 55.08 wt%, and mixing rate of 720 rpm. Under optimum formulation conditions, the corresponding predicted response values for droplet size and polydispersity index were 15.51 nm and 0.12, respectively, which showed excellent agreement with the actual values (15.8 nm and 0.108, respectively), with no significant (P>0.05) differences. Keywords: response surface methodology, nanoemulsions, optimization, particle size, polydispersity inde
Study on eye movement characteristics and intervention of basketball shooting skill
No full textBACKGROUND: The shooting aiming point is very important in basketball because it may affect the field goal percentage (FG%). The purpose of this study was to explore the influence of shooting aiming point practice on FG% and to search for new training methods for shooting improvement in basketball. METHODS: A total of 24 expert basketball players and 24 amateur basketball players participated in the shooting task of Experiment 1. The participants in the two groups wore an eye movement instrument while shooting the ball. The shooting techniques included free throws, 45° direct shots and 45° bank shots to verify the differences in shooting aiming points between expert basketball players and amateur basketball players. Forty-eight amateur basketball players participated in the teaching experiment of Experiment 2. Twenty-four participants participated in routine teaching, and 24 participants had shooting aiming point practice for nine weeks to verify the difference in FG% between the two groups. The shooting aiming points of the participants were assessed immediately after shooting. RESULTS: Experiment 1 found that expert basketball players used shorter fixation duration, fewer fixation numbers and more reasonable (simple and efficient) fixation distributions than amateur players. Moreover, expert basketball players took the front edge of the hoop as the aiming point, and amateur players took the central or back edge of the hoop as the aiming point; the FG% of the expert group (83.47%) was significantly higher than that of the amateur group (34.86%) (P 0.05). After 9 weeks of shooting aiming point training, the FG% of the intervention group (36.39%) was significantly higher than that of the control group (30.14%) (P < 0.05), and the FG% of the intervention group increased faster than that of the control group. Additionally, the aiming point of the intervention players changed from the center and back edge of the hoop to the front. CONCLUSION: (1) There was a correlation between basketball shooting aiming point and FG%. FG% with the front edge of the hoop as the aiming point was higher than the back edge hoop or center. (2) The FG% could be more quickly improved by shooting aiming point practice; it will not be affected in a short time (5 weeks); however, 9 weeks of practice can significantly improve the FG%
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