NMR Study of Structure and Orientation of S4-S5 Linker Peptides from Shaw Related Potassium Ion Channels in Micelles and Binding of ZNF29R Protein to HIV RREIIBTR RNA

Potassium ion channels play a key role in the generation and propagation of action potentials. The S4-S5 linker peptide (L45) is believed to be responsible for the anesthetic/alcohol response of voltage-gated K+ channels. We investigated this region to define the structural basis of 1-alkanol binding site in dShaw2 K+ channel. L45 peptides derived from dShaw2 and hKv3.4 K+ channel, which, if part of the complete channel, demonstrate different sensitivity to 1-alcohols. Specifically, dShaw2 is alcohol sensitive and hKv3.4 is alcohol resistant. Structural analysis of L45 with NMR and CD suggested a direct correlation between alpha-helicity and the inhibition of dShaw2 channel by 1-butanol. We used CD and NMR to determine the structure of L45 peptides in micelles and vesicles. We measured spin-lattice relaxation time (T1) and determined the location and surface accessibility of L45 in micelles. These experiments confirm that L45 of dShaw2 adopts an α-helical conformation, partially buried in the membrane and parallel to the surface. The binding and accumulation of rev proteins to an internal loop of RRE (rev responsive element) of unspliced mRNA precursors is a key step of propagation of human immunodeficiency (HIV) virus. Molecules that interfere with this process can be expected to show anti-HIV activity. Our work is based on an assumption that zinc fingers could compete with rev proteins, therefore impeding the life cycle of HIV and stopping its infection. We studied the influence of different cations, anions, and the concentration of salts and osmolytes on the binding affinity with Polyacrylamide Gel Electrophoresis (PAGE) and Isothermal Titration Calorimetry (ITC). We conclude that the types of anions and/or cations and their concentrations affect the enthalpy and entropy of the binding interacitons. Using a gel assay, we confirm that there are three products in RNA-Protein reaction, and both EDTA and salts (and their concentrations) in the gel or samples interfere with RNA-protein complex mobility

Rebels Lead to the Doctrine of the Mean: Opinion Dynamic in a Heterogeneous DeGroot Model

We study an extension of the DeGroot model where part of the players may be rebels. The updating rule for rebels is quite different with that of normal players (which are referred to as conformists): at each step a rebel first takes the opposite value of the weighted average of her neighbors' opinions, i.e. 1 minus that average (the opinion space is assumed to be [0,1] as usual), and then updates her opinion by taking another weighted average between that value and her own opinion in the last round. We find that the effect of rebels is rather significant: as long as there is at least one rebel in every closed and strongly connected group, under very weak conditions, the opinion of each player in the whole society will eventually tend to 0.5.Comment: 7 pages, Proceedings of The 6th International Conference on Knowledge, Information and Creativity Support Systems, Beijing, 201

Insight into the Modulation of Shaw2 Kv Channels by General Anesthetics: Structural and Functional Studies of S4-S5 linker and S6 C-terminal peptides in micelles by NMR

The modulation of the Drosophila Shaw2 Kv channel by 1-alkanols and inhaled anesthetics is correlated with the involvement of the S4–S5 linker and C-terminus of S6, and consistent with stabilization of the channel\u27s closed state. Structural analysis of peptides from S4–S5 (L45) and S6 (S6c), by nuclear magnetic resonance and circular dichroism spectroscopy supports that an α-helical conformation was adopted by L45, while S6c was only in an unstable/dynamic partially folded α-helix in dodecylphosphocholine micelles. Solvent accessibility and paramagnetic probing of L45 revealed that L45 lies parallel to the surface of micelles with charged and polar residues pointing towards the solution while hydrophobic residues are buried inside the micelles. Chemical shift perturbation introduced by 1-butanol on residues Gln320, Thr321, Phe322 and Arg323 of L45, as well as Thr423 and Gln424 of S6c indicates possible anesthetic binding sites on these two important components in the channel activation apparatus. Diffusion measurements confirmed the association of L45, S6c and 1-butanol with micelles which suggests the capability of 1-butanol to influence a possible interaction of L45 and S6c in the micelle environment

Constraints on aerosol sources using GEOS-Chem adjoint and MODIS radiances, and evaluation with multisensor (OMI, MISR) data

We present a new top-down approach that spatially constrains the amount of aerosol emissions using satellite (Moderate Resolution Imaging Spectroradiometer (MODIS)) observed radiances with the adjoint of a chemistry transport model (GEOS-Chem). This paper aims to demonstrate the approach through applying it to a case study that yields the following emission estimates over China for April 2008: 1.73 Tg for SO2, 0.72 Tg for NH3, 1.38 Tg for NOx, 0.10 Tg for black carbon, and 0.18 Tg for organic carbon from anthropogenic sources, which reflects, respectively, a reduction of 33.5%, 34.5%, 18.8%, 9.1%, and 15% in comparison to the prior bottom-up inventories of INTEX-B 2006. The mineral dust emission from the online dust entrainment and mobilization module is reduced by 56.4% of 19.02 to 8.30 Tg. Compared to the prior simulation, the posterior simulation shows a much better agreement with the following independent measurements: aerosol optical depth (AOD) measured by AERONET sun-spectrophotometers and retrieved from Multi-angle Imaging SpectroRadiometer (MISR), atmospheric NO2 and SO2 columnar amount retrieved from Ozone Monitoring Instrument (OMI), and in situ data of sulfate-nitrate-ammonium and PM10 (particular matter with aerodynamic diameter less than 10 mm) mass concentrations over both anthropogenic pollution and dust source regions. Assuming the bottom-up (prior) anthropogenic emissions are the best estimates for their base year of 2006, the overwhelming reduction in the posterior (top-down) estimate indicates less emission in April 2008 especially for the SO2 tracer in the central and eastern parts of China, and/or an overestimation in the prior emission. The former is supported by the AOD change detected by MODIS and MISR sensors, while the latter is likely the case for NOx and NH3 emissions because no evidence shows that their atmospheric concentration has declined over China. With the promising results shown in this study, continuous efforts are needed toward a holistic and comprehensive inversion of emission using multisensor remote sensing data (of trace gases and aerosols) for constraining aerosol primary and precursor emissions at various temporal and spatial scales

Inverse modeling of SO2 and NOx emissions over China using multisensor satellite data - Part 1: Formulation and sensitivity analysis

SO2 and NO2 observations from the Ozone Mapping and Profiler Suite (OMPS) sensor are used for the first time in conjunction with the GEOS-Chem adjoint model to optimize both SO2 and NOx emission estimates over China for October 2013. Separate and joint (simultaneous) optimizations of SO2 and NO2 emissions are both conducted and compared. Posterior emissions, compared to the prior, yield improvements in simulating columnar SO2 and NO2, in comparison to measurements from the Ozone Monitoring Instrument (OMI) and OMPS. The posterior SO2 and NOx emissions from separate inversions are 748&thinsp;Gg&thinsp;S and 672&thinsp;Gg&thinsp;N, which are 36&thinsp;% and 6&thinsp;% smaller than prior MIX emissions (valid for 2010), respectively. In spite of the large reduction of SO2 emissions over the North China Plain, the simulated sulfate&ndash;nitrate&ndash;ammonium aerosol optical depth (AOD) only decrease slightly, which can be attributed to (a)&nbsp;nitrate rather than sulfate as the dominant contributor to AOD and (b)&nbsp;replacement of ammonium sulfate with ammonium nitrate as SO2 emissions are reduced. For joint inversions, both data quality control and the weight given to SO2 relative to NO2 observations can affect the spatial distributions of the posterior emissions. When the latter is properly balanced, the posterior emissions from assimilating OMPS SO2 and NO2 jointly yield a difference of &minus;3&thinsp;% to 15&thinsp;% with respect to the separate assimilations for total anthropogenic SO2 emissions and &plusmn;2&thinsp;% for total anthropogenic NOx emissions; but the differences can be up to 100&thinsp;% for SO2 and 40&thinsp;% for NO2 in some grid cells. Improvements on SO2 and NO2 simulations from the joint inversions are overall consistent with those from separate inversions. Moreover, the joint assimilations save &sim;&thinsp;50&thinsp;% of the computational time compared to assimilating SO2 and NO2 separately in a sequential manner of computation. The sensitivity analysis shows that a perturbation of NH3 to 50&thinsp;% (20&thinsp;%) of the prior emission inventory can (a)&nbsp;have a negligible impact on the separate SO2 inversion but can lead to a decrease in posterior SO2 emissions over China by &minus;2.4&thinsp;% (&minus;7.0&thinsp;%) in total and up to &minus;9.0&thinsp;% (&minus;27.7&thinsp;%) in some grid cells in the joint inversion with NO2 and (b)&nbsp;yield posterior NOx emission decreases over China by &minus;0.7&thinsp;% (&minus;2.8&thinsp;%) for the separate NO2 inversion and by &minus;2.7&thinsp;% (&minus;5.3&thinsp;%) in total and up to &minus;15.2&thinsp;% (&minus;29.4&thinsp;%) in some grid cells for the joint inversion. The large reduction of SO2 between 2010 and 2013, however, only leads to &sim;&thinsp;10&thinsp;% decrease in AOD regionally; reducing surface aerosol concentration requires the reduction of emissions of NH3 as well. </div

Fashion, Cooperation, and Social Interactions

Fashion plays such a crucial rule in the evolution of culture and society that it is regarded as a second nature to the human being. Also, its impact on economy is quite nontrivial. On what is fashionable, interestingly, there are two viewpoints that are both extremely widespread but almost opposite: conformists think that what is popular is fashionable, while rebels believe that being different is the essence. Fashion color is fashionable in the first sense, and Lady Gaga in the second. We investigate a model where the population consists of the afore-mentioned two groups of people that are located on social networks (a spatial cellular automata network and small-world networks). This model captures two fundamental kinds of social interactions (coordination and anti-coordination) simultaneously, and also has its own interest to game theory: it is a hybrid model of pure competition and pure cooperation. This is true because when a conformist meets a rebel, they play the zero sum matching pennies game, which is pure competition. When two conformists (rebels) meet, they play the (anti-) coordination game, which is pure cooperation. Simulation shows that simple social interactions greatly promote cooperation: in most cases people can reach an extraordinarily high level of cooperation, through a selfish, myopic, naive, and local interacting dynamic (the best response dynamic). We find that degree of synchronization also plays a critical role, but mostly on the negative side. Four indices, namely cooperation degree, average satisfaction degree, equilibrium ratio and complete ratio, are defined and applied to measure people's cooperation levels from various angles. Phase transition, as well as emergence of many interesting geographic patterns in the cellular automata network, is also observed.Comment: 21 pages, 12 figure

Synthesis, Biological Evaluation and Mechanism Studies of Deoxytylophorinine and Its Derivatives as Potential Anticancer Agents

Previous studies indicated that (+)-13a-(S)-Deoxytylophorinine (1) showed profound anti-cancer activities both in vitro and in vivo and could penetrate the blood brain barrier to distribute well in brain tissues. CNS toxicity, one of the main factors to hinder the development of phenanthroindolizidines, was not obviously found in 1. Based on its fascinating activities, thirty-four derivatives were designed, synthesized; their cytotoxic activities in vitro were tested to discover more excellent anticancer agents. Considering the distinctive mechanism of 1 and interesting SAR of deoxytylophorinine and its derivatives, the specific impacts of these compounds on cellular progress as cell signaling transduction pathways and cell cycle were proceeded with seven representative compounds. 1 as well as three most potent compounds, 9, 32, 33, and three less active compounds, 12, 16, 35, were selected to proform this study to have a relatively deep view of cancer cell growth-inhibitory characteristics. It was found that the expressions of phospho-Akt, Akt, phospho-ERK, and ERK in A549 cells were greater down-regulated by the potent compounds than by the less active compounds in the Western blot analysis. To the best of our knowledge, this is the first report describing phenanthroindolizidines alkaloids display influence on the crucial cell signaling proteins, ERK. Moreover, the expressions of cyclin A, cyclin D1 and CDK2 proteins depressed more dramatically when the cells were treated with 1, 9, 32, and 33. Then, these four excellent compounds were subjected to flow cytometric analysis, and an increase in S-phase was observed in A549 cells. Since the molecular level assay results of Western blot for phospho-Akt, Akt, phospho-ERK, ERK, and cyclins were relevant to the potency of compounds in cellular level, we speculated that this series of compounds exhibit anticancer activities through blocking PI3K and MAPK signaling transduction pathways and interfering with the cell cycle progression

Experimental study on mixture proportion design of recycled aggregate concrete using small particle size of recycled concrete aggregates

The purpose in this paper is to achieve the application of recycled aggregate concrete (RAC) in a practical engineering. Particle size of recycled concrete aggregates (RCAs) is required as only 4~8 mm. Based on Bolomey ideal gradation curve, through six tests, RAC with C35 strength grade and 180 mm slump is developed, which will realize the applications of RAC on concrete members with small section. The mixture proportion is cement∶water∶sand∶RCAs∶superplasticizer (SP) = 1∶0.6∶3.75∶1.81∶0.005. Furthermore, compared with European code, the coefficient in model of early age compressive strength is modified, that is s = 0.44, which can apply to RAC.status: publishe

Revealing multiphysics effects on microstructure characteristics in powder-fed laser cladding based on a comprehensive model

To accurately and quantitatively reveal the physical mechanism underlying the formation of microstructure during coaxial powder-fed laser cladding, a three-dimensional comprehensive model, coupling laser-powder interaction, temperature field, and flow field, is developed to identify the effects of multiphysics on microstructure characteristics. The high-speed camera and numerical simulation are employed to characterize the powder distribution, which is converted into the corresponding cladding layer growth rate and applied to solve the temperature rise and flow behavior of the molten pool. The energy conservation equation and the Navier-Stokes equation are applied to describe the physical field government, and the free surface motion of metallic liquid is tracked utilizing the Level Set method. The comprehensive model accurately visualizes the molten pool hydrodynamic behavior and temperature field distribution during laser cladding. In addition, the experimental results are combined to analyze the formation mechanism of microstructure. The direction and magnitude of forces acting on the metallic liquid in the flow field (such as surface tension, Marangoni force, recoil pressure) intuitively explain the formation of circulation in the molten pool, ultimately reflected in the grain growth direction. The evolution of cooling rates in the molten pool indicates that the specific location and varied temperature field dominates the grain type and size of the cladding layer, which contributes to the planar crystal, cellular crystal, columnar dendrite, equiaxed dendrite and equiaxed crystal from bottom to top