The Effect of Ligands and Transducers on the Neurotensin Recep-tor 1 (NTS1) Conformational Ensemble

Using a discrete, intracellular 19F-NMR probe on Neurotensin receptor 1 (NTS1) transmembrane helix (TM) 6, we aim to understand how ligands and transducers modulate the receptors structural ensemble in solution. For apo NTS1, 19F-NMR spectra reveal an ensemble of at least three states (one inactive and two active-like) in equilibrium that exchange on the ms-s timescale. Dynamic NMR experiments reveal that these substates follow a linear three-site exchange process that is both thermodynamically and kinetically remodeled by orthosteric ligands. As previously observed in other GPCRs, the full agonist is insufficient to completely stabilize the active state. Receptor coupling to b-arrestin-1 or the C-terminal helix of Gaq, which comprises >60% of the GPCR/G protein interface surface area, abolishes the inactive substate. But whereas b-arrestin-1 selects for preexisting active-like substates, the Gaq peptide induces two new substates. Both transducer molecules promote substantial line-broadening of active states suggesting contributions from additional us-ms exchange processes. Together, our study suggests i) the NTS1 allosteric activation mechanism is alternatively dominated by induced fit or conformational selection depending on the coupled transducer, and ii) the available static structures do not represent the entire conformational ensemble observed in solution.

A Proposed Approach for Accurate Estimation of Interface Surface Area in Multiphase Simulations

Multiphase simulations and computational methods with precisely quantified interfaces are important for variety of engineering applications. A few of these applications are: heat transfer utilizing boiling processes, optimizing combustion, and additive printing/deposition processes. In these applications, calculating the length of the interface between two phases (e.g. a vapor and liquid) is particularly critical. Errors in the calculation of the size of the interface propagate over subsequent time steps thereby producing inaccurate rates of phase-change, fluid velocities, and convection heat transfer. This work proposes a method to reduce the reduce error in interface calculations in multiphase simulations. The proposed method uses the interface inclination and the vapor volume-fraction on each computational cell to compute the interface surface area. Moreover, this work provides details on proper declaration and computation of mass transfer with the Volume-of-Fluid sharp interface tracking algorithm. The performance of the proposed approach is compared with the accepted method that estimates interface surface area with gradients of vapor volume fractions. Computer simulations of spherical bubble growth in superheated liquid demonstrate the relevance of the proposed approach. Results indicate that the errors with the accepted method could propagate to 20% (relative to the theoretical estimation) in the prediction of bubble growth rate and fluid velocities. The proposed approach leads to errors of less than 1% in the prediction of bubble growth rate and fluid velocities.

Characterization of aluminum/alumina/TiC hybrid composites in 3D produced by anodizing and accumulating roll bonding process using synchrotron radiation tomography

Hybrid composites of Al/Al2O3/TiC were produced by anodizing and accumulative roll bonding processes. We implemented 3D imaging of the composites using synchrotron radiation tomography at Biomedical Imaging and Therapy’s 05B1-1 beamline at Canadian Light Source to collect information on internal structure of these hybrid composites i.e. distribution of particles and voids, particle/matrix interface and surface area distribution after different accumulative roll bonding passes. The volume and interface surface area distribution are responsible for strength and toughness of the composites along with other factors such as strain hardening and formation of ultrafine grains. We found that the mechanical properties improved as the number of accumulative roll bonding passes increases and the internal homogeneity of structure also improved. The composites after different accumulative roll bonding passes are studied where the number of reinforced particles and voids and their shape and size distribution were accurately being quantified in 3D to relate with mechanical properties of the composite. Such information should be of importance in analysis and improvement of the manufacturing process of these types of composites.

Numerical Investigation of Melt Jet Breakup With Different Shapes in Water Pool

During a severe accident in nuclear power plant, core damage may occur due to decay heat and molten fuel can pour into and interact with water resulting in steam explosion. The energetics of steam explosion strongly depends on the initial premixing stage during which the molten fuel undergoes a coarse fragmentation process, which determines the surface area for fuel-coolant contact and heat transfer. Extensive research has been done to understand the premixing stage, however, most of the studies are focused on the cylindrical jet interaction with water. In fact, during core melt, the molten fuel may pour near the edge of core, so the shapes and size of melt jet may differ significantly based on specific conditions. In this paper, numerically study on the melt jet breakup with different shapes in pool water are conducted, such as elliptical shape with VOF method. Firstly, the deformation of molten jet under the same conditions in 2D model is compared with 3D model and shows that the breakup of 3D model is quite different from 2D model, the integration of 3D model is maintained much better than 2D model. Then the characteristics of breakup of elliptic cylindrical melt jet are analyzed and compared with cylindrical melt jet. The results shows that the interface surface area of elliptic cylindrical jet is nearly twice the cylindrical jet.

On the Significance and Predicted Functional Effects of the Crown-to-Implant Ratio: A Finite Element Study of Long-Term Implant Stability Using High-Resolution, Nonlinear Numerical Analysis

With the rising popularity of short dental implants, the effects of the crown-to-implant (C/I) ratio on stress and strain distributions remain controversial. Previous research disagrees on results of interest and level of necessary technical detail. The present study aimed to evaluate the strain distribution and its functional implications in a single implant-supported crown with various C/I ratios placed in the maxillary molar region. A high-fidelity, nonlinear finite-element model was generated to simulate multiple clinical scenarios by laterally loading a set of single implants with various implant lengths (IL) and crown heights (CH). Strain distribution and maximum equivalent strain (MES) were analyzed to evaluate the effects and significance of the CH, IL and C/I. Predicted functional response to strain at the implant interface was analyzed by interface surface area. Results. Results were evaluated according to the mechanostat hypothesis to predict functional response. Overloading and effects of strain concentrations were more prevalent with increasing C/I. Overloading was predicted for all configurations to varying degrees, and increased with decreasing IL. Fracture in trabecular bone was predicted for at least one C/I and all IL of 10 mm or less. Higher C/I ratios and lower IL increase the risk of overloading and fracture. Increasing C/I augments the functional effects of other implant design factors. Greater C/I ratios may be achieved with implant designs that induce less significant strain concentrations.

The formation of nanoscale clusters – nanofilms / quantum dots predicted using a capillary model of nucleation

This paper describes the theoretical and simulation studies of both homogenous and heterogeneous nucleation, the phenomena that refers to the formation of stable nuclei prior to the growth of nanoclusters including nanofilms and quantum dots. Essentially, a single cluster may contain few thousand of atoms, and interaction with the surface may be preceded via processes, such as diffusion, hopping, sorption and coalescences. These complicated physical-chemical phenomena require in-depth theoretical understanding on how the various interacting quantities can be formulated and then resolved using specific mathematical approximation. In the case of a capillary model for heterogeneous nucleation, the nuclei are assumed to be in spherical shapes, which increase in both energies and diameters, and finally reach their critical points and settled to oval shapes prior to dome-like wetting on the substrate, essentially just like water droplet resting on a surface. The net change of energy, ΔG for the formation of cluster is found to be the functions of nucleus volume, surface area of atomic-nucleus interface, surface area of nucleus-surface interface and energy lost at substrate-atomic interface. The results for ΔG, ΔG*, r* and Ω and their respective changes with r, s and T were obtained and experimentally verified using existing data.

Two-Phase Damping and Interface Surface Area in Tubes With Internal Flow

Two-phase flow is common in the nuclear industry. It is a potential source of vibration in piping systems. In this paper, two-phase damping in the bubbly flow regime is related to the interface surface area between phases and, therefore, to flow configuration. Two sets of experiments were performed with a vertical tube clamped at both ends. First, gas bubbles of controlled geometry were simulated with glass spheres let to settle in stagnant water. Second, air was injected in stagnant alcohol to generate a uniform and measurable bubble flow. In both cases, the two-phase damping ratio is correlated to the number of bubbles (or spheres). Two-phase damping is directly related to the interface surface area, based on a spherical bubble model. Further experiments were carried out on tubes with internal two-phase air-water flows. A strong dependence of two-phase damping on flow configuration in bubbly flow regime is observed. A series of photographs attests to the fact that two-phase damping increases for a larger number of bubbles, and for smaller bubbles. It is highest immediately prior to the transition from bubbly flow to slug or churn flow regimes. Beyond the transition, damping decreases. An analytical model is proposed to predict two-phase flow damping in bubbly flow, based on a spherical bubble model. The results also reveal that the transition between bubbly flow and slug/churn flow depends on tube diameter. Consequently, the tube diameter also has an effect on two-phase damping. The above results could lead to some modifications of existing flow regime maps for small diameter tubes.