Protein-protein interactions (PPIs) are of pivotal importance in the regulation of biological systems and are consequently implicated in the development of disease states. Recent work has begun to ...show that, with the right tools, certain classes of PPI can yield to the efforts of medicinal chemists to develop inhibitors, and the first PPI inhibitors have reached clinical development. In this Review, we describe the research leading to these breakthroughs and highlight the existence of groups of structurally related PPIs within the PPI target class. For each of these groups, we use examples of successful discovery efforts to illustrate the research strategies that have proved most useful.
The dependence of powder flowability on particle cohesion can often be captured by a dimensionless Bond number, however, whether the same is true for powder spreadability remains unclear. This paper ...thus presents a particle-scale study on the spreading of cohesive fine powders for additive manufacturing, focusing on the combined effect of particle size and surface cohesiveness. With an experimental validated model, detailed analysis revealed two competing mechanisms due to geometrical constraint and interparticle cohesion. For small particles that allows multiple particles across blade clearance, layer homogeneity is largely maintained before deteriorating sharply, while for large particles that forming a mono-layered packing structure, an optimum homogeneity can be obtained at a moderate level of particle cohesion. The efficacy of increasing blade clearance to improve layer quality was also evaluated. This study can help to identify a critical set of powder descriptors that defines spreading performance.
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•Combined effects of particle size and surface cohesiveness analyzed by DEM modelling.•Model validated with experimental results on static angle of repose.•Detailed packing structure, density and surface profile revealed.•Layer quality controlled by both geometrical effect and interparticle cohesion.•The efficacy of increasing blade clearance to improve layer quality evaluated.
Many important engineering applications involve the interaction of free-moving objects with dispersed multi-phase flows, however due to the challenge and complexity of modelling these systems, ...modelling approaches remain very limited and very few studies have been reported. This work presents a new method capable of addressing these problems. It integrates a dynamic meshing approach, used to explicitly capture the flow induced by free-moving large object(s), with a conventional CFD-DEM method to capture the behaviour of small particles in particle-fluid flow. The force and torque acting on the large object due to the fluid flow are explicitly calculated by integrating pressure and viscous stress acting on the object's surface and the forces due to collisions with both the smaller particles and other structures are calculated using a soft-sphere DEM approach. The developed model has been fully implemented on the ANSYS/Fluent platform due to its efficient handling of dynamic meshing and complex and/or free-moving boundaries, thus it can be applied to a wide range of industrial applications. Validation tests have been carried out for two typical gas-solid fluidization cases, they show good qualitative and quantitative agreement with reported experimental literature data. The developed model was then successfully applied to gas fluidization with a large immersed tube which was either fixed or free-moving. The predicted interacting dynamics of the gas, particle and tube were highly complex and highlighted the value of fully resolving the flow around the large object. The results demonstrated that the capability of a conventional CFD-DEM approach could be enhanced to address free-body fluid-structure interaction problems encountered in particle-fluid systems.
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•A new model is developed for fluid-structure interaction in particle-fluid flow.•Dynamic meshing is combined with CFD-DEM coupling.•The present model enables a fully resolved flow field around the moving object.•The proposed model is implemented on the ANSYS/Fluent platform.•Validation is conducted against available literature data of fluidization.
Particle-fluid flows with free-surfaces are commonly encountered in many industrial processes, such as wet ball milling, slurry transport and mixing. Accurate prediction of particle behaviors in ...these systems is critical to establish fundamental understandings of the processes, however the presence of the free-surface makes modelling them a challenge for most traditional, continuum, multi-phase methodologies. Coupling of smoothed particle hydrodynamics and discrete element method (SPH-DEM) has the potential to be an effective numerical method to achieve this goal. However, practical application of this method remains challenging due to high computational demands. In this work, a general purposed SPH-DEM model that runs entirely on a Graphic Processing Unit (GPU) is developed to accelerate the simulation. Fluid-solid coupling is based on local averaging techniques and, to accelerate neighbor searching, a dual-grid searching approach is adapted to a GPU architecture to tackle the size difference in the searching area between SPH and DEM. Simulation results compare well with experimental results on dam-breaking of a free-surface flow and particle-fluid flow both qualitatively and quantitatively, confirming the validity of the developed model. More than 10 million fluid particles can be simulated on a single GPU using double-precision floating point operations. A linear scalability of calculation time with the number of particles is obtained for both single-phase and two-phase flows. Practical application of the developed model is demonstrated by simulations of an agitated tubular reactor and a rotating drum, showing its capability in handling complex engineering problems involving both free-surfaces and particle-fluid interactions.
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•A GPU-based SPH and coupled SPH-DEM were developed.•A dual-grid searching approach was proposed to speed up the coupled simulations.•Calculation time scales linearly with the number of particles.•Model was validated with dam-breaking of a free-surface and particle-fluid flow.•Practical applications were shown by simulating tubular reactor and rotating drum.
Flocculation occurring in a feedwell plays a critical role in tailings slurry thickening process, which is complicated and significantly influenced by flow characteristics. This work presents a ...numerical approach to explore the effect of flow characteristics on flocculation performance. It combines an aggregation kernel and a breakage kernel, used to describe the polymer-bridging flocculation kinetics, with a conventional Computational Fluid Dynamics-Population Balance Model (CFD-PBM) coupling to model the complex flocculation-thickening behavior in a lab-scale gravity thickener. The solid-liquid phase interaction is described by an Euler-Euler approach with a modified Schiller-Naumann drag model. The turbulence of liquid phase is resolved by the RNG k-ε turbulence model, while the solid kinematic eddy viscosity is described by a dispersed phase zero equation model. The capability of this proposed model is validated by a good agreement between experimental and predicted results in terms of single-liquid velocity and floc size distribution. The momentum and turbulence dissipation rates are investigated in and around the feedwell over a wide range of feed velocities, showing that the momentum and turbulence dissipation rates have a positive correlation with feed velocity. The momentum and turbulence dissipation rates decrease with the increase in scaled depth in the feedwell. The formation of large vortexes in the feedwell may cause a locally low turbulence dissipation rate. A reasonable increase of feed velocity favours the flocculation, however, an excessive feed velocity can cause a decrease in mean floc size. Modelling tailings flocculation is of great significance for understanding the flocculation behavior and revealing the effect of flow characteristics on flocculation performance.
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•A population balance model (PBM) was used to describe the polymer-bridging flocculation kinetics.•The Tailings flocculation process in a thickener was modelled by a coupled CFD-PBM approach.•The capability of the proposed model was validated both in liquid velocity and floc size distribution.•The effects of feed velocity on flow characteristics and flocculation performance were explored.
Maximizing separation sharpness is critical for the design and operation of hydrocyclones but remains difficult to achieve. This work presents a numerical study on the relationship between separation ...performance and the characteristics of axial velocity wave zone to understand the reasons for the limited separation sharpness. The results showed that this zone is featured as an inherent transition region, with extensive secondary vortices formed between inner and outer spiral flows. The presence of this zone adversely affects the fluid-solid momentum transfer, causing prolonged residence time and accumulation of intermediate-sized particles. The separation sharpness shows a strong dependence on the characteristics of axial velocity wave zone, which are further controlled by geometric parameters. Increasing the symmetry of flow field and optimizing the spatial distribution of this zone can help increase the separation sharpness while its size shows little effect.
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•Two-fluid model and Lagrangian particle tracking method are used.•The flow field characteristics of axial velocity wave zone are studied.•Limited separation sharpness is attributed to the presence of this zone.•Dependence of separation sharpness on the characteristics of this zone is assessed.
The complex multiscale structure of spray dried detergent granules has been characterized using a complementary range of techniques including scanning electron microscopy (SEM), image analysis, wide ...angle and small angle X-ray scattering (WAXS, SAXS) and X-ray microtomography. A complex composite structure is revealed due to the multiphase nature of the starting slurry and its evolution during the drying process. Four simple model formulations based on linear alkylbenzene sulphonate (NaLAS) and sodium sulphate were used to probe the influence of initial slurry water content and binder, sodium silicate (SiO_2:nNa_2 O), on the structure. The structure revealed can be viewed as a continuous matrix consisting of NaLAS, sodium sulphate and binder in which large, dense, crystals of sodium sulphate are embedded. These large crystals were initially undissolved in the slurry and are consequently reduced in number in the product made from higher water content slurry. Air is also dispersed in this matrix at two length scales, large vacuoles, typically larger than 0.1x the particle diameter driven by ‘puffing’ i.e. water boiling, and micro-scale porosity which evolved during the crystallisation of the drying matrix. The matrix is formed from the dried slurry liquid phases and is a composite structure of binder, dried surfactant liquid crystalline phase and sub-micron scale crystallites of sodium sulphate. The liquid phase compositions change with the slurry water content, as well as the addition of binder; this changes both the sulphate polymorphs present and the spacing of the liquid crystalline lamellae, i.e. d-spacing, of the NaLAS phase. The composition and crystalline structure of the surface is also affected. The particle morphology can also be significantly affected with the high initial moisture content particle having a distinct agglomerated and blistered structure. The multiscale influence of formulation on particle structure, and consequently product properties and performance, highlights the challenge in predictive design of these important detergent products.
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•The complex multi-scale structure of spray dried detergent formulations is revealed.•Structure consists of inorganic crystallites and vacuoles bound by porous matrix.•Sub-micron sodium sulphate crystals are embedded in the surfactant, binder matrix.•Formulation changes affect structures across all scales; nano - colloidal - particle.•Slurry water content plays a key role in structure and therefore properties.
In this paper, discrete element method simulations were used to study the spreading of an idealised, blade based, powder coating system representative of the spreading of spherical, mono-sized, ...non-cohesive titanium alloy (Ti6AlV4) particles in additive layer manufacturing applications. A vertical spreader blade was used to accelerate a powder heap across a horizontal surface, with a thin gap between the blade and the surface, resulting in the deposition of a thin powder layer. The results showed that it is inevitable to deposit a powder layer with a lower packing fraction than the initial powder heap due to three mechanisms: shear-induced dilation during the initiation of powder motion by the spreader; dilation and rearrangement due to powder motion through the gap; and the inertia of the particles in the deposited powder layer. It was shown that the process conditions control the contribution of these three mechanisms, and that the velocity profile in the shear layer in front of the gap is critical to the final deposited layer packing fraction. The higher the mean normalised velocity in the shear layer the lower the deposited layer packing fraction. The gap thickness and the spreader blade velocity affect the properties of the deposited layer; with the former increasing its packing fraction and the latter decreasing it. The analysis presented in this study could be adapted to powders of different materials, morphologies and surface properties.
Sodium lauryl ether sulfate (SLES) is a common anionic surfactant used in a large number of personal care products. Commercial products typically contain a distribution in the number of ethoxy ...groups; despite this, there is limited existing work studying the effect of the ethoxy groups on the phase formation and structure. This is particularly important for the effect the structure has on the viscosity, an important consideration for commercial products. Dissipative particle dynamics is used to simulate the full phase diagram of SLES in water, including both micellar and lyotropic liquid crystal phases. Phase transitions occur at locations which are in good agreement with experimental data, and we find that these boundaries can shift as a result of varying the number of ethoxy groups. Varying the ethoxy groups has a significant effect on the micellar shape and crystalline spacing, with a reduction leading to more nonspherical micelles and decreased periodic spacing of the hexagonal and lamellar phases. Finally, while typical commercial products contain a distribution of ethoxy groups, computational work tends to focus on simulations containing a single chain length. We show that it is valid to use monodisperse simulations to infer behavior about solutions with a polydisperse chain length, based on its mean molecular length.
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