The effect of non-Newtonian behavior on contact formation in an external gear pump

In an extrusion process, an external gear pump can be used to control the flow rate of the system. When extruding polymers, the viscosity is quite high, resulting in negligible inertia and thus laminar flow. The external gear pump contains two gears, one driven by a motor and one driven by means of contact with the other gear. In our previous work, the flow of a viscous fluid through an external gear pump was studied using the finite element method. Local mesh refinement was applied based on the respective distance between boundaries. Furthermore, the rotation of both gears was imposed. In this work, the rotation of one gear is imposed, whereas the other gear is freely rotating. However, the minimum distance between the gears is limited to a minimum value. When this value is reached, contact is assumed and also the rotation of second gear is imposed. A reversion of the torque on this gear results in a release of contact. In this manner, a quasi driver/driven situation is created in the numerical simulations. It is observed that contact is released periodically, and thus cannot be assumed present continuously, as is often prescribed. Non-Newtonian material properties, such as shear thinning and the pressure dependence of the density or the viscosity, alter how long contact is released during a tooth rotation

Missense mutations in the copper transporter gene ATP7A cause X-Linked distal hereditary motor neuropathy

Distal hereditary motor neuropathies comprise a clinically and genetically heterogeneous group of disorders. We recently mapped an X-linked form of this condition to chromosome Xq13.1-q21 in two large unrelated families. The region of genetic linkage included ATP7A, which encodes a copper-transporting P-type ATPase mutated in patients with Menkes disease, a severe infantile-onset neurodegenerative condition. We identified two unique ATP7A missense mutations (p.P1386S and p.T994I) in males with distal motor neuropathy in two families. These molecular alterations impact highly conserved amino acids in the carboxyl half of ATP7A and do not directly involve the copper transporter's known critical functional domains. Studies of p.P1386S revealed normal ATP7A mRNA and protein levels, a defect in ATP7A trafficking, and partial rescue of a S. cerevisiae copper transport knockout. Although ATP7A mutations are typically associated with severe Menkes disease or its milder allelic variant, occipital horn syndrome, we demonstrate here that certain missense mutations at this locus can cause a syndrome restricted to progressive distal motor neuropathy without overt signs of systemic copper deficiency. This previously unrecognized genotype-phenotype correlation suggests an important role of the ATP7A copper transporter in motor-neuron maintenance and function

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies

The effect of an adhesive interaction on predicting the scratch response of PS/PPO blends

Single-asperity scratching is used as a simplified contact problem to investigate the deformation due to two materials touching each other. Coupling the intrinsic polymer characteristics to the scratch response for blends of polystyrene (PS) and poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) with varying composition is the main challenge of this study. The intrinsic deformation properties of these blends are strongly influenced by their composition. A combination of experiments and simulations is essential to understand the influence of friction on the interplay between intrinsic deformation properties and contact mechanics. Without an adhesive component in the numerical simulations, no influence of scratch velocity on the penetration depth or lateral force is observed. Furthermore, the lateral force is highly underestimated. Inclusion of an adhesive component between the indenter tip and polymer substrate results in a bow-wave in front of the sliding indenter tip. The experimentally measured lateral forces can only be predicted when the velocity-independent constant friction coefficient varies with blend composition. Therefore, knowing the intrinsic material properties, i.e. deformation kinetics and the intrinsic friction parameter, enables a quantitative prediction of the single-asperity scratch response

Three-Dimensional Finite Element Modeling of a Viscous Fluid Flowing through an External Gear Pump

An external gear pump is a relatively simple and inexpensive pump, that is used in a variety of production systems. Numerous works have studied the external gear pump using numerical simulations; however, typically low-viscosity fluids and turbulent flow conditions are considered. Previous work of the authors focused on predicting the output fluctuation and the volumetric efficiency of an external gear pump processing high-viscosity fluids using a 2D representation. For certain conditions, backflow through all clearances could occur, resulting in a drop in volumetric efficiency. This calls for a full 3D model. Furthermore, high residence time zones are observed in the inflow channel of the pump. The 3D shape of these zones is still unknown. The aim of this work is to investigate the effect of the axial clearances on the performance of the external gear pump. A 3D mesh is generated by extruding the 2D mesh in the third direction, resulting in prism elements. This reduces the required number of elements and therewith makes the simulations computationally feasible. Introducing the axial clearances results in a lower efficiency compared to the 2D simulations. With particle tracking, the high residence time zones in the inflow channel are visualized in the 3D simulations

The extrusion of EPDM using an external gear pump: experiments and simulations

External gear pumps are used in fluid transport systems because of their tight clearances and accurate flow control. These tight clearances are a challenge for numerical studies in terms of spatial discretization. In earlier work, the flow of a viscous fluid in an external gear pump is computed using the finite element method (FEM). An element size based on the respective distance between boundaries is proposed. In this study, results based on the earlier work are compared to extrusion experiments of EPDM. The aim of this study is not only to validate the numerical simulations, but also to determine what material characteristics need to be taken into account for an accurate output prediction of the external gear pump. Especially the introduction of shear-thinning behavior results in an improvement of the amplitude of the pressure difference fluctuation. Taking into account compressibility, alters the torque fluctuation in such a way that it mimics the experiments. Unfortunately, the fluctuation in torque still has a too high amplitude. Eventually, simulations are performed including shear-thinning behavior, a temperature- and pressure-dependent viscosity, and compressibility. The effect of measuring the material behavior using oscillatory or shear experiments is shown. Furthermore, the simulations are applied to a second EPDM. Finally, different processing conditions are tested. For the simulations, only qualitative agreement is found, possibly as a result of the no slip boundary condition

Numerical Modeling of the Blend Morphology Evolution in Twin-Screw Extruders

The blend morphology model developed by Wong et al., based on Peters et al., is used to investigate the development of the disperse polymer blend morphology in twin-screw extruder flow. First, the model is written in a point-wise form suitable for using in conjunction with particle tracking. Particle tracking methods are used to generate trajectories along the flow field. Macroscopic droplet populations are placed along these trajectories and the velocity gradient tensor is extracted and applied on the point-wise blend morphology model. Very large morphology differences arise between trajectories that pass through the middle gap and those that do not. In the global distribution of (macroscopically averaged, monodisperse) droplet sizes, two distinct peaks appear due to these different trajectories. Given enough number of screw rotations, a droplet population can reach almost every position in the twin-screw extruder and travel along both types of particle trajectories. The effect of varying the gap size is that the largest droplets are unaffected, but the smallest droplets are smaller for a smaller gap size due to the higher maximum shear rate. The effect of varying the viscosity ratio on the global droplet size distribution is found to be nonlinear and is strongly determined by the Grace curve. The effect on polydisperse droplet populations is found to be that trajectories that do not pass through the gap evolve toward a single peak, whereas trajectories that do pass through the gap lead to a split into two peaks that ultimately rejoin as one peak. It is concluded that the initial position of a population in the twin-screw extruder has a very large effect on the developing transient blend morphology, though future work should be done on the importance of the initial position on the steady-state blend morphology after a very large number of screw rotations