A porohyperelastic lubrication model for articular cartilage in the natural synovial joint

This work focuses on the proposed mechanisms for the lubrication of synovial joints and applies them to an idealised bearing geometry considering a porohyperelastic material (cartilage) rotating against a stationary rigid impermeable surface. The model captures the behaviour of all lubrication regimes including fluid film formation and boundary contact as the load capacity is increased, representing a major advancement in modelling cartilage mechanics. Transient responses in the fluid phase are shown to be faster than those in the solid phase with the former decaying over time as fluid is exuded from the material. The complex behaviour of fluid migrating to and from the lubricating film is captured which leads to a better understanding of the hydration and friction mechanisms observed

Fabrication of cartilage-inspired hydrogel/entangled polymer–elastomer structures possessing poro-elastic properties

The ability to replicate the load-bearing properties of articular cartilage is attractive for many engineering applications, particularly bearings where low friction, low wear, and high durability are required. Hydrogels are widely used materials spanning many diverse applications owing to their lubricity and unique mechanical/chemical properties. The poor mechanical characteristics of conventional hydrogels, especially their compressive behavior, limit their application in load-bearing applications despite their favorable properties such as poro/viscoelasticity and lubricity. This paper demonstrates a cartilage-inspired approach to produce a structure that benefits from water-swelling resistant and ultrafast recovery behavior of elastomers as well as the stress-relaxation and energy dissipation properties of hydrogels. A method is presented in this work to fabricate interconnected macro-porous elastomers based on sintering poly(methyl methacrylate) beads. The porous elastomer imparted structural support and resilience to its composite with an infused-grafted hydrogel. At 30% strain and depending upon the strain rate, the composite exhibited a load-bearing behavior that was 14–19 times greater than that of pristine hydrogel and approximately 3 times greater than that of the porous elastomer. The equilibrium elastic modulus of the composite was 452 kPa at a strain range of 10%–30%, which was close to the values reported for the modulus of cartilage tested with similar experimental parameters defined in this study. The dissipated energy for the composite at strain rates of 1 and 10–3 s–1 was enhanced by 25-, 25-, 5-, and 15-fold as compared to that for the pristine hydrogel and the porous elastomer, respectively. The cyclic loading tests at two strain rates showed that the composite immediately recovers its load-bearing properties with the maximum load recovery staying above 95% of its initial values throughout the testing. The permeability of the structures was measured experimentally, and the results showed a decrease of permeability by 3 orders of magnitude following hydrogel grafting

Aerodynamic Drag Reduction of Emergency Response Vehicles

This paper presents the first experimental and computational investigation into the aerodynamics of emergency response vehicles and focusses on reducing the additional drag that results from the customary practice of adding light-bars onto the vehicles’ roofs. A series of wind tunnel experiments demonstrate the significant increase in drag that results from the light bars and show these can be minimized by reducing the flow separation caused by them. Simple potential improvements in the aerodynamic design of the light bars are investigated by combining Computational Fluid Dynamics (CFD) with Design of Experiments and metamodelling methods. An aerofoil-based roof design concept is shown to reduce the overall aerodynamic drag by up to 20% and an analysis of its effect on overall fuel consumption indicates that it offers a significant opportunity for improving the fuel economy and reducing emissions from emergency response vehicles. These benefits are now being realised by the UK’s ambulance service

A multiscale method for optimising surface topography in elastohydrodynamic lubrication (EHL) using metamodels

The frictional performance of a bearing is of significant interest in any mechanical system where there are lubricated surfaces under load and in relative motion. Surface topography plays a major role in determining the coefficient of friction for the bearing because the size of the fluid film and topography are of a comparable order. The problem of optimising topography for such a system is complicated by the separation in scales between the size of the lubricated domain and that of the topography, which is of at least one order of magnitude or more smaller. This paper introduces a multiscale method for optimising the small scale topography for improved frictional performance of the large scale bearing. The approach fully couples the elastohydrodynamic lubrication at both scales between pressure generated in the lubricant and deformation of the bounding surfaces. Homogenised small scale data is used to inform the large scale model and is represented using Moving Least Squares metamodels calibrated by cross validation. An optimal topography for a minimum coefficient of friction for the bearing is identified and comparisons made of local minima in the response, where very different topographies with similar frictional performance are observed. Comparisons of the optimal topography with the smooth surface model demonstrated the complexity of capturing the non-linear effect of topography and the necessity of the multiscale method in capturing this. Deviations from the smooth surface model were quantified by the metamodel coefficients and showed how topographies with a similar frictional performance have very different characteristics

Comparison of printed glycan array, suspension array and ELISA in the detection of human anti-glycan antibodies

Anti-glycan antibodies represent a vast and yet insufficiently investigated subpopulation of naturally occurring and adaptive antibodies in humans. Recently, a variety of glycan-based microarrays emerged, allowing high-throughput profiling of a large repertoire of antibodies. As there are no direct approaches for comparison and evaluation of multi-glycan assays we compared three glycan-based immunoassays, namely printed glycan array (PGA), fluorescent microsphere-based suspension array (SA) and ELISA for their efficacy and selectivity in profiling anti-glycan antibodies in a cohort of 48 patients with and without ovarian cancer. The ABO blood group glycan antigens were selected as well recognized ligands for sensitivity and specificity assessments. As another ligand we selected P1, a member of the P blood group system recently identified by PGA as a potential ovarian cancer biomarker. All three glyco-immunoassays reflected the known ABO blood groups with high performance. In contrast, anti-P1 antibody binding profiles displayed much lower concordance. Whilst anti-P1 antibody levels between benign controls and ovarian cancer patients were significantly discriminated using PGA (p = 0.004), we got only similar results using SA (p = 0.03) but not for ELISA. Our findings demonstrate that whilst assays were largely positively correlated, each presents unique characteristic features and should be validated by an independent patient cohort rather than another array technique. The variety between methods presumably reflects the differences in glycan presentation and the antigen/antibody ratio, assay conditions and detection technique. This indicates that the glycan-antibody interaction of interest has to guide the assay selection

The Role of Teachers' Expectations in the Association between Children's SES and Performance in Kindergarten: A Moderated Mediation Analysis

This study examines the role of teachers' expectations in the association between children's socio-economic background and achievement outcomes. Furthermore, the role of children's ethnicity in moderating this mediated relation is investigated. In the present study, 3,948 children from kindergarten are examined. Data are analysed by means of structural equation modeling. First, results show that teachers' expectations mediate the relation between children's SES and their later language and math achievement, after controlling for children's ethnicity, prior achievement and gender. This result indicates that teachers may exacerbate individual differences between children. Second, children's ethnicity moderates the mediation effect of teachers' expectations with respect to math outcomes. The role of teachers' expectations in mediating the relation between SES and math outcomes is stronger for majority children than for minority children

Endocannabinoid Regulation of Acute and Protracted Nicotine Withdrawal: Effect of FAAH Inhibition

Evidence shows that the endocannabinoid system modulates the addictive properties of nicotine. In the present study, we hypothesized that spontaneous withdrawal resulting from removal of chronically implanted transdermal nicotine patches is regulated by the endocannabinoid system. A 7-day nicotine dependence procedure (5.2 mg/rat/day) elicited occurrence of reliable nicotine abstinence symptoms in Wistar rats. Somatic and affective withdrawal signs were observed at 16 and 34 hours following removal of nicotine patches, respectively. Further behavioral manifestations including decrease in locomotor activity and increased weight gain also occurred during withdrawal. Expression of spontaneous nicotine withdrawal was accompanied by fluctuation in levels of the endocannabinoid anandamide (AEA) in several brain structures including the amygdala, the hippocampus, the hypothalamus and the prefrontal cortex. Conversely, levels of 2-arachidonoyl-sn-glycerol were not significantly altered. Pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for the intracellular degradation of AEA, by URB597 (0.1 and 0.3 mg/kg, i.p.), reduced withdrawal-induced anxiety as assessed by the elevated plus maze test and the shock-probe defensive burying paradigm, but did not prevent the occurrence of somatic signs. Together, the results indicate that pharmacological strategies aimed at enhancing endocannabinoid signaling may offer therapeutic advantages to treat the negative affective state produced by nicotine withdrawal, which is critical for the maintenance of tobacco use

Host Control of Malaria Infections: Constraints on Immune and Erythropoeitic Response Kinetics

The two main agents of human malaria, Plasmodium vivax and Plasmodium falciparum, can induce severe anemia and provoke strong, complex immune reactions. Which dynamical behaviors of host immune and erythropoietic responses would foster control of infection, and which would lead to runaway parasitemia and/or severe anemia? To answer these questions, we developed differential equation models of interacting parasite and red blood cell (RBC) populations modulated by host immune and erythropoietic responses. The model immune responses incorporate both a rapidly responding innate component and a slower-responding, long-term antibody component, with several parasite developmental stages considered as targets for each type of immune response. We found that simulated infections with the highest parasitemia tended to be those with ineffective innate immunity even if antibodies were present. We also compared infections with dyserythropoiesis (reduced RBC production during infection) to those with compensatory erythropoiesis (boosted RBC production) or a fixed basal RBC production rate. Dyserythropoiesis tended to reduce parasitemia slightly but at a cost to the host of aggravating anemia. On the other hand, compensatory erythropoiesis tended to reduce the severity of anemia but with enhanced parasitemia if the innate response was ineffective. For both parasite species, sharp transitions between the schizont and the merozoite stages of development (i.e., with standard deviation in intra-RBC development time ≤2.4 h) were associated with lower parasitemia and less severe anemia. Thus tight synchronization in asexual parasite development might help control parasitemia. Finally, our simulations suggest that P. vivax can induce severe anemia as readily as P. falciparum for the same type of immune response, though P. vivax attacks a much smaller subset of RBCs. Since most P. vivax infections are nonlethal (if debilitating) clinically, this suggests that P. falciparum adaptations for countering or evading immune responses are more effective than those of P. vivax