Three-Dimensional Fracture Analysis in Functionally Graded Materials Using the Finite Block Method in Strong Form.

In this paper, the application of the strong-form finite block method (FBM) to three-dimensional fracture analysis with functionally graded materials is presented. The main idea of the strong-form FBM is that it transforms the arbitrary physical domain into a normalized domain and utilizes the direct collocation method to form a linear system. Using the mapping technique, partial differential matrices of any order can be constructed directly. Frameworks of the strong-form FBM for three-dimensional problems based on Lagrange polynomial interpolation and Chebyshev polynomial interpolation were developed. As the dominant parameters in linear elastic fracture mechanics, the stress intensity factors with functionally graded materials (FGMs) were determined according to the crack opening displacement criteria. Several numerical examples are presented using a few blocks to demonstrate the accuracy and efficiency of the strong-form FBM.

Influence of Taper surface topographies on contact deformation and stresses.

The role of bore and trunnion surface topography on the failure rate of total hip joint replacements due to trunnionosis is not clear despite significant variations in the design of taper components between manufacturers. Taper surface topography, along with other taper design parameters such as clearance, diameter, and assembly force, determine the initial interlock of the contacting surfaces after assembly; this has been related to relative motions that can cause fretting and corrosion at the taper interface. However, in most in-silico parametrical taper studies associated with taper micromotions, the bore and trunnion surfaces have been simplified using a flat surface and/or sinusoidal functions to mimic the surface roughness. The current study tests the hypothesis that the use of simple geometrical functions for the taper surface topography can predict the surface mechanics developed in assembled tapers. Measured and simulated surfaces of bores and trunnions were characterised using common roughness parameters and spectral density estimations. Using the same characterised surface profiles, 2D Finite Element (FE) models of CoCr alloy femoral heads and Ti alloy trunnions were developed. Models simulated assembly conditions at different resultant forces ranging from 0.5 to 4.0 kN, contact conditions were determined and associated with their topographical characteristics. Measured surfaces of bore and trunnion components comprise up to seven dominant spatial frequencies. Flattening of the trunnion microgrooved peaks was observed during the assembly of the taper. When the femoral head bore and trunnion topography were both considered a reduced number of microgrooved peaks were in contact, from 51 in an idealised taper surfaces to 35 in measured surfaces using an assembly reaction force of 4 kN. The contact points in the models developed high plastic strains, which were greater than that associated with failure of the material. Results showed that line and sine wave functions over estimate contact points at the taper interface compared to those surfaces that consider roughness and peak variation. These findings highlight the important role of modelling the full surface topography on the taper contact mechanics, as surface variations in the roughness and waviness change the performance of tapers.

Influence of taper design and loading on taper micromotion.

Debris originating at the bore-trunnion interface of modular total hip replacements has been identified as one of the causes of hip replacements failure. Friction associated with fretting and corrosion represents a potential generator of these harmful particles. Understanding the motions at the interface will help to interpret the different damage patterns found in retrieval studies and minimize the risk of fluid ingress/egress into the taper interface. Accordingly, the present study is designed to characterise the nature of the relative motions generated at the bore-trunnion interface of different taper designs during typical loading profiles. 3D Finite Element (FE) models of a CoCr femoral head assembled onto a Ti alloy trunnion were generated and variables including taper clearance, deviation from roundness, assembly force and loading conditions were introduced. Resulting micromotions relative to the trunnion surface, separation and contact area of the bore-trunnion interface were shown to be affected by both taper design and types of activities. Results indicated that, in some cases, the largest component of motion corresponded to that developed normal to the trunnion surface. Furthermore, out of roundness as small as 6 µm across the diameter, in particular orientations, significantly changed the contact mechanics and magnitude of relative motions. From the resulting parameters at the bore-trunnion interface, a pump type of motion was identified during walking, jogging and stairs up activities. The components of relative motions at the bore-trunnion interface were found to be different regardless of the resultant magnitude of the relative motions. The findings highlight the importance of high-quality manufacturing processes as small changes in the trunnion component will significantly affect the clinical performance of this common type of modular approach in total hip replacements.

Study on bending behaviour of nickel-titanium rotary endodontic instruments by analytical and numerical analyses.

AIM: To develop analytical models and analyse the stress distribution and flexibility of nickel-titanium (NiTi) instruments subject to bending forces. METHODOLOGY: The analytical method was used to analyse the behaviours of NiTi instruments under bending forces. Two NiTi instruments (RaCe and Mani NRT) with different cross-sections and geometries were considered. Analytical results were derived using Euler-Bernoulli nonlinear differential equations that took into account the screw pitch variation of these NiTi instruments. In addition, the nonlinear deformation analysis based on the analytical model and the finite element nonlinear analysis was carried out. Numerical results are obtained by carrying out a finite element method. RESULTS: According to analytical results, the maximum curvature of the instrument occurs near the instrument tip. Results of the finite element analysis revealed that the position of maximum von Mises stress was near the instrument tip. Therefore, the proposed analytical model can be used to predict the position of maximum curvature in the instrument where fracture may occur. Finally, results of analytical and numerical models were compatible. CONCLUSION: The proposed analytical model was validated by numerical results in analysing bending deformation of NiTi instruments. The analytical model is useful in the design and analysis of instruments. The proposed theoretical model is effective in studying the flexibility of NiTi instruments. Compared with the finite element method, the analytical model can deal conveniently and effectively with the subject of bending behaviour of rotary NiTi endodontic instruments.

Movement of a spherical cell in capillaries using a boundary element method.

This study aims to investigate the translation and rotation of a spherical particle in capillaries and overcomes limitations in previous studies by using a boundary element method. The capillary, a straight cylindrical tube, is filled with a Newtonian viscous fluid. A spherical particle is arbitrarily positioned in the capillary either co-centrically or eccentrically and is free to translate and rotate. Flow in the capillary is first assumed to be caused solely by the movement of the sphere under the gravity. When a steady state is reached, the net force and torque on the sphere are zero. The translating velocity and rotation of the particle are calculated from equilibrium equations. For a co-centric sphere, our result agrees to Bohlin's analytical solution (Bohlin, 1960) and the difference is less than 1%. For an eccentrically positioned sphere in the tube, there are no analytical solutions unless the eccentricity is infinitesimal. Results by boundary element method (BEM) give an improved estimations on the velocity and rotation of the sphere than earlier results by a boundary singularity method (BSM), particularly when the clearance between the tube and the sphere becomes small. Movement of a spherical particle in a capillary driven by a pressure gradient is further investigated, which has closer relevance to movement of blood cells in capillaries. The current study using BEM enables investigation on cell movement in close proximities of the capillary wall.

Entorhinal cortex lesioning promotes neurogenesis in the hippocampus of adult mice.

Hippocampal neurogenesis in adult mammals is influenced by many factors. Lesioning of the entorhinal cortex is a standard model used to study injury and repair in the hippocampus. Here we use bromodeoxyuridine (BrdU) labeling combined with immunohistochemical identification using cell type specific markers to follow the fate of neural progenitors in the hippocampus following entorhinal cortex lesioning in mice. We show that unilateral entorhinal cortex lesioning does not alter the rate of neural progenitor proliferation in the ipsilateral dentate gyrus during the first 3 days after lesioning. However it enhances cell survival at 42 days post-lesioning leading to an increased number of beta-III tubulin and calbindin-immunoreactive neurons being produced. By contrast, when BrdU was administered 21 days post-lesioning, the number of surviving cells 21 days later was similar on the lesioned and non-lesioned sides. Thus, acutely entorhinal cortex lesioning promotes neurogenesis by enhancing survival of either neural progenitors or their progeny. However, this stimulus to neurogenesis is not sustained into the recovery period.

Transgenic rescue of Krabbe disease in the twitcher mouse.

The twitcher mouse is a natural model of Krabbe disease caused by galactocerebrosidase (GALC) deficiency. Previous attempts at rescuing the twitcher mouse by bone marrow transplantion, viral transduction, or transgenesis were only partially successful. Here, we report the transgenic (tg) rescue of the twitcher mouse with a BAC clone harboring the entire GALC. The twi/twi/hGALC tg mice exhibited growth, motor function, and fertility similar to those of nonaffected animals. These animals had normal levels of GALC activity in brain and were free of the typical twitcher demyelinating pathology. Surprisingly, GALC expression in twi/twi hGALC tg kidneys was low and galactocerebroside storage was only partially cleared. Nonetheless, these mice have been maintained for over 1 year without any sign of disease. Since pathological damage associated with GALC deficiency is confined to the nervous system, our work represents the first successful rescue of the twitcher mouse and opens the possibility of developing novel therapeutic approaches.

Structure and function of Cerebratulus lacteus neurotoxin B-IV: tryptophan-30 is critical for function while lysines-18, -19, -29, and -33 are not required.

The Cerebratulus lacteus B-toxins are a family of polypeptide neurotoxins known to bind to crustacean voltage-sensitive sodium channels. We have previously shown that in the most abundant homolog, toxin B-IV, Arg-17 in the N-terminal helix and a positive charge at position 25 in the loop region are essential for function. In this report, we target a tryptophan residue at position 30, as well as lysine residues found in both the N-terminal helix and loop regions by polymerase chain reaction mutagenesis, to determine their contributions to toxin activity. Substitution of Trp-30 with a serine causes a more than 40-fold reduction in specific toxicity, whereas replacement by tyrosine and phenylalanine is well tolerated. The secondary structures of both these muteins are identical to that of the wild-type toxin as determined by circular dichroism spectroscopy. Thermal denaturation experiments also show that their conformational stabilities are intact. These results demonstrate that an aromatic residue at this position is required for toxin function. Charge neutralizing substitutions of Lys-18 and Lys-19 located in the N-terminal helix have very little effect on toxicity, suggesting the nonessentiality of these residues. Similar results are also obtained for the charge neutralizing muteins for Lys-29 and Lys-33 in the loop region. Interestingly, reduction experiments demonstrate that both K29N and W30S are more sensitive to reducing agent than wild-type B-IV, raising the possibility that the loop sequence may modulate toxin stability.

Potential effect of sodium nitrite on the expression of nuclear proto-oncogenes during 2-acetyl aminofluorene-induced hepatocarcinogenesis in rats.

2-acetyl aminofluorene (AAF) reacts in acidic conditions with nitrous fume yielding N-nitroso-AAF (N-NO-AAF), as previously described, that exerts more toxic and mutagenic effects than its parental compound. In this study, the effect of sodium nitrite (NaNO2) on the tumorigenicity of AAF in rats fed with AAF and NaNO2 was observed. Wistar rats were divided into five groups: group I served as control; group II were treated with NaNO2 (0.3%); group III was given 0.02% AAF alone; groups IV and V received both AAF and NaNO2 (0.2 and 0.3% respectively) in their diet for 12 weeks. At the end of the experiment, all rats in groups III, IV and V developed early stage phenomena of hepatocellular carcinoma, including hepatomegaly with variable-sized foci and neoplastic nodules. Severe damage was observed in the rats treated with AAF and NaNO2. Feeding of AAF (0.02%) for 3 months elevated the levels of c-Fos, c-Jun and c-Myc proteins in the rat livers. The AAF-induced c-Jun, c-Fos and c-Myc expressions were significantly magnified (P < 0.001) by NaNO2. These data confirmed that the strengthening of AAF-induced hepatocarcinogenesis by NaNO2 should be associated with its enhancing effect on the AAF-induced increases in the expressions of c-Jun, c-Fos and c-Myc.

Role of electrostatic interactions in defining the potency of neurotoxin B-IV from Cerebratulus lacteus.

Chemical modification implicates arginine residues of the Cerebratulus lacteus neurotoxin B-IV in biological activity. In the present study, we used site-directed mutagenesis to assess the functional contributions of each of these residues. Panels of mutants at each site have been constructed by polymerase chain reaction and recombinant proteins expressed and purified to homogeneity using an Escherichia coli expression system developed in this laboratory. All substitutions for Arg-17 (Gln, Ala, or Lys) yield proteins having undetectable levels of activity, while charge neutralizing replacement of Arg-25 (R25Q) causes a 400-fold reduction in specific toxicity. However, the R25K mutein is almost as active as natural toxin. Circular dichroism spectroscopy indicates that there are no major conformational changes in any of these muteins. These results therefore demonstrate the requirement for a guanidinium group at position 17, and a positive charge at position 25. NMR analyses (Hansen, P. E., Kem, W. R., Bieber, A. L., and Norton, R. S. (1992) Eur. J. Biochem. 210, 231-240) reveal neurotoxin B-IV to contain two antiparallel alpha-helices, which together include 57% of the sequence. Both Arg-17 and Arg-25 lie on the same face of the N-terminal helix (residues 13-26), as do the carboxyl groups of Glu-13 and Asp-21. However, charge neutralizing mutations of the latter two sites have no effects on biological activity. Arg-34, situated near the N terminus of helix 2 (residues 33-49) is also important for activity, as its replacement by Gln or Ala diminishes activity by 20- and 80-fold, respectively. However, unlike Arg-17 and Arg-25, thermal denaturation experiments suggest that R34Q may be structurally destabilized relative to wild-type B-IV.