Biomechanics of the anterior cruciate ligament under simulated molecular degradation.

Injuries to the knee anterior cruciate ligament (ACL) are common, with a known but poorly understood association with intrinsic and extrinsic risk factors. Some of these factors are enzymatically or mechanically mediated, creating acute focal injuries that may cause significant ligament damage. Understanding the relationship between the basic molecular structure and external loading of the ACL requires a hierarchical connection between the two levels. In the present study, a multi-domain frame was developed connecting the molecular dynamics of the collagen networks to the continuum mechanics of the ACL. The model was used to elucidate the effect of the two possible collagen degradation mechanisms on the aggregate ACL behaviour. Results indicated that collagen content and ACL stiffness were reduced significantly, regardless of the degradation mechanism. Furthermore, the volumetric degradation at the molecular level had a devastating effect on the mechanical behaviour of the ACL when it was compared with the superficial degradation. ACL damage initiation and propagation were clearly influenced by collagen degradation. To summarise, the new insights provided by the predicted results revealed the significance of the collagen network structural integrity to the aggregate mechanical response of the ACL and, hence, underlined the biomechanical factors that may help develop an engineering-based approach towards improving the therapeutic intervention for ACL pathologies.

Effect of humidification of reactive gases on the performance of a proton exchange membrane fuel cell.

This work studies the impact of water formation on the performance of Proton Exchange Membrane Fuel Cells (PEMFCs). The work examines water management in PEM fuel cells both experimentally and theoretically. Experiments are conducted using a one stack PEM fuel cell fitted with Nafion membrane to evaluate its performance using both dry and humidified hydrogen and air. Results obtained confirms the importance of fuel humidification in improving the performance of the fuel cell with all levels of humidification producing better performance than that obtained using dry hydrogen or dry air. Experiments using air with 50% relative humidity indicate drop in the fuel cell performance when comparing the results to those from air with 100% relative humidity. The experimental data provides the basis to validate a computation fluid dynamics model for the fuel cell that is used to carry out further studies and conduct a parametric analysis of the fuel cell performance to examine the effects of flow plates designs, flow patterns such as parallel and counter flow and level of humidification on membrane water saturation, flooding, water management, reactants concentrations and overall cell performance by observing parameters such as membrane protonic conductivity, current density, cell voltage and power. The CFD model studies and compares the use of air and oxygen in PEM fuel cells and the results show that for 100% relative humidity the performance obtained using pure oxygen is only marginally better than the one obtained when using air. This indicates that it is more beneficial to use air at the right conditions in PEM fuel cells given the cost of pure oxygen as the overall economic balance and the ease of use favour the utilisation of air.

Numerical modelling and CFD simulation of a polymer electrolyte membrane (PEM) fuel cell flow channel using an open pore cellular foam material.

Fuel cell performances vary with different structural configurations and materials. However, the two main areas that determine this performance metric are the membrane electrode assembly (MEA) and the bipolar plates. The MEA provides the platform for the electrochemical reaction to occur and the bipolar plate serves as a medium between the reactants (hydrogen and air) and the catalyst layer. The bipolar plate is the first point of contact for the reactants inside the fuel cell, so a badly designed item with a high pressure drop will have a negative impact on fuel cell performance. Numerical modelling and simulation tools like ANSYS have a huge impact on engineering industry as they help designs to be validated and analysed before any physical construction. This investigation considers five suitable flow plate designs for PEM fuel cell, each completely different from the readily available, traditional serpentine designs on the market. The work explored the possibility of replacing these flow channels with an aluminium cellular foam with different inlet and outlet orientations. The designs were further optimised and modelled in ANSYS. The results obtained were compared with other designs in the literature. Compared to the serpentine flow design, the open pore cellular foam material showed a very small pressure drop in the range of 30-40 Pa. This indicates a possibility of replacing the traditional flow plate designs with the proposed ones.

Multilocus phylogeny and ecological differentiation of the "Eupelmus urozonus species group" (Hymenoptera, Eupelmidae) in the West-Palaearctic.

BACKGROUND: The ecological differentiation of insects with parasitic life-style is a complex process that may involve phylogenetic constraints as well as morphological and/or behavioural adaptations. In most cases, the relative importance of these driving forces remains unexplored. We investigate here this question for the "Eupelmus urozonus species group" which encompasses parasitoid wasps of potential interest in biological control. This was achieved using seven molecular markers, reliable records on 91 host species and a proxy of the ovipositor length. RESULTS: After using an adequate partitioning scheme, Maximum likelihood and Bayesian approaches provide a well-resolved phylogeny supporting the monophyly of this species group and highlighting its subdivision into three sub-groups. Great variations of both the ovipositor length and the host range (specialist versus generalist) were observed at this scale, with these two features being not significantly constrained by the phylogeny. Ovipositor length was not shown as a significant predictor of the parasitoid host range. CONCLUSIONS: This study provides firstly the first evidence for the strong lability of both the ovipositor's length and the realised host range in a set of phylogenetically related and sympatric species. In both cases, strong contrasts were observed between sister species. Moreover, no significant correlation was found between these two features. Alternative drivers of the ecological differentiation such as interspecific interactions are proposed and the consequences on the recruitment of these parasitoids on native and exotic pests are discussed.

Assessment of propofol usefulness as an anesthetic agent during colonoscopy.

BACKGROUND Propofol is used as a sedative drug during colonoscopy. In this study we analyzed the adverse effects of propofol (i.e., hemodynamic and respiratory) on patients who underwent colonoscopies. METHODS This study was performed in Qom Province, Iran. In this study, 125 patients (63 females, 62 males) were enrolled. Study patients were administered (0.5-1.5 mg/kg) intravenous propofol by an anesthesiologist. Oxygen saturation and blood pressure were recorded at three minute intervals. We used the American Society of Anesthesiology (ASA) classification to stratify patients by risk prior to the procedure. For statistical analysis, the chi-square and paired t-tests were used. A p -value less than 0.05 was considered significant. RESULTS Patients' mean age was 45.36 ± 16.19 years. ASA-I comprised 25.6% of study patients and 74.4% were categorized as ASA-II. Hypopnea occurred in 56.8% of patients and was prolonged in 32.4%. Of the study patients, 5.6% developed hypoxemia which was successfully controlled by the administration of nasal oxygen and no need for mechanical ventilation. The mean arterial blood pressure (p < 0.0001), oxygen saturation (p < 0.0001) and heart rate (p < 0.0001) significantly decreased during colonoscopy. The occurrence of hypopnea significantly increased in patients with pre-procedure oxygen saturation levels ≤ 95% (p < 0.02), age <50 years (p < 0.0001) and ASA class II (p < 0.0001) Agitation, hypotension and cough were seen in 1.6%, 1.6% and 0.8% of patients, respectively. CONCLUSION Propofol has a short half life that enables faster recovery of normal neurologic and social functions we recommend the use of propofol under supervision of anesthesiologist or a trained gastroenterologist.

Efficacy and safety of pamapimod in patients with active rheumatoid arthritis receiving stable methotrexate therapy.

OBJECTIVE: To determine the efficacy and safety of pamapimod in adult patients with active rheumatoid arthritis (RA) who had an inadequate clinical response to methotrexate (MTX). METHODS: Patients receiving stable doses of MTX were randomised to one of six dose groups and received 12 weeks of double-blind pamapimod (up to 300 mg once daily) or matching placebo. The primary efficacy measure was the proportion of patients with > or =20% improvement in RA based on the American College of Rheumatology criteria (ACR20) at 12 weeks. Secondary measures were ACR50, Disease Activity Score (DAS)/European League Against Rheumatism (EULAR) responses and the individual ACR core set of parameters. Safety measures included adverse events (AEs), laboratory testing and immunology assessments. RESULTS: On a background of MTX, the percentage of patients with an ACR20 response at week 12 in the pamapimod groups (31% to 43%) was not significantly different from placebo (34%). Secondary efficacy end points showed a similar pattern. AEs were typically mild and included infections, gastrointestinal disturbances, dizziness and rashes; AEs resulting in discontinuation of study drug were primarily attributed to infections. CONCLUSION: In patients with active RA receiving stable doses of MTX, pamapimod showed non-significant improvement in efficacy outcomes compared to placebo.

Cancer by negative heterosis: breast and ovarian cancer excess in hybrids of inbred ethnic groups.

Breast and ovarian cancer rates in Pakistan are significantly higher than in neighboring countries. The cancer rate discrepancies cannot be explained with discrepancies of their risk factors. We propose that observed cancer excess in Pakistan is due to cancer development by negative heterosis. Heterosis occurs when a hybrid has a phenotypic characteristic significantly different from that in either parent (hybrid vigor). At a molecular level, heterosis occurs in a heterozygote when one of the two alleles is inactivated. Gene inactivation occurs by methylation of cytosine in a promoter region of a gene. Initiation of allele inactivation is linked to the factors like stress, gender, diet, or another gene. In heterozygote, inactivation of one of the two tumor-suppressor alleles leads to monoallelic expression. This increases cancer risk in the same way the risk is increased in individual who inherit a single mutated tumor-suppressor gene (hereditary cancer syndrome). In both, cancer by heterosis and inherited cancer syndrome, cancer develops after inactivation of a second allele (second hit hypothesis). In a population, conditions that favor development of cancer by heterosis are those that favor mating of a large number of different homozygotes because they produce a large number of different heterozygotes. Among a large number of heterozygotes, there is an increased chance that some of hybrids will develop cancer by heterosis. In Pakistan, conditions were favorable for cancer development by heterosis because country has a high number of different ethnic groups and brotherhoods all of which have a higher rate of homozygosity due to a high frequency of consanguineous marriages, and marriages between members of different groups occurred because of intense population mixing. Result was birth of a large number of inter-ethnic/brotherhood hybrids (heterozygotes), some of which have developed cancer by heterosis.

Linear and nonlinear analyses of pulsatile blood flow in a cylindrical tube.

A non-Newtonian shear-thinning constitutive relation is proposed to study pulsatile flow of whole blood in a cylindrical tube. The constitutive relation, which satisfies the principle of material frame indifference, is derived from viscometric data obtained from whole blood over a range of hematocrits. Assuming axisymmetric flow in a rigid cylindrical tube of constant diameter, a second-order, nonlinear partial differential equation governing the axial velocity component is obtained. Imposing a periodic pressure gradient, the governing equation was solved numerically using finite difference methods over a range of Stokes values and hematocrits. For a forcing frequency of 1 Hz, results are presented over tube diameters ranging between 0.1 and 2 cm and over hematocrits ranging between 10 and 80%. For a given hematocrit, velocity profiles predicted for the non-Newtonian model under sinusoidal forcing reveal attenuated volume flow rate and enhanced vorticity transport over the tube cross-section relative to a Newtonian fluid having a viscosity corresponding to the high shear-rate limit. For moderate to high Stokes numbers, consistent with flow in large arteries, our results revealed a viscosity distribution that was nearly time invariant. An analytic solution was obtained for a fluid having arbitrarily prescribed radially varying, temporally invariant viscosity and density distributions under arbitrary periodic pressure forcing. Close agreement was observed between our numerical and analytical results when the imposed viscosity distribution was chosen to approximate the time-averaged viscosity distribution predicted by the shear-thinning non-Newtonian model. For St > or approximately= 100, the disparity between our results and those of a Newtonian fluid of constant viscosity grows with a decreasing ratio of the DC to AC components of the pressure-gradient amplitude below 50%. In particular, for any purely oscillatory pressure-gradient (vanishing DC component), the Womersley solution is a particularly poor predictor of the amplitude and phase of wall shear rate for over half of the flow cycle. Under such circumstances, the analytical models presented here provide a simple and accurate means of estimating instantaneous wall shear rate, knowing only the pressure gradient and hematocrit.

Strength and fatigue resistance of thoracolumbar spine implants: an experimental study of selected clinical devices.

Results of strength and endurance tests of several screw/rod thoracolumbar spinal implants are presented. The devices tested were: AcroMed ISOLA, CD systems, Depuy systems, and Synergy systems. The AcroMed ISOLA devices had the greatest stiffness and strength. The Synergy and AcroMed systems had the greatest fatigue resistance. The predominant failure mode was screw bending, although several instances of rod fracture and screw fracture were observed. A number of design improvements are identified, including reducing the number of components, thereby reducing the number of failure mechanisms; avoiding notches and knurled surfaces to provide greater resistance to crack initiation; and strengthening attachments between components, particularly between pedicle screws and horizontal rods.

Effects of cross-linkage on fatigue life and failure modes of stainless steel posterior spinal constructs.

This study tested the effects of cross-linkage on the fatigue performance of posterior spinal constructs (i.e., AcroMed stainless steel Isola systems). The failure modes encountered during fatigue were also examined. The results of this study confirmed earlier findings that the use of cross-linkage does not significantly affect the stability of posterior constructs during axial loading. Their influence in torsion loading is much more pronounced. During the fatigue tests, posterior stainless steel spinal implants instrumented without cross-linkage reached 1 million cycles at 500- and 750-N loads. When the load was increased to 1,000 N, the number of cycles to failure dropped by two-thirds. These findings demonstrate that the endurance limit was between 750 N and 1,000 N for spinal constructs without cross-linkage, with the limit being closer to 750 N. Devices equipped with one or two cross-linkages reached 1 million cycles at 500 N. The number of cycles to failure dropped dramatically as the load was increased to 750 and 1,000 N. It appears that the endurance limits for spinal devices using cross-linkage should be 500 and 750 N, with the limit closer to the 500-N load. All rod fractures occurred near the junction between the longitudinal and transverse rods. Stress concentration was greatly in the vicinity of that contact point. These results should provide a basis for future improvement in endurance limits of spinal implants equipped with cross-linkage. Higher endurance limits will reduce the toxic effects encountered during fracture modes. The implants will also be better able to withstand the high physiologic loads experienced by obese individuals.

Biomechanical assessment of titanium and stainless steel posterior spinal constructs: effects of absolute/relative loading and frequency on fatigue life and determination of failure modes.

The goal of this study was to examine the effects of absolute/relative loads and frequency on the fatigue life of titanium and stainless steel posterior spinal constructs, and to determine the failure fracture modes. The stainless steel constructs had higher stiffness and yield strength than the titanium constructs, but the ultimate static strength was almost equal for both types of constructs. Titanium constructs, however, exhibited higher variability than the stainless steel constructs. In fatigue tests, the stainless steel constructs were significantly affected by the external load and were frequency independent. It appears from fatigue curves that 500 N can be approximated as the endurance limit for the stainless steel constructs. Titanium constructs were load-frequency dependent, and their endurance limit was somewhere between the 500 and 750 N load levels. There were no differences in performance between the stainless steel and titanium constructs at 16 Hz. At 4 Hz, titanium constructs performed as well or better than stainless steel constructs. Also, the titanium constructs resulted in better performance than the stainless steel constructs in the elastic region, and with smaller differences in the plastic region. Most of the failure modes for stainless steel constructs were in screw bending at 16 Hz with a smaller percentage of rod fractures at high loads, with a higher percentage of rod fractures observed for the stainless steel constructs at 4 Hz. Most of the failure modes for titanium constructs occurred in screw bending or fracture.

Properties of purified actin depolymerizing factor from chick brain.

Actin depolymerizing factor (ADF) from 19-day embryonic chick brains has been purified to greater than 98% homogeneity with a yield of 7.2 mg/100 g of brain. Quantitative immunoblotting with a monospecific antibody to ADF indicated that ADF comprises 0.3% of the total brain protein, resulting in an actual purification yield of about 20%. Brain ADF migrates as a single polypeptide of 19,000 kDa on SDS-containing polyacrylamide gels. The molecular weight of the native protein determined from sedimentation equilibrium in buffers containing from 50 to 200 mM KCl is 20,000. The secondary structure of ADF calculated from the circular dichroic spectrum consists of about 22% alpha-helix, 24% beta-sheet, and 18% beta-turn. ADF contains a blocked N-terminus, a single tryptophan residue located about one-third of the way from one end of the protein, and six cysteine residues (all in reduced form in the native protein). All six cysteine residues could be chemically modified with eosinylmaleimide under nondenaturing conditions; however, ADF activity was lost when more than one cysteine residue was modified. ADF microheterogeneity has been observed upon nonequilibrium pH gradient electrophoresis in polyacrylamide gels containing 9 M urea, the major isoform having a pI of congruent to 7.9-8.0. ADF can interact with either monomeric or filamentous actin to give a complex which can be isolated by gel filtration chromatography. Both major and minor isoforms of the ADF are found in the complex. Assembly-competent actin and active ADF can both be recovered from the complex by chromatography on ATP-saturated DEAE-cellulose.(ABSTRACT TRUNCATED AT 250 WORDS)