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ABSTRACT: Measurements of three-dimensional displacements in a scaffold implant under uniaxial compression have been obtained by two digital volume correlation (DVC) methods, and compared with those obtained from micro-finite element models. The DVC methods were based on two approaches, a local approach which registers independent small volumes and yields discontinuous displacement fields; and a global approach where the registration is performed on the whole volume of interest, leading to continuous displacement fields. A customised mini-compression device was used to perform in situ step-wise compression of the scaffold within a micro-computed tomography (μCT) chamber, and the data were collected at steps of interest. Displacement uncertainties, ranging from 0.006 to 0.02 voxel (i.e. 0.12-0.4μm), with a strain uncertainty between 60 and 600μɛ, were obtained with a spatial resolution of 32 voxels using both approaches, although the global approach has lower systematic errors. Reduced displacement and strain uncertainties may be obtained using the global approach by increasing the element size; and using the local approach by increasing the number of intermediary sub-volumes. Good agreements between the results from the DVC measurements and the FE simulations were obtained in the primary loading direction as well as in the lateral directions. This study demonstrates that volumetric strain measurements can be obtained successfully using DVC, which may be a useful tool to investigate mechanical behaviour of porous implants.
Medical Engineering & Physics 03/2013; · 1.62 Impact Factor
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ABSTRACT: REV3Lp, the catalytic subunit of DNA polymerase zeta, is the major participant in translesion DNA synthesis. Recent evidence suggests that REV3L has an important role in the maintenance of genome stability despite its mutagenic characteristics. Such a function makes it a cancer susceptibility candidate gene. To investigate association between REV3L polymorphisms and lung cancer risk in a Chinese population, we first genotyped 15 common polymorphisms of the REV3L gene and found that three single nucleotide polymorphisms (rs465646, rs459809 and rs1002481) were significantly associated with lung cancer risk. One of the strongest associations observed was for the 3'-terminal untranslated region (3'UTR) 460 T>C polymorphism (rs465646) (adjusted odds ratio (OR)=0.69 for TC/CC; P=0.007, compared with TT). Similar results were obtained in a subsequent replication study (adjusted OR=0.72; P=0.016). Combined data from the two studies of 1072 lung cancer patients and 1064 cancer-free controls generated an even stronger association (adjusted OR=0.71; P=3.04 × 10(-4)). This 3'UTR 460 T>C variant was predicted to modulate the binding of several micro RNAs. Surface plasmon resonance analysis and luciferase assays showed that the T allele demonstrated a stronger binding affinity for miR-25 and miR-32, resulting in significantly weaker reporter expression levels. Additional experiments revealed that miR-25/32 could downregulate endogenous REV3L. Furthermore, the tumor-suppressing role of REV3L was confirmed by the foci formation assay. These results support our hypothesis that the REV3L rs465646 variant modifies lung cancer susceptibility in Chinese Han population by affecting miRNA-mediated gene regulation.Oncogene advance online publication, 20 February 2012; doi:10.1038/onc.2012.32.
Oncogene 02/2012; · 6.37 Impact Factor
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ABSTRACT: We report a single-center experience in treating 18 consecutive patients with severe aplastic anemia (SAA) who received unrelated cord blood transplantation (CBT). The median age was 17 years (range 5-61 years). Sixteen cases received a reduced-intensity regimen composed of CY (total dose1200 mg/m(2)), rabbit antithymocyte globulin (ATG, total dose 30 mg/kg) and fludarabine (FLU, total dose 120 mg/m(2)). CYA and mycophenolate mofetil were used as GVHD prophylaxis. Two patients were not evaluable for engraftment because of early death on day +21 and +22. Only one of the sixteen cases achieved engraftment, but experienced secondary graft failure 3 months post transplantation. Fifteen patients experienced primary graft rejection, but all of them acquired autologous recovery. The 3-month and 6-month cumulative incidence of response was 56% and 81%, respectively. So far, 16 patients have survived for 330-1913 days (median, 750 days) after transplantation. The probability of OS at 2 years was 88.9%. Our data indicate that CBT for newly diagnosed SAA using no irradiation but FLU and ATG-based conditioning still seems to inevitably lead to the high risk of rejection, but may facilitate autologous recovery and improve survival with low risk of transplant-related mortality.
Bone marrow transplantation 01/2012; 47(9):1186-90. · 3.00 Impact Factor
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ABSTRACT: Damage development in cemented acetabular reconstructs has been studied under a combined cyclic loading block representative of routine activities in a saline environment. A custom-made environmental chamber was designed and installed on the Portsmouth hip simulator to allow testing of acetabular reconstructs in a wet condition for the first time. Damage was monitored and detected by scanning at selected loading intervals using micro-focus computed tomography (μCT). The preliminary results show that, although, as in dry cases, debonding at the bone-cement interface defined the failure of the cement fixation, the combination of mechanical loading and saline environment significantly affected the damage initiation and development, with drastically reduced survival lives of the reconstructs. Debonding was found to be initiated at the bone-cement interface near the rim of the acetabular cup, or DeLee zone I, in wet condition, as opposed to initiation in DeLee zone II near the dome region in dry cases. The survival time of the reconstruct in wet condition is less than 10% of that in dry condition under a given applied hip contact force.
Journal of biomechanics 01/2012; 45(2):405-8. · 2.66 Impact Factor
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ABSTRACT: Compressive behaviour of bovine cancellous bone and three open-cell metallic foams (AlSi7Mg (30 ppi and 45 ppi); CuSn12Ni2 (30 ppi)) has been studied using mechanical testing, micro-focus computed tomography and finite element modelling. Whilst the morphological parameters of the foams and the bone appear to be similar, the mechanical properties vary significantly between the foams and the bone. Finite element models were built from the CT images of the samples and multi-linear constitutive relations were used for modelling of the bone and the foams. The global responses of the bone and foam samples were reasonably well captured by the FE models, whilst the percentage of yielded elements as a measure of damage evolution during compression seems to be indicative of the micro-mechanical behaviour of the samples. The damage evolution and distribution patterns across the bone and the foams are broadly similar for the strain range studied, suggesting possible substitution of trabecular bones with appropriate foams for biomechanical studies.
Journal of the mechanical behavior of biomedical materials. 10/2011; 4(7):1452-61.
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ABSTRACT: We report a case of liver cancer with features consistent with fibrolamellar hepatocellular carcinoma (FLHCC) detected by PET-CT scan. A 20-year-old female with a large liver tumor was diagnosed with 'malignant hepatic tumor' 2 years earlier and received five courses of transhepatic arterial chemoembolization (TACE) before she presented to our hospital with abdominal distension and mild pain at the right upper quadrant. Ultrasound and CT scan showed a large tumor in the right lobe of the liver. Contrast CT scan and (18)F-FDG PET-CT showed metastatic lesions in multiple organs. The imaging diagnosis was confirmed by an ultrasound-guided fine needle biopsy of the hepatic lesion which showed features of FLHCC. Immunohistochemical staining showed a marked increase in the expressions of Hepar, CD99, MIB1, proliferating cell nuclear antigen (PCNA), Fibronectin, E-cadherin and CK7. The recent knowledge on the FLHCC and the possible applications of PET-CT were discussed.
QJM: monthly journal of the Association of Physicians 06/2011; 104(6):477-83. · 2.33 Impact Factor
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ABSTRACT: Interfacial behaviour of the bone-cement interface has been studied under tensile, shear and mixed mode loading conditions. Bovine cancellous bone was used to bond with acrylic bone cement to form bone-cement interface samples, which were mechanically tested under selected tensile, shear and mixed mode loading conditions. The influence of the loading angle and the extent of the cement penetration on the interfacial behaviour were examined. The failure mechanisms with regard to loading mode were examined using micro-focus computed tomography. The measured tensile and shear responses were utilized in a cohesive zone constitutive model, from which the pre-yield linear and the post-yield exponential strain softening behaviour under mixed mode loading conditions was predicted. The implications of the work on the studies of cemented joint replacements are also discussed.
Journal of the mechanical behavior of biomedical materials. 07/2010; 3(5):392-8.
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ABSTRACT: To establish the quantitative model of the dragonfly wing the reconfiguration and nanoindentation technique were used. The mechanical properties of wings were measured by nanoindentre. Generally, the costa undertake is mainly pressure, and its mechanical properties should be the largest. However, in the nanoindentation test, the largest value of the reduced modulus (E<sub>r</sub>) and hardness (H) mainly appear in the radius, except the value at 0.7L (L is the wing length). The E<sub>r</sub> and H of the forewing were larger than that of the hindwing, except the value at 0.7L. The reversing engineering (3-D scanner) and AutoCAD were cooperated to reconfigure the dragonfly wing. Then the material parameters and skeleton transforms to a finite element analysis. The quantitative models were discussed in static range.
IET Nanobiotechnology 04/2010; · 1.83 Impact Factor
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ABSTRACT: Mosquito coils are used to prevent mosquito exposures indoors by approximately 2 billion people worldwide. However, the smoldering of organic matters used as base materials of mosquito coils emits particulate and gaseous toxic compounds. A previous study indicates that emission rates of toxic compounds depend on types of base materials and can be high enough to generate room concentrations markedly higher than health based standards or references. The objective of this study is to evaluate a new type of mosquito coil that uses charcoal powder as base material and to compare its emission rates with those of several current-market brands and several brands tested in the previous study. Results show that the charcoal-based coil had emission rates of PM(2.5) mass, total particle number, polycyclic aromatic hydrocarbons (PAH), and aldehydes, substantially (up to 10 times) lower than other tested conventional mosquito coils. Results also show that particles freshly generated from burning mosquito coils were all fine and mostly ultrafine in size. This study presents emission rates for PM(2.5) mass, total particle number, gas-phase and particle-phase PAHs, 14 aldehydes and acetone, and 10 volatile hydrocarbons. These data, along with emission rates presented in the previous study are useful for estimating indoor concentrations of toxic compounds generated from mosquito coil uses. Practical Implications Mosquito coils are widely used indoors to prevent mosquitoes from entering indoor environments. This is achieved through the release of insecticides impregnated in biomass base materials of mosquito coils during coil combustion. A previous study reported that burning one mosquito coil releases the same amount of fine particles as burning 75-135 cigarettes, largely depending on what biomass (saw dust or coconut husk) is used as base material. This 'follow-up' study measured several current-market brands of mosquito coils, including a new charcoal-based coil labeled as smokeless coil by the China Environmental Labeling, for their emissions of particulate and gaseous pollutants. Results show that using charcoal powder as base material reduces fine particle emissions by a factor of 5-10 and also reduces emissions of pollutants such as formaldehyde and PAHs substantially.
Indoor Air 04/2010; 20(2):176-84. · 2.55 Impact Factor
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ABSTRACT: To establish the quantitative model of the dragonfly wing the reconfiguration and nanoindentation technique were used. The mechanical properties of wings were measured by nanoindentre. Generally, the costa undertake is mainly pressure, and its mechanical properties should be the largest. However, in the nanoindentation test, the largest value of the reduced modulus (E(r)) and hardness (H) mainly appear in the radius, except the value at 0.7L (L is the wing length). The E(r) and H of the forewing were larger than that of the hindwing, except the value at 0.7L. The reversing engineering (3-D scanner) and AutoCAD were cooperated to reconfigure the dragonfly wing. Then the material parameters and skeleton transforms to a finite element analysis. The quantitative models were discussed in static range.
IET Nanobiotechnology 03/2010; 4(1):10-8. · 1.83 Impact Factor
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ABSTRACT: Common carp (Cyprinus carpio) is an important fish for aquaculture, but genomics of this species is still in its infancy. In this study, a linkage map of common carp based on Amplified Fragment Length Polymorphism (AFLP) and microsatellite (SSR) markers has been generated using gynogenetic haploids. Of 926 markers genotyped, 151 (149 AFLPs, two SSRs) were distorted and eliminated from the linkage analyses. A total of 699 AFLP and 20 microsatellite (SSR) markers were assigned to the map, which comprised 64 linkage groups and covered 5506.9 cM Kosambi, with an average interval distance of 7.66 cM Kosambi. The normality tests on interval map distances showed a non-normal marker distribution. Visual inspection of the map distance distribution histogram showed a cluster of interval map distances on the left side of the chart, which suggested the occurrence of AFLP marker clusters. On the other hand, the lack of an obvious cluster on the right side showed that there were a few big gaps which need more markers to bridge. The correlation analysis showed a highly significant relatedness between the length of linkage group and the number of markers, indicating that the AFLP markers in this map were randomly distributed among different linkage groups. This study is helpful for research into the common carp genome and for further studies of genetics and marker-assisted breeding in this species.
Animal Genetics 11/2009; 41(2):191-8. · 2.40 Impact Factor
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J Li,
E K O Ng,
Y P Ng,
C Y P Wong,
J Yu,
H Jin,
V Y Y Cheng,
M Y Y Go,
P K F Cheung,
M P A Ebert, J Tong,
K F To,
F K L Chan,
J J Y Sung,
N Y Ip,
W K Leung
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ABSTRACT: Retinoic acid-regulated nuclear matrix-associated protein (RAMP) is a WD40 repeat-containing protein that is involved in various biological functions, but little is known about its role in human cancer. This study aims to delineate the oncogenic role of RAMP in gastric carcinogenesis.
RAMP expression was examined by real-time quantitative RT-PCR, immunohistochemistry and western blotting. Inhibition of RAMP expression was performed by siRNA-mediated knockdown. The functional effects of RAMP on cell kinetics were measured by cell viability assay, colony formation assay and flow cytometry. Cell lines stably expressing RAMP were established to investigate the oncogenic effects of RAMP in vitro.
Ramp was readily expressed in all seven gastric cancer cell lines and was significantly increased in human gastric cancer tissues when compared with their adjacent non-cancerous tissues (P<0.001). In keeping with this, expression of RAMP protein was higher in gastric cancer tissues compared with their adjacent non-cancerous tissues, whereas moderate protein expression were noted in intestinal metaplasia. Knockdown of RAMP in gastric cancer cells significantly reduced cell proliferation (P<0.01) and soft agar colony formation (P<0.001), but induced apoptosis and G(2)/M arrest. In additional, knockdown RAMP induced cell apoptosis is dependent on functional accumulation of p53 and p21 and induction of cleaved caspases-9, caspases-3 and PARP. Strikingly, overexpression of RAMP promoted anchorage-independent cell growth in soft agar.
Our findings demonstrate that RAMP plays an oncogenic role in gastric carcinogenesis. Inhibition of RAMP may be a promising approach for gastric cancer therapy.
British Journal of Cancer 09/2009; 101(4):691-8. · 5.04 Impact Factor
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ABSTRACT: Enhancing skeletal muscle growth is crucial for animal agriculture because skeletal muscle provides meat for human consumption. An increasing body of evidence shows that the level of maternal nutrition alters fetal skeletal muscle development, with long-term effects on offspring growth and performance. Fetal skeletal muscle development mainly involves myogenesis (i.e., muscle cell development), but also involves adipogenesis (i.e., adipocyte development) and fibrogenesis (i.e., fibroblast development). These tissues in fetal muscle are mainly derived from mesenchymal stem cells (MSC). Shifting the commitment of MSC from myogenesis to adipogenesis increases intramuscular fat (i.e., marbling), improving the quality grade of meats. Strong experimental evidence indicates that Wingless and Int (Wnt)/beta-catenin signaling regulates MSC differentiation. Upregulation of Wnt/beta-catenin promotes myogenesis, and downregulation enhances adipogenesis. A lack of nutrients in early to midgestation reduces the formation of secondary muscle fibers in ruminant animals. Nutrient deficiency during mid- to late gestation decreases the number of intramuscular adipocytes and muscle fiber sizes. Knowledge of this regulatory mechanism will allow the development of strategies to enhance muscle growth and marbling in offspring, especially in the setting of nutrient deficiency.
Journal of Animal Science 09/2009; 88(13 Suppl):E51-60. · 2.10 Impact Factor
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ABSTRACT: Determine whether preeclampsia is associated with developing diabetes.
Subsequent diabetes was ascertained using ICD-9 codes, pharmacy and glucose data in a retrospective cohort study of 2,032 women with preeclampsia and 29,431 without preeclampsia.
During a median follow-up of 8.2 years, 342 women developed diabetes. Preeclampsia was associated with a higher risk of diabetes adjusting for age, primigravidity, and gestational diabetes (hazard ratio, HR 1.82, 95%CI 1.26, 2.62) and in women without gestational diabetes (n = 30,109; HR 1.86, 95%CI 1.22, 2.84).
Women with preeclampsia have greater risk of developing diabetes, even in the absence of gestational diabetes.
Hypertension in Pregnancy 08/2009; 28(4):435-47. · 1.69 Impact Factor
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ABSTRACT: Damage development in cemented acetabular replacements has been studied in bovine pelvic bones under long-term physiological loading conditions, including normal walking, stair climbing and a combined block loading with representative routine activities. The physiological loading conditions were achieved using a specially designed hip simulator for fixation endurance testing. Damage was detected and monitored using micro-CT scanning at regular intervals of the experiments, and verified by microscopic studies post testing. The results show that debonding at the bone-cement interface defined the failure of cement fixation in all cases, and debondings initiated near the dome of the acetabulum in the superior-posterior quadrant, consistent with the high-stress region identified from the finite element analysis of implanted acetabular models Zant, N.P., Heaton-Adegbile, P., Hussell, J.G., Tong, J., 2008b. In-vitro fatigue failure of cemented acetabular replacements-a hip simulator study. Journal of Biomechanical Engineering, Transactions of the ASME, 130, 021019-1-9]; [Tong, J., Zant, N.P., Wang, J-Y., Heaton-Adegbile, P., Hussell, J.G., 2008. Fatigue in cemented acetabulum. International Journal of Fatigue, 30(8), 1366-1375].
Journal of biomechanics 05/2009; 42(8):1061-8. · 2.66 Impact Factor
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ABSTRACT: Islet transplantation is a potential cure for diabetes; however, rates of graft failure remain high. The aim of the present study was to determine whether amyloid deposition is associated with reduced beta cell volume in islet grafts and the recurrence of hyperglycaemia following islet transplantation.
We transplanted a streptozotocin-induced mouse model of diabetes with 100 islets from human IAPP (which encodes islet amyloid polypeptide) transgenic mice that have the propensity to form islet amyloid (n = 8-12) or from non-transgenic mice that do not develop amyloid (n = 6-10) in sets of studies that lasted 1 or 6 weeks.
Plasma glucose levels before and for 1 week after transplantation were similar in mice that received transgenic or non-transgenic islets, and at that time amyloid was detected in all transgenic grafts and, as expected, in none of the non-transgenic grafts. However, over the 6 weeks following transplantation, plasma glucose levels increased in transgenic but remained stable in non-transgenic islet graft recipients (p < 0.05). At 6 weeks, amyloid was present in 92% of the transgenic grafts and in none of the non-transgenic grafts. Beta cell volume was reduced by 30% (p < 0.05), beta cell apoptosis was twofold higher (p < 0.05), and beta cell replication was reduced by 50% (p < 0.001) in transgenic vs non-transgenic grafts. In summary, amyloid deposition in islet grafts occurs prior to the recurrence of hyperglycaemia and its accumulation over time is associated with beta cell loss.
Islet amyloid formation may explain, in part, the non-immune loss of beta cells and recurrence of hyperglycaemia following clinical islet transplantation.
Diabetologia 11/2008; 52(1):145-53. · 6.81 Impact Factor
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ABSTRACT: The long-term stability of cemented total hip replacements critically depends on the lasting integrity of the bond between the cement and the bone, often referred to as fixation. In vitro assessment of fatigue behaviour of cemented acetabular, as opposed to femoral, replacements is of particular interest due to the more aggressive nature of late "loosening" found in acetabular replacements, reported to be three times that in femoral cases. Quantitative assessment of fatigue behaviour of cement fixation on acetabular side has been difficult due to the complexity of the pelvic bone geometry and the associated loading conditions.The purpose of this work was to develop a framework for in vitro assessment of fatigue integrity of cement fixation in acetabular replacements. To this end, a newly developed hip simulator was utilised, where the direction and the magnitude of the hip contact force (Bergmann et al., 2001) under typical physiological loading conditions including normal walking and stair climbing were simulated for the first time. Preliminary hip simulator experimental results seem to be consistent with those from constant amplitude fatigue tests, in that debonding at the bone-cement interface is identified as the main failure mechanism, although the numbers of cycles to failure are significantly reduced in samples tested in the hip simulator. Finite element analysis of implanted bone samples was carried out, where the effects of loading mode on the stress distribution in the cement mantle and at the bone-cement interface were evaluated. The effects of model geometry on the stress state and failure modes were also examined and discussed based on the results of the present and previously published work.
International Journal of Fatigue 09/2008; 30(8):1366-1375. · 1.55 Impact Factor
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ABSTRACT: Marbling, or i.m. fat, is an important factor determining beef quality. Both adipogenesis and hypertrophy of existing adipocytes contribute to enhanced marbling. We hypothesized that the fetal stage is important for the formation of i.m. adipocytes and that AMP-activated protein kinase (AMPK) has a key role in adipogenesis during this stage. The objective of this study was to assess the role of AMPK in adipogenesis in fetal sheep muscle and 3T3-L1 cells. Nonpregnant ewes were randomly assigned to a control (Con, 100% of NRC recommendations, n = 7) or overfed (OF, 150% of NRC, n = 7) diet from 60 d before to 75 d after conception, when the ewes were killed. The fetal LM was collected at necropsy for biochemical analyses. The activity of AMPK was less in the fetal muscle of OF sheep. The expression of peroxisome proliferator-activated receptor (PPAR)gamma, a marker of adipogenesis, was greater in OF fetal muscle compared with Con fetal muscle. To further show the role of AMPK in adipogenesis, we used 3T3-L1 cells. The 3T3-L1 cells were incubated in a standard adipogenic medium for 24 h and 10 d. Activation of AMPK by 5-aminoimidazole-4-car-boxamide-1-beta-d-ribonucleoside dramatically inhibited the expression of PPARgamma and reduced the presence of adipocytes after 10 d of differentiation. Inhibition of AMPK by compound C enhanced the expression of PPARgamma. In conclusion, these data show that AMPK activity is inversely related to adipogenesis in fetal sheep muscle and 3T3-L1 cells.
Journal of Animal Science 07/2008; 86(6):1296-305. · 2.10 Impact Factor
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ABSTRACT: Although hip simulators for in vitro wear testing of prosthetic materials used in total hip arthroplasty (THA) have been available for a number of years, similar equipment has yet to appear for endurance testing of fixation in cemented THA, despite considerable evidence of late aseptic loosening as one of the most significant failure mechanisms in this type of replacements. An in vitro study of fatigue behavior in cemented acetabular replacements has been carried out, utilizing a newly developed hip simulator. The machine was designed to simulate the direction and the magnitude of the hip contact force under typical physiological loading conditions, including normal walking and stair climbing, as reported by Bergmann et al. (2001, Hip 98, Freie Universitaet, Berlin). A 3D finite element analysis has been carried out to validate the function of the hip simulator and to evaluate the effects of boundary conditions and geometry of the specimen on the stress distribution in the cement mantle. Bovine pelvic bones were implanted with a Charnley cup, using standard manual cementing techniques. Experiments were carried out under normal walking and descending stairs loading conditions with selected load levels from a body weight of 75-125 kg. Periodically, the samples were removed from the test rigs to allow CT scanning for the purpose of monitoring damage development in the cement fixation. The hip simulator was found to be satisfactory in reproducing the hip contact force during normal walking and stair climbing, as reported by Bergmann et al. Finite element analysis shows that the stress distributions in the cement mantle and at the bone-cement interface are largely unaffected by the geometry and the boundary conditions of the model. Three samples were tested up to 17 x 10(6) cycles and sectioned post-testing for microscopic studies. Debonding at the bone-cement interface of various degrees in the posterior-superior quadrant was revealed in these samples, and the location of the failures corresponds to the highest stressed region from the finite-element analysis. Preliminary experimental results from a newly developed hip simulator seem to suggest that debonding at the bone-cement interface is the main failure mechanism in cemented acetabular replacements, and descending stairs seem to be more detrimental than normal walking or ascending stairs with regard to fatigue integrity of cement fixation.
Journal of Biomechanical Engineering 05/2008; 130(2):021019. · 1.90 Impact Factor
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ABSTRACT: A (GT)(n) enriched partial genomic library of bighead carp (Aristichthys nobilis) was constructed by employing the (fast isolation by AFLP of sequences containing repeats) FIASCO protocol. Sixteen loci exhibited polymorphism with two to seven alleles/locus (mean 3.263) in a test population and the observed heterozygosity ranging from 0.100 to 0.690 (mean 0.392). Eleven of the 16 bighead carp microsatellites were found to be also polymorphic in silver carp. These polymorphic loci should provide sufficient level of genetic diversity to evaluate population structure of bighead carp.
Molecular Ecology Resources 05/2008; 8(3):656-8. · 3.06 Impact Factor
