Computational Analysis of Microstructure of Ultra High Molecular Weight Polyethylene for Total Joint Replacement

Ultra high molecular weight polyethylene (UHMWPE, or ultra high), a frequently used material in orthopedic joint replacements, is often the cause of joint failure due to wear, fatigue, or fracture. These mechanical failures have been related to ultra high's strength and stiffness, and ultimately to the underlying microstructure, in previous experimental studies. Ultra high's semicrystalline microstructure consists of about 50% crystalline lamellae and 50% amorphous regions. Through common processing treatments, lamellar percentage and size can be altered, producing a range of mechanical responses. However, in the orthopedic field the basic material properties of the two microstructural phases are not typically studied independently, and their manipulation is not computationally optimized to produce desired mechanical properties. Therefore, the purpose of this study is to: (1) develop a 2D linear elastic finite element model of actual ultra high microstructure and fit the mechanical properties of the microstructural phases to experimental data and (2) systematically alter the dimensions of lamellae in the model to begin to explore optimizing the bulk stiffness while decreasing localized stress. The results show that a 2D finite element model can be built from a scanning electron micrograph of real ultra high lamellar microstructure, and that linear elastic constants can be fit to experimental results from those same ultra high formulations. Upon altering idealized lamellae dimensions, we found that bulk stiffness decreases as the width and length of lamellae increase. We also found that maximum localized Von Mises stress increases as the width of the lamellae decrease and as the length and aspect ratio of the lamellae increase. Our approach of combining finite element modeling based on scanning electron micrographs with experimental results from those same ultra high formulations and then using the models to computationally alter microstructural dimensions and properties could advance our understanding of how microstructure affects bulk mechanical properties. This advanced understanding could allow for the engineering of next-generation ultra high microstructures to optimize mechanical behavior and increase device longevity

MicroRNA Controlled Adenovirus Mediates Anti-Cancer Efficacy without Affecting Endogenous MicroRNA Activity

MicroRNAs are small non-coding RNA molecules that regulate mRNA translation and stability by binding to complementary sequences usually within the 3′ un-translated region (UTR). We have previously shown that the hepatic toxicity caused by wild-type Adenovirus 5 (Ad5WT) in mice can be prevented by incorporating 4 binding sites for the liver-specific microRNA, mir122, into the 3′ UTR of E1A mRNA. This virus, termed Ad5mir122, is a promising virotherapy candidate and causes no obvious liver pathology. Herein we show that Ad5mir122 maintains wild-type lytic activity in cancer cells not expressing mir122 and assess any effects of possible mir122 depletion in host cells. Repeat administration of 2×1010 viral particles of Admir122 to HepG2 tumour bearing mice showed significant anti-cancer efficacy. RT-QPCR showed that E1A mRNA was down-regulated 29-fold in liver when compared to Ad5WT. Western blot for E1A confirmed that all protein variants were knocked down. RT-QPCR for mature mir122 in infected livers showed that quantity of mir122 remained unaffected. Genome wide mRNA microarray profiling of infected livers showed that although the transcript level of >3900 different mRNAs changed more than 2-fold following Ad5WT infection, less than 600 were changed by Ad5mir122. These were then filtered to select mRNAs that were only altered by Ad5mir122 and the remaining 21 mRNAs were compared to predicted mir122 targets. No mir122 target mRNAs were affected by Ad5 mir122. These results demonstrate that the exploitation of microRNA regulation to control virus replication does not necessarily affect the level of the microRNA or the endogenous mRNA targets

Use of Tissue-Specific MicroRNA to Control Pathology of Wild-Type Adenovirus without Attenuation of Its Ability to Kill Cancer Cells

Replicating viruses have broad applications in biomedicine, notably in cancer virotherapy and in the design of attenuated vaccines; however, uncontrolled virus replication in vulnerable tissues can give pathology and often restricts the use of potent strains. Increased knowledge of tissue-selective microRNA expression now affords the possibility of engineering replicating viruses that are attenuated at the RNA level in sites of potential pathology, but retain wild-type replication activity at sites not expressing the relevant microRNA. To assess the usefulness of this approach for the DNA virus adenovirus, we have engineered a hepatocyte-safe wild-type adenovirus 5 (Ad5), which normally mediates significant toxicity and is potentially lethal in mice. To do this, we have included binding sites for hepatocyte-selective microRNA mir-122 within the 39 UTR of the E1A transcription cassette. Imaging versions of these viruses, produced by fusing E1A with luciferase, showed that inclusion of mir-122 binding sites caused up to 80-fold decreased hepatic expression of E1A following intravenous delivery to mice. Animals administered a ten-times lethal dose of wild-type Ad5 (5610 10 viral particles/mouse) showed substantial hepatic genome replication and extensive liver pathology, while inclusion of 4 microRNA binding sites decreased replication 50-fold and virtually abrogated liver toxicity. This modified wild-type virus retained full activity within cancer cells and provided a potent, liver-safe oncolytic virus. In addition to providing many potent new viruses for cancer virotherapy, microRNA control of virus replication should provide a new strategy for designing safe attenuated vaccines applied across a broad range of viral disease

Spintronics: Fundamentals and applications

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic physical principles underlying the generation of carrier spin polarization, spin dynamics, and spin-polarized transport in semiconductors and metals. Spin transport differs from charge transport in that spin is a nonconserved quantity in solids due to spin-orbit and hyperfine coupling. The authors discuss in detail spin decoherence mechanisms in metals and semiconductors. Various theories of spin injection and spin-polarized transport are applied to hybrid structures relevant to spin-based devices and fundamental studies of materials properties. Experimental work is reviewed with the emphasis on projected applications, in which external electric and magnetic fields and illumination by light will be used to control spin and charge dynamics to create new functionalities not feasible or ineffective with conventional electronics.Comment: invited review, 36 figures, 900+ references; minor stylistic changes from the published versio

Measurement of the ttˉproductioncrosssectionint\bar{t} production cross section in p\bar{p}collisionsat collisions at \sqrt{s}$ = 1.8 TeV

We update the measurement of the top production cross section using the CDF detector at the Fermilab Tevatron. This measurement uses $t\bar{t}$ decays to the final states $e+\nu$+jets and $\mu+\nu$+jets. We search for $b$ quarks from $t$ decays via secondary-vertex identification or the identification of semileptonic decays of the $b$ and cascade $c$ quarks. The background to the $t\bar{t}$ production is determined primarily through a Monte Carlo simulation. However, we calibrate the simulation and evaluate its uncertainty using several independent data samples. For a top mass of 175 $GeV/c^2$, we measure $\sigma_{t\bar{t}}=5.1 \pm 1.5$ pb and $\sigma_{t\bar{t}}=9.2 \pm 4.3$ pb using the secondary vertex and the lepton tagging algorithms, respectively. Finally, we combine these results with those from other $t\bar{t}$ decay channels and obtain $\sigma_{t\bar{t}} = 6.5^{+1.7}_{-1.4}$ pb.Comment: The manuscript consists of 130 pages, 35 figures and 42 tables in RevTex. The manuscript is submitted to Physical Review D. Fixed typo in author lis

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Crop Updates - 2003 Pulses

This session covers fifty one papers from different authors 2002 PULSE INDUSTRY HIGHLIGHTS CONTRIBUTORS BACKGROUND 2002 REGIONAL ROUNDUP 1.Northern Agricultural Region, M. Harries, Department of Agriculture 2.Central agricultural Region, R. French and I. Pritchard, Department of Agriculture 3.Great Southern and Lakes, R. Beermier, N. Poulish and S. White, Department of Agriculture 4.Esperance Mallee, M. Seymour, Department of Agriculture PULSE PRODUCTION ECONOMY AND GENETIC IMPROVEMENT 5.Faba Bean, P. White, Department of Agriculture 6.Germplasm evaluation, P. White, T. Pope, M. Harries and M. Seymour, Department of Agriculture 7.Row spacing and sowing rate, M. Seymour, Department of Agriculture 8.Tolerance to post emergent herbicides, M. Seymour, M. Harries, R. Beermier, M. Blyth and L. Young, Department of Agriculture 9.Investigation of environmental staining and storage discolouration, N. Abbas1,2, J. Plummer1, P. White3, D. Harris4 and K. Siddique1,2, 1Plant Biology, The University of Western Australia, 2CLIMA, The University of Western Australia, 3Department of Agriculture, 4Chemistry Centre of Western Australia. Desi chickpea 10.Breeding highlights, T. Khan1,2 and K. Siddique2 1Department of Agriculture, 2CLIMA, The University of Western Australia 11. Variety evaluation, T. Khan and K. Regan, Department of Agriculture 12. Residual effect of chickpea row spacing and sowing rate on wheat yield, G. Riethmuller and B. MacLeod, Department of Agriculture 13. Genotype x environmental interaction studies to help explain adaptation, J. Berger1, N. Turner1,2, K. Siddique1, 1CLIMA, The University of Western Australia, 2CSIRO Plant Industry 14. Genetic characterisation of wild relatives, F. Shan and H. Clarke, CLIMA, The University of Western Australia 15. Tolerance to chilling at flowering, H. Clarke, CLIMA, The University of Western Australia 16. Kabuli chickpea, K. Regan, Department of Agriculture 17. Premium quality varieties for the Ord River Irrigation Area, K. Siddique1, K. Regan2 and P. Smith2 1CLIMA, The University of Western Australia, 2Department of Agriculture 18. Development of aschochyta resistant varieties for Australia, K. Siddique1, K. Regan2 and M. Baker2 1CLIMA, University of Western Australia, 2Department of Agriculture Field pea 19. Breeding highlights, T. Khan and B. French, Department of Agriculture 20. Variety evaluation, T. Khan, Department of Agriculture 21. Specialty types for the high rainfall regions, P. White and T. Khan, Department of Agriculture 22. Are new varieties more sensitive to delayed sowing than Dundale? R. French, M. Seymour and R. Beermier, Department of Agriculture 23. Does the size of sown seed affect seed size and yield at harvest? R. Beermier and N. Poulish, Department of Agriculture 24. Tolerance to post emergent herbicides, H. Dhammu, T. Piper and D. Nicholson, Department of Agriculture 25. Lentil, K. Regan, Department of Agriculture 26. Variety evaluation, K. Regan and M. Harries, Department of Agriculture 27. Interstate evaluation of advanced breeding lines, K. Regan1 and M. Materne2 1Department of Agriculture, 2Victorian Institute for Dryland Agriculture, Agriculture Victoria 28. Timing of harvest for the best seed yield, M. Harries and M. Blyth, Department of Agriculture 29. Tolerance to post emergent herbicides, M. Harries and D. Nicholson, Department of Agriculture, H. Dhammu, T. Piper and L. Young, Department of Agriculture 30. Row spacing and stubble, G. Riethmuller, Department of Agriculture Pulse species 31. High value pulses for the high rainfall areas, N. Poulish1, P. White1,2 and K. Siddique1,2 , 1Department of Agriculture, 2CLIMA, The University of Western Australia 32. Alternative Rhizobium inoculant carrier technologies, J. Howieson and R. Yates, Centre for Rhizobium Studies (CRS), Murdoch University 33. Time of harvest to improve seed yield and quality of pulses, G. Riethmuller and R. French, Department of Agriculture 34. Phosphorus and zinc responses in pulses, S. Loss1, Z. Rengel2, B. Bowden3, M. Bolland3 and K. Siddique4 , 1Wesfarmers CSBP, 2Soil Science and Plant Nutrition, The University of Western Australia, 3Department of Agriculture, 4CLIMA, The University of Western Australia 35. Robust protocols for doubled haploid production in field pea and chickpea, J. Croser and K. Siddique, CLIMA, The University of Western Australia DEMONSTRATION OF PULSES IN THE FARMING SYSTEM 36. Field pea and lentil on clayed sandplain, M. Seymour, Department of Agriculture 37. Field pea variety demonstration, M. Harries and M. Blyth, Department of Agriculture 38. The benefit of field peas compared to lupins, R. Beermier, Department of Agriculture DISEASE AND PEST MANAGEMENT 39. Ascochyta blight of chickpea, B. MacLeod, Department of Agriculture 40. Management of chickpeas with improved ascochyta resistance, B. Macleod, A. Harrod, M. Harries and M. Blyth, Department of Agriculture 41. Chlorothalonil provides the most effective control, B. Macleod, A. Harrod, M. Harries and M. Blyth, Department of Agriculture 42. Importance of early sprays and value of seed dressing (post emergence), B. Macleod and A. Harrod, Department of Agriculture 43. A windborne stage of ascochyta blight in WA, J. Galloway and B. MacLeod, Department of Agriculture Ascochyta disease of pulses 44. Geographic location effects ascochyta spore maturation on pulse stubble, J. Galloway and B. MacLeod, Department of Agriculture Blackspot of field pea 45. Rapid recurrent selection to improve resistance to black spot, C. Beeck1, J. Wroth1, W. Cowling1 and T. Khan2, 1Plant Science, The University of Western Australia, 2Department of Agriculture 46. Survival of blackspot on old field pea stubble, J. Galloway and B. MacLeod, Department of Agriculture 47. Blackspot spores mature earlier in the southern regions, M. Salam, J. Galloway, A. Diggle and B. MacLeod, Department of Agriculture Viruses in pulses 48. Early insecticide application suppresses spread of Beet Western Yellows virus in field pea, R. Jones, B. Coutts and L. Smith, Department of Agriculture, and CLIMA, The University of Western Australia Insect pests and nematodes 49. Incorporation of pea weevil resistance from Pisum fulvum into field pea, O. Byrne1 and D. Hardie2, 1CLIMA, The University of Western Australia 2Department of Agriculture 50. Resistance to Helicoverpa in wild species of chickpea, J. Ridsdill-Smith1, H. Sharma2 and K. Mann1, 1CSIRO Entomology, Western Australia, 2 ICRISAT, Hyderabad, India 51. Relative hosting ability of field pea genotypes to root lesion nematode, S. Kelly, S. Sharma, H. Hunter and V. Vanstone, Department of Agriculture ACKNOWLEDGEMENTS APPENDIX I: Publications by Pulse Productivity Project Staff 2002 APPENDIX II: Summary of previous results APPENDIX III: List of common acronym

Substrate Type Determines Metagenomic Profiles from Diverse Chemical Habitats

Environmental parameters drive phenotypic and genotypic frequency variations in microbial communities and thus control the extent and structure of microbial diversity. We tested the extent to which microbial community composition changes are controlled by shifting physiochemical properties within a hypersaline lagoon. We sequenced four sediment metagenomes from the Coorong, South Australia from samples which varied in salinity by 99 Practical Salinity Units (PSU), an order of magnitude in ammonia concentration and two orders of magnitude in microbial abundance. Despite the marked divergence in environmental parameters observed between samples, hierarchical clustering of taxonomic and metabolic profiles of these metagenomes showed striking similarity between the samples (>89%). Comparison of these profiles to those derived from a wide variety of publically available datasets demonstrated that the Coorong sediment metagenomes were similar to other sediment, soil, biofilm and microbial mat samples regardless of salinity (>85% similarity). Overall, clustering of solid substrate and water metagenomes into discrete similarity groups based on functional potential indicated that the dichotomy between water and solid matrices is a fundamental determinant of community microbial metabolism that is not masked by salinity, nutrient concentration or microbial abundance

Pooled Safety and Efficacy Analysis Examining the Effect of Performance Status on Outcomes in Nine First-Line Treatment Trials Using Individual Data From Patients With Metastatic Colorectal Cancer

Performance status (PS) is a prognostic factor in patients with metastatic colorectal cancer. Clinical trials typically enroll less than 10% of patients with a PS of 2 (PS2); thus, the benefit of systemic chemotherapy in PS2 patients is uncertain