Bone response to unloaded titanium implants in the fibula, iliac crest, and scapula: an animal study in the Yorkshire pig

The reconstruction of extended maxillary and mandibular defects with prefabricated free flaps is a two stage procedure, that allows immediate function with implant supported dentures. The appropriate delay between prefabrication and reconstruction depends on the interfacial strength of the bone–implant surface. The purpose of this animal study was to evaluate the removal torque of unloaded titanium implants in the fibula, the scapula and the iliac crest. Ninety implants with a sandblasted and acid-etched (SLA) surface were tested after healing periods of 3, 6, and 12 weeks, respectively. Removal torque values (RTV) were collected using a computerized counterclockwise torque driver. The bicortical anchored 8 mm implants in the fibula revealed values of 63.73 Ncm, 91.50 Ncm, and 101.83 Ncm at 3, 6, and 12 weeks, respectively. The monocortical anchorage in the iliac crest showed values of 71.40 Ncm, 63.14 Ncm, and 61.59 Ncm with 12 mm implants at the corresponding times. The monocortical anchorage in the scapula demonstrated mean RTV of 62.28 Ncm, 97.63 Ncm, and 99.7 Ncm with 12 mm implants at 3, 6, and 12 weeks, respectively. The study showed an increase of removal torque with increasing healing time. The interfacial strength for bicortical anchored 8 mm implants in the fibula was comparable to monocortical anchored 12 mm implants in the iliac crest and the scapula at the corresponding times. The resistance to shear seemed to be determined by the type of anchorage (monocortical vs. bicortical) and the length of the implant with greater amount of bone–implant interface.

Raman spectroscopic study of the uranyl titanate mineral betafite (Ca,U)2(Ti,Nb)2O6(OH) –Effect of Metamictization

Raman spectra of the uranyl titanate mineral betafite were obtained and related to the mineral structure. A comparison is made with the spectra of uranyl oxyhydroxide hydrates. Observed bands are attributed to the (UO2)2+ stretching and bending vibrations, U-OH bending vibrations, H2O and (OH)- stretching, bending and libration modes. U-O bond lengths in uranyls and O-H…O bond lengths are calculated from the wavenumbers assigned to the stretching vibrations. Raman bands of betafite are comparable with those of the uranyl oxyhydroxides. The mineral betafite is metamict as is evidenced by the intensity of the UO stretching and bending modes being of lower intensity than expected and with bands that are significantly broader.

A comprehensive condition monitoring of modern railway

The demand for high quality rail services in the twenty-first century has put an ever increasing demand on all rail operators. In order to meet the expectation of their patrons, the maintenance regime of railway systems has to be tightened up, the track conditions have to be well looked after, the rolling stock must be designed to withstand heavy duty. In short, in an ideal world where resources are unlimited, one needs to implement a very rigorous inspection regime in order to take care of the modem needs of a railway system [1]. If cost were not an issue, the maintenance engineers could inspect the train body by the most up-to-date techniques such as ultra-sound examination, x-ray inspection, magnetic particle inspection, etc. on a regular basis. However it is inconceivable to have such a perfect maintenance regime in any commercial railway. Likewise, it is impossible to have a perfect rolling stock which can weather all the heavy duties experienced in a modem railway. Hence it is essential that some condition monitoring schemes are devised to pick up potential defects which could manifest into safety hazards. This paper introduces an innovative condition monitoring system for track profile and, together with an instrumented car to carry out surveillance of the track, will provide a comprehensive railway condition monitoring system which is free from the usual difficulty of electromagnetic compatibility issues in a typical railway environment

Raman spectroscopic study of the uranyl titanate mineral holfertite CaxU2-xTi(O8-xOH4x)•3H2O and the lack of metamictization

Raman spectra of the uranyl titanate mineral holfertite CaxU2-xTi(O8-xOH4x)•3H2O were analysed and related to the mineral structure. Observed bands are attributed to the TiO and (UO2)2+ stretching and bending vibrations, U-OH bending vibrations, H2O stretching, bending. The mineral holfertite is metamict as is evidenced by order/disorder of the mineral. Unexpectedly the Raman spectrum of holfertite does not show any metamictization. The intensity of the UO stretching and bending modes show normal intensity and the bands are sharp.

Resorbable composite scaffolds for craniofacial bone tissue engineering

Aim: Bone loss associated with trauma, osteo-degenerative diseases and tumors has tremendous socioeconomic impact related to personal and occupation disability and health care costs. In the present climate of increasing life expectancy with an ensuing increase in bone-related injuries, orthopaedic surgery is undergoing a paradigm shift from bone-grafting to bone engineering, where a scaffold is implanted to provide adequate load bearing and enhance tissue regeneration. We aim to develop composite scaffolds for bone tissue engineering applications to replace the current gold standard of autografting. ---------- Methods: Medical grade polycaprolactone-tricalcium phosphate (mPCL/TCP) scaffolds (80/20 wt%) were custom made using fused deposition modelling to produce 1x1.5x2 cm sized implants for critical-sized pig cranial implantations, empty defects were used as a control. Autologous bone marrow stromal cells (BMSCs) were extracted and precultured for 2 weeks, dispersed within fibrin glue and injected during scaffold implantation. After 2 years, microcomputed tomography and histology were used to assess bone regenerative capabilities of cell versus cell-free scaffolds. ---------- Results: Extensive bone regeneration was evident throughout the entire scaffold. Clear osteocytes embedded within mineralised matrix and active osteoblasts present around scaffold struts were observed. Cell groups performed better than cell-free scaffolds. ---------- Conclusions: Bone regeneration within defects which cannot heal unassisted can be achieved using mPCL/TCP scaffolds. This is improved by the inclusion of autogenous BMSCs. Further work will include the inclusion of growth factors including BMP-2, VEGF and PDGF to provide multifunctional scaffolds, where the three-dimensional (3D) template itself acts as a biomimetic, programmable and multi-drug delivery device.

Resorbable composite scaffolds for bone tissue engineering

Bone loss associated with trauma osteo-degenerative diseases and tumors has tremendous socioeconomic impact related to personal and occupation disability and health care costs. Bone grafting is often critical to surgical therapies. Autogenous bone is presently the preferred grafting material; however, this holds several disadvantages such as donor site morbidity. In the present climate of increasing life expectancy with an ensuing increase in bone-related injuries, orthopaedic surgery is undergoing a paradigm shift from bone-grafting to bone engineering, where a scaffold is implanted to provide adequate load bearing and enhance tissue regeneration. Our group at Queensland University of Technology (QUT) have developed, characterised and tested polycaprolactone/ tricalcium phosphate (PCL/TCP) composite scaffolds for low load-bearing bone defects. These scaffolds are being further developed for application in higher load bearing sites. Our approach emphasizes the importance of the biomaterials’ structural design, the scaffold architecture and structural and nutritional requirements for cell culture. These first-generation scaffolds made from medical grade PCL (mPCL) have been studied for more than 5 years within a clinical setting 1. This paper describes the application of second-generation scaffolds in small and large animal bone defect models and the ensuing bone regeneration as shown by histology and µCT.

Differential roles of the pRb and Arf/p53 pathways in murine naevus and melanoma genesis

We report on a systematic analysis of genotype-specific melanocyte (MC) UVR responses in transgenic mouse melanoma models along with tumour penetrance and comparative histopathology. pRb or p53 pathway mutations cooperated with NrasQ61K to transform MCs. We previously reported that MCs migrate from the follicular outer root sheath into the epidermis after neonatal UVR. Here, we found that Arf or p53 loss markedly diminished this response. Despite this, mice carrying these mutations developed melanoma with very early age of onset after neonatal UVR. Cdk4R24C did not affect the MC migration. Instead, independent of UVR exposure, interfollicular dermal MCs were more prevalent in Cdk4R24C mice. Subsequently, in adulthood, these mutants developed dermal MC proliferations reminiscent of superficial congenital naevi. Two types of melanoma were observed in this model. The location and growth pattern of the first was consistent with derivation from the naevi, while the second appeared to be of deep dermal origin. In animals carrying the Arf or p53 defects, no naevi were detected, with all tumours ostensibly skipping the benign precursor stage in progression.

The effect of metamictization on the Raman spectroscopy of the uranyl titanate mineral davidite (La,Ce)(Y,U,Fe2+)(Ti,Fe3+)20(O,OH)38

Raman spectra of the uranyl titanate mineral davidite-(La) (La,Ce)(Y,U,Fe2+)(Ti,Fe3+)20(O,OH)38 were analysed and related to the mineral structure. Observed bands are attributed to the TiO and (UO2)2+ stretching and bending vibrations, U-OH bending vibrations, H2O and (OH)- stretching, bending and libration modes. U-O bond lengths in uranyls and O-H…O bond lengths are calculated from the wavenumbers assigned to the stretching vibrations. Raman bands of davidite-(La) are in harmony with those of the uranyl oxyhydroxides. The mineral davidite-(La) is metamict as is evidenced by the intensity of the UO stretching and bending modes being of lower intensity than expected and with bands that are significantly broader.

Differences between in vitro viability and differentiation and in vivo bone-forming efficacy of human mesenchymal stem cells cultured on PCL-TCP scaffolds

Human mesenchymal stem cells (hMSCs) possess great therapeutic potential for the treatment of bone disease and fracture non-union. Too often however, in vitro evidence alone of the interaction between hMSCs and the biomaterial of choice is used as justification for continued development of the material into the clinic. Clearly for hMSC-based regenerative medicine to be successful for the treatment of orthopaedic trauma, it is crucial to transplant hMSCs with a suitable carrier that facilitates their survival, optimal proliferation and osteogenic differentiation in vitro and in vivo. This motivated us to evaluate the use of polycaprolactone-20% tricalcium phosphate (PCL-TCP) scaffolds produced by fused deposition modeling for the delivery of hMSCs. When hMSCs were cultured on the PCL-TCP scaffolds and imaged by a combination of phase contrast, scanning electron and confocal laser microscopy, we observed five distinct stages of colonization over a 21-day period that were characterized by cell attachment, spreading, cellular bridging, the formation of a dense cellular mass and the accumulation of a mineralized extracellular matrix when induced with osteogenic stimulants. Having established that PCL-TCP scaffolds are able to support hMSC proliferation and osteogenic differentiation, we next tested the in vivo efficacy of hMSC-loaded PCL-TCP scaffolds in nude rat critical-sized femoral defects. We found that fluorescently labeled hMSCs survived in the defect site for up to 3 weeks post-transplantation. However, only 50% of the femoral defects treated with hMSCs responded favorably as determined by new bone volume. As such, we show that verification of hMSC viability and differentiation in vitro is not sufficient to predict the efficacy of transplanted stem cells to consistently promote bone formation in orthotopic defects in vivo.

Cystine-mediated oxidative defence in Lactobacillus reuteri BR11

Lactobacillus reuteri BR11 possesses an abundant cystine uptake (Cyu) ABC-transporter that was previously found to be involved in a novel mechanism of oxidative defence mediated by cystine. The current study aimed to elucidate this mechanism with a focus on the role of the co-transcribed cystathionine ã-lyase (Cgl). Growth studies of wild-type L. reuteri BR11 and mutants inactivated in cgl and the cystine-binding protein encoding gene cyuC showed that in contrast to the Cyu transporter, whose inactivation led to growth arrest in aerated cultures, Cgl is not crucial for oxidative defence. However, the role of Cgl in oxidative defence became apparent in the presence of severe oxidative damage and cysteine deprivation. Cysteine was found to be protective against oxidative stress, and the action of Cgl in both cysteine biosynthesis and degradation poses a seemingly futile pathway that deprives the intracellular cysteine pool. To further characterise the relationship between Cgl activity and cysteine and their roles in oxidative defence, enzymatic assays were performed on purified Cgl, and intracellular concentrations of cysteine, cystathionine and methionine were determined. Cgl was highly active towards cystine and cystathionine and less active towards cysteine in vitro, suggesting the main function of Cgl to be cysteine biosynthesis. Cysteine was found at high concentrations in the cell, but the levels were not significantly affected by inactivation of cgl or growth under aerobic conditions. It was concluded that both anabolic and catabolic activities of Cgl towards cysteine contribute to oxidative defence, the former by maintaining an intracellular reservoir of thiol analogous to glutathione, and the latter by producing H2S which is readily secreted, thus creating a reducing extracellular environment. The significance of the Cyu transporter to the physiology of L. reuteri BR11 prompted a phylogenetic study to determine its presence in bacteria. Orthologs of the Cyu transporter that are closest matches to the Cyu transporter are only limited to several species of Lactobacillus and Leuconostoc. Outside the Lactobacillales order, the closest matching orthologs belong to Proteobacteria, and there are more orthologs in Proteobacteria than non-Lactobacillales Firmicutes, suggesting that the Cyu transporter locus was present in the ancestor of the Proteobacteria and Firmicutes, and over evolutionary time has been lost or diverged in many Firmicutes. The clustering of the Cyu transporter locus with a gene encoding a Cgl family protein is even rarer. It was only found in L. reuteri, Lactobacillus vaginalis, Weissella paramesenteroides, the Lactobacillus casei group, and several Campylobacter sp. An accompanying phylogenetic study of L. reuteri BR11 using multi-locus sequence analysis showed that L. reuteri BR11 had diverged from more than 100 strains of L. reuteri isolated from various hosts and geographical locations. However, comparison with other Lactobacillus species supported the current classification of BR11 as L. reuteri. The most closely related species to L. reuteri is L. vaginalis or Lactobacillus antri, depending on the housekeeping gene used for analysis. The close evolutionary relationship of L. vaginalis to L. reuteri and the high degree of sequence identity between the cgl-cyuABC loci in both species suggest that the Cyu system is highly likely to perform similar functions in L. vaginalis. In search of other genes that function in oxidative defence, a number of mutants which were inactivated in genes that confer increased resistance to oxidative stress in other bacteria were constructed. The genes targeted were ahpC (peroxidase component of the alkyl hydroperoxide reductase system), tpx (thiol peroxidase), osmC (osmotically induced protein C), mntH (Mn2+/Fe2+ transporter), gshA (ã-glutamylcysteine synthetase) and msrA (methionine sulfoxide reductase). The ahpC and mntH mutants had slightly lower minimum inhibitory concentrations of organic peroxides, suggesting these genes might be involved in resistance to organic peroxides in L. reuteri. However, none of the mutants exhibited growth defects in aerated cultures, in stark contrast to the cyuC mutant. This may be due to compensatory functions of other genes, a hypothesis which cannot be tested until a robust protocol for constructing markerless multiple gene deletion mutants in L. reuteri is developed. These results highlight the importance of the Cyu transporter in oxidative defence and provide a foundation for extending the research of this system in other bacteria.

Assessing the leanness in product design : a model for planned design reuse

Shrinking product lifecycles, tough international competition, swiftly changing technologies, ever increasing customer quality expectation and demanding high variety options are some of the forces that drive next generation of development processes. To overcome these challenges, design cost and development time of product has to be reduced as well as quality to be improved. Design reuse is considered one of the lean strategies to win the race in this competitive environment. design reuse can reduce the product development time, product development cost as well as number of defects which will ultimately influence the product performance in cost, time and quality. However, it has been found that no or little work has been carried out for quantifying the effectiveness of design reuse in product development performance such as design cost, development time and quality. Therefore, in this study we propose a systematic design reuse based product design framework and developed a design leanness index (DLI) as a measure of effectiveness of design reuse. The DLI is a representative measure of reuse effectiveness in cost, development time and quality. Through this index, a clear relationship between reuse measure and product development performance metrics has been established. Finally, a cost based model has been developed to maximise the design leanness index for a product within the given set of constraints achieving leanness in design process.

A compact mock circulation loop for the in vitro testing of cardiovascular devices

In vitro cardiovascular device performance evaluation in a mock circulation loop (MCL) is a necessary step prior to in vivo testing.A MCL that accurately represents the physiology of the cardiovascular system accelerates the assessment of the device’s ability to treat pathological conditions. To serve this purpose, a compact MCL measuring 600 ¥ 600 ¥ 600 mm (L ¥ W¥ H) was constructed in conjunction with a computer mathematical simulation.This approach allowed the effective selection of physical loop characteristics, such as pneumatic drive parameters, to create pressure and flow, and pipe dimensions to replicate the resistance, compliance, and fluid inertia of the native cardiovascular system. The resulting five-element MCL reproduced the physiological hemodynamics of a healthy and failing heart by altering ventricle contractility, vascular resistance/compliance, heart rate, and vascular volume. The effects of interpatient anatomical variability, such as septal defects and valvular disease, were also assessed. Cardiovascular hemodynamic pressures (arterial, venous, atrial, ventricular), flows (systemic, bronchial, pulmonary), and volumes (ventricular, stroke) were analyzed in real time. The objective of this study is to describe the developmental stages of the compact MCL and demonstrate its value as a research tool for the accelerated development of cardiovascular devices.

Recent advances in cancer therapy targeting proteins involved in DNA double-strand break repair

Damage to genetic material represents a persistent and ubiquitous threat to genomic stability. Once DNA damage is detected, a multifaceted signaling network is activated that halts the cell cycle, initiates repair, and in some instances induces apoptotic cell death. In this article, we will review DNA damage surveillance networks, which maintain the stability of our genome, and discuss the efforts underway to identify chemotherapeutic compounds targeting the core components of DNA double-strand breaks (DSB) response pathway. The majority of tumor cells have defects in maintaining genomic stability owing to the loss of an appropriate response to DNA damage. New anticancer agents are exploiting this vulnerability of cancer cells to enhance therapeutic indexes, with limited normal tissue toxicity. Recently inhibitors of the checkpoint kinases Chk1 and Chk2 have been shown to sensitize tumor cells to DNA damaging agents. In addition, the treatment of BRCA1- or BRCA2-deficient tumor cells with poly(ADP-ribose) polymerase (PARP) inhibitors also leads to specific tumor killing. Due to the numerous roles of p53 in genomic stability and its defects in many human cancers, therapeutic agents that restore p53 activity in tumors are the subject of multiple clinical trials. In this article we highlight the proteins mentioned above and catalog several additional players in the DNA damage response pathway, including ATM, DNA-PK, and the MRN complex, which might be amenable to pharmacological interventions and lead to new approaches to sensitize cancer cells to radio- and chemotherapy. The challenge is how to identify those patients most receptive to these treatments.

Development of an online condition monitoring system for slow speed machinery

One of the main challenges of slow speed machinery condition monitoring is that the energy generated from an incipient defect is too weak to be detected by traditional vibration measurements due to its low impact energy. Acoustic emission (AE) measurement is an alternative for this as it has the ability to detect crack initiations or rubbing between moving surfaces. However, AE measurement requires high sampling frequency and consequently huge amount of data are obtained to be processed. It also requires expensive hardware to capture those data, storage and involves signal processing techniques to retrieve valuable information on the state of the machine. AE signal has been utilised for early detection of defects in bearings and gears. This paper presents an online condition monitoring (CM) system for slow speed machinery, which attempts to overcome those challenges. The system incorporates relevant signal processing techniques for slow speed CM which include noise removal techniques to enhance the signal-to-noise and peak-holding down sampling to reduce the burden of massive data handling. The analysis software works under Labview environment, which enables online remote control of data acquisition, real-time analysis, offline analysis and diagnostic trending. The system has been fully implemented on a site machine and contributing significantly to improve the maintenance efficiency and provide a safer and reliable operation.

Risky driving or risky drivers? Exploring driving and crash histories of illegal street racing offenders

Illegal street racing has received increased attention in recent years from road safety professionals and the media as jurisdictions in Australia, Canada, and the United States have implemented laws to address the problem, which primarily involves young male drivers. Although some evidence suggests that the prevalence of illegal street racing is increasing, obtaining accurate estimates of the crash risk of this behavior is difficult because of limitations in official data sources. Although crash risk can be explored by examining the proportion of incidents of street racing that result in crashes, or the proportion of all crashes that involve street racing, this paper reports on the findings of a study that explored the riskiness of involved drivers. The driving histories of 183 male drivers with an illegal street racing conviction in Queensland, Australia, were compared with a random sample of 183 male Queensland drivers with the same age distribution. The offender group was found to have significantly more traffic infringements, license sanctions, and crashes than the comparison group. Drivers in the offender group were more likely than the comparison group to have committed infringements related to street racing, such as speeding, "hooning," and offenses related to vehicle defects or illegal modifications. Insufficient statistical capacity prevented full exploration of group differences in the type and nature of earlier crashes. It was concluded, however, that street racing offenders generally can be considered risky drivers who warrant attention and whose risky behavior cannot be explained by their youth alone.