The evaluation of a biphasic osteochondral implant coupled with an electrospun membrane in a large animal model

Conventional clinical therapies are unable to resolve osteochondral defects adequately, hence tissue engineering solutions are sought to address the challenge. A biphasic implant which was seeded with Mesenchymal Stem Cells (MSC) and coupled with an electrospun membrane was evaluated as an alternative. This dual phase construct comprised of a Polycaprolactone (PCL) cartilage scaffold and a Polycaprolactone - Tri Calcium Phosphate (PCL - TCP) osseous matrix. Autologous MSC was seeded into the entire implant via fibrin and the construct was inserted into critically sized osteochondral defects located at the medial condyle and patellar groove of pigs. The defect was resurfaced with a PCL - collagen electrospun mesh that served as a substitute for periosteal flap in preventing cell leakage. Controls either without implanted MSC or resurfacing membrane were included. After 6 months, cartilaginous repair was observed with a low occurrence of fibrocartilage at the medial condyle. Osteochondral repair was promoted and host cartilage degeneration was arrested as shown by the superior Glycosaminoglycan (GAG) maintenance. This positive morphological outcome was supported by a higher relative Young's modulus which indicated functional cartilage restoration. Bone in growth and remodeling occurred in all groups with a higher degree of mineralization in the experimental group. Tissue repair was compromised in the absence of the implanted cells or the resurfacing membrane. Moreover healing was inferior at the patellar groove as compared to the medial condyle and this was attributed to the native biomechanical features.

Behaviour and design of cold-formed steel compression members at elevated temperatures

Cold-formed steel members have been widely used in residential, industrial and commercial buildings as primary load bearing structural elements and non-load bearing structural elements (partitions) due to their advantages such as higher strength to weight ratio over the other structural materials such as hot-rolled steel, timber and concrete. Cold-formed steel members are often made from thin steel sheets and hence they are more susceptible to various buckling modes. Generally short columns are susceptible to local or distortional buckling while long columns to flexural or flexural-torsional buckling. Fire safety design of building structures is an essential requirement as fire events can cause loss of property and lives. Therefore it is essential to understand the fire performance of light gauge cold-formed steel structures under fire conditions. The buckling behaviour of cold-formed steel compression members under fire conditions is not well investigated yet and hence there is a lack of knowledge on the fire performance of cold-formed steel compression members. Current cold-formed steel design standards do not provide adequate design guidelines for the fire design of cold-formed steel compression members. Therefore a research project based on extensive experimental and numerical studies was undertaken at the Queensland University of Technology to investigate the buckling behaviour of light gauge cold-formed steel compression members under simulated fire conditions. As the first phase of this research, a detailed review was undertaken on the mechanical properties of light gauge cold-formed steels at elevated temperatures and the most reliable predictive models for mechanical properties and stress-strain models based on detailed experimental investigations were identified. Their accuracy was verified experimentally by carrying out a series of tensile coupon tests at ambient and elevated temperatures. As the second phase of this research, local buckling behaviour was investigated based on the experimental and numerical investigations at ambient and elevated temperatures. First a series of 91 local buckling tests was carried out at ambient and elevated temperatures on lipped and unlipped channels made of G250-0.95, G550-0.95, G250-1.95 and G450-1.90 cold-formed steels. Suitable finite element models were then developed to simulate the experimental conditions. These models were converted to ideal finite element models to undertake detailed parametric study. Finally all the ultimate load capacity results for local buckling were compared with the available design methods based on AS/NZS 4600, BS 5950 Part 5, Eurocode 3 Part 1.2 and the direct strength method (DSM), and suitable recommendations were made for the fire design of cold-formed steel compression members subject to local buckling. As the third phase of this research, flexural-torsional buckling behaviour was investigated experimentally and numerically. Two series of 39 flexural-torsional buckling tests were undertaken at ambient and elevated temperatures. The first series consisted 2800 mm long columns of G550-0.95, G250-1.95 and G450-1.90 cold-formed steel lipped channel columns while the second series contained 1800 mm long lipped channel columns of the same steel thickness and strength grades. All the experimental tests were simulated using a suitable finite element model, and the same model was used in a detailed parametric study following validation. Based on the comparison of results from the experimental and parametric studies with the available design methods, suitable design recommendations were made. This thesis presents a detailed description of the experimental and numerical studies undertaken on the mechanical properties and the local and flexural-torsional bucking behaviour of cold-formed steel compression member at ambient and elevated temperatures. It also describes the currently available ambient temperature design methods and their accuracy when used for fire design with appropriately reduced mechanical properties at elevated temperatures. Available fire design methods are also included and their accuracy in predicting the ultimate load capacity at elevated temperatures was investigated. This research has shown that the current ambient temperature design methods are capable of predicting the local and flexural-torsional buckling capacities of cold-formed steel compression members at elevated temperatures with the use of reduced mechanical properties. However, the elevated temperature design method in Eurocode 3 Part 1.2 is overly conservative and hence unsuitable, particularly in the case of flexural-torsional buckling at elevated temperatures.

Flexural behaviour and design of cold-formed steel beams with rectangular hollow flanges

Until recently, the hot-rolled steel members have been recognized as the most popular and widely used steel group, but in recent times, the use of cold-formed high strength steel members has rapidly increased. However, the structural behavior of light gauge high strength cold-formed steel members characterized by various buckling modes is not yet fully understood. The current cold-formed steel sections such as C- and Z-sections are commonly used because of their simple forming procedures and easy connections, but they suffer from certain buckling modes. It is therefore important that these buckling modes are either delayed or eliminated to increase the ultimate capacity of these members. This research is therefore aimed at developing a new cold-formed steel beam with two torsionally rigid rectangular hollow flanges and a slender web formed using intermittent screw fastening to enhance the flexural capacity while maintaining a minimum fabrication cost. This thesis describes a detailed investigation into the structural behavior of this new Rectangular Hollow Flange Beam (RHFB), subjected to flexural action The first phase of this research included experimental investigations using thirty full scale lateral buckling tests and twenty two section moment capacity tests using specially designed test rigs to simulate the required loading and support conditions. A detailed description of the experimental methods, RHFB failure modes including local, lateral distortional and lateral torsional buckling modes, and moment capacity results is presented. A comparison of experimental results with the predictions from the current design rules and other design methods is also given. The second phase of this research involved a methodical and comprehensive investigation aimed at widening the scope of finite element analysis to investigate the buckling and ultimate failure behaviours of RHFBs subjected to flexural actions. Accurate finite element models simulating the physical conditions of both lateral buckling and section moment capacity tests were developed. Comparison of experimental and finite element analysis results showed that the buckling and ultimate failure behaviour of RHFBs can be simulated well using appropriate finite element models. Finite element models simulating ideal simply supported boundary conditions and a uniform moment loading were also developed in order to use in a detailed parametric study. The parametric study results were used to review the current design rules and to develop new design formulae for RHFBs subjected to local, lateral distortional and lateral torsional buckling effects. Finite element analysis results indicate that the discontinuity due to screw fastening has a noticeable influence only for members in the intermediate slenderness region. Investigations into different combinations of thicknesses in the flange and web indicate that increasing the flange thickness is more effective than web thickness in enhancing the flexural capacity of RHFBs. The current steel design standards, AS 4100 (1998) and AS/NZS 4600 (1996) are found sufficient to predict the section moment capacity of RHFBs. However, the results indicate that the AS/NZS 4600 is more accurate for slender sections whereas AS 4100 is more accurate for compact sections. The finite element analysis results further indicate that the current design rules given in AS/NZS 4600 is adequate in predicting the member moment capacity of RHFBs subject to lateral torsional buckling effects. However, they were inadequate in predicting the capacities of RHFBs subject to lateral distortional buckling effects. This thesis has therefore developed a new design formula to predict the lateral distortional buckling strength of RHFBs. Overall, this thesis has demonstrated that the innovative RHFB sections can perform well as economically and structurally efficient flexural members. Structural engineers and designers should make use of the new design rules and the validated existing design rules to design the most optimum RHFB sections depending on the type of applications. Intermittent screw fastening method has also been shown to be structurally adequate that also minimises the fabrication cost. Product manufacturers and builders should be able to make use of this in their applications.

Structural behaviour and design of cold-formed steel beams at elevated temperatures

Cold-formed steel members are extensively used in the building construction industry, especially in residential, commercial and industrial buildings. In recent times, fire safety has become important in structural design due to increased fire damage to properties and loss of lives. However, past research into the fire performance of cold-formed steel members has been limited, and was confined to compression members. Therefore a research project was undertaken to investigate the structural behaviour of compact cold-formed steel lipped channel beams subject to inelastic local buckling and yielding, and lateral-torsional buckling effects under simulated fire conditions and associated section and member moment capacities. In the first phase of this research, an experimental study based on tensile coupon tests was undertaken to obtain the mechanical properties of elastic modulus and yield strength and the stress-strain relationship of cold-formed steels at uniform ambient and elevated temperatures up to 700oC. The mechanical properties deteriorated with increasing temperature and are likely to reduce the strength of cold-formed beams under fire conditions. Predictive equations were developed for yield strength and elastic modulus reduction factors while a modification was proposed for the stressstrain model at elevated temperatures. These results were used in the numerical modelling phases investigating the section and member moment capacities. The second phase of this research involved the development and validation of two finite element models to simulate the behaviour of compact cold-formed steel lipped channel beams subject to local buckling and yielding, and lateral-torsional buckling effects. Both models were first validated for elastic buckling. Lateral-torsional buckling tests of compact lipped channel beams were conducted at ambient temperature in order to validate the finite element model in predicting the non-linear ultimate strength behaviour. The results from this experimental study did not agree well with those from the developed experimental finite element model due to some unavoidable problems with testing. However, it highlighted the importance of magnitude and direction of initial geometric imperfection as well as the failure direction, and thus led to further enhancement of the finite element model. The finite element model for lateral-torsional buckling was then validated using the available experimental and numerical ultimate moment capacity results from past research. The third phase based on the validated finite element models included detailed parametric studies of section and member moment capacities of compact lipped channel beams at ambient temperature, and provided the basis for similar studies at elevated temperatures. The results showed the existence of inelastic reserve capacity for compact cold-formed steel beams at ambient temperature. However, full plastic capacity was not achieved by the mono-symmetric cold-formed steel beams. Suitable recommendations were made in relation to the accuracy and suitability of current design rules for section moment capacity. Comparison of member capacity results from finite element analyses with current design rules showed that they do not give accurate predictions of lateral-torsional buckling capacities at ambient temperature and hence new design rules were developed. The fourth phase of this research investigated the section and member moment capacities of compact lipped channel beams at uniform elevated temperatures based on detailed parametric studies using the validated finite element models. The results showed the existence of inelastic reserve capacity at elevated temperatures. Suitable recommendations were made in relation to the accuracy and suitability of current design rules for section moment capacity in fire design codes, ambient temperature design codes as well as those proposed by other researchers. The results showed that lateral-torsional buckling capacities are dependent on the ratio of yield strength and elasticity modulus reduction factors and the level of non-linearity in the stress-strain curves at elevated temperatures in addition to the temperature. Current design rules do not include the effects of non-linear stress-strain relationship and therefore their predictions were found to be inaccurate. Therefore a new design rule that uses a nonlinearity factor, which is defined as the ratio of the limit of proportionality to the yield stress at a given temperature, was developed for cold-formed steel beams subject to lateral-torsional buckling at elevated temperatures. This thesis presents the details and results of the experimental and numerical studies conducted in this research including a comparison of results with predictions using available design rules. It also presents the recommendations made regarding the accuracy of current design rules as well as the new developed design rules for coldformed steel beams both at ambient and elevated temperatures.

Flexural behaviour and design of hollow flange steel beams

The LiteSteel Beam (LSB) is a new hollow flange channel section developed by OneSteel Australian Tube Mills using a patented Dual Electric Resistance Welding technique. The LSB has a unique geometry consisting of torsionally rigid rectangular hollow flanges and a relatively slender web. It is commonly used as rafters, floor joists and bearers and roof beams in residential, industrial and commercial buildings. It is on average 40% lighter than traditional hot-rolled steel beams of equivalent performance. The LSB flexural members are subjected to a relatively new Lateral Distortional Buckling mode, which reduces the member moment capacity. Unlike the commonly observed lateral torsional buckling of steel beams, lateral distortional buckling of LSBs is characterised by simultaneous lateral deflection, twist and web distortion. Current member moment capacity design rules for lateral distortional buckling in AS/NZS 4600 (SA, 2005) do not include the effect of section geometry of hollow flange beams although its effect is considered to be important. Therefore detailed experimental and finite element analyses (FEA) were carried out to investigate the lateral distortional buckling behaviour of LSBs including the effect of section geometry. The results showed that the current design rules in AS/NZS 4600 (SA, 2005) are over-conservative in the inelastic lateral buckling region. New improved design rules were therefore developed for LSBs based on both FEA and experimental results. A geometrical parameter (K) defined as the ratio of the flange torsional rigidity to the major axis flexural rigidity of the web (GJf/EIxweb) was identified as the critical parameter affecting the lateral distortional buckling of hollow flange beams. The effect of section geometry was then included in the new design rules using the new parameter (K). The new design rule developed by including this parameter was found to be accurate in calculating the member moment capacities of not only LSBs, but also other types of hollow flange steel beams such as Hollow Flange Beams (HFBs), Monosymmetric Hollow Flange Beams (MHFBs) and Rectangular Hollow Flange Beams (RHFBs). The inelastic reserve bending capacity of LSBs has not been investigated yet although the section moment capacity tests of LSBs in the past revealed that inelastic reserve bending capacity is present in LSBs. However, the Australian and American cold-formed steel design codes limit them to the first yield moment. Therefore both experimental and FEA were carried out to investigate the section moment capacity behaviour of LSBs. A comparison of the section moment capacity results from FEA, experiments and current cold-formed steel design codes showed that compact and non-compact LSB sections classified based on AS 4100 (SA, 1998) have some inelastic reserve capacity while slender LSBs do not have any inelastic reserve capacity beyond their first yield moment. It was found that Shifferaw and Schafer’s (2008) proposed equations and Eurocode 3 Part 1.3 (ECS, 2006) design equations can be used to include the inelastic bending capacities of compact and non-compact LSBs in design. As a simple design approach, the section moment capacity of compact LSB sections can be taken as 1.10 times their first yield moment while it is the first yield moment for non-compact sections. For slender LSB sections, current cold-formed steel codes can be used to predict their section moment capacities. It was believed that the use of transverse web stiffeners could improve the lateral distortional buckling moment capacities of LSBs. However, currently there are no design equations to predict the elastic lateral distortional buckling and member moment capacities of LSBs with web stiffeners under uniform moment conditions. Therefore, a detailed study was conducted using FEA to simulate both experimental and ideal conditions of LSB flexural members. It was shown that the use of 3 to 5 mm steel plate stiffeners welded or screwed to the inner faces of the top and bottom flanges of LSBs at third span points and supports provided an optimum web stiffener arrangement. Suitable design rules were developed to calculate the improved elastic buckling and ultimate moment capacities of LSBs with these optimum web stiffeners. A design rule using the geometrical parameter K was also developed to improve the accuracy of ultimate moment capacity predictions. This thesis presents the details and results of the experimental and numerical studies of the section and member moment capacities of LSBs conducted in this research. It includes the recommendations made regarding the accuracy of current design rules as well as the new design rules for lateral distortional buckling. The new design rules include the effects of section geometry of hollow flange steel beams. This thesis also developed a method of using web stiffeners to reduce the lateral distortional buckling effects, and associated design rules to calculate the improved moment capacities.

Structural and thermal performance of cold-formed steel stud wall systems under fire conditions

Cold-formed steel stud walls are a major component of Light Steel Framing (LSF) building systems used in commercial, industrial and residential buildings. In the conventional LSF stud wall systems, thin steel studs are protected from fire by placing one or two layers of plasterboard on both sides with or without cavity insulation. However, there is very limited data about the structural and thermal performance of stud wall systems while past research showed contradicting results, for example, about the benefits of cavity insulation. This research was therefore conducted to improve the knowledge and understanding of the structural and thermal performance of cold-formed steel stud wall systems (both load bearing and non-load bearing) under fire conditions and to develop new improved stud wall systems including reliable and simple methods to predict their fire resistance rating. Full scale fire tests of cold-formed steel stud wall systems formed the basis of this research. This research proposed an innovative LSF stud wall system in which a composite panel made of two plasterboards with insulation between them was used to improve the fire rating. Hence fire tests included both conventional steel stud walls with and without the use of cavity insulation and the new composite panel system. A propane fired gas furnace was specially designed and constructed first. The furnace was designed to deliver heat in accordance with the standard time temperature curve as proposed by AS 1530.4 (SA, 2005). A compression loading frame capable of loading the individual studs of a full scale steel stud wall system was also designed and built for the load-bearing tests. Fire tests included comprehensive time-temperature measurements across the thickness and along the length of all the specimens using K type thermocouples. They also included the measurements of load-deformation characteristics of stud walls until failure. The first phase of fire tests included 15 small scale fire tests of gypsum plasterboards, and composite panels using different types of insulating material of varying thickness and density. Fire performance of single and multiple layers of gypsum plasterboards was assessed including the effect of interfaces between adjacent plasterboards on the thermal performance. Effects of insulations such as glass fibre, rock fibre and cellulose fibre were also determined while the tests provided important data relating to the temperature at which the fall off of external plasterboards occurred. In the second phase, nine small scale non-load bearing wall specimens were tested to investigate the thermal performance of conventional and innovative steel stud wall systems. Effects of single and multiple layers of plasterboards with and without vertical joints were investigated. The new composite panels were seen to offer greater thermal protection to the studs in comparison to the conventional panels. In the third phase of fire tests, nine full scale load bearing wall specimens were tested to study the thermal and structural performance of the load bearing wall assemblies. A full scale test was also conducted at ambient temperature. These tests showed that the use of cavity insulation led to inferior fire performance of walls, and provided good explanations and supporting research data to overcome the incorrect industry assumptions about cavity insulation. They demonstrated that the use of insulation externally in a composite panel enhanced the thermal and structural performance of stud walls and increased their fire resistance rating significantly. Hence this research recommends the use of the new composite panel system for cold-formed LSF walls. This research also included steady state tensile tests at ambient and elevated temperatures to address the lack of reliable mechanical properties for high grade cold-formed steels at elevated temperatures. Suitable predictive equations were developed for calculating the yield strength and elastic modulus at elevated temperatures. In summary, this research has developed comprehensive experimental thermal and structural performance data for both the conventional and the proposed non-load bearing and load bearing stud wall systems under fire conditions. Idealized hot flange temperature profiles have been developed for non-insulated, cavity insulated and externally insulated load bearing wall models along with suitable equations for predicting their failure times. A graphical method has also been proposed to predict the failure times (fire rating) of non-load bearing and load bearing walls under different load ratios. The results from this research are useful to both fire researchers and engineers working in this field. Most importantly, this research has significantly improved the knowledge and understanding of cold-formed LSF walls under fire conditions, and developed an innovative LSF wall system with increased fire rating. It has clearly demonstrated the detrimental effects of using cavity insulation, and has paved the way for Australian building industries to develop new wall panels with increased fire rating for commercial applications worldwide.

The dual orexin/hypocretin receptor antagonist, almorexant, in the ventral tegmental area attenuates ethanol self-administration

Recent studies have implicated the hypocretin/orexinergic system in reward-seeking behavior. Almorexant, a dual orexin/hypocretin R1 and R2 receptor antagonist, has proven effective in preclinical studies in promoting sleep in animal models and was in Phase III clinical trials for sleep disorders. The present study combines behavioral assays with in vitro biochemical and electrophysiological techniques to elucidate the role of almorexant in ethanol and sucrose intake. Using an operant self-administration paradigm, we demonstrate that systemic administration of almorexant decreased operant selfadministration of both 20% ethanol and 5% sucrose. We further demonstrate that intraventral tegmental area (VTA) infusions, but not intra substantia nigra infusions, of almorexant reduced ethanol self-administration. Extracellular recordings performed in VTA neurons revealed that orexin-A increased firing and this enhancement of firing was blocked by almorexant. The results demonstrate that orexin/hypocretin receptors in distinct brain regions regulate ethanol and sucrose mediated behaviors.

A dual-scale modelling approach for drying hygroscopic porous media

A new dualscale modelling approach is presented for simulating the drying of a wet hygroscopic porous material that couples the porous medium (macroscale) with the underlying pore structure (microscale). The proposed model is applied to the convective drying of wood at low temperatures and is valid in the so-called hygroscopic range, where hygroscopically held liquid water is present in the solid phase and water exits only as vapour in the pores. Coupling between scales is achieved by imposing the macroscopic gradients of moisture content and temperature on the microscopic field using suitably-defined periodic boundary conditions, which allows the macroscopic mass and thermal fluxes to be defined as averages of the microscopic fluxes over the unit cell. This novel formulation accounts for the intricate coupling of heat and mass transfer at the microscopic scale but reduces to a classical homogenisation approach if a linear relationship is assumed between the microscopic gradient and flux. Simulation results for a sample of spruce wood highlight the potential and flexibility of the new dual-scale approach. In particular, for a given unit cell configuration it is not necessary to propose the form of the macroscopic fluxes prior to the simulations because these are determined as a direct result of the dual-scale formulation.

Exponential integrators and a dual-scale model for wood drying

For the timber industry, the ability to simulate the drying of wood is invaluable for manufacturing high quality wood products. Mathematically, however, modelling the drying of a wet porous material, such as wood, is a diffcult task due to its heterogeneous and anisotropic nature, and the complex geometry of the underlying pore structure. The well{ developed macroscopic modelling approach involves writing down classical conservation equations at a length scale where physical quantities (e.g., porosity) can be interpreted as averaged values over a small volume (typically containing hundreds or thousands of pores). This averaging procedure produces balance equations that resemble those of a continuum with the exception that effective coeffcients appear in their deffnitions. Exponential integrators are numerical schemes for initial value problems involving a system of ordinary differential equations. These methods differ from popular Newton{Krylov implicit methods (i.e., those based on the backward differentiation formulae (BDF)) in that they do not require the solution of a system of nonlinear equations at each time step but rather they require computation of matrix{vector products involving the exponential of the Jacobian matrix. Although originally appearing in the 1960s, exponential integrators have recently experienced a resurgence in interest due to a greater undertaking of research in Krylov subspace methods for matrix function approximation. One of the simplest examples of an exponential integrator is the exponential Euler method (EEM), which requires, at each time step, approximation of φ(A)b, where φ(z) = (ez - 1)/z, A E Rnxn and b E Rn. For drying in porous media, the most comprehensive macroscopic formulation is TransPore [Perre and Turner, Chem. Eng. J., 86: 117-131, 2002], which features three coupled, nonlinear partial differential equations. The focus of the first part of this thesis is the use of the exponential Euler method (EEM) for performing the time integration of the macroscopic set of equations featured in TransPore. In particular, a new variable{ stepsize algorithm for EEM is presented within a Krylov subspace framework, which allows control of the error during the integration process. The performance of the new algorithm highlights the great potential of exponential integrators not only for drying applications but across all disciplines of transport phenomena. For example, when applied to well{ known benchmark problems involving single{phase liquid ow in heterogeneous soils, the proposed algorithm requires half the number of function evaluations than that required for an equivalent (sophisticated) Newton{Krylov BDF implementation. Furthermore for all drying configurations tested, the new algorithm always produces, in less computational time, a solution of higher accuracy than the existing backward Euler module featured in TransPore. Some new results relating to Krylov subspace approximation of '(A)b are also developed in this thesis. Most notably, an alternative derivation of the approximation error estimate of Hochbruck, Lubich and Selhofer [SIAM J. Sci. Comput., 19(5): 1552{1574, 1998] is provided, which reveals why it performs well in the error control procedure. Two of the main drawbacks of the macroscopic approach outlined above include the effective coefficients must be supplied to the model, and it fails for some drying configurations, where typical dual{scale mechanisms occur. In the second part of this thesis, a new dual{scale approach for simulating wood drying is proposed that couples the porous medium (macroscale) with the underlying pore structure (microscale). The proposed model is applied to the convective drying of softwood at low temperatures and is valid in the so{called hygroscopic range, where hygroscopically held liquid water is present in the solid phase and water exits only as vapour in the pores. Coupling between scales is achieved by imposing the macroscopic gradient on the microscopic field using suitably defined periodic boundary conditions, which allows the macroscopic ux to be defined as an average of the microscopic ux over the unit cell. This formulation provides a first step for moving from the macroscopic formulation featured in TransPore to a comprehensive dual{scale formulation capable of addressing any drying configuration. Simulation results reported for a sample of spruce highlight the potential and flexibility of the new dual{scale approach. In particular, for a given unit cell configuration it is not necessary to supply the effective coefficients prior to each simulation.

Analysis of acute-phase proteins, AHSG, C3, CLI, HP and SAA, reveals distinctive expression patterns associated with breast, colorectal and lung cancer

Early detection, clinical management and disease recurrence monitoring are critical areas in cancer treatment in which specific biomarker panels are likely to be very important in each of these key areas. We have previously demonstrated that levels of alpha-2-heremans-schmid-glycoprotein (AHSG), complement component C3 (C3), clusterin (CLI), haptoglobin (HP) and serum amyloid A (SAA) are significantly altered in serum from patients with squamous cell carcinoma of the lung. Here, we report the abundance levels for these proteins in serum samples from patients with advanced breast cancer, colorectal cancer (CRC) and lung cancer compared to healthy controls (age and gender matched) using commercially available enzyme-linked immunosorbent assay kits. Logistic regression (LR) models were fitted to the resulting data, and the classification ability of the proteins was evaluated using receiver-operating characteristic curve and leave-one-out cross-validation (LOOCV). The most accurate individual candidate biomarkers were C3 for breast cancer [area under the curve (AUC) = 0.89, LOOCV = 73%], CLI for CRC (AUC = 0.98, LOOCV = 90%), HP for small cell lung carcinoma (AUC = 0.97, LOOCV = 88%), C3 for lung adenocarcinoma (AUC = 0.94, LOOCV = 89%) and HP for squamous cell carcinoma of the lung (AUC = 0.94, LOOCV = 87%). The best dual combination of biomarkers using LR analysis were found to be AHSG + C3 (AUC = 0.91, LOOCV = 83%) for breast cancer, CLI + HP (AUC = 0.98, LOOCV = 92%) for CRC, C3 + SAA (AUC = 0.97, LOOCV = 91%) for small cell lung carcinoma and HP + SAA for both adenocarcinoma (AUC = 0.98, LOOCV = 96%) and squamous cell carcinoma of the lung (AUC = 0.98, LOOCV = 84%). The high AUC values reported here indicated that these candidate biomarkers have the potential to discriminate accurately between control and cancer groups both individually and in combination with other proteins. Copyright © 2011 UICC.

Molecular biomarkers in non-small-cell lung cancer : a retrospective analysis of data from the phase 3 FLEX study

Background: Findings from the phase 3 FLEX study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival, compared with cisplatin and vinorelbine alone, in the first-line treatment of EGFR-expressing, advanced non-small-cell lung cancer (NSCLC). We investigated whether candidate biomarkers were predictive for the efficacy of chemotherapy plus cetuximab in this setting. Methods: Genomic DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour tissue of patients enrolled in the FLEX study was screened for KRAS codon 12 and 13 and EGFR kinase domain mutations with PCR-based assays. In FFPE tissue sections, EGFR copy number was assessed by dual-colour fluorescence in-situ hybridisation and PTEN expression by immunohistochemistry. Treatment outcome was investigated according to biomarker status in all available samples from patients in the intention-to-treat population. The primary endpoint in the FLEX study was overall survival. The FLEX study, which is ongoing but not recruiting participants, is registered with ClinicalTrials.gov, number NCT00148798. Findings: KRAS mutations were detected in 75 of 395 (19%) tumours and activating EGFR mutations in 64 of 436 (15%). EGFR copy number was scored as increased in 102 of 279 (37%) tumours and PTEN expression as negative in 107 of 303 (35%). Comparisons of treatment outcome between the two groups (chemotherapy plus cetuximab vs chemotherapy alone) according to biomarker status provided no indication that these biomarkers were of predictive value. Activating EGFR mutations were identified as indicators of good prognosis, with patients in both treatment groups whose tumours carried such mutations having improved survival compared with those whose tumours did not (chemotherapy plus cetuximab: median 17·5 months [95% CI 11·7-23·4] vs 8·5 months [7·1-10·8], hazard ratio [HR] 0·52 [0·32-0·84], p=0·0063; chemotherapy alone: 23·8 months [15·2-not reached] vs 10·0 months [8·7-11·0], HR 0·35 [0·21-0·59], p<0·0001). Expression of PTEN seemed to be a potential indicator of good prognosis, with patients whose tumours expressed PTEN having improved survival compared with those whose tumours did not, although this finding was not significant (chemotherapy plus cetuximab: median 11·4 months [8·6-13·6] vs 6·8 months [5·9-12·7], HR 0·80 [0·55-1·16], p=0·24; chemotherapy alone: 11·0 months [9·2-12·6] vs 9·3 months [7·6-11·9], HR 0·77 [0·54-1·10], p=0·16). Interpretation: The efficacy of chemotherapy plus cetuximab in the first-line treatment of advanced NSCLC seems to be independent of each of the biomarkers assessed. Funding: Merck KGaA. © 2011 Elsevier Ltd.

Nonlinear pre-fire and post-fire analysis of steel frames

A numerical procedure based on the plastic hinge concept for study of the structural behaviour of steel framed structures exposed to fire is described. Most previous research on fire analysis considered the structural performance due to rising temperature. When strain reversal occurs during the cooling phase, the stress–strain curve is different. The plastic deformation is incorporated into the stress–strain curve to model the strain reversal effect in which unloading under elastic behaviour is allowed. This unloading response is traced by the incremental–iterative Newton–Raphson method. The mechanical properties of the steel member in the present fire analysis follows both Eurocode 3 Part 1.2 and BS5950 Part 8, which implicitly allow for thermal creep deformation. This paper presents an efficient fire analysis procedure for predicting thermal and cooling effects on an isolated element and a multi-storey frame. Several numerical and experimental examples related to structural behaviour in cooling phase are studied and compared with results obtained by other researchers. The proposed method is effective in the fire safety design and analysis of a building in a real fire scenario. The scope of investigation is of great significance since a large number of rescuers would normally enter a fire site as soon as the fire is extinguished and during the cooling phase, so a structural collapse can be catastrophic.

Modeling and position-sensorless control of a dual-airgap axial flux permanent magnet machine for flywheel energy storage systems

This paper presents the modeling and position-sensorless vector control of a dual-airgap axial flux permanent magnet (AFPM) machine optimized for use in flywheel energy storage system (FESS) applications. The proposed AFPM machine has two sets of three-phase stator windings but requires only a single power converter to control both the electromagnetic torque and the axial levitation force. The proper controllability of the latter is crucial as it can be utilized to minimize the vertical bearing stress to improve the efficiency of the FESS. The method for controlling both the speed and axial displacement of the machine is discussed. An inherent speed sensorless observer is also proposed for speed estimation. The proposed observer eliminates the rotary encoder, which in turn reduces the overall weight and cost of the system while improving its reliability. The effectiveness of the proposed control scheme has been verified by simulations and experiments on a prototype machine.

An investigation of goethite-seeded Al(OH)3 precipitation using in situ X-ray diffraction and Rietveld-based quantitative phase analysis

An in situ X-ray diffraction investigation of goethite-seeded Al(OH)3 precipitation from synthetic Bayer liquor at 343 K has been performed. The presence of iron oxides and oxyhydroxides in the Bayer process has implications for alumina reversion, which causes significant process losses through unwanted gibbsite precipitation, and is also relevant for the nucleation and growth of scale on mild steel process equipment. The gibbsite, bayerite and nordstrandite polymorphs of Al(OH)3 precipitated from the liquor; gibbsite appeared to precipitate first, with subsequent formation of bayerite and nordstrandite. A Rietveld-based approach to quantitative phase analysis was implemented for the determination of absolute phase abundances as a function of time, from which kinetic information for the formation of the Al(OH)3 phases was determined.

A novel matrix converter based resonant dual active bridge for V2G applications

Dual-active bridges (DABs) can be used to deliver isolated and bidirectional power to electric vehicles (EVs) or to the grid in vehicle-to-grid (V2G) applications. However, such a system essentially requires a two-stage power conversion process, which significantly increases the power losses. Furthermore, the poor power factor associated with DAB converters further reduces the efficiency of such systems. This paper proposes a novel matrix converter based resonant DAB converter that requires only a single-stage power conversion process to facilitate isolated bi-directional power transfer between EVs and the grid. The proposed converter comprises a matrix converter based front end linked with an EV side full-bridge converter through a high frequency isolation transformer and a tuned LCL network. A mathematical model, which predicts the behavior of the proposed system, is presented to show that both the magnitude and direction of the power flow can be controlled through either relative phase angle or magnitude modulation of voltages produced by converters. Viability of the proposed concept is verified through simulations. The proposed matrix converter based DAB, with a single power conversion stage, is low in cost, and suites charging and discharging in single or multiple EVs or V2G applications.