A two-metal ion mechanism operates in the hammerhead ribozyme-mediated cleavage of an RNA substrate

Evidence for a two-metal ion mechanism for cleavage of the HH16 hammerhead ribozyme is provided by monitoring the rate of cleavage of the RNA substrate as a function of La3+ concentration in the presence of a constant concentration of Mg2+. We show that a bell-shaped curve of cleavage activation is obtained as La3+ is added in micromolar concentrations in the presence of 8 mM Mg2+, with a maximal rate of cleavage being attained in the presence of 3 microM La3+. These results show that two-metal ion binding sites on the ribozyme regulate the rate of the cleavage reaction and, on the basis of earlier estimates of the Kd values for Mg2+ of 3.5 mM and > 50 mM, that these sites bind La3+ with estimated Kd values of 0.9 and > 37.5 microM, respectively. Furthermore, given the very different effects of these metal ions at the two binding sites, with displacement of Mg2+ by La3+ at the stronger (relative to Mg2+) binding site activating catalysis and displacement of Mg2+ by La3+ at the weaker (relative to Mg2+) (relative to Mg2+) binding site inhibiting catalysis, we show that the metal ions at these two sites play very different roles. We argue that the metal ion at binding site 1 coordinates the attacking 2'-oxygen species in the reaction and lowers the pKa of the attached proton, thereby increasing the concentration of the attacking alkoxide nucleophile in an equilibrium process. In contrast, the role of the metal ion at binding site 2 is to catalyze the reaction by absorbing the negative charge that accumulates at the leaving 5'-oxygen in the transition state. We suggest structural reasons why the Mg(2+)-La3+ ion combination is particularly suited to demonstrating these different roles of the two-metal ions in the ribozyme cleavage reaction.

An improved method to detect damage using modal strain energy based damage index

This paper presents two novel concepts to enhance the accuracy of damage detection using the Modal Strain Energy based Damage Index (MSEDI) with the presence of noise in the mode shape data. Firstly, the paper presents a sequential curve fitting technique that reduces the effect of noise on the calculation process of the MSEDI, more effectively than the two commonly used curve fitting techniques; namely, polynomial and Fourier’s series. Secondly, a probability based Generalized Damage Localization Index (GDLI) is proposed as a viable improvement to the damage detection process. The study uses a validated ABAQUS finite-element model of a reinforced concrete beam to obtain mode shape data in the undamaged and damaged states. Noise is simulated by adding three levels of random noise (1%, 3%, and 5%) to the mode shape data. Results show that damage detection is enhanced with increased number of modes and samples used with the GDLI.

Numerical and experimental studies of cold-formed steel floor systems under standard fire conditions

Light gauge cold-formed steel frame (LSF) structures are increasingly used in industrial, commercial and residential buildings because of their non-combustibility, dimensional stability, and ease of installation. A floor-ceiling system is an example of its applications. LSF floor-ceiling systems must be designed to serve as fire compartment boundaries and provide adequate fire resistance. Fire rated floor-ceiling assemblies formed with new materials and construction methodologies have been increasingly used in buildings. However, limited research has been undertaken in the past and hence a thorough understanding of their fire resistance behaviour is not available. Recently a new composite panel in which an external insulation layer is used between two plasterboards has been developed at QUT to provide a higher fire rating to LSF floors under standard fire conditions. But its increased fire rating could not be determined using the currently available design methods. Research on LSF floor systems under fire conditions is relatively recent and the behaviour of floor joists and other components in the systems is not fully understood. The present design methods thus require the use of expensive fire protection materials to protect them from excessive heat increase during a fire. This leads to uneconomical and conservative designs. Fire rating of these floor systems is provided simply by adding more plasterboard sheets to the steel joists and such an approach is totally inefficient. Hence a detailed fire research study was undertaken into the structural and thermal performance of LSF floor systems including those protected by the new composite panel system using full scale fire tests and extensive numerical studies. Experimental study included both the conventional and the new steel floor-ceiling systems under structural and fire loads using a gas furnace designed to deliver heat in accordance with the standard time- temperature curve in AS 1530.4 (SA, 2005). Fire tests included the behavioural and deflection characteristics of LSF floor joists until failure as well as related time-temperature measurements across the section and along the length of all the specimens. Full scale fire tests have shown that the structural and thermal performance of externally insulated LSF floor system was superior than traditional LSF floors with or without cavity insulation. Therefore this research recommends the use of the new composite panel system for cold-formed LSF floor-ceiling systems. The numerical analyses of LSF floor joists were undertaken using the finite element program ABAQUS based on the measured time-temperature profiles obtained from fire tests under both steady state and transient state conditions. Mechanical properties at elevated temperatures were considered based on the equations proposed by Dolamune Kankanamge and Mahendran (2011). Finite element models were calibrated using the full scale test results and used to further provide a detailed understanding of the structural fire behaviour of the LSF floor-ceiling systems. The models also confirmed the superior performance of the new composite panel system. The validated model was then used in a detailed parametric study. Fire tests and the numerical studies showed that plasterboards provided sufficient lateral restraint to LSF floor joists until their failure. Hence only the section moment capacity of LSF floor joists subjected to local buckling effects was considered in this research. To predict the section moment capacity at elevated temperatures, the effective section modulus of joists at ambient temperature is generally considered adequate. However, this research has shown that it leads to considerable over- estimation of the local buckling capacity of joist subject to non-uniform temperature distributions under fire conditions. Therefore new simplified fire design rules were proposed for LSF floor joist to determine the section moment capacity at elevated temperature based on AS/NZS 4600 (SA, 2005), NAS (AISI, 2007) and Eurocode 3 Part 1.3 (ECS, 2006). The accuracy of the proposed fire design rules was verified with finite element analysis results. A spread sheet based design tool was also developed based on these design rules to predict the failure load ratio versus time, moment capacity versus time and temperature for various LSF floor configurations. Idealised time-temperature profiles of LSF floor joists were developed based on fire test measurements. They were used in the detailed parametric study to fully understand the structural and fire behaviour of LSF floor panels. Simple design rules were also proposed to predict both critical average joist temperatures and failure times (fire rating) of LSF floor systems with various floor configurations and structural parameters under any given load ratio. Findings from this research have led to a comprehensive understanding of the structural and fire behaviour of LSF floor systems including those protected by the new composite panel, and simple design methods. These design rules were proposed within the guidelines of the Australian/New Zealand, American and European cold- formed steel structures standard codes of practice. These may also lead to further improvements to fire resistance through suitable modifications to the current composite panel system.

Experimental studies of non-load bearing steel wall systems under fire conditions

Fire safety of buildings has been recognised as very important by the building industry and the community at large. Traditionally, increased fire rating is provided by simply adding more plasterboards to light gauge steel frame (LSF) walls, which is inefficient. Many research studies have been undertaken to investigate the thermal behaviour of traditional LSF stud wall systems under standard fire conditions. However, no research has been undertaken on the thermal behaviour of LSF stud walls using the recently proposed composite panel. Extensive fire testing of both non-load bearing and load bearing wall panels was conducted in this research based on the standard time-temperature curve in AS1530.4. Three groups of LSF wall specimens were tested with no insulation, cavity insulation and the new composite panel based on an external insulation layer between plasterboards. This paper presents the details of this experimental study into the thermal performance of non-load bearing walls lined with various configurations of plasterboard and insulation. Extensive descriptive and numerical results of the tested non-load bearing wall panels given in this paper provide a thorough understanding of their thermal behaviour, and valuable time-temperature data that can be used to validate numerical models. Test results showed that the innovative composite stud wall systems outperformed the traditional stud wall systems in terms of their thermal performance, giving a much higher fire rating.

Finite element modelling of load bearing steel stud walls under real building fires

Fire safety has become an important part in structural design due to the ever increasing loss of properties and lives during fires. Conventionally the fire rating of load bearing wall systems made of Light gauge Steel Frames (LSF) is determined using fire tests based on the standard time-temperature curve given in ISO 834 (ISO, 1999). The standard time-temperature curve given in ISO 834 (ISO, 1999) originated from the application of wood burning furnaces in the early 1900s. However, modern commercial and residential buildings make use of thermoplastic materials, which mean considerably high fuel loads. Hence a detailed fire research study into the performance of LSF walls was undertaken using the developed real fire curves based on Eurocode parametric curves (ECS, 2002) and Barnett’s BFD curves (Barnett, 2002) using both full scale fire tests and numerical studies. It included LSF walls without any insulation, and the recently developed externally insulated composite panel system. This paper presents the details of the numerical studies and the results. It also includes brief details of the development of real building fire curves and experimental studies.

Fire tests of load bearing steel stud walls exposed to real building fires

Abstract. Fire resistance has become an important part in structural design due to the ever increasing loss of properties and lives every year. Conventionally the fire rating of load bearing Light gauge Steel Frame (LSF) walls is determined using standard fire tests based on the time-temperature curve given in ISO 834 [1]. Full scale fire testing based on this standard time-temperature curve originated from the application of wood burning furnaces in the early 1900s and it is questionable whether it truly represents the fuel loads in modern buildings. Hence a detailed fire research study into the performance of LSF walls was undertaken using real design fires based on Eurocode parametric curves [2] and Barnett’s ‘BFD’ curves [3]. This paper presents the development of these real fire curves and the results of full scale experimental study into the structural and fire behaviour of load bearing LSF stud wall systems.

Quantitative studies of lower motor neuron degeneration in amyotrophic lateral sclerosis : Evidence for exponential decay of motor unit numbers and greatest rate of loss at the site of onset

Objective: To use our Bayesian method of motor unit number estimation (MUNE) to evaluate lower motor neuron degeneration in ALS. Methods: In subjects with ALS we performed serial MUNE studies. We examined the repeatability of the test and then determined whether the loss of MUs was fitted by an exponential or Weibull distribution. Results: The decline in motor unit (MU) numbers was well-fitted by an exponential decay curve. We calculated the half life of MUs in the abductor digiti minimi (ADM), abductor pollicis brevis (APB) and/or extensor digitorum brevis (EDB) muscles. The mean half life of the MUs of ADM muscle was greater than those of the APB or EDB muscles. The half-life of MUs was less in the ADM muscle of subjects with upper limb than in those with lower limb onset. Conclusions: The rate of loss of lower motor neurons in ALS is exponential, the motor units of the APB decay more quickly than those of the ADM muscle and the rate of loss of motor units is greater at the site of onset of disease. Significance: This shows that the Bayesian MUNE method is useful in following the course and exploring the clinical features of ALS. 2012 International Federation of Clinical Neurophysiology.

Effects of extreme temperatures on years of life lost for cardiovascular deaths : a time series study in Brisbane, Australia

Background: Extreme temperatures are associated with cardiovascular disease (CVD) deaths. Previous studies have investigated the relative CVD mortality risk of temperature, but this risk is heavily influenced by deaths in frail elderly persons. To better estimate the burden of extreme temperatures we estimated their effects on years of life lost due to CVD. Methods and Results: The data were daily observations on weather and CVD mortality for Brisbane, Australia between 1996 and 2004. We estimated the association between daily mean temperature and years of life lost due to CVD, after adjusting for trend, season, day of the week, and humidity. To examine the non-linear and delayed effects of temperature, a distributed lag non-linear model was used. The model’s residuals were examined to investigate if there were any added effects due to cold spells and heat waves. The exposure-response curve between temperature and years of life lost was U-shaped, with the lowest years of life lost at 24 °C. The curve had a sharper rise at extremes of heat than of cold. The effect of cold peaked two days after exposure, whereas the greatest effect of heat occurred on the day of exposure. There were significantly added effects of heat waves on years of life lost. Conclusions: Increased years of life lost due to CVD are associated with both cold and hot temperatures. Research on specific interventions is needed to reduce temperature-related years of life lost from CVD deaths.

Extracting deck trend to plan descent trajectory for safe landing of UAVs

This paper outlines a feasible scheme to extract deck trend when a rotary-wing unmanned aerial vehicle (RUAV)approaches an oscillating deck. An extended Kalman filter (EKF) is de- veloped to fuse measurements from multiple sensors for effective estimation of the unknown deck heave motion. Also, a recursive Prony Analysis (PA) procedure is proposed to implement online curve-fitting of the estimated heave mo- tion. The proposed PA constructs an appropriate model with parameters identified using the forgetting factor recursive least square (FFRLS)method. The deck trend is then extracted by separating dominant modes. Performance of the proposed procedure is evaluated using real ship motion data, and simulation results justify the suitability of the proposed method into safe landing of RUAVs operating in a maritime environment.

The effect of a high fat meal on postprandial arterial stiffness in men with obesity and type 2 diabetes

Context: Postprandial dysmetabolism is emerging as an important cardiovascular risk factor. Augmentation index (AIx) is a measure of systemic arterial stiffness and independently predicts cardiovascular outcome. Objective: The objective of this study was to assess the effect of a standardized high-fat meal on metabolic parameters and AIx in 1) lean, 2) obese nondiabetic, and 3) subjects with type 2 diabetes mellitus (T2DM). Design and Setting: Male subjects (lean, n = 8; obese, n = 10; and T2DM, n = 10) were studied for 6 h after a high-fat meal and water control. Glucose, insulin, triglycerides, and AIx (radial applanation tonometry) were measured serially to determine the incremental area under the curve (iAUC). Results: AIx decreased in all three groups after a high-fat meal. A greater overall postprandial reduction in AIx was seen in lean and T2DM compared with obese subjects (iAUC, 2251 +/- 1204, 2764 +/- 1102, and 1187 +/- 429% . min, respectively; P < 0.05). The time to return to baseline AIx was significantly delayed in subjects with T2DM (297 +/- 68 min) compared with lean subjects (161 +/- 88 min; P < 0.05). There was a significant correlation between iAUC AIx and iAUC triglycerides (r = 0.50; P < 0.05). Conclusions: Obesity is associated with an attenuated overall postprandial decrease in AIx. Subjects with T2DM have a preserved, but significantly prolonged, reduction in AIx after a high-fat meal. The correlation between AIx and triglycerides suggests that postprandial dysmetabolism may impact on vascular dynamics. The markedly different response observed in the obese subjects compared with those with T2DM was unexpected and warrants additional evaluation.

Earned value management insights using inferential statistics

Purpose – The purpose of this paper is to summarise a successfully defended doctoral thesis. The main purpose of this paper is to provide a summary of the scope, and main issues raised in the thesis so that readers undertaking studies in the same or connected areas may be aware of current contributions to the topic. The secondary aims are to frame the completed thesis in the context of doctoral-level research in project management as well as offer ideas for further investigation which would serve to extend scientific knowledge on the topic. Design/methodology/approach – Research reported in this paper is based on a quantitative study using inferential statistics aimed at better understanding the actual and potential usage of earned value management (EVM) as applied to external projects under contract. Theories uncovered during the literature review were hypothesized and tested using experiential data collected from 145 EVM practitioners with direct experience on one or more external projects under contract that applied the methodology. Findings – The results of this research suggest that EVM is an effective project management methodology. The principles of EVM were shown to be significant positive predictors of project success on contracted efforts and to be a relatively greater positive predictor of project success when using fixed-price versus cost-plus (CP) type contracts. Moreover, EVM's work-breakdown structure (WBS) utility was shown to positively contribute to the formation of project contracts. The contribution was not significantly different between fixed-price and CP contracted projects, with exceptions in the areas of schedule planning and payment planning. EVM's “S” curve benefited the administration of project contracts. The contribution of the S-curve was not significantly different between fixed-price and CP contracted projects. Furthermore, EVM metrics were shown to also be important contributors to the administration of project contracts. The relative contribution of EVM metrics to projects under fixed-price versus CP contracts was not significantly different, with one exception in the area of evaluating and processing payment requests. Practical implications – These results have important implications for project practitioners, EVM advocates, as well as corporate and governmental policy makers. EVM should be considered for all projects – not only for its positive contribution to project contract development and administration, for its contribution to project success as well, regardless of contract type. Contract type should not be the sole determining factor in the decision whether or not to use EVM. More particularly, the more fixed the contracted project cost, the more the principles of EVM explain the success of the project. The use of EVM mechanics should also be used in all projects regardless of contract type. Payment planning using a WBS should be emphasized in fixed-price contracts using EVM in order to help mitigate performance risk. Schedule planning using a WBS should be emphasized in CP contracts using EVM in order to help mitigate financial risk. Similarly, EVM metrics should be emphasized in fixed-price contracts in evaluating and processing payment requests. Originality/value – This paper provides a summary of cutting-edge research work and a link to the published thesis that researchers can use to help them understand how the research methodology was applied as well as how it can be extended.

An investigation into factors affecting electron density calibration for a megavoltage cone-beam CT system

There is a growing interest in the use of megavoltage cone-beam computed tomography (MV CBCT) data for radiotherapy treatment planning. To calculate accurate dose distributions, knowledge of the electron density (ED) of the tissues being irradiated is required. In the case of MV CBCT, it is necessary to determine a calibration-relating CT number to ED, utilizing the photon beam produced for MV CBCT. A number of different parameters can affect this calibration. This study was undertaken on the Siemens MV CBCT system, MVision, to evaluate the effect of the following parameters on the reconstructed CT pixel value to ED calibration: the number of monitor units (MUs) used (5, 8, 15 and 60 MUs), the image reconstruction filter (head and neck, and pelvis), reconstruction matrix size (256 by 256 and 512 by 512), and the addition of extra solid water surrounding the ED phantom. A Gammex electron density CT phantom containing EDs from 0.292 to 1.707 was imaged under each of these conditions. The linear relationship between MV CBCT pixel value and ED was demonstrated for all MU settings and over the range of EDs. Changes in MU number did not dramatically alter the MV CBCT ED calibration. The use of different reconstruction filters was found to affect the MV CBCT ED calibration, as was the addition of solid water surrounding the phantom. Dose distributions from treatment plans calculated with simulated image data from a 15 MU head and neck reconstruction filter MV CBCT image and a MV CBCT ED calibration curve from the image data parameters and a 15 MU pelvis reconstruction filter showed small and clinically insignificant differences. Thus, the use of a single MV CBCT ED calibration curve is unlikely to result in any clinical differences. However, to ensure minimal uncertainties in dose reporting, MV CBCT ED calibration measurements could be carried out using parameter-specific calibration measurements.

A new technique for optimal allocation and sizing of capacitors and setting of LTC

An iterative based strategy is proposed for finding the optimal rating and location of fixed and switched capacitors in distribution networks. The substation Load Tap Changer tap is also set during this procedure. A Modified Discrete Particle Swarm Optimization is employed in the proposed strategy. The objective function is composed of the distribution line loss cost and the capacitors investment cost. The line loss is calculated using estimation of the load duration curve to multiple levels. The constraints are the bus voltage and the feeder current which should be maintained within their standard range. For validation of the proposed method, two case studies are tested. The first case study is the semi-urban 37-bus distribution system which is connected at bus 2 of the Roy Billinton Test System which is located in the secondary side of a 33/11 kV distribution substation. The second case is a 33 kV distribution network based on the modification of the 18-bus IEEE distribution system. The results are compared with prior publications to illustrate the accuracy of the proposed strategy.

Behaviour and design of cold-formed steel beams subject to lateral-torsional buckling at elevated temperatures

Cold-formed steel beams are increasingly used as floor joists and bearers in buildings and often their behaviour and moment capacities are influenced by lateral-torsional buckling. With increasing usage of cold-formed steel beams their fire safety design has become an important issue. Fire design rules are commonly based on past research on hot-rolled steel beams. Hence a detailed parametric study was undertaken using validated finite element models to investigate the lateral-torsional buckling behaviour of simply supported cold-formed steel lipped channel beams subjected to uniform bending at uniform elevated temperatures. The moment capacity results were compared with the predictions from the available ambient temperature and fire design rules and suitable recommendations were made. European fire design rules were found to be over-conservative while the ambient temperature design rules could not be used based on single buckling curve. Hence a new design method was proposed that includes the important non-linear stress-strain characteristics observed for cold-formed steels at elevated temperatures. Comparison with numerical moment capacities demonstrated the accuracy of the new design method. This paper presents the details of the parametric study, comparisons with current design rules and the new design rules proposed in this research for lateral-torsional buckling of cold-formed steel lipped channel beams at elevated temperatures.