ERK-1/2 and p38 in the Regulation of Hypertrophic Changes of Normal Articular Cartilage Chondrocytes Induced by Osteoarthritic Subchondral Osteoblasts

Objective. Previous studies have shown the influence of subchondral bone osteoblasts (SBOs) on phenotypical changes of articular cartilage chondrocytes (ACCs) during the development of osteoarthritis (OA). The molecular mechanisms involved during this process remain elusive, in particular, the signal transduction pathways. The aim of this study was to investigate the in vitro effects of OA SBOs on the phenotypical changes in normal ACCs and to unveil the potential involvement of MAPK signaling pathways during this process. Methods. Normal and arthritic cartilage and bone samples were collected for isolation of ACCs and SBOs. Direct and indirect coculture models were applied to study chondrocyte hypertrophy under the influence of OA SBOs. MAPKs in the regulation of the cell–cell interactions were monitored by phosphorylated antibodies and relevant inhibitors. Results. OA SBOs led to increased hypertrophic gene expression and matrix calcification in ACCs by means of both direct and indirect cell–cell interactions. In this study, we demonstrated for the first time that OA SBOs suppressed p38 phosphorylation and induced ERK-1/2 signal phosphorylation in cocultured ACCs. The ERK-1/2 pathway inhibitor PD98059 significantly attenuated the hypertrophic changes induced by conditioned medium from OA SBOs, and the p38 inhibitor SB203580 resulted in the up-regulation of hypertrophic genes in ACCs. Conclusion. The findings of this study suggest that the pathologic interaction of OA SBOs and ACCs is mediated via the activation of ERK-1/2 phosphorylation and deactivation of p38 phosphorylation, resulting in hypertrophic differentiation of ACCs.

The application of phonetic distribution normalisation to likelihood-maximising speech enhancement for robust ASR

Traditional speech enhancement methods optimise signal-level criteria such as signal-to-noise ratio, but such approaches are sub-optimal for noise-robust speech recognition. Likelihood-maximising (LIMA) frameworks on the other hand, optimise the parameters of speech enhancement algorithms based on state sequences generated by a speech recogniser for utterances of known transcriptions. Previous applications of LIMA frameworks have generated a set of global enhancement parameters for all model states without taking in account the distribution of model occurrence, making optimisation susceptible to favouring frequently occurring models, in particular silence. In this paper, we demonstrate the existence of highly disproportionate phonetic distributions on two corpora with distinct speech tasks, and propose to normalise the influence of each phone based on a priori occurrence probabilities. Likelihood analysis and speech recognition experiments verify this approach for improving ASR performance in noisy environments.

Fold back current control and admittance protection scheme for a distribution network containing distributed generators

Islanded operation, protection, reclosing and arc extinguishing are some of the challenging issues related to the connection of converter interfaced distributed generators (DGs) into a distribution network. The isolation of upstream faults in grid connected mode and fault detection in islanded mode using overcurrent devices are difficult. In the event of an arc fault, all DGs must be disconnected in order to extinguish the arc. Otherwise, they will continue to feed the fault, thus sustaining the arc. However, the system reliability can be increased by maximising the DG connectivity to the system: therefore, the system protection scheme must ensure that only the faulted segment is removed from the feeder. This is true even in the case of a radial feeder as the DG can be connected at various points along the feeder. In this paper, a new relay scheme is proposed which, along with a novel current control strategy for converter interfaced DGs, can isolate permanent and temporary arc faults. The proposed protection and control scheme can even coordinate with reclosers. The results are validated through PSCAD/EMTDC simulation and MATLAB calculations.

Analysis of distrubances in large interconnected power systems

World economies increasingly demand reliable and economical power supply and distribution. To achieve this aim the majority of power systems are becoming interconnected, with several power utilities supplying the one large network. One problem that occurs in a large interconnected power system is the regular occurrence of system disturbances which can result in the creation of intra-area oscillating modes. These modes can be regarded as the transient responses of the power system to excitation, which are generally characterised as decaying sinusoids. For a power system operating ideally these transient responses would ideally would have a “ring-down” time of 10-15 seconds. Sometimes equipment failures disturb the ideal operation of power systems and oscillating modes with ring-down times greater than 15 seconds arise. The larger settling times associated with such “poorly damped” modes cause substantial power flows between generation nodes, resulting in significant physical stresses on the power distribution system. If these modes are not just poorly damped but “negatively damped”, catastrophic failures of the system can occur. To ensure system stability and security of large power systems, the potentially dangerous oscillating modes generated from disturbances (such as equipment failure) must be quickly identified. The power utility must then apply appropriate damping control strategies. In power system monitoring there exist two facets of critical interest. The first is the estimation of modal parameters for a power system in normal, stable, operation. The second is the rapid detection of any substantial changes to this normal, stable operation (because of equipment breakdown for example). Most work to date has concentrated on the first of these two facets, i.e. on modal parameter estimation. Numerous modal parameter estimation techniques have been proposed and implemented, but all have limitations [1-13]. One of the key limitations of all existing parameter estimation methods is the fact that they require very long data records to provide accurate parameter estimates. This is a particularly significant problem after a sudden detrimental change in damping. One simply cannot afford to wait long enough to collect the large amounts of data required for existing parameter estimators. Motivated by this gap in the current body of knowledge and practice, the research reported in this thesis focuses heavily on rapid detection of changes (i.e. on the second facet mentioned above). This thesis reports on a number of new algorithms which can rapidly flag whether or not there has been a detrimental change to a stable operating system. It will be seen that the new algorithms enable sudden modal changes to be detected within quite short time frames (typically about 1 minute), using data from power systems in normal operation. The new methods reported in this thesis are summarised below. The Energy Based Detector (EBD): The rationale for this method is that the modal disturbance energy is greater for lightly damped modes than it is for heavily damped modes (because the latter decay more rapidly). Sudden changes in modal energy, then, imply sudden changes in modal damping. Because the method relies on data from power systems in normal operation, the modal disturbances are random. Accordingly, the disturbance energy is modelled as a random process (with the parameters of the model being determined from the power system under consideration). A threshold is then set based on the statistical model. The energy method is very simple to implement and is computationally efficient. It is, however, only able to determine whether or not a sudden modal deterioration has occurred; it cannot identify which mode has deteriorated. For this reason the method is particularly well suited to smaller interconnected power systems that involve only a single mode. Optimal Individual Mode Detector (OIMD): As discussed in the previous paragraph, the energy detector can only determine whether or not a change has occurred; it cannot flag which mode is responsible for the deterioration. The OIMD seeks to address this shortcoming. It uses optimal detection theory to test for sudden changes in individual modes. In practice, one can have an OIMD operating for all modes within a system, so that changes in any of the modes can be detected. Like the energy detector, the OIMD is based on a statistical model and a subsequently derived threshold test. The Kalman Innovation Detector (KID): This detector is an alternative to the OIMD. Unlike the OIMD, however, it does not explicitly monitor individual modes. Rather it relies on a key property of a Kalman filter, namely that the Kalman innovation (the difference between the estimated and observed outputs) is white as long as the Kalman filter model is valid. A Kalman filter model is set to represent a particular power system. If some event in the power system (such as equipment failure) causes a sudden change to the power system, the Kalman model will no longer be valid and the innovation will no longer be white. Furthermore, if there is a detrimental system change, the innovation spectrum will display strong peaks in the spectrum at frequency locations associated with changes. Hence the innovation spectrum can be monitored to both set-off an “alarm” when a change occurs and to identify which modal frequency has given rise to the change. The threshold for alarming is based on the simple Chi-Squared PDF for a normalised white noise spectrum [14, 15]. While the method can identify the mode which has deteriorated, it does not necessarily indicate whether there has been a frequency or damping change. The PPM discussed next can monitor frequency changes and so can provide some discrimination in this regard. The Polynomial Phase Method (PPM): In [16] the cubic phase (CP) function was introduced as a tool for revealing frequency related spectral changes. This thesis extends the cubic phase function to a generalised class of polynomial phase functions which can reveal frequency related spectral changes in power systems. A statistical analysis of the technique is performed. When applied to power system analysis, the PPM can provide knowledge of sudden shifts in frequency through both the new frequency estimate and the polynomial phase coefficient information. This knowledge can be then cross-referenced with other detection methods to provide improved detection benchmarks.

Post-tensioning and its effect on multi-level formwork load distribution

Multi-level concrete buildings requrre substantial temporary formwork structures to support the slabs during construction. The primary function of this formwork is to safely disperse the applied loads so that the slab being constructed, or the portion of the permanent structure already constructed, is not overloaded. Multi-level formwork is a procedure in which a limited number of formwork and shoring sets are cycled up the building as construction progresses. In this process, each new slab is supported by a number of lower level slabs. The new slab load is, essentially, distributed to these supporting slabs in direct proportion to their relative stiffness. When a slab is post-tensioned using draped tendons, slab lift occurs as a portion of the slab self-weight is balanced. The formwork and shores supporting that slab are unloaded by an amount equivalent to the load balanced by the post-tensioning. This produces a load distribution inherently different from that of a conventionally reinforced slab. Through , theoretical modelling and extensive on-site shore load measurement, this research examines the effects of post-tensioning on multilevel formwork load distribution. The research demonstrates that the load distribution process for post-tensioned slabs allows for improvements to current construction practice. These enhancements include a shortening of the construction period; an improvement in the safety of multi-level form work operations; and a reduction in the quantity of form work materials required for a project. These enhancements are achieved through the general improvement in safety offered by post-tensioning during the various formwork operations. The research demonstrates that there is generally a significant improvement in the factors of safety over those for conventionally reinforced slabs. This improvement in the factor of safety occurs at all stages of the multi-level formwork operation. The general improvement in the factors of safety with post-tensioned slabs allows for a shortening of the slab construction cycle time. Further, the low level of load redistribution that occurs during the stripping operations makes post-tensioned slabs ideally suited to reshoring procedures. Provided the overall number of interconnected levels remains unaltered, it is possible to increase the number of reshored levels while reducing the number of undisturbed shoring levels without altering the factors of safety, thereby, reducing the overall quantity of formwork and shoring materials.

Theory of radar imaging using time-frequency distribution

The concept of radar was developed for the estimation of the distance (range) and velocity of a target from a receiver. The distance measurement is obtained by measuring the time taken for the transmitted signal to propagate to the target and return to the receiver. The target's velocity is determined by measuring the Doppler induced frequency shift of the returned signal caused by the rate of change of the time- delay from the target. As researchers further developed conventional radar systems it become apparent that additional information was contained in the backscattered signal and that this information could in fact be used to describe the shape of the target itself. It is due to the fact that a target can be considered to be a collection of individual point scatterers, each of which has its own velocity and time- delay. DelayDoppler parameter estimation of each of these point scatterers thus corresponds to a mapping of the target's range and cross range, thus producing an image of the target. Much research has been done in this area since the early radar imaging work of the 1960s. At present there are two main categories into which radar imaging falls. The first of these is related to the case where the backscattered signal is considered to be deterministic. The second is related to the case where the backscattered signal is of a stochastic nature. In both cases the information which describes the target's scattering function is extracted by the use of the ambiguity function, a function which correlates the backscattered signal in time and frequency with the transmitted signal. In practical situations, it is often necessary to have the transmitter and the receiver of the radar system sited at different locations. The problem in these situations is 'that a reference signal must then be present in order to calculate the ambiguity function. This causes an additional problem in that detailed phase information about the transmitted signal is then required at the receiver. It is this latter problem which has led to the investigation of radar imaging using time- frequency distributions. As will be shown in this thesis, the phase information about the transmitted signal can be extracted from the backscattered signal using time- frequency distributions. The principle aim of this thesis was in the development, and subsequent discussion into the theory of radar imaging, using time- frequency distributions. Consideration is first given to the case where the target is diffuse, ie. where the backscattered signal has temporal stationarity and a spatially white power spectral density. The complementary situation is also investigated, ie. where the target is no longer diffuse, but some degree of correlation exists between the time- frequency points. Computer simulations are presented to demonstrate the concepts and theories developed in the thesis. For the proposed radar system to be practically realisable, both the time- frequency distributions and the associated algorithms developed must be able to be implemented in a timely manner. For this reason an optical architecture is proposed. This architecture is specifically designed to obtain the required time and frequency resolution when using laser radar imaging. The complex light amplitude distributions produced by this architecture have been computer simulated using an optical compiler.