Modulation of the SHBG signalling axis

Sex hormone-binding globulin (SHBG) is a homodimeric plasma glycoprotein that is the major sex steroid carrier-protein in the bloodstream and functions also as a key regulator of steroid bioavailability within target tissues, such as the prostate. Additionally, SHBG binds to prostatic cell membranes via the putative and unidentified SHBG receptor (RSHBG), activating a signal transduction pathway implicated in stimulating both proliferation and expression of prostate specific antigen (PSA) in prostate cell lines in vitro. A yeast-two hybrid assay suggested an interaction between SHBG and kallikrein-related protease (KLK) 4, which is a serine protease implicated in the progression of prostate cancer. The potential interaction between these two proteins was investigated in this PhD thesis to determine whether SHBG is a proteolytic substrate of KLK4 and other members of the KLK family including KLK3/PSA, KLK7 and KLK14. Furthermore, the effects from SHBG proteolytic degradation on SHBG-regulated steroid bioavailability and the activation of the putative RSHBG signal transduction pathway were examined in the LNCaP prostate cancer cell line. SHBG was found to be a proteolytic substrate of the trypsin-like KLK4 and KLK14 in vitro, yielding several proteolysis fragments. Both chymotrypsin-like PSA and KLK7 displayed insignificant proteolytic activity against SHBG. The kinetic parameters of SHBG proteolysis by KLK4 and KLK14 demonstrate a strong enzyme-substrate binding capacity, possessing a Km of 1.2 ± 0.7 µM and 2.1 ± 0.6 µM respectively. The catalytic efficiencies (kcat/Km) of KLK4 and KLK14 proteolysis of SHBG were 1.6 x 104 M-1s-1 and 3.8 x 104 M-1s-1 respectively, which were comparable to parameters previously reported for peptide substrates. N-terminal sequencing of the fragments revealed cleavage near the junction of the N- and C-terminal laminin globulin-like (G-like) domains of SHBG, resulting in the division of the two globulins and ultimately the full degradation of these fragments by KLK4 and KLK14 over time. Proteolytic fragments that may retain steroid binding were rapidly degraded by both proteases, while fragments containing residues beyond the steroid binding pocket were less degraded over the same period of time. Degradation of SHBG was inhibited by the divalent metal cations calcium and zinc for KLK4, and calcium, zinc and magnesium for KLK14. The human secreted serine protease inhibitors (serpins), α1-antitrypsin and α2-antiplasmin, inhibited KLK4 and KLK14 proteolysis of SHBG; α1-antichymotrypsin inhibited KLK4 but not KLK14 activity. The inhibition by these serpins was comparable and in some cases more effective than general trypsin protease inhibitors such as aprotinin and phenylmethanesulfonyl fluoride (PMSF). The binding of 5α-dihydrotestosterone (DHT) to SHBG modulated interactions with KLK4 and KLK14. Steroid-free SHBG was more readily digested by both enzymes than DHT-bound SHBG. Moreover, a binding interaction exists between SHBG and pro-KLK4 and pro-KLK14, with DHT strengthening the binding to pro-KLK4 only. The inhibition of androgen uptake by cultured prostate cancer cells, mediated by SHBG steroid-binding, was examined to assess whether SHBG proteolysis by KLK4 and KLK14 modulated this process. Proteolytic digestion eliminated the ability of SHBG to inhibit the uptake of DHT from conditioned media into LNCaP cells. Therefore, the proteolysis of SHBG by KLK4 and KLK14 increased steroid bioavailability in vitro, leading to an increased uptake of androgens by prostate cancer cells. Interestingly, different transcriptional responses of PSA and KLK2, which are androgen-regulated genes, to DHT-bounsd SHBG treatment were observed between low and high passage number LNCaP cells (lpLNCaP and hpLNCaP respectively). HpLNCaP cells treated with DHT-bound SHBG demonstrated a significant synergistic upregulation of PSA and KLK2 above DHT or SHBG treatment alone, which is similar to previously reported downstream responses from RSHBG-mediated signaling activation. As this result was not seen in lpLNCaP cells, only hpLNCaP cells were further investigated to examine the modulation of potential RSHBG activity by KLK4 and KLK14 proteolysis of SHBG. Contrary to reported results, no increase in intracellular cAMP was observed in hpLNCaP cells when treated with SHBG in the presence and absence of either DHT or estradiol. As a result, the modulation of RSHBG-mediated signaling activation could not be determined. Finally, the identification of the RSHBG from both breast (MCF-7) and prostate cancer (LNCaP) cell lines was attempted. Fluorescently labeled peptides corresponding to the putative receptor binding domain (RBD) of SHBG were shown to be internalized by MCF-7 cells. Crosslinking of the RBD peptide to the cell surfaces of both MCF-7 and LNCaP cells, demonstrated the interaction of the peptide with several targets. These targets were then captured using RBD peptides synthesized onto a hydrophilic scaffold and analysed by mass spectrometry. The samples captured by the RBD peptide returned statistically significantly matches for cytokeratin 8, 18 and 19 as well as microtubule-actin crosslinking factor 1, which may indicate a novel interaction between SHBG and these proteins, but ultimately failed to detect a membrane receptor potentially responsible for the putative RSHBG-mediated signaling. This PhD project has reported the proteolytic processing of SHBG by two members of the kallikrein family, KLK4 and KLK14. The effect of SHBG proteolysis by KLK4 and KLK14 on RSHBG-mediated signaling activation was unable to be determined as the reported signal transduction pathway was not activated after treatment with SHBG, in combination with either DHT or estradiol. However, the digestion of SHBG by these two proteases positively regulated androgen bioavailability to prostate cancer cells in vitro. The increased uptake of androgens is deleterious in prostate cancer due to the promotion of proliferation, metastasis, invasion and the inhibition of apoptosis. The increased bioavailability of androgens, from SHBG proteolysis by KLK4 and KLK14, may therefore promote both carcinogenesis and progression of prostate cancer. Finally, this information may contribute to the development of therapeutic treatment strategies for prostate cancer by inhibiting the proteolysis of SHBG, by KLK4 and KLK14, to prevent the increased uptake of androgens by hormone-dependent cancerous tissues.

The influence of travel time and size of shopping center towards the frequencies of visiting customers in shopping centers in surabaya

Visiting a modern shopping center is becoming vital in our society nowadays. The fast growth of shopping center, transportation system, and modern vehicles has given more choices for consumers in shopping. Although there are many reasons for the consumers in visiting the shopping center, the influence of travel time and size of shopping center are important things to be considered towards the frequencies of visiting customers in shopping centers. A survey to the customers of three major shopping centers in Surabaya has been conducted to evaluate the Ellwood’s model and Huff’s model. A new exponent value N of 0.48 and n of 0.50 has been found from the Ellwood’s model, while a coefficient of 0.267 and an add value of 0.245 have been found from the Huff’s model.

The modulation of outdoor running speed : the influence of gradient

This thesis aimed to investigate the way in which distance runners modulate their speed in an effort to understand the key processes and determinants of speed selection when encountering hills in natural outdoor environments. One factor which has limited the expansion of knowledge in this area has been a reliance on the motorized treadmill which constrains runners to constant speeds and gradients and only linear paths. Conversely, limits in the portability or storage capacity of available technology have restricted field research to brief durations and level courses. Therefore another aim of this thesis was to evaluate the capacity of lightweight, portable technology to measure running speed in outdoor undulating terrain. The first study of this thesis assessed the validity of a non-differential GPS to measure speed, displacement and position during human locomotion. Three healthy participants walked and ran over straight and curved courses for 59 and 34 trials respectively. A non-differential GPS receiver provided speed data by Doppler Shift and change in GPS position over time, which were compared with actual speeds determined by chronometry. Displacement data from the GPS were compared with a surveyed 100m section, while static positions were collected for 1 hour and compared with the known geodetic point. GPS speed values on the straight course were found to be closely correlated with actual speeds (Doppler shift: r = 0.9994, p < 0.001, Δ GPS position/time: r = 0.9984, p < 0.001). Actual speed errors were lowest using the Doppler shift method (90.8% of values within ± 0.1 m.sec -1). Speed was slightly underestimated on a curved path, though still highly correlated with actual speed (Doppler shift: r = 0.9985, p < 0.001, Δ GPS distance/time: r = 0.9973, p < 0.001). Distance measured by GPS was 100.46 ± 0.49m, while 86.5% of static points were within 1.5m of the actual geodetic point (mean error: 1.08 ± 0.34m, range 0.69-2.10m). Non-differential GPS demonstrated a highly accurate estimation of speed across a wide range of human locomotion velocities using only the raw signal data with a minimal decrease in accuracy around bends. This high level of resolution was matched by accurate displacement and position data. Coupled with reduced size, cost and ease of use, the use of a non-differential receiver offers a valid alternative to differential GPS in the study of overground locomotion. The second study of this dissertation examined speed regulation during overground running on a hilly course. Following an initial laboratory session to calculate physiological thresholds (VO2 max and ventilatory thresholds), eight experienced long distance runners completed a self- paced time trial over three laps of an outdoor course involving uphill, downhill and level sections. A portable gas analyser, GPS receiver and activity monitor were used to collect physiological, speed and stride frequency data. Participants ran 23% slower on uphills and 13.8% faster on downhills compared with level sections. Speeds on level sections were significantly different for 78.4 ± 7.0 seconds following an uphill and 23.6 ± 2.2 seconds following a downhill. Speed changes were primarily regulated by stride length which was 20.5% shorter uphill and 16.2% longer downhill, while stride frequency was relatively stable. Oxygen consumption averaged 100.4% of runner’s individual ventilatory thresholds on uphills, 78.9% on downhills and 89.3% on level sections. Group level speed was highly predicted using a modified gradient factor (r2 = 0.89). Individuals adopted distinct pacing strategies, both across laps and as a function of gradient. Speed was best predicted using a weighted factor to account for prior and current gradients. Oxygen consumption (VO2) limited runner’s speeds only on uphill sections, and was maintained in line with individual ventilatory thresholds. Running speed showed larger individual variation on downhill sections, while speed on the level was systematically influenced by the preceding gradient. Runners who varied their pace more as a function of gradient showed a more consistent level of oxygen consumption. These results suggest that optimising time on the level sections after hills offers the greatest potential to minimise overall time when running over undulating terrain. The third study of this thesis investigated the effect of implementing an individualised pacing strategy on running performance over an undulating course. Six trained distance runners completed three trials involving four laps (9968m) of an outdoor course involving uphill, downhill and level sections. The initial trial was self-paced in the absence of any temporal feedback. For the second and third field trials, runners were paced for the first three laps (7476m) according to two different regimes (Intervention or Control) by matching desired goal times for subsections within each gradient. The fourth lap (2492m) was completed without pacing. Goals for the Intervention trial were based on findings from study two using a modified gradient factor and elapsed distance to predict the time for each section. To maintain the same overall time across all paced conditions, times were proportionately adjusted according to split times from the self-paced trial. The alternative pacing strategy (Control) used the original split times from this initial trial. Five of the six runners increased their range of uphill to downhill speeds on the Intervention trial by more than 30%, but this was unsuccessful in achieving a more consistent level of oxygen consumption with only one runner showing a change of more than 10%. Group level adherence to the Intervention strategy was lowest on downhill sections. Three runners successfully adhered to the Intervention pacing strategy which was gauged by a low Root Mean Square error across subsections and gradients. Of these three, the two who had the largest change in uphill-downhill speeds ran their fastest overall time. This suggests that for some runners the strategy of varying speeds systematically to account for gradients and transitions may benefit race performances on courses involving hills. In summary, a non – differential receiver was found to offer highly accurate measures of speed, distance and position across the range of human locomotion speeds. Self-selected speed was found to be best predicted using a weighted factor to account for prior and current gradients. Oxygen consumption limited runner’s speeds only on uphills, speed on the level was systematically influenced by preceding gradients, while there was a much larger individual variation on downhill sections. Individuals were found to adopt distinct but unrelated pacing strategies as a function of durations and gradients, while runners who varied pace more as a function of gradient showed a more consistent level of oxygen consumption. Finally, the implementation of an individualised pacing strategy to account for gradients and transitions greatly increased runners’ range of uphill-downhill speeds and was able to improve performance in some runners. The efficiency of various gradient-speed trade- offs and the factors limiting faster downhill speeds will however require further investigation to further improve the effectiveness of the suggested strategy.

Multilevel converter structure and control

In recent years, multilevel converters are becoming more popular and attractive than traditional converters in high voltage and high power applications. Multilevel converters are particularly suitable for harmonic reduction in high power applications where semiconductor devices are not able to operate at high switching frequencies or in high voltage applications where multilevel converters reduce the need to connect devices in series to achieve high switch voltage ratings. This thesis investigated two aspects of multilevel converters: structure and control. The first part of this thesis focuses on inductance between a DC supply and inverter components in order to minimise loop inductance, which causes overvoltages and stored energy losses during switching. Three dimensional finite element simulations and experimental tests have been carried out for all sections to verify theoretical developments. The major contributions of this section of the thesis are as follows: The use of a large area thin conductor sheet with a rectangular cross section separated by dielectric sheets (planar busbar) instead of circular cross section wires, contributes to a reduction of the stray inductance. A number of approximate equations exist for calculating the inductance of a rectangular conductor but an assumption was made that the current density was uniform throughout the conductors. This assumption is not valid for an inverter with a point injection of current. A mathematical analysis of a planar bus bar has been performed at low and high frequencies and the inductance and the resistance values between the two points of the planar busbar have been determined. A new physical structure for a voltage source inverter with symmetrical planar bus bar structure called Reduced Layer Planar Bus bar, is proposed in this thesis based on the current point injection theory. This new type of planar busbar minimises the variation in stray inductance for different switching states. The reduced layer planar busbar is a new innovation in planar busbars for high power inverters with minimum separation between busbars, optimum stray inductance and improved thermal performances. This type of the planar busbar is suitable for high power inverters, where the voltage source is supported by several capacitors in parallel in order to provide a low ripple DC voltage during operation. A two layer planar busbar with different materials has been analysed theoretically in order to determine the resistance of bus bars during switching. Increasing the resistance of the planar busbar can gain a damping ratio between stray inductance and capacitance and affects the performance of current loop during switching. The aim of this section is to increase the resistance of the planar bus bar at high frequencies (during switching) and without significantly increasing the planar busbar resistance at low frequency (50 Hz) using the skin effect. This contribution shows a novel structure of busbar suitable for high power applications where high resistance is required at switching times. In multilevel converters there are different loop inductances between busbars and power switches associated with different switching states. The aim of this research is to consider all combinations of the switching states for each multilevel converter topology and identify the loop inductance for each switching state. Results show that the physical layout of the busbars is very important for minimisation of the loop inductance at each switch state. Novel symmetrical busbar structures are proposed for multilevel converters with diode-clamp and flying-capacitor topologies which minimise the worst case in stray inductance for different switching states. Overshoot voltages and thermal problems are considered for each topology to optimise the planar busbar structure. In the second part of the thesis, closed loop current techniques have been investigated for single and three phase multilevel converters. The aims of this section are to investigate and propose suitable current controllers such as hysteresis and predictive techniques for multilevel converters with low harmonic distortion and switching losses. This section of the thesis can be classified into three parts as follows: An optimum space vector modulation technique for a three-phase voltage source inverter based on a minimum-loss strategy is proposed. One of the degrees of freedom for optimisation of the space vector modulation is the selection of the zero vectors in the switching sequence. This new method improves switching transitions per cycle for a given level of distortion as the zero vector does not alternate between each sector. The harmonic spectrum and weighted total harmonic distortion for these strategies are compared and results show up to 7% weighted total harmonic distortion improvement over the previous minimum-loss strategy. The concept of SVM technique is a very convenient representation of a set of three-phase voltages or currents used for current control techniques. A new hysteresis current control technique for a single-phase multilevel converter with flying-capacitor topology is developed. This technique is based on magnitude and time errors to optimise the level change of converter output voltage. This method also considers how to improve unbalanced voltages of capacitors using voltage vectors in order to minimise switching losses. Logic controls require handling a large number of switches and a Programmable Logic Device (PLD) is a natural implementation for state transition description. The simulation and experimental results describe and verify the current control technique for the converter. A novel predictive current control technique is proposed for a three-phase multilevel converter, which controls the capacitors' voltage and load current with minimum current ripple and switching losses. The advantage of this contribution is that the technique can be applied to more voltage levels without significantly changing the control circuit. The three-phase five-level inverter with a pure inductive load has been implemented to track three-phase reference currents using analogue circuits and a programmable logic device.

Modulation of dermal microvascular endithelial cell responses to growth factors and haemostatic factors in the presence of vitronectin

In order to effect permanent closure in burns patients suffering from full thickness wounds, replacing their skin via split thickness autografting, is essential. Dermal substitutes in conjunction with widely meshed split thickness autografts (+/- cultured keratinocytes) reduce scarring at the donor and recipient sites of burns patients by reducing demand for autologous skin (both surface area and thickness), without compromising dermal delivery at the wound face. Tissue engineered products such as Integra consist of a dermal template which is rapidly remodelled to form a neodermis, at which time the temporary silicone outer layer is removed and replaced with autologous split thickness skin. Whilst provision of a thick tissue engineered dermis at full thickness burn sites reduces scarring, it is hampered by delays in vascularisation which results in clinical failure. The ultimate success of any skin graft product is dependent upon a number of basic factors including adherence, haemostasis and in the case of viable tissue grafts, success is ultimately dependent upon restoration of a normal blood supply, and hence this study. Ultimately, the goal of this research is to improve the therapeutic properties of tissue replacements, through impregnation with growth factors aimed at stimulating migration and proliferation of microvascular endothelial cells into the donor tissue post grafting. For the purpose of my masters, the aim was to evaluate the responsiveness of a dermal microvascular endothelial cell line to growth factors and haemostatic factors, in the presence of the glycoprotein vitronectin. Vitronectin formed the backbone for my hypothesis and research due to its association with both epithelial and, more specifically, endothelial migration and proliferation. Early work using a platform technology referred to as VitroGro (Tissue Therapies Ltd), which is comprised of vitronectin bound BP5/IGF-1, aided keratinocyte proliferation. I hypothesised that this result would translate to another epithelium - endothelium. VitroGro had no effect on endothelial proliferation or migration. Vitronectin increases the presence of Fibroblast Growth Factor (FGF) and Vascular Endothelial Growth Factor (VEGF) receptors, enhancing cell responsiveness to their respective ligands. So, although Human Microvascular Endothelial Cell line 1 (HMEC-1) VEGF receptor expression is generally low, it was hypothesised that exposure to vitronectin would up-regulate this receptor. HMEC-1 migration, but not proliferation, was enhanced by vitronectin bound VEGF, as well as vitronectin bound Epidermal Growth Factor (EGF), both of which could be used to stimulate microvascular endothelial cell migration for the purpose of transplantation. In addition to vitronectin's synergy with various growth factors, it has also been shown to play a role in haemostasis. Vitronectin binds thrombin-antithrombin III (TAT) to form a trimeric complex that takes on many of the attributes of vitronectin, such as heparin affinity, which results in its adherence to endothelium via heparan sulfate proteoglycans (HSP), followed by unaltered transcytosis through the endothelium, and ultimately its removal from the circulation. This has been documented as a mechanism designed to remove thrombin from the circulation. Equally, it could be argued that it is a mechanism for delivering vitronectin to the matrix. My results show that matrix-bound vitronectin dramatically alters the effect that conformationally altered antithrombin three (cATIII) has on proliferation of microvascular endothelial cells. cATIII stimulates HMEC-1 proliferation in the presence of matrix-bound vitronectin, as opposed to inhibiting proliferation in its absence. Binding vitronectin to tissues and organs prior to transplant, in the presence of cATIII, will have a profound effect on microvascular infiltration of the graft, by preventing occlusion of existing vessels whilst stimulating migration and proliferation of endothelium within the tissue.

Hysteresis modulation of multilevel inverters

The hysteresis modulation for power electronic converters is attractive in many different applications because of its unmatched dynamic response and wide command-tracking bandwidth. Its application and beneftis for two-level converters are well understood, but the extension of this strategy to multilevel converters is still under development. This paper summarizes and reviews the various hysteresis modulation approaches available in the literature for multilevel converters. The pros and cons of various techniques are described and compared for tracking the reference signal in order to attain an adequate switching optimization, excellent dynamic responses and high accuracy in steady-state operation. By using the recently developed multilevel hysteresis modulation approaches the advantages of using several accessible dc potentials in a multilevel inverter has been fully exploited. All of these hysteresis modulation approaches are testing for tracking a current reference when applied to a fivelevel inveter. The relevant simulation and experimental result are also presented. This study will provide a useful framweork and point of reference for the future development of hysteresis modulation for multilevel converters.

Interpreting regional frequencies from synchronized phasor measurement in multi-area power systems

In this paper a new approach is proposed for interpreting of regional frequencies in multi machine power systems. The method uses generator aggregation and system reduction based on coherent generators in each area. The reduced system structure is able to be identified and a kalman estimator is designed for the reduced system to estimate the inter-area modes using the synchronized phasor measurement data. The proposed method is tested on a six machine, three area test system and the obtained results show the estimation of inter-area oscillations in the system with a high accuracy.

Modulation of depth-dependent properties in tissue-engineered cartilage with a semi-permeable membrane and perfusion : a continuum model of matrix metabolism and transport

The functional properties of cartilaginous tissues are determined predominantly by the content, distribution, and organization of proteoglycan and collagen in the extracellular matrix. Extracellular matrix accumulates in tissue-engineered cartilage constructs by metabolism and transport of matrix molecules, processes that are modulated by physical and chemical factors. Constructs incubated under free-swelling conditions with freely permeable or highly permeable membranes exhibit symmetric surface regions of soft tissue. The variation in tissue properties with depth from the surfaces suggests the hypothesis that the transport processes mediated by the boundary conditions govern the distribution of proteoglycan in such constructs. A continuum model (DiMicco and Sah in Transport Porus Med 50:57-73, 2003) was extended to test the effects of membrane permeability and perfusion on proteoglycan accumulation in tissue-engineered cartilage. The concentrations of soluble, bound, and degraded proteoglycan were analyzed as functions of time, space, and non-dimensional parameters for several experimental configurations. The results of the model suggest that the boundary condition at the membrane surface and the rate of perfusion, described by non-dimensional parameters, are important determinants of the pattern of proteoglycan accumulation. With perfusion, the proteoglycan profile is skewed, and decreases or increases in magnitude depending on the level of flow-based stimulation. Utilization of a semi-permeable membrane with or without unidirectional flow may lead to tissues with depth-increasing proteoglycan content, resembling native articular cartilage.

Digital signal processing

Signal Processing (SP) is a subject of central importance in engineering and the applied sciences. Signals are information-bearing functions, and SP deals with the analysis and processing of signals (by dedicated systems) to extract or modify information. Signal processing is necessary because signals normally contain information that is not readily usable or understandable, or which might be disturbed by unwanted sources such as noise. Although many signals are non-electrical, it is common to convert them into electrical signals for processing. Most natural signals (such as acoustic and biomedical signals) are continuous functions of time, with these signals being referred to as analog signals. Prior to the onset of digital computers, Analog Signal Processing (ASP) and analog systems were the only tool to deal with analog signals. Although ASP and analog systems are still widely used, Digital Signal Processing (DSP) and digital systems are attracting more attention, due in large part to the significant advantages of digital systems over the analog counterparts. These advantages include superiority in performance,s peed, reliability, efficiency of storage, size and cost. In addition, DSP can solve problems that cannot be solved using ASP, like the spectral analysis of multicomonent signals, adaptive filtering, and operations at very low frequencies. Following the recent developments in engineering which occurred in the 1980's and 1990's, DSP became one of the world's fastest growing industries. Since that time DSP has not only impacted on traditional areas of electrical engineering, but has had far reaching effects on other domains that deal with information such as economics, meteorology, seismology, bioengineering, oceanology, communications, astronomy, radar engineering, control engineering and various other applications. This book is based on the Lecture Notes of Associate Professor Zahir M. Hussain at RMIT University (Melbourne, 2001-2009), the research of Dr. Amin Z. Sadik (at QUT & RMIT, 2005-2008), and the Note of Professor Peter O'Shea at Queensland University of Technology. Part I of the book addresses the representation of analog and digital signals and systems in the time domain and in the frequency domain. The core topics covered are convolution, transforms (Fourier, Laplace, Z. Discrete-time Fourier, and Discrete Fourier), filters, and random signal analysis. There is also a treatment of some important applications of DSP, including signal detection in noise, radar range estimation, banking and financial applications, and audio effects production. Design and implementation of digital systems (such as integrators, differentiators, resonators and oscillators are also considered, along with the design of conventional digital filters. Part I is suitable for an elementary course in DSP. Part II (which is suitable for an advanced signal processing course), considers selected signal processing systems and techniques. Core topics covered are the Hilbert transformer, binary signal transmission, phase-locked loops, sigma-delta modulation, noise shaping, quantization, adaptive filters, and non-stationary signal analysis. Part III presents some selected advanced DSP topics. We hope that this book will contribute to the advancement of engineering education and that it will serve as a general reference book on digital signal processing.