863 resultados para cross phase modulation


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In this paper we propose a new method for utilising phase information by complementing it with traditional magnitude-only spectral subtraction speech enhancement through Complex Spectrum Subtraction (CSS). The proposed approach has the following advantages over traditional magnitude-only spectral subtraction: (a) it introduces complementary information to the enhancement algorithm; (b) it reduces the total number of algorithmic parameters, and; (c) is designed for improving clean speech magnitude spectra and is therefore suitable for both automatic speech recognition (ASR) and speech perception applications. Oracle-based ASR experiments verify this approach, showing an average of 20% relative word accuracy improvements when accurate estimates of the phase spectrum are available. Based on sinusoidal analysis and assuming stationarity between observations (which is shown to be better approximated as the frame rate is increased), this paper also proposes a novel method for acquiring the phase information called Phase Estimation via Delay Projection (PEDEP). Further oracle ASR experiments validate the potential for the proposed PEDEP technique in ideal conditions. Realistic implementation of CSS with PEDEP shows performance comparable to state of the art spectral subtraction techniques in a range of 15-20 dB signal-to-noise ratio environments. These results clearly demonstrate the potential for using phase spectra in spectral subtractive enhancement applications, and at the same time highlight the need for deriving more accurate phase estimates in a wider range of noise conditions.

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Background: Factors that individually influence blood sugar control, health-related quality of life, and diabetes self-care behaviors have been widely investigated; however, most previous diabetes studies have not tested an integrated association between a series of factors and multiple health outcomes. ---------- Objectives: The purposes of this study are to identify risk factors and protective factors and to examine the impact of risk factors and protective factors on adaptive outcomes in people with type 2 diabetes.---------- Design: A descriptive correlational design was used to examine a theoretical model of risk factors, protective factors, and adaptive outcomes.---------- Settings: This study was conducted at the endocrine outpatient departments of three hospitals in Taiwan. Participants A convenience sample of 334 adults with type 2 diabetes aged 40 and over.---------- Methods: Data were collected by a self-reported questionnaire and physiological examination. Using the structural equation modeling technique, measurement and structural regression models were tested.---------- Results: Age and life events reflected the construct of risk factors. The construct of protective factors was explained by diabetes symptoms, coping strategy, and social support. The construct of adaptive outcomes comprised HbA1c, health-related quality of life, and self-care behaviors. Protective factors had a significant direct effect on adaptive outcomes (β = 0.68, p < 0.001); however, risk factors did not predict adaptive outcomes (β = − 0.48, p = 0.118).---------- Conclusions: Identifying and managing risk factors and protective factors are an integral part of diabetes care. This theoretical model provides a better understanding of how risk factors and protective factors work together to influence multiple adaptive outcomes in people living with type 2 diabetes.

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To date, biodegradable networks and particularly their kinetic chain lengths have been characterized by analysis of their degradation products in solution. We characterize the network itself by NMR analysis in the solvent-swollen state under magic angle spinning conditions. The networks were prepared by photoinitiated cross-linking of poly(dl-lactide)−dimethacrylate macromers (5 kg/mol) in the presence of an unreactive diluent. Using diffusion filtering and 2D correlation spectroscopy techniques, all network components are identified. By quantification of network-bound photoinitiator fragments, an average kinetic chain length of 9 ± 2 methacrylate units is determined. The PDLLA macromer solution was also used with a dye to prepare computer-designed structures by stereolithography. For these networks structures, the average kinetic chain length is 24 ± 4 methacrylate units. In all cases the calculated molecular weights of the polymethacrylate chains after degradation are maximally 8.8 kg/mol, which is far below the threshold for renal clearance. Upon incubation in phosphate buffered saline at 37 °C, the networks show a similar mass loss profile in time as linear high-molecular-weight PDLLA (HMW PDLLA). The mechanical properties are preserved longer for the PDLLA networks than for HMW PDLLA. The initial tensile strength of 47 ± 2 MPa does not decrease significantly for the first 15 weeks, while HMW PDLLA lost 85 ± 5% of its strength within 5 weeks. The physical properties, kinetic chain length, and degradation profile of these photo-cross-linked PDLLA networks make them most suited materials for orthopedic applications and use in (bone) tissue engineering.

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Osteoarthritis (OA) is the most common musculoskeletal disorder and represents a major health burden to society. In the course of the pathological development of OA, articular cartilage chondrocytes (ACCs) undergo atypical phenotype changes characterized by the expression of hypertrophic differentiation markers. Also, the adjacent subchondral bone shows signs of abnormal mineral density and enhanced production of bone turnover markers, indicative of osteoblast dysfunction. Collectively these findings indicate that the pathological changes typical of OA, involve alterations of the phenotypic properties of cells in both the subchondral bone and articular cartilage. However, the mechanism(s) by which these changes occur during OA development are not completely understood. The purpose of this project was to address the question of how subchondral bone osteoblasts (SBOs) and ACCs interact with each other with respect to regulation of respective cells’ phenotypic properties and in particular the involvement of mitogen activated protein kinase (MAPK) signalling pathways under normal and OA joint condition. We also endeavoured to test the influence of cross-talk between SBOs and ACCs isolated from normal and OA joint on matrix metalloproteinase (MMP) expression. For this purpose tissues from the knees of OA patients and normal controls were collected to isolate SBOs and ACCs. The cellular cross-talk of SBOs and ACCs were studied by means of both direct and indirect co-culture systems, which made it possible to identify the role of both membrane bound and soluble factors. Histology, immunohistochemistry, qRT-PCR, zymography, ELISA and western blotting were some of the techniques applied to distinguish the changes in the co-cultured vs. non co-cultured cells. The MAPK signalling pathways were probed by using targeted MAPK inhibitors, and their activity monitored by western blot analysis using phospho MAPK specific antibodies. Our co-culture studies demonstrated that OA ACCs enhanced the SBOs differentiation compared to normal ACCs. We demonstrated that OA ACCs induced these phenotypic changes in the SBOs via activating an ERK1/2 signalling pathway. The findings from this study thus provided clear evidence that OA ACCs play an integral role in altering the SBO phenotype. In the second study, we tested the influence of normal SBOs and OA SBOs on ACCs phenotype changes. The results showed that OA SBOs increased the hypertrophic gene expression in co-cultured ACCs compared to normal SBOs, a phenotype which is considered as pathological to the health and integrity of articular cartilage. It was demonstrated that these phenotype changes occurred via de-activation of p38 and activation of ERK1/2 signaling pathways. These findings suggest that the pathological interaction of OA SBOs with ACCs is mediated by cross-talking between ERK1/2 and p38 pathways, resulting in ACCs undergoing hypertrophic differentiation. Subsequent experiments to determine the effect on MMP regulation, of SBOs and ACCs cross-talk, revealed that co-culturing OA SBOs with ACCs significantly enhanced the proteolytic activity and expression of MMP-2 and MMP-9. In turn, co-culture of OA ACCs with SBOs led to abundant MMP-2 expression in SBOs. Furthermore, we showed that the addition of ERK1/2 and JNK inhibitors reversed the elevated MMP-2 and MMP-9 production which otherwise resulted from the interactions of OA SBOs-ACCs. Thus, this study has demonstrated that the altered interactions between OA SBOs-ACCs are capable of triggering the pathological pathways leading to degenerative changes seen in the osteoarthritic joint. In conclusion, the body of work presented in this dissertation has given clear in vitro evidence that the altered bi-directional communication of SBOs and ACCs may play a role in OA development and that this process was mediated by MAPK signalling pathways. Targeting these altered interactions by the use of MAPK inhibitors may provide the scientific rationale for the development of novel therapeutic strategies in the treatment and management of OA.

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A Flat Bed Rail Wagon (FBRW) has been proposed as an alternative solution for replacing bridges on low traffic volume roads. The subject matter for this paper is to investigate the impediment to load transfer from cross girders to main girder, through visually identifiable structural flaws. Namely, the effect of having large openings at close proximity to the connection of the main girder to the cross girder of a FBRW was examined. It was clear that openings locally reduce the section modulus of the secondary members; however it was unclear how these reductions would affect the load transfer to the main girder. The results are presented through modeling grillage action for which the loads applied onto the FBRW were distributed through cross girders to the main girder.

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AC motors are largely used in a wide range of modern systems, from household appliances to automated industry applications such as: ventilations systems, fans, pumps, conveyors and machine tool drives. Inverters are widely used in industrial and commercial applications due to the growing need for speed control in ASD systems. Fast switching transients and the common mode voltage, in interaction with parasitic capacitive couplings, may cause many unwanted problems in the ASD applications. These include shaft voltage and leakage currents. One of the inherent characteristics of Pulse Width Modulation (PWM) techniques is the generation of the common mode voltage, which is defined as the voltage between the electrical neutral of the inverter output and the ground. Shaft voltage can cause bearing currents when it exceeds the amount of breakdown voltage level of the thin lubricant film between the inner and outer rings of the bearing. This phenomenon is the main reason for early bearing failures. A rapid development in power switches technology has lead to a drastic decrement of switching rise and fall times. Because there is considerable capacitance between the stator windings and the frame, there can be a significant capacitive current (ground current escaping to earth through stray capacitors inside a motor) if the common mode voltage has high frequency components. This current leads to noises and Electromagnetic Interferences (EMI) issues in motor drive systems. These problems have been dealt with using a variety of methods which have been reported in the literature. However, cost and maintenance issues have prevented these methods from being widely accepted. Extra cost or rating of the inverter switches is usually the price to pay for such approaches. Thus, the determination of cost-effective techniques for shaft and common mode voltage reduction in ASD systems, with the focus on the first step of the design process, is the targeted scope of this thesis. An introduction to this research – including a description of the research problem, the literature review and an account of the research progress linking the research papers – is presented in Chapter 1. Electrical power generation from renewable energy sources, such as wind energy systems, has become a crucial issue because of environmental problems and a predicted future shortage of traditional energy sources. Thus, Chapter 2 focuses on the shaft voltage analysis of stator-fed induction generators (IG) and Doubly Fed Induction Generators DFIGs in wind turbine applications. This shaft voltage analysis includes: topologies, high frequency modelling, calculation and mitigation techniques. A back-to-back AC-DC-AC converter is investigated in terms of shaft voltage generation in a DFIG. Different topologies of LC filter placement are analysed in an effort to eliminate the shaft voltage. Different capacitive couplings exist in the motor/generator structure and any change in design parameters affects the capacitive couplings. Thus, an appropriate design for AC motors should lead to the smallest possible shaft voltage. Calculation of the shaft voltage based on different capacitive couplings, and an investigation of the effects of different design parameters are discussed in Chapter 3. This is achieved through 2-D and 3-D finite element simulation and experimental analysis. End-winding parameters of the motor are also effective factors in the calculation of the shaft voltage and have not been taken into account in previous reported studies. Calculation of the end-winding capacitances is rather complex because of the diversity of end winding shapes and the complexity of their geometry. A comprehensive analysis of these capacitances has been carried out with 3-D finite element simulations and experimental studies to determine their effective design parameters. These are documented in Chapter 4. Results of this analysis show that, by choosing appropriate design parameters, it is possible to decrease the shaft voltage and resultant bearing current in the primary stage of generator/motor design without using any additional active and passive filter-based techniques. The common mode voltage is defined by a switching pattern and, by using the appropriate pattern; the common mode voltage level can be controlled. Therefore, any PWM pattern which eliminates or minimizes the common mode voltage will be an effective shaft voltage reduction technique. Thus, common mode voltage reduction of a three-phase AC motor supplied with a single-phase diode rectifier is the focus of Chapter 5. The proposed strategy is mainly based on proper utilization of the zero vectors. Multilevel inverters are also used in ASD systems which have more voltage levels and switching states, and can provide more possibilities to reduce common mode voltage. A description of common mode voltage of multilevel inverters is investigated in Chapter 6. Chapter 7 investigates the elimination techniques of the shaft voltage in a DFIG based on the methods presented in the literature by the use of simulation results. However, it could be shown that every solution to reduce the shaft voltage in DFIG systems has its own characteristics, and these have to be taken into account in determining the most effective strategy. Calculation of the capacitive coupling and electric fields between the outer and inner races and the balls at different motor speeds in symmetrical and asymmetrical shaft and balls positions is discussed in Chapter 8. The analysis is carried out using finite element simulations to determine the conditions which will increase the probability of high rates of bearing failure due to current discharges through the balls and races.

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Impedance cardiography is an application of bioimpedance analysis primarily used in a research setting to determine cardiac output. It is a non invasive technique that measures the change in the impedance of the thorax which is attributed to the ejection of a volume of blood from the heart. The cardiac output is calculated from the measured impedance using the parallel conductor theory and a constant value for the resistivity of blood. However, the resistivity of blood has been shown to be velocity dependent due to changes in the orientation of red blood cells induced by changing shear forces during flow. The overall goal of this thesis was to study the effect that flow deviations have on the electrical impedance of blood, both experimentally and theoretically, and to apply the results to a clinical setting. The resistivity of stationary blood is isotropic as the red blood cells are randomly orientated due to Brownian motion. In the case of blood flowing through rigid tubes, the resistivity is anisotropic due to the biconcave discoidal shape and orientation of the cells. The generation of shear forces across the width of the tube during flow causes the cells to align with the minimal cross sectional area facing the direction of flow. This is in order to minimise the shear stress experienced by the cells. This in turn results in a larger cross sectional area of plasma and a reduction in the resistivity of the blood as the flow increases. Understanding the contribution of this effect on the thoracic impedance change is a vital step in achieving clinical acceptance of impedance cardiography. Published literature investigates the resistivity variations for constant blood flow. In this case, the shear forces are constant and the impedance remains constant during flow at a magnitude which is less than that for stationary blood. The research presented in this thesis, however, investigates the variations in resistivity of blood during pulsataile flow through rigid tubes and the relationship between impedance, velocity and acceleration. Using rigid tubes isolates the impedance change to variations associated with changes in cell orientation only. The implications of red blood cell orientation changes for clinical impedance cardiography were also explored. This was achieved through measurement and analysis of the experimental impedance of pulsatile blood flowing through rigid tubes in a mock circulatory system. A novel theoretical model including cell orientation dynamics was developed for the impedance of pulsatile blood through rigid tubes. The impedance of flowing blood was theoretically calculated using analytical methods for flow through straight tubes and the numerical Lattice Boltzmann method for flow through complex geometries such as aortic valve stenosis. The result of the analytical theoretical model was compared to the experimental impedance measurements through rigid tubes. The impedance calculated for flow through a stenosis using the Lattice Boltzmann method provides results for comparison with impedance cardiography measurements collected as part of a pilot clinical trial to assess the suitability of using bioimpedance techniques to assess the presence of aortic stenosis. The experimental and theoretical impedance of blood was shown to inversely follow the blood velocity during pulsatile flow with a correlation of -0.72 and -0.74 respectively. The results for both the experimental and theoretical investigations demonstrate that the acceleration of the blood is an important factor in determining the impedance, in addition to the velocity. During acceleration, the relationship between impedance and velocity is linear (r2 = 0.98, experimental and r2 = 0.94, theoretical). The relationship between the impedance and velocity during the deceleration phase is characterised by a time decay constant, ô , ranging from 10 to 50 s. The high level of agreement between the experimental and theoretically modelled impedance demonstrates the accuracy of the model developed here. An increase in the haematocrit of the blood resulted in an increase in the magnitude of the impedance change due to changes in the orientation of red blood cells. The time decay constant was shown to decrease linearly with the haematocrit for both experimental and theoretical results, although the slope of this decrease was larger in the experimental case. The radius of the tube influences the experimental and theoretical impedance given the same velocity of flow. However, when the velocity was divided by the radius of the tube (labelled the reduced average velocity) the impedance response was the same for two experimental tubes with equivalent reduced average velocity but with different radii. The temperature of the blood was also shown to affect the impedance with the impedance decreasing as the temperature increased. These results are the first published for the impedance of pulsatile blood. The experimental impedance change measured orthogonal to the direction of flow is in the opposite direction to that measured in the direction of flow. These results indicate that the impedance of blood flowing through rigid cylindrical tubes is axisymmetric along the radius. This has not previously been verified experimentally. Time frequency analysis of the experimental results demonstrated that the measured impedance contains the same frequency components occuring at the same time point in the cycle as the velocity signal contains. This suggests that the impedance contains many of the fluctuations of the velocity signal. Application of a theoretical steady flow model to pulsatile flow presented here has verified that the steady flow model is not adequate in calculating the impedance of pulsatile blood flow. The success of the new theoretical model over the steady flow model demonstrates that the velocity profile is important in determining the impedance of pulsatile blood. The clinical application of the impedance of blood flow through a stenosis was theoretically modelled using the Lattice Boltzman method (LBM) for fluid flow through complex geometeries. The impedance of blood exiting a narrow orifice was calculated for varying degrees of stenosis. Clincial impedance cardiography measurements were also recorded for both aortic valvular stenosis patients (n = 4) and control subjects (n = 4) with structurally normal hearts. This pilot trial was used to corroborate the results of the LBM. Results from both investigations showed that the decay time constant for impedance has potential in the assessment of aortic valve stenosis. In the theoretically modelled case (LBM results), the decay time constant increased with an increase in the degree of stenosis. The clinical results also showed a statistically significant difference in time decay constant between control and test subjects (P = 0.03). The time decay constant calculated for test subjects (ô = 180 - 250 s) is consistently larger than that determined for control subjects (ô = 50 - 130 s). This difference is thought to be due to difference in the orientation response of the cells as blood flows through the stenosis. Such a non-invasive technique using the time decay constant for screening of aortic stenosis provides additional information to that currently given by impedance cardiography techniques and improves the value of the device to practitioners. However, the results still need to be verified in a larger study. While impedance cardiography has not been widely adopted clinically, it is research such as this that will enable future acceptance of the method.

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Objective Uterine Papillary Serous Carcinoma (UPSC) is uncommon and accounts for less than 5% of all uterine cancers. Therefore the majority of evidence about the benefits of adjuvant treatment comes from retrospective case series. We conducted a prospective multi-centre non-randomized phase 2 clinical trial using four cycles of adjuvant paclitaxel plus carboplatin chemotherapy followed by pelvic radiotherapy, in order to evaluate the tolerability and safety of this approach. Methods This trial enrolled patients with newly diagnosed, previously untreated patients with stage 1b-4 (FIGO-1988) UPSC with a papillary serous component of at least 30%. Paclitaxel (175 mg/m2) and carboplatin (AUC 6) were administered on day 1 of each 3-week cycle for 4 cycles. Chemotherapy was followed by external beam radiotherapy to the whole pelvis (50.4 Gy over 5.5 weeks). Completion and toxicity of treatment (Common Toxicity Criteria, CTC) and quality of life measures were the primary outcome indicators. Results Twenty-nine of 31 patients completed treatment as planned. Dose reduction was needed in 9 patients (29%), treatment delay in 7 (23%), and treatment cessation in 2 patients (6.5%). Hematologic toxicity, grade 3 or 4 occurred in 19% (6/31) of patients. Patients' self-reported quality of life remained stable throughout treatment. Thirteen of the 29 patients with stages 1–3 disease (44.8%) recurred (average follow up 28.1 months, range 8–60 months). Conclusion This multimodal treatment is feasible, safe and tolerated reasonably well and would be suitable for use in multi-institutional prospective randomized clinical trials incorporating novel therapies in patients with UPSC.

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Raman spectrum of burgessite, Co2(H2O)4[AsO3OH]2.H2O was studied, interpreted and compared with its infrared spectrum. The stretching and bending vibrations of (AsO3) and As-OH units together with the stretching, bending and libration modes of water molecules and hydroxyl ions were assigned. The range of O-H...O hydrogen bond lengths was inferred from the Raman and infrared spectra of burgessite. The presence of (AsO3OH)2- units in the crystal structure of burgessite was proved in agreement with its recently solved crystal structure. Raman and infrared spectra of erythrite inferred from the RRUFF database are used for comparison.

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For several reasons, the Fourier phase domain is less favored than the magnitude domain in signal processing and modeling of speech. To correctly analyze the phase, several factors must be considered and compensated, including the effect of the step size, windowing function and other processing parameters. Building on a review of these factors, this paper investigates a spectral representation based on the Instantaneous Frequency Deviation, but in which the step size between processing frames is used in calculating phase changes, rather than the traditional single sample interval. Reflecting these longer intervals, the term delta-phase spectrum is used to distinguish this from instantaneous derivatives. Experiments show that mel-frequency cepstral coefficients features derived from the delta-phase spectrum (termed Mel-Frequency delta-phase features) can produce broadly similar performance to equivalent magnitude domain features for both voice activity detection and speaker recognition tasks. Further, it is shown that the fusion of the magnitude and phase representations yields performance benefits over either in isolation.

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Stereo vision is a method of depth perception, in which depth information is inferred from two (or more) images of a scene, taken from different perspectives. Applications of stereo vision include aerial photogrammetry, autonomous vehicle guidance, robotics, industrial automation and stereomicroscopy. A key issue in stereo vision is that of image matching, or identifying corresponding points in a stereo pair. The difference in the positions of corresponding points in image coordinates is termed the parallax or disparity. When the orientation of the two cameras is known, corresponding points may be projected back to find the location of the original object point in world coordinates. Matching techniques are typically categorised according to the nature of the matching primitives they use and the matching strategy they employ. This report provides a detailed taxonomy of image matching techniques, including area based, transform based, feature based, phase based, hybrid, relaxation based, dynamic programming and object space methods. A number of area based matching metrics as well as the rank and census transforms were implemented, in order to investigate their suitability for a real-time stereo sensor for mining automation applications. The requirements of this sensor were speed, robustness, and the ability to produce a dense depth map. The Sum of Absolute Differences matching metric was the least computationally expensive; however, this metric was the most sensitive to radiometric distortion. Metrics such as the Zero Mean Sum of Absolute Differences and Normalised Cross Correlation were the most robust to this type of distortion but introduced additional computational complexity. The rank and census transforms were found to be robust to radiometric distortion, in addition to having low computational complexity. They are therefore prime candidates for a matching algorithm for a stereo sensor for real-time mining applications. A number of issues came to light during this investigation which may merit further work. These include devising a means to evaluate and compare disparity results of different matching algorithms, and finding a method of assigning a level of confidence to a match. Another issue of interest is the possibility of statistically combining the results of different matching algorithms, in order to improve robustness.

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A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever (YF) vaccine (YF-17D strain; Stamaril(®), Sanofi Pasteur) or administered successively. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE virus strains was determined using a 50% serum-dilution plaque reduction neutralization test. Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82-100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart.

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Common mode voltage generated by a power converter in combination with parasitic capacitive couplings is a potential source of shaft voltage in an AC motor drive system. In this paper, a three-phase motor drive system supplied with a single-phase AC-DC diode rectifier is investigated in order to reduce shaft voltage in a three-phase AC motor drive system. In this topology, the common mode voltage generated by the inverter is influenced by the AC-DC diode rectifier because the placement of the neutral point is changing in different rectifier circuit states. A pulse width modulation technique is presented by a proper placement of the zero vectors to reduce the common mode voltage level, which leads to a cost effective shaft voltage reduction technique without load current distortion, while keeping the switching frequency constant. Analysis and simulations have been presented to investigate the proposed method.

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The success rate of carrier phase ambiguity resolution (AR) is the probability that the ambiguities are successfully fixed to their correct integer values. In existing works, an exact success rate formula for integer bootstrapping estimator has been used as a sharp lower bound for the integer least squares (ILS) success rate. Rigorous computation of success rate for the more general ILS solutions has been considered difficult, because of complexity of the ILS ambiguity pull-in region and computational load of the integration of the multivariate probability density function. Contributions of this work are twofold. First, the pull-in region mathematically expressed as the vertices of a polyhedron is represented by a multi-dimensional grid, at which the cumulative probability can be integrated with the multivariate normal cumulative density function (mvncdf) available in Matlab. The bivariate case is studied where the pull-region is usually defined as a hexagon and the probability is easily obtained using mvncdf at all the grid points within the convex polygon. Second, the paper compares the computed integer rounding and integer bootstrapping success rates, lower and upper bounds of the ILS success rates to the actual ILS AR success rates obtained from a 24 h GPS data set for a 21 km baseline. The results demonstrate that the upper bound probability of the ILS AR probability given in the existing literatures agrees with the actual ILS success rate well, although the success rate computed with integer bootstrapping method is a quite sharp approximation to the actual ILS success rate. The results also show that variations or uncertainty of the unit–weight variance estimates from epoch to epoch will affect the computed success rates from different methods significantly, thus deserving more attentions in order to obtain useful success probability predictions.

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Intrinsically photosensitive retinal ganglion cells (ipRGC) signal environmental light level to the central circadian clock and contribute to the pupil light reflex. It is unknown if ipRGC activity is subject to extrinsic (central) or intrinsic (retinal) network-mediated circadian modulation during light entrainment and phase shifting. Eleven younger persons (18–30 years) with no ophthalmological, medical or sleep disorders participated. The activity of the inner (ipRGC) and outer retina (cone photoreceptors) was assessed hourly using the pupil light reflex during a 24 h period of constant environmental illumination (10 lux). Exogenous circadian cues of activity, sleep, posture, caffeine, ambient temperature, caloric intake and ambient illumination were controlled. Dim-light melatonin onset (DLMO) was determined from salivary melatonin assay at hourly intervals, and participant melatonin onset values were set to 14 h to adjust clock time to circadian time. Here we demonstrate in humans that the ipRGC controlled post-illumination pupil response has a circadian rhythm independent of external light cues. This circadian variation precedes melatonin onset and the minimum ipRGC driven pupil response occurs post melatonin onset. Outer retinal photoreceptor contributions to the inner retinal ipRGC driven post-illumination pupil response also show circadian variation whereas direct outer retinal cone inputs to the pupil light reflex do not, indicating that intrinsically photosensitive (melanopsin) retinal ganglion cells mediate this circadian variation.