FGFR2 point mutations in 466 Endometrioid Endometrial Tumors : relationship with MSI, KRAS, PIK3CA, CTNNB1 mutations and Clinicopathological features

Mutations in multiple oncogenes including KRAS, CTNNB1, PIK3CA and FGFR2 have been identified in endometrial cancer. The aim of this study was to provide insight into the clinicopathological features associated with patterns of mutation in these genes, a necessary step in planning targeted therapies for endometrial cancer. 466 endometrioid endometrial tumors were tested for mutations in FGFR2, KRAS, CTNNB1, and PIK3CA. The relationships between mutation status, tumor microsatellite instability (MSI) and clinicopathological features including overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier survival analysis and Cox proportional hazard models. Mutations were identified in FGFR2 (48/466); KRAS (87/464); CTNNB1 (88/454) and PIK3CA (104/464). KRAS and FGFR2 mutations were significantly more common, and CTNNB1 mutations less common, in MSI positive tumors. KRAS and FGFR2 occurred in a near mutually exclusive pattern (p = 0.05) and, surprisingly, mutations in KRAS and CTNNB1 also occurred in a near mutually exclusive pattern (p = 0.0002). Multivariate analysis revealed that mutation in KRAS and FGFR2 showed a trend (p = 0.06) towards longer and shorter DFS, respectively. In the 386 patients with early stage disease (stage I and II), FGFR2 mutation was significantly associated with shorter DFS (HR = 3.24; 95% confidence interval, CI, 1.35-7.77; p = 0.008) and OS (HR = 2.00; 95% CI 1.09-3.65; p = 0.025) and KRAS was associated with longer DFS (HR = 0.23; 95% CI 0.05-0.97; p = 0.045). In conclusion, although KRAS and FGFR2 mutations share similar activation of the MAPK pathway, our data suggest very different roles in tumor biology. This has implications for the implementation of anti-FGFR or anti-MEK biologic therapies.

Effects of enhanced somatosensory information on postural stability in older people and people with Parkinson’s disease

The somatosensory system plays an important role in balance control and age-related changes to this system have been implicated in falls. Parkinson’s disease (PD) is a chronic and progressive disease of the brain, characterized by postural instability and gait disturbance. Previous research has shown that deficiencies in somatosensory feedback may contribute to the poorer postural control demonstrated by PD individuals. However, few studies have comprehensively explored differences in somatosensory function and postural control between PD participants and healthy older individuals. The soles of the feet contain many cutaneous mechanoreceptors that provide important somatosensory information sources for postural control. Different types of insole devices have been developed to enhance this somatosensory information and improve postural stability, but these devices are often too complex and expensive to integrate into daily life. Textured insoles provide a more passive intervention that may be an inexpensive and accessible means to enhance the somatosensory input from the plantar surface of the feet. However, to date, there has been little work conducted to test the efficacy of enhanced somatosensory input induced by textured insoles in both healthy and PD populations during standing and walking. Therefore, the aims of this thesis were to determine: 1) whether textured insole surfaces can improve postural stability by enhancing somatosensory information in younger and older adults, 2) the differences between healthy older participants and PD participants for measures of physiological function and postural stability during standing and walking, 3) how changes in somatosensory information affect postural stability in both groups during standing and walking; and 4), whether textured insoles can improve postural stability in both groups during standing and walking. To address these aims, Study 1 recruited seven older individuals and ten healthy young controls to investigate the effects of two textured insole surfaces on postural stability while performing standing balance tests on a force plate. Participants were tested under three insole surface conditions: 1) barefoot; 2) standing on a hard textured insole surface; and 3), standing on a soft textured insole surface. Measurements derived from the centre of pressure displacement included the range of anterior-posterior and medial-lateral displacement, path length and the 90% confidence elliptical area (C90 area). Results of study 1 revealed a significant Group*Surface*Insole interaction for the four measures. Both textured insole surfaces reduced postural sway for the older group, especially in the eyes closed condition on the foam surface. However, participants reported that the soft textured insole surface was more comfortable and, hence, the soft textured insoles were adopted for Studies 2 and 3. For Study 2, 20 healthy older adults (controls) and 20 participants with Parkinson’s disease were recruited. Participants were evaluated using a series of physiological assessments that included touch sensitivity, vibratory perception, and pain and temperature threshold detection. Furthermore, nerve function and somatosensory evoked potentials tests were utilized to provide detailed information regarding peripheral nerve function for these participants. Standing balance and walking were assessed on different surfaces using a force plate and the 3D Vicon motion analysis system, respectively. Data derived from the force plate included the range of anterior-posterior and medial-lateral sway, while measures of stride length, stride period, cadence, double support time, stance phase, velocity and stride timing variability were reported for the walking assessment. The results of this study demonstrated that the PD group had decrements in somatosensory function compared to the healthy older control group. For electrodiagnosis, PD participants had poorer nerve function than controls, as evidenced by slower nerve conduction velocities and longer latencies in sural nerve and prolonged latency in the P37 somatosensory evoked potential. Furthermore, the PD group displayed more postural sway in both the anterior-posterior and medial-lateral directions relative to controls and these differences were increased when standing on a foam surface. With respect to the gait assessment, the PD group took shorter strides and had a reduced stride period compared with the control group. Furthermore, the PD group spent more time in the stance phase and had increased cadence and stride timing variability than the controls. Compared with walking on the firm surface, the two groups demonstrated different gait adaptations while walking on the uneven surface. Controls increased their stride length and stride period and decreased their cadence, which resulted in a consistent walking velocity on both surfaces. Conversely, while the PD patients also increased their stride period and decreased their cadence and stance period on the uneven surface, they did not increase their stride length and, hence walked slower on the uneven surface. In the PD group, there was a strong positive association between decreased somatosensory function and decreased clinical balance, as assessed by the Tinetti test. Poorer somatosensory function was also strongly positively correlated with the temporospatial gait parameters, especially shorter stride length. Study 3 evaluated the effects of manipulating the somatosensory information from the plantar surface of the feet using textured insoles in the same populations assessed in Study 2. For this study, participants performed the standing and walking balance tests under three footwear conditions: 1) barefoot; 2) with smooth insoles; and 3), with textured insoles. Standing balance and walking were evaluated using a force plate and a Vicon motion analysis system and the data were analysed in the same way outlined for Study 2. The findings showed that the smooth and textured insoles caused different effects on postural control during both the standing and walking trials. Both insoles decreased medial-lateral sway to the same level on the firm surface. The greatest benefits were observed in the PD group while wearing the textured insole. When standing under a more challenging condition on the foam surface with eyes closed, only the textured insole decreased medial-lateral sway in the PD group. With respect to the gait trials, both insoles increased walking velocity, stride length and stride time and decreased cadence, but these changes were more pronounced for the textured insoles. The effects of the textured insoles were evident under challenging conditions in the PD group and increased walking velocity and stride length, while decreasing cadence. Textured insoles were also effective in reducing the time spent in the double support and stance phases of the gait cycle and did not increase stride timing variability, as was the case for the smooth insoles for the PD group. The results of this study suggest that textured insoles, such as those evaluated in this research, may provide a low-cost means of improving postural stability in high-risk groups, such as people with PD, which may act as an important intervention to prevent falls.

Impact of region-of-interest video coding on perceived quality in mobile video

Effective streaming of video can be achieved by providing more bits to the most important region in the frame at the cost of reduced bits in the less important regions. This strategy can be beneficial for delivering high quality videos in mobile devices, especially when the availability of bandwidth is usually low and limited. While the state-of-the-art video codecs such as H.264 may have been optimised for perceived quality, it is hypothesised that users will give more attention to interesting region/object when watching videos. Therefore, giving a higher quality to region of interest (ROI)while reducing quality of other areas may result in improving the overall perceived quality without necessarily increasing the bitrate. In this paper, the impact of ROI-based encoded video on perceived quality is investigated by conducting a user study for varous target bitrates. The results from the user study demonstrate that ROI-based video coding has superior perceived quality compared to normal encoded video at the same bitrate in the lower bitrate range.

Assessing of circuit breaker restrike risks using computer simulation and wavelet analysis

A breaker restrike is an abnormal arcing phenomenon, leading to a possible breaker failure. Eventually, this failure leads to interruption of the transmission and distribution of the electricity supply system until the breaker is replaced. Before 2008, there was little evidence in the literature of monitoring techniques based on restrike measurement and interpretation produced during switching of capacitor banks and shunt reactor banks in power systems. In 2008 a non-intrusive radiometric restrike measurement method and a restrike hardware detection algorithm were developed by M.S. Ramli and B. Kasztenny. However, the limitations of the radiometric measurement method are a band limited frequency response as well as limitations in amplitude determination. Current restrike detection methods and algorithms require the use of wide bandwidth current transformers and high voltage dividers. A restrike switch model using Alternative Transient Program (ATP) and Wavelet Transforms which support diagnostics are proposed. Restrike phenomena become a new diagnostic process using measurements, ATP and Wavelet Transforms for online interrupter monitoring. This research project investigates the restrike switch model Parameter „A. dielectric voltage gradient related to a normal and slowed case of the contact opening velocity and the escalation voltages, which can be used as a diagnostic tool for a vacuum circuit-breaker (CB) at service voltages between 11 kV and 63 kV. During current interruption of an inductive load at current quenching or chopping, a transient voltage is developed across the contact gap. The dielectric strength of the gap should rise to a point to withstand this transient voltage. If it does not, the gap will flash over, resulting in a restrike. A straight line is fitted through the voltage points at flashover of the contact gap. This is the point at which the gap voltage has reached a value that exceeds the dielectric strength of the gap. This research shows that a change in opening contact velocity of the vacuum CB produces a corresponding change in the slope of the gap escalation voltage envelope. To investigate the diagnostic process, an ATP restrike switch model was modified with contact opening velocity computation for restrike waveform signature analyses along with experimental investigations. This also enhanced a mathematical CB model with the empirical dielectric model for SF6 (sulphur hexa-fluoride) CBs at service voltages above 63 kV and a generalised dielectric curve model for 12 kV CBs. A CB restrike can be predicted if there is a similar type of restrike waveform signatures for measured and simulated waveforms. The restrike switch model applications are used for: computer simulations as virtual experiments, including predicting breaker restrikes; estimating the interrupter remaining life of SF6 puffer CBs; checking system stresses; assessing point-on-wave (POW) operations; and for a restrike detection algorithm development using Wavelet Transforms. A simulated high frequency nozzle current magnitude was applied to an Equation (derived from the literature) which can calculate the life extension of the interrupter of a SF6 high voltage CB. The restrike waveform signatures for a medium and high voltage CB identify its possible failure mechanism such as delayed opening, degraded dielectric strength and improper contact travel. The simulated and measured restrike waveform signatures are analysed using Matlab software for automatic detection. Experimental investigation of a 12 kV vacuum CB diagnostic was carried out for the parameter determination and a passive antenna calibration was also successfully developed with applications for field implementation. The degradation features were also evaluated with a predictive interpretation technique from the experiments, and the subsequent simulation indicates that the drop in voltage related to the slow opening velocity mechanism measurement to give a degree of contact degradation. A predictive interpretation technique is a computer modeling for assessing switching device performance, which allows one to vary a single parameter at a time; this is often difficult to do experimentally because of the variable contact opening velocity. The significance of this thesis outcome is that it is a non-intrusive method developed using measurements, ATP and Wavelet Transforms to predict and interpret a breaker restrike risk. The measurements on high voltage circuit-breakers can identify degradation that can interrupt the distribution and transmission of an electricity supply system. It is hoped that the techniques for the monitoring of restrike phenomena developed by this research will form part of a diagnostic process that will be valuable for detecting breaker stresses relating to the interrupter lifetime. Suggestions for future research, including a field implementation proposal to validate the restrike switch model for ATP system studies and the hot dielectric strength curve model for SF6 CBs, are given in Appendix A.

Context-aware multicast protocol for emergency message dissemination in vehicular networks

Road traffic accidents can be reduced by providing early warning to drivers through wireless ad hoc networks. When a vehicle detects an event that may lead to an imminent accident, the vehicle disseminates emergency messages to alert other vehicles that may be endangered by the accident. In many existing broadcast-based dissemination schemes, emergency messages may be sent to a large number of vehicles in the area and can be propagated to only one direction. This paper presents a more efficient context aware multicast protocol that disseminates messages only to endangered vehicles that may be affected by the emergency event. The endangered vehicles can be identified by calculating the interaction among vehicles based on their motion properties. To ensure fast delivery, the dissemination follows a routing path obtained by computing a minimum delay tree. The multicast protocol uses a generalized approach that can support any arbitrary road topology. The performance of the multicast protocol is compared with existing broadcast protocols by simulating chain collision accidents on a typical highway. Simulation results show that the multicast protocol outperforms the other protocols in terms of reliability, efficiency, and latency.

Context-aware rate-adaptive beaconing for efficient and scalable vehicular safety communication

Vehicular safety applications, such as cooperative collision warning systems, rely on beaconing to provide situational awareness that is needed to predict and therefore to avoid possible collisions. Beaconing is the continual exchange of vehicle motion-state information, such as position, speed, and heading, which enables each vehicle to track its neighboring vehicles in real time. This work presents a context-aware adaptive beaconing scheme that dynamically adapts the beaconing repetition rate based on an estimated channel load and the danger severity of the interactions among vehicles. The safety, efficiency, and scalability of the new scheme is evaluated by simulating vehicle collisions caused by inattentive drivers under various road traffic densities. Simulation results show that the new scheme is more efficient and scalable, and is able to improve safety better than the existing non-adaptive and adaptive rate schemes.

Orthogonality defect and reduced search-space size for solving integer least-squares problems

In the context of ambiguity resolution (AR) of Global Navigation Satellite Systems (GNSS), decorrelation among entries of an ambiguity vector, integer ambiguity search and ambiguity validations are three standard procedures for solving integer least-squares problems. This paper contributes to AR issues from three aspects. Firstly, the orthogonality defect is introduced as a new measure of the performance of ambiguity decorrelation methods, and compared with the decorrelation number and with the condition number which are currently used as the judging criterion to measure the correlation of ambiguity variance-covariance matrix. Numerically, the orthogonality defect demonstrates slightly better performance as a measure of the correlation between decorrelation impact and computational efficiency than the condition number measure. Secondly, the paper examines the relationship of the decorrelation number, the condition number, the orthogonality defect and the size of the ambiguity search space with the ambiguity search candidates and search nodes. The size of the ambiguity search space can be properly estimated if the ambiguity matrix is decorrelated well, which is shown to be a significant parameter in the ambiguity search progress. Thirdly, a new ambiguity resolution scheme is proposed to improve ambiguity search efficiency through the control of the size of the ambiguity search space. The new AR scheme combines the LAMBDA search and validation procedures together, which results in a much smaller size of the search space and higher computational efficiency while retaining the same AR validation outcomes. In fact, the new scheme can deal with the case there are only one candidate, while the existing search methods require at least two candidates. If there are more than one candidate, the new scheme turns to the usual ratio-test procedure. Experimental results indicate that this combined method can indeed improve ambiguity search efficiency for both the single constellation and dual constellations respectively, showing the potential for processing high dimension integer parameters in multi-GNSS environment.

Reliability of partial ambiguity fixing with multiple GNSS constellations

Reliable ambiguity resolution (AR) is essential to Real-Time Kinematic (RTK) positioning and its applications, since incorrect ambiguity fixing can lead to largely biased positioning solutions. A partial ambiguity fixing technique is developed to improve the reliability of AR, involving partial ambiguity decorrelation (PAD) and partial ambiguity resolution (PAR). Decorrelation transformation could substantially amplify the biases in the phase measurements. The purpose of PAD is to find the optimum trade-off between decorrelation and worst-case bias amplification. The concept of PAR refers to the case where only a subset of the ambiguities can be fixed correctly to their integers in the integer least-squares (ILS) estimation system at high success rates. As a result, RTK solutions can be derived from these integer-fixed phase measurements. This is meaningful provided that the number of reliably resolved phase measurements is sufficiently large for least-square estimation of RTK solutions as well. Considering the GPS constellation alone, partially fixed measurements are often insufficient for positioning. The AR reliability is usually characterised by the AR success rate. In this contribution an AR validation decision matrix is firstly introduced to understand the impact of success rate. Moreover the AR risk probability is included into a more complete evaluation of the AR reliability. We use 16 ambiguity variance-covariance matrices with different levels of success rate to analyse the relation between success rate and AR risk probability. Next, the paper examines during the PAD process, how a bias in one measurement is propagated and amplified onto many others, leading to more than one wrong integer and to affect the success probability. Furthermore, the paper proposes a partial ambiguity fixing procedure with a predefined success rate criterion and ratio-test in the ambiguity validation process. In this paper, the Galileo constellation data is tested with simulated observations. Numerical results from our experiment clearly demonstrate that only when the computed success rate is very high, the AR validation can provide decisions about the correctness of AR which are close to real world, with both low AR risk and false alarm probabilities. The results also indicate that the PAR procedure can automatically chose adequate number of ambiguities to fix at given high-success rate from the multiple constellations instead of fixing all the ambiguities. This is a benefit that multiple GNSS constellations can offer.

Hybrid light-emitting diodes based on ZnO nanowires

ZnO is a wide band-gap semiconductor that has several desirable properties for optoelectronic devices. With its large exciton binding energy of ~60 meV, ZnO is a promising candidate for high stability, room-temperature luminescent and lasing devices [1]. Ultraviolet light-emitting diodes (LEDs) based on ZnO homojunctions had been reported [2,3], while preparing stable p-type ZnO is still a challenge. An alternative way is to use other p-type semiconductors, ether inorganic or organic, to form heterojunctions with the naturally n-type ZnO. The crystal structure of wurtzite ZnO can be described as Zn and O atomic layers alternately stacked along the [0001] direction. Because of the fastest growth rate over the polar (0001) facet, ZnO crystals tend to grow into one-dimensional structures, such as nanowires and nanobelts. Since the first report of ZnO nanobelts in 2001 [4], ZnO nanostructures have been particularly studied for their potential applications in nano-sized devices. Various growth methods have been developed for growing ZnO nanostructures, such as chemical vapor deposition (CVD), Metal-organic CVD (MOCVD), aqueous growth and electrodeposition [5]. Based on the successful synthesis of ZnO nanowires/nanorods, various types of hybrid light-emitting diodes (LEDs) were made. Inorganic p-type semiconductors, such as GaN, Si and SiC, have been used as substrates to grown ZnO nanorods/nanowires for making LEDs. GaN is an ideal material that matches ZnO not only in the crystal structure but also in the energy band levels. However, to prepare Mg-doped p-GaN films via epitaxial growth is still costly. In comparison, the organic semiconductors are inexpensive and have many options to select, for a large variety of p-type polymer or small-molecule semiconductors are now commercially available. The organic semiconductor has the limitation of durability and environmental stability. Many polymer semiconductors are susceptible to damage by humidity or mere exposure to oxygen in the air. Also the carrier mobilities of polymer semiconductors are generally lower than the inorganic semiconductors. However, the combination of polymer semiconductors and ZnO nanostructures opens the way for making flexible LEDs. There are few reports on the hybrid LEDs based on ZnO/polymer heterojunctions, some of them showed the characteristic UV electroluminescence (EL) of ZnO. This chapter reports recent progress of the hybrid LEDs based on ZnO nanowires and other inorganic/organic semiconductors. We provide an overview of the ZnO-nanowire-based hybrid LEDs from the perspectives of the device configuration, growth methods of ZnO nanowires and the selection of p-type semiconductors. Also the device performances and remaining issues are presented.

Analytical model for fault section estimation and state identification of unobserved protective relays in power systems [电力系统故障诊断与不可观测保护状态识别的解析模型]

In recent years, some models have been proposed for the fault section estimation and state identification of unobserved protective relays (FSE-SIUPR) under the condition of incomplete state information of protective relays. In these models, the temporal alarm information from a faulted power system is not well explored although it is very helpful in compensating the incomplete state information of protective relays, quickly achieving definite fault diagnosis results and evaluating the operating status of protective relays and circuit breakers in complicated fault scenarios. In order to solve this problem, an integrated optimization mathematical model for the FSE-SIUPR, which takes full advantage of the temporal characteristics of alarm messages, is developed in the framework of the well-established temporal constraint network. With this model, the fault evolution procedure can be explained and some states of unobserved protective relays identified. The model is then solved by means of the Tabu search (TS) and finally verified by test results of fault scenarios in a practical power system.

Regression and hypothesis tests for multivariate GNSS state time series

A satellite based observation system can continuously or repeatedly generate a user state vector time series that may contain useful information. One typical example is the collection of International GNSS Services (IGS) station daily and weekly combined solutions. Another example is the epoch-by-epoch kinematic position time series of a receiver derived by a GPS real time kinematic (RTK) technique. Although some multivariate analysis techniques have been adopted to assess the noise characteristics of multivariate state time series, statistic testings are limited to univariate time series. After review of frequently used hypotheses test statistics in univariate analysis of GNSS state time series, the paper presents a number of T-squared multivariate analysis statistics for use in the analysis of multivariate GNSS state time series. These T-squared test statistics have taken the correlation between coordinate components into account, which is neglected in univariate analysis. Numerical analysis was conducted with the multi-year time series of an IGS station to schematically demonstrate the results from the multivariate hypothesis testing in comparison with the univariate hypothesis testing results. The results have demonstrated that, in general, the testing for multivariate mean shifts and outliers tends to reject less data samples than the testing for univariate mean shifts and outliers under the same confidence level. It is noted that neither univariate nor multivariate data analysis methods are intended to replace physical analysis. Instead, these should be treated as complementary statistical methods for a prior or posteriori investigations. Physical analysis is necessary subsequently to refine and interpret the results.

Comparison of two suspension control strategies for multi-axle heavy truck

Two simple and effective control strategies for a multi-axle heavy truck, modified skyhook damping (MSD) control and proportional-integration-derivative (PID) control, were implemented into functional virtual prototype (FVP) model and compared in terms of road friendliness and ride comfort. A four-axle heavy truck-road coupling system model was established using FVP technology and validated through a ride comfort test. Then appropriate passive air suspensions were chosen to replace the rear tandem suspensions of the original truck model for preliminary optimization. The mechanical properties and time lag of dampers were taken into account in simulations of MSD and PID semi-active dampers implemented using MATLAB/Simulink. Through co-simulations with Adams and MATLAB, the effects of semi-active MSD and PID control were analyzed and compared, and control parameters which afforded the best comprehensive performance for each control strategy were chosen. Simulation results indicate that compared with the passive air suspension truck, semi-active MSD control improves both ride comfort and road-friendliness markedly, with optimization ratios of RMS vertical acceleration and RMS tyre force ranging from 10.1% to 44.8%. However, semi-active PID control only reduces vertical vibration of the driver’s seat by 11.1%, 11.1% and 10.9% on A, B and C level roads respectively. Both strategies are robust to the variation of road level.

Ammonia emissions from a representative in-use fleet of vehicles in Guangzhou

Emission rates of ammonia (NH3) are reported for a fleet of 130 light-, medium-, and heavy-duty vehicles recruited in Guangzhou, China. NH3 measurements were performed using Nessler's Reagents spectrophotometry and nationwide standard chassis dynamometer test cycles required by Chinese EPA. Emissions of CO and NOx were also measured during these test cycles. Emission factors of NH3 were calculated for each type of vehicle and used to estimate the total emissions of NH3 from motor vehicles in Guangzhou (GZ) in 2009. Emission factors of NH3 show large variations among different categories of vehicles, with a range from 4 to 138 mg km-1. The average emissions of NH3 in Guangzhou in 2009 were estimated to be 983 t, with a range from 373 to 2136 t. In addition, it was found that vehicles with the highest NH3 emission rates possess the following characteristics: mediumand heavy-duty vehicles, certified with out-of-date emission standards, mid-range odometer readings, and higher CO and NOx emission rates. The results of this study will be useful for developing NH3 emissions inventories in Guangzhou and other urban areas in China.