Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer characterized by Epstein-Barr virus (EBV) infection and dense lymphocyte infiltration. The scarcity of NPC genomic data hinders the understanding of NPC biology, disease progression and rational therapy design. Here we performed whole-exome sequencing (WES) on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome sequencing (WGS), to determine its mutational landscape. We identified enrichment for genomic aberrations of multiple negative regulators of the NF-kB pathway, including CYLD, TRAF3, NFKBIA and NLRC5, in a total of 41% of cases. Functional analysis confirmed inactivating CYLD mutations as drivers for NPC cell growth. The EBV oncoprotein latent membrane protein 1 (LMP1) functions to constitutively activate NF-kB signalling, and we observed mutual exclusivity among tumours with somatic NF-kB pathway aberrations and LMP1-overexpression, suggesting that NF-kB activation is selected for by both somatic and viral events during NPC pathogenesis.
Many bioelectric signals result from the electrical response of physiological systems to an impulse that can be internal (ECG signals) or external (evoked potentials). In this paper an adaptive impulse correlated filter (AICF) for event-related signals that are time-locked to a stimulus is presented. This filter estimates the deterministic component of the signal and removes the noise uncorrelated with the stimulus, even if this noise is colored, as in the case of evoked potentials. The filter needs two inputs: the signal (primary input) and an impulse correlated with the deterministic component (reference input). We use the LMS algorithm to adjust the weights in the adaptive process. First, we show that the AICF is equivalent to exponentially weighted averaging (EWA) when using the LMS algorithm. A quantitative analysis of the signal-to-noise ratio improvement, convergence, and misadjustment error is presented. A comparison of the AICF with ensemble averaging (EA) and moving window averaging (MWA) techniques is also presented. The adaptive filter is applied to real high-resolution ECG signals and time-varying somatosensory evoked potentials.
We conclude that in peritoneal dialysis patients, the AA genotype of VEGF promoter at -2578 position was associated with progressive increase in peritoneal transport. The CA/AA genotype at -2578 position was also associated with an excess mortality. Our finding also suggests that systemic and local peritoneal VEGF production may be differentially regulated.
A method of detecting brainstem auditory evoked potential (BAEP) using adaptive signal enhancement (ASE) is proposed and tested in humans and cats. The ASE in this system estimates the signal component of the primary input, which is correlated with the reference input to the adaptive filter. The reference input is carefully designed to make an optimal and rapid estimation of the signal corrupted with noise, such as ongoing EEG. With a good choice of reference input, it is possible to track the variability of BAEP efficiently and rapidly. Moreover, the number of repetitions required could be markedly reduced and the result of the system is superior to that of ensemble averaging (EA). To detect BAEP in cats, only 30 ensemble averages are needed to obtain a reasonable reference input to the adaptive filter, and, for humans, 350-750 ensemble averages are sufficient for a satisfactory result. Using the LMS adaptive algorithm, individual BAEP can be obtained in real-time.
The introduction of air bubbles into the systemic circulation can result in significant morbidity. Real-time monitoring of continuous heart sound in patients detected by precordial Doppler ultrasound is, thus, vital for early detection of venous air embolism (VAE) during surgery. In this study, the multiscale feature of wavelet transforms (WT's) is exploited to examine the embolic Doppler heart sound (DHS) during intravenous air injections in dogs. As both humans and dogs share similar physiological conditions, our methods and results for dogs are expected to be applicable to humans. The WT of DHS at scale 2j (j = 1, 2) selectively magnified the power of embolic, but not the normal, heart sound. Statistically, the enhanced embolic power was found to be sensitive (P < 0.01 at 0.01 ml of injected air) and correlated significantly (P < 0.0005, r = 0.83) with the volume of injected air from 0.01 to 0.10 ml. A fast detection algorithm of O(N) complexity with unit complexity constant for VAE was developed (processing speed = 8 ms per heartbeat), which confirmed the feasibility of real-time processing for both humans and dogs.
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