Abstract-A comparative performance study of seven pitch detection algorithms was conducted. A speech data base, consisting of eight utterances spoken by three males, three females, and one child was constructed. Telephone, close talking microphone, and wideband recordings were made of each of the utterances. For each of the utterances in the data base; a "standard" pitch contour was semiautomatically measured using a highly sophisticated interactive pitch detection program. The "standard" pitch contour was then compared with the pitch contour that was obtained from each of the seven programmed pitch detectors. The algorithms used in this study were 1) a center clipping, infinite-peak clipping, modified autocorrelation method (AUTOC), 2) the cepstral method (CEP), 3) the simplified inverse filtering technique (SIFT) method, 4) the parallel processing time-domain method (PPROC), 5) the data reduction method (DARD), 6) a spectral flattening linear predictive coding (LPC) method, and 7) the average magnitude difference function (AMDF) method. A set of measurements was made on the pitch contours to quantify the various types of errors which occur in each of the above methods. Included among the error measurements were the average and standard deviation of the error in pitch period during voiced regions, the number of gross errors in the pitch period, and the average number of voiced-unvoiced classification errors. For each of the error measurements, the individual pitch detectors could be rank ordered as a measure of their relative performance as a function of recording condition, and pitch range of the various speakers. Performance scores are presented for each of the seven pitch detectors based on each of the categories of error.

BackgroundElevated plasma homocysteine (Hcy) levels have been indicated as a strong and modifiable risk factor of ischemic stroke; the previous studies have shown that exposure to Hcy activates cultured microglia. However, whether neurotoxicity of Hcy involves microglia activation following brain ischemia and the underlying mechanisms remains incompletely understood.MethodsThe cerebral damage was evaluated by staining with 2,3,5-triphenyltetrazolium chloride, hematoxylin-eosin, and Fluoro Jade B. The activation state of microglia was assessed via immunoreaction using the microglial markers Iba1 and OX-42. Then, the inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) were examined by Western blot analysis and fluorescence immunohistochemistry.ResultsElevated Hcy level augmented brain damage and neural cell toxicity in the brain cortex and the dentate gyrus region of the hippocampus after cerebral ischemia/reperfusion. Meanwhile, Hcy activated microglia and induced the expression of the inflammatory factors such as TNF-α and IL-6. Moreover, Hcy caused an increase in pSTAT3 expression which occurs in microglial cells. AG490, a JAK2-STAT3 inhibitor, effectively inhibited the phosphorylation of STAT3, microglial cell activation and the secretion of IL-6, TNF-α raised by Hcy treatment.ConclusionsSTAT3 signaling pathway located in microglia plays a critical role in mediating Hcy-induced activation of microglia and neuroinflammation in rat MCAO model. This suggests the feasibility of targeting the JAK2/STAT3 pathway as an effective therapeutic strategy to alleviate the progression of Hcy-associated ischemia stroke.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-0963-x) contains supplementary material, which is available to authorized users.

The role of plasmacytoid dendritic cells (pDC) in human immunodeficiency virus type 1 (HIV-1) infection and pathogenesis remains unclear. HIV-1 infection in the humanized mouse model leads to persistent HIV-1 infection and immunopathogenesis, including type I interferons (IFN-I) induction, immune-activation and depletion of human leukocytes, including CD4 T cells. We developed a monoclonal antibody that specifically depletes human pDC in all lymphoid organs in humanized mice. When pDC were depleted prior to HIV-1 infection, the induction of IFN-I and interferon-stimulated genes (ISGs) were abolished during acute HIV-1 infection with either a highly pathogenic CCR5/CXCR4-dual tropic HIV-1 or a standard CCR5-tropic HIV-1 isolate. Consistent with the anti-viral role of IFN-I, HIV-1 replication was significantly up-regulated in pDC-depleted mice. Interestingly, the cell death induced by the highly pathogenic HIV-1 isolate was severely reduced in pDC-depleted mice. During chronic HIV-1 infection, depletion of pDC also severely reduced the induction of IFN-I and ISGs, associated with elevated HIV-1 replication. Surprisingly, HIV-1 induced depletion of human immune cells including T cells in lymphoid organs, but not the blood, was reduced in spite of the increased viral replication. The increased cell number in lymphoid organs was associated with a reduced level of HIV-induced cell death in human leukocytes including CD4 T cells. We conclude that pDC play opposing roles in suppressing HIV-1 replication and in promoting HIV-1 induced immunopathogenesis. These findings suggest that pDC-depletion and IFN-I blockade will provide novel strategies for treating those HIV-1 immune non-responsive patients with persistent immune activation despite effective anti-retrovirus treatment.

The elevated level of the amino acid metabolite homocysteine (Hcy) is known as a risk factor for ischemic stroke. The molecular mechanisms responsible for neurotoxicity of Hcy remain largely unknown in ischemic brains. The previous studies have shown that Hcy decreases the proliferation and viability of neural stem cells (NSCs) in vivo and in vitro. Autophagy is required for the maintenance of NSCs homeostasis. In the current study, we hypothesized that the toxic effect of Hcy on NSCs may involve the changes in autophagy level following cerebral ischemia/reperfusion injury. The results showed that Hcy reduced cell viability, increased LDH release, and induced nonapoptotic cell death in primary NSCs exposed to oxygen–glucose deprivation)/reoxygenation (OGD/R). Treatment with autophagy inhibitor 3-methyladenine (3MA) partly reversed the decrease in the viability and prevented LDH release triggered by Hcy combined with OGD/R. Increased punctate LC3 dots co-localizing with Nestin-stained NSCs were also observed in the subventricular zone of Hcy-treated MCAO animals, which were partially blocked by 3MA. In vitro studies further revealed that Hcy induced the formation of autophagosomes, markedly increased the expression of the autophagic markers and decreased p-ERK, p-PI3K, p-AKT, and p-mTOR levels. In addition, MHY1485, an activator of mTOR, reduced Hcy-induced increase in LC3 and Beclin 1 protein levels, meanwhile ERK and PI3K activators (TPA, curcumin for ERK and IGF-1 for PI3K, respectively) enhanced Hcy-triggered mTOR inhibition in OGD/R NSCs. Our findings suggest that Hcy may cause excessive autophagy by downregulation of both PI3K-AKT- and ERK- dependent mTOR signaling, thereby facilitates the toxicity of Hcy on NSCs in ischemic brains.

Accurate assessment of spatial and temporal precipitation is crucial for simulating hydrological processes in basins, but is challenging due to insufficient rain gauges. Our study aims to analyze different precipitation interpolation schemes and their performances in runoff simulation during light and heavy rain periods. In particular, combinations of different interpolation estimates are explored and their performances in runoff simulation are discussed. The study was carried out in the Pengxi River basin of the Three Gorges Basin. Precipitation data from 16 rain gauges were interpolated using the Thiessen Polygon (TP), Inverse Distance Weighted (IDW), and Co-Kriging (CK) methods. Results showed that streamflow predictions employing CK inputs demonstrated the best performance in the whole process, in terms of the Nash-Sutcliffe Coefficient (NSE), the coefficient of determination (R 2 ), and the Root Mean Square Error (RMSE) indices. The TP, IDW, and CK methods showed good performance in the heavy rain period but poor performance in the light rain period compared with the default method (least sophisticated nearest neighbor technique) in Soil and Water Assessment Tool (SWAT). Furthermore, the correlation between the dynamic weight of one method and its performance during runoff simulation followed a parabolic function. The combination of CK and TP achieved a better performance in decreasing the largest and lowest absolute errors compared to any single method, but the IDW method outperformed all methods in terms of the median absolute error. However, it is clear from our findings that interpolation methods should be chosen depending on the amount of precipitation, adaptability of the method, and accuracy of the estimate in different rain periods.

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