A Rare Case of Falsely Elevated High-Sensitivity Cardiac Troponin T due to Antibody Interference and a Literature Review.

BACKGROUND: This study aimed to demonstrate potential measures to discern interference and establish an algorithm for identifying interference in an hs-cTnT assay with a clinical discrepancy. METHODS: Laboratory error and disease factors were first excluded. Then, a serial dilution test, polyethylene glycol (PEG) precipitation, and heterophile antibody blocking reagents (HBRs) were performed to confirm the interference substance. In addition, high-speed centrifugation and western blot were tried. RESULTS: The sample diluted linearly (R2 = 0.9966). However, there was a dramatic reduction in the concentration of hs-cTnT concentration to a normal level after both PEG precipitation and HBR1 treatment. The results were inconclusive in high-speed centrifugation and western blot assay. CONCLUSIONS: This study elucidated a heterophile antibody interference in measurement of hs-cTnT alone on a Roche analyzer.

Research Progress on Phytopathogenic Fungi and Their Role as Biocontrol Agents.

Phytopathogenic fungi decrease crop yield and quality and cause huge losses in agricultural production. To prevent the occurrence of crop diseases and insect pests, farmers have to use many synthetic chemical pesticides. The extensive use of these pesticides has resulted in a series of environmental and ecological problems, such as the increase in resistant weed populations, soil compaction, and water pollution, which seriously affect the sustainable development of agriculture. This review discusses the main advances in research on plant-pathogenic fungi in terms of their pathogenic factors such as cell wall-degrading enzymes, toxins, growth regulators, effector proteins, and fungal viruses, as well as their application as biocontrol agents for plant pests, diseases, and weeds. Finally, further studies on plant-pathogenic fungal resources with better biocontrol effects can help find new beneficial microbial resources that can control diseases.

[Molecular mechanism of Puerariae Lobatae Radix in treatment of hepatocellular carcinoma based on network pharmacology].

To investigate the potential mechanism of Puerariae Lobatae Radix in the treatment of hepatocellular carcinoma by network pharmacology and in vitro cell experiment. The main active components of Puerariae Lobatae Radix and their predicted targets were obtained from TCMSP, and the disease targets were obtained from GeneCards database. The disease and drug prediction targets were intersected to select the common potential therapeutic targets. The "compound-target-disease" network diagram was constructed in Cytoscape 3.7.1, and the common targets were input into the STRING database to build the PPI network of proteins interaction. GO function and KEGG pathway enrichment analysis on effective targets were performed by using R software. Autodock vina 1.1.2 was used for molecular docking. Finally, the core targets and pathways were preliminarily verified by in vitro experiments. The proliferation of human hepatocellular carcinoma cells was detected by CCK-8 and EDU enzyme staining, and the expressions of PTEN, PDK1, Akt and GSK3 were detected by Western blot. In this study, 10 components of Puerariae Lobatae Radix(9 components involved in hepatocellular carcinoma-related targets and signaling pathways), and 149 hepatocellular carcinoma-related targets and 156 signaling pathways were screened out. The results of network analysis indicated that Puerariae Lobatae Radix may play an anti-hepatocellular carcinoma effect on key targets, such as Akt, IL6, MAPK3, EGFR, and key pathways, such as PI3 K-Akt. The results of molecular docking indicated that puerarin, genistein and daidzein had a good binding ability with the key targets such as AKT1, MAPK3, MAPK1 and CASP3, and puerarin had the lowest Vina score with AKT1 and MAPK3 and also similar to them. In vitro cell experiments confirmed that puerarin has a significantly inhibitory effect on the proliferation of human hepatocellular carcinoma cells. Western blot results showed that puerarin could increase the phosphorylation of PTEN in human hepatocellular carcinoma cells through the PTEN/Akt/GSK3ß signaling pathway, and the phosphorylation level of its downstream Akt decreased. This series of studies confirm that puerarin can treat hepatocellular carcinoma by blocking PTEN/Akt/GSK3ß cellular signaling pathway, so as to provide ideas for subsequent studies for the molecular mechanism of puerarin in the treatment of liver cancer.

Structure-Based Macrocyclization of Substrate Analogue NS2B-NS3 Protease Inhibitors of Zika, West Nile and Dengue viruses.

A series of cyclic active-site-directed inhibitors of the NS2B-NS3 proteases from Zika (ZIKV), West Nile (WNV), and dengue-4 (DENV4) viruses has been designed. The most potent compounds contain a reversely incorporated d-lysine residue in the P1 position. Its side chain is connected to the P2 backbone, its α-amino group is converted into a guanidine to interact with the conserved Asp129 side chain in the S1 pocket, and its C terminus is connected to the P3 residue via different linker segments. The most potent compounds inhibit the ZIKV protease with Ki values <5 nM. Crystal structures of seven ZIKV protease inhibitor complexes were determined to support the inhibitor design. All the cyclic compounds possess high selectivity against trypsin-like serine proteases and furin-like proprotein convertases. Both WNV and DENV4 proteases are inhibited less efficiently. Nonetheless, similar structure-activity relationships were observed for these enzymes, thus suggesting their potential application as pan-flaviviral protease inhibitors.

Enhanced breast cancer progression by mutant p53 is inhibited by the circular RNA circ-Ccnb1.

TP53 mutations occur in many different types of cancers that produce mutant p53 proteins. The mutant p53 proteins have lost wild-type p53 activity and gained new functions that contribute to malignant tumor progression. Different p53 mutations create distinct profiles in loss of wild-type p53 activity and gain of functions. Targeting the consequences generated by the great number of p53 mutations would be extremely complex. Therefore, in this study we used a workaround and took advantage of the fact that mutant p53 cannot bind H2AX. Using this, we developed a new approach to repress the acquisition of mutant p53 functions. We show here that the delivery of a circular RNA circ-Ccnb1 inhibited the function of three p53 mutations. By microarray analysis and real-time PCR, we detected decreased circ-Ccnb1 expression levels in patients bearing breast carcinoma. Ectopic delivery of circ-Ccnb1 inhibited tumor growth and extended mouse viability. Using proteomics, we found that circ-Ccnb1 precipitated p53 in p53 wild-type cells, but instead precipitated Bclaf1 in p53 mutant cells. Further experiments showed that H2AX serves as a bridge, linking the interaction of circ-Ccnb1 and wild-type p53, thus allowing Bclaf1 to bind Bcl2 resulting in cell survival. In the p53 mutant cells, circ-Ccnb1 formed a complex with H2AX and Bclaf1, resulting in the induction of cell death. We found that this occurred in three p53 mutations. These results shed light on the possible development of new approaches to inhibit the malignancy of p53 mutations.

Laser absorption spectroscopy data processing method based on co-frequency and dual-wavelength and its application.

In the detection process of atmospheric laser absorption spectroscopy in open space, the transmitted beam is inevitably affected by atmospheric turbulence, resulting in superimposed fluctuation noise in the received optical signal. First, the correction method of atmospheric turbulence is theoretically analyzed. In order to reduce the error influence factors and the error transfer coefficient, a new method of spectral data processing based on co-frequency and dual-wave has been proposed. By modifying scintillation noise and background noise, the influence of atmospheric turbulence noise in open space is reduced. An atmospheric detection system in open space based on co-frequency and dual-wave has been established. The experimental results show that the maximum fluctuation of the spectral signal processed by the method of spectrum data processing based on the co-frequency and dual-wave is reduced from 12.854% to 4.635%, and the single-intensity absorbance is fitted by Voigt with its correlation coefficient of 0.9525. The mean of the standard deviation of the algorithm is 0.1370, while the mean value of the standard deviation of the existing algorithm in a short time is 0.6928. And, through the comparative experiment, the standard deviation of the existing data processing techniques of two-wavelength differential absorption is 0.2974, while the standard deviation of the method of spectrum data processing based on the co-frequency and dual-wave is 0.1038. It can be concluded that the co-frequency and dual-wave method can effectively reduce the influence of atmospheric turbulence noise and laser flashing to improve the stability of concentration measurement, which has practical engineering value.

A hemoglobin-based oxygen carrier sensitized Cisplatin based chemotherapy in hepatocellular carcinoma.

Background and Objective: Our previous study showed that liver graft injury not only promotes tumor recurrence, but also induces chemoresistance in recurrent HCC after liver transplantation. Recently, we found that the hemoglobin-based oxygen carrier"YQ23" significantly ameliorates hepatic IR injury and prevent tumor recurrence. Here, we intended to explore the novel therapeutic strategy using oxygen carrier "YQ23"to sensitize chemotherapy in HCC. Methods: To investigate the role of YQ23 combined with Cisplatin, the proliferation of HCC cells was examined under combined treatment by MTT and colony formation. To explore the effect of YQ23 on sensitization of Cisplatin based chemotherapy, the orthotopic liver cancer model was established. To characterize the delivery of YQ23 in tumor tissue, the intravital imaging system was applied for longitudinal observation in ectopic liver cancer model. The distribution of YQ23 was examined by IVIS spectrum. Results: YQ23 significantly suppressed the proliferation of HCC cells under Cisplatin treatment in a dose and time dependent manner. Moreover, YQ23 administration significantly sensitized Cisplatin based chemotherapy in orthotopic liver cancer model. Down-regulation of DHFR may be one of the reasons for YQ23 sensitizing Cisplatin based chemotherapy. Real-time intravital imaging showed that YQ23 accumulated in the tumor tissue and maintained as long as 3 days in ectopic liver cancer model. The IVIS spectrum examination showed that YQ23 distributed mainly at liver and bladder within the first 36 hours after administration in orthotopic liver cancer model. Conclusion: YQ23 treatment may be a potential therapeutic strategy to sensitize chemotherapy in HCC.

Beneficial effects of novel cross-linked hemoglobin YQ23 on hemorrhagic shock in rats and pigs.

BACKGROUND: To overcome the problems of previously reported hemoglobin-based oxygen carriers, we developed a stabilized nonpolymeric cross-linked tetrameric hemoglobin solution (YQ23). The aims of this study were to investigate the oxygen carrying and releasing properties of this novel hemoglobin-based oxygen carrier and to determine whether it has beneficial effects for hemorrhagic shock. METHODS: Using a hemorrhagic shock model in Sprague-Dawley rats and mini-pigs, we tested the effects of infusing 0.1, 0.3, and 0.5 g/kg YQ23 on animal survival, tissue oxygen delivery (DO2) and consumption (VO2), hemodynamics parameters, and liver, renal, and cardiac function. RESULTS: YQ23 infusion increased the survival rate of rats and pigs with severe hemorrhagic shock in a dose-dependent manner. Moreover, it improved the hemodynamic parameters, cardiac output, DO2 and VO2, and the mitochondrial respiratory function of vital organs. Among the three doses of YQ23, 0.5 gHb/kg YQ23 achieved a similar beneficial effect as whole blood. CONCLUSIONS: This study indicated that the novel cross-linked tetrameric hemoglobin YQ23 has good oxygen carrying and releasing properties and exhibits beneficial effects on hemorrhagic shock in rats and pigs by improving the oxygen carrying and delivery function of blood, which maintains organ function.

[Establishment of response system to emergency parasitic disease affairs in China].

China's prevention and control of parasitic diseases has made remarkable achievements. However, the prevalence and transmission of parasitic diseases is impacted by the complicated natural and social factors of environment, natural disasters, population movements, and so on. Therefore, there are still the risks of the outbreak of emergency parasitic diseases affairs, which may affect the control effectiveness of parasitic diseases and endanger the social stability seriously. In this article, we aim at the analysis of typical cases of emergency parasitic disease affairs and their impacts on public health security in China in recently years, and we also elaborate the disposal characteristics of emergency parasitic disease affairs, and propose the establishment of response system to emergency parasitic disease affairs in China, including the organizational structure and response flow path, and in addition, point out that, in the future, we should strengthen the system construction and measures of the response system to emergency parasitic disease affairs, so as to control the risk and harm of parasitic disease spread as much as possible and to realize the early intervention and proper disposal of emergency parasitic disease affairs.

[Effect of comprehensive schistosomiasis control strategy with focus on cattle and sheep removal in Junshan District, Yueyang City].

Objective To evaluate the effect of comprehensive schistosomiasis control measures with focus on total removal of cattle and sheep in Junshan District, Yueyang City. Methods The retrospective review and field survey were implemented in the pilot villages in Junshan District. The data of Schistosoma japonicum infection status of human, cattle, sheep and Oncomelania hupensis snails, and density of snails were gathered and modeled in the period of 2006 to 2016. Results The prevalence of schistosome infection in residents in the pilot villages decreased from 3.44% in 2006 to 0.59% in 2012 (F = 14.501, P = 0.013). After removal of all the cattle and sheep in 2013, the prevalence of schistosome infection in the residents decreased to zero in 2016 (F = 14.148, P = 0.033). The density of living snails decreased from 0.883 3/0.1 m2 in 2006 to 0.308 8/0.1 m2 in 2012 (F = 76.250, P = 0.005). Conclusion The comprehensive schistosomiasis control strategy with focus on cattle and sheep removal is remarkably effective.

Regional Values of Diffusional Kurtosis Estimates in the Healthy Brain during Normal Aging.

OBJECTIVE: To provide estimates of the diffusional kurtosis in different anatomical regions of a healthy brain and to assess age dependency of diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) derived parametric values in these regions. MATERIALS AND METHODS: Eighty healthy volunteers underwent DKI of the brain with 3.0 T magnetic resonance imaging. The DKI was obtained by using three b values of 0, 1000, 2000 s/mm2, and with 50 diffusion directions. The regions of interest-based measurements were calculated to obtain several DKI estimates of 21 different locations of brain, and then, the age dependency for DKI- and DTI-derived parameters in these regions were assessed by using linear and nonlinear regressions. RESULTS: The mean kurtosis varied from 0.73 ± 0.01 (head of caudate nucleus) to 1.07 ± 0.08 (splenium of corpus callosum (CC)). The radial kurtosis varied from 0.84 ± 0.06 (head of caudate nucleus) to 1.05 ± 0.07 (splenium of CC), and axial kurtosis from 0.41 ± 0.02 (genu of CC) to 0.78 ± 0.02 (pallidum). DTI-derived parametric values also varied across the region. Age dependence was found for DKI-derived parameters in almost all measured regions except for corona radiata and centrum semiovale. On the contrary, DTI failed to show age dependency in many regions including gray matter structure. CONCLUSION: In conclusion, the knowledge of range of diffusion kurtosis parameters in each anatomical region in different age group is important before its clinical application to diagnose the pathology.

Oxygen carrier YQ23 can enhance the chemotherapeutic drug responses of chemoresistant esophageal tumor xenografts.

PURPOSE: Adjunct chemoradiation is offered to unresectable esophageal squamous cell carcinoma (ESCC) patients, while its use is limited in tumors with strong resistance. Oxygen carriers or anti-hypoxic drugs belong to an emerging class of regulators that can alleviate tumor hypoxia. METHODS: We investigate the potential use of a novel oxygen carrier YQ23 in sensitizing chemoresistant ESCC in a series of subcutaneous tumor xenograft models developed using ESCC cell lines with different strengths of chemosensitivities. RESULTS: Tumor xenografts were developed using SLMT-1 and HKESC-2 ESCC cell lines with different strengths of resistance to two chemotherapeutic drugs, 5-fluorouracil and cisplatin. More resistant SLMT-1 xenografts responded better to YQ23 treatment than HKESC-2, as reflected by the induced tumor oxygen level. YQ23 sensitized SLMT-1 xenografts toward 5-fluorouracil via its effect on reducing the level of a hypoxic marker HIF-1α. Furthermore, a derangement of tumor microvessel density and integrity was demonstrated with a concurrent decrease in the level of a tumor mesenchymal marker vimentin. Similar to the 5-fluorouracil sensitizing effect, YQ23 also enhanced the response of SLMT-1 xenografts toward cisplatin by reducing the tumor size and the number of animals with invasive tumors. Chemosensitive HKESC-2 xenografts were irresponsive to combined YQ23 and cisplatin treatment. CONCLUSIONS: In all, YQ23 functions selectively on chemoresistant ESCC xenografts, which implicates its potential use as a chemosensitizing agent for ESCC patients.

A novel oxygen carrier "YQ23" suppresses the liver tumor metastasis by decreasing circulating endothelial progenitor cells and regulatory T cells.

BACKGROUND: Surgical therapies are the first-line treatments for hepatocellular carcinoma (HCC) patients. However, the high incidence of tumor metastasis after liver surgery remains a severe problem. We aim to investigate the roles and the underlying mechanism of YQ23, stabilized non-polymeric diaspirin cross-linked tetrameric hemoglobin, in liver tumor metastasis after major hepatectomy and partial hepatic ischemia reperfusion (I/R) injury. METHODS: An orthotopic liver tumor model in Buffalo rat was established using the hepatocellular carcinoma cell line McA-RH7777. Major hepatectomy for tumor-bearing lobe and partial hepatic I/R injury were performed at two weeks after orthotopic liver tumor implantation. YQ23 (0.2 g/kg) was administered at 1 hour before ischemia and immediately after reperfusion. Blood samples were collected at day 0, 1, 7, 14, 21 and 28 for detection of circulating endothelial progenitor cells (EPCs) and regulatory T cells (Tregs). RESULTS: Our results showed that YQ23 treatment effectively inhibited intrahepatic and lung metastases together with less tumor angiogenesis at 4 weeks after major hepatectomy and partial hepatic I/R injury. The levels of circulating EPCs and Tregs were significantly decreased in YQ23 treatment group. Furthermore, YQ23 treatment also increased liver tissue oxygenation during hepatic I/R injury. Up-regulation of HO1 and down-regulation of CXCR3, TNF-α and IL6 were detected after YQ23 treatment. CONCLUSIONS: YQ23 treatment suppressed liver tumor metastasis after major hepatectomy and partial hepatic I/R injury in a rat liver tumor model through increasing liver oxygen and reducing the populations of circulating EPCs and Tregs.

The role of versican in modulating breast cancer cell self-renewal.

Versican is highly expressed during the early stages of tissue development and its expression is elevated during wound repair and tumor growth. There is little literature on the potential role of breast cancer stem cells on the cellular-extracellular matrix interactions involving versican. An anti-versican short hairpin RNA (shRNA) was used to observe the effect of reduction of versican on breast cancer self-renewal. A versican G3 construct was exogenously expressed in breast cancer cell lines. Colony formation and mammosphere formation assays were conducted; flow cytometry was applied to analyze the prevalence of side population cells. The versican G3- and vector-transfected 66c14 cells were injected transdermally into BALB/c mice as a 10-fold dilution series from 1 × 10(5) to 1 × 10(2) cells per mouse. Versican G3 domain enhanced breast cancer self-renewal in both experimental in vitro and in vivo models. Versican G3-transfected cells contained high levels of side population cells, formed more mammospheres when cultured in the serum-free medium, and formed a greater number and larger colonies. Reduction of versican's functionality through anti-versican shRNA or knocking out the EGF-like motifs reduced the effect of versican on enhancing mammosphere and colony formation. Versican-enhanced self-renewal played a role in enhanced chemotherapeutic drug resistance, relating partly to the upregulated expression of EGF receptor (EGFR) signaling. Versican is highly expressed in breast cancer progenitor cells and was maintained at high levels before cell differentiation. Overexpression of versican enhanced breast cancer self-renewal through EGFR/AKT/GSK-3ß (S9P) signaling and conferred resistant to chemotherapeutic drugs tested.

Granulocyte colony-stimulating factor improves alternative activation of microglia under microenvironment of spinal cord injury.

Granulocyte colony-stimulating factor (G-CSF) was investigated in the present study to examine whether it could affect the activation status of microglia under microenvironment of spinal cord injury and provide a potential therapeutic treatment for spinal cord injury. We established mouse spinal cord hemisection model and injected recombinant human G-CSF (rhG-CSF) subcutaneously. The results demonstrated that G-CSF could recruit microglia to the injury site in the first 72h after spinal cord injury. Moreover, G-CSF inhibits the expression of pro-inflammatory factors and promotes the expression of neurotrophic factors. Additionally, G-CSF also increases the expression of markers of M2 macrophage and inhibits the expression of markers of M1 macrophage in BV2 microglia in vitro model, favoring the M2 polarization of microglia under the microenvironment of spinal cord hemisection. NFκB signal pathway was involved in G-CSF-induced polarization of BV2 microglia. As a conclusion, we suggested that administration of G-CSF within the first 72h after spinal cord injury might reduce early inflammation-induced detrimental effect and promote an anti-inflammatory response that favors repair via improving alternative activation of microglia. Administration of G-CSF in the acute phase of spinal cord injury may be a promising strategy in restorative therapy after spinal cord injury.

Versican G3 domain modulates breast cancer cell apoptosis: a mechanism for breast cancer cell response to chemotherapy and EGFR therapy.

Overexpression of EGFR and versican has been reported in association with breast cancers. Considered oncogenic, these molecules may be attractive therapeutic targets. Possessing anti-apoptotic and drug resistant properties, overexpression of these molecules is accompanied by selective sensitization to the process of apoptosis. In this study, we exogenously expressed a versican G3 construct in breast cancer cell lines and analyzed the effects of G3 on cell viability in fetal bovine serum free conditioned media and evaluated the effects of apoptotic agent C2-ceramide, and chemotherapeutic agents including Docetaxel, Doxorubicin, and Epirubicin. Versican G3 domain enhanced tumor cell resistance to apoptosis when cultured in serum free medium, Doxorubicin, or Epirubicin by up-regulating pERK and GSK-3ß (S9P). However, it could be prevented by selective EGFR inhibitor AG 1478 and selective MEK inhibitor PD 98059. Both AG 1478 and PD 98059 enhanced expression of pSAPK/JNK, while selective JNK inhibitor SP 600125 enhanced expression of GSK-3ß (S9P). Versican G3 promoted cell apoptosis induced by C2-ceramide or Docetaxel by enhancing expression of pSAPK/JNK and decreasing expression of GSK-3ß (S9P), an observation blocked by AG 1478 or SP 6000125. Inhibition of endogenous versican expression by siRNA or reduction of versican G3's expression by linking G3 with 3'UTR prevented G3 modulated cell apoptosis. The dual roles of G3 in modulating breast cancer cell resistance to chemotherapeutic agents may in part explain a potential mechanism for breast cancer cell resistance to chemotherapy and EGFR therapy. The apoptotic effects of chemotherapeutics depend upon the activation and balance of down stream signals in the EGFR pathway. GSK-3ß (S9P) appears to function as a key checkpoint in this balance of apoptosis and anti-apoptosis. Investigation and potential consideration of targeting GSK-3ß (S9P) merits further study.

Versican G3 promotes mouse mammary tumor cell growth, migration, and metastasis by influencing EGF receptor signaling.

Increased versican expression in breast tumors is predictive of relapse and has negative impact on survival rates. The C-terminal G3 domain of versican influences local and systemic tumor invasiveness in pre-clinical murine models. However, the mechanism(s) by which G3 influences breast tumor growth and metastasis is not well characterized. Here we evaluated the expression of versican in mouse mammary tumor cell lines observing that 4T1 cells expressed highest levels while 66c14 cells expressed low levels. We exogenously expressed a G3 construct in 66c14 cells and analyzed its effects on cell proliferation, migration, cell cycle progression, and EGFR signaling. Experiments in a syngeneic orthotopic animal model demonstrated that G3 promoted tumor growth and systemic metastasis in vivo. Activation of pERK correlated with high levels of G3 expression. In vitro, G3 enhanced breast cancer cell proliferation and migration by up-regulating EGFR signaling, and enhanced cell motility through chemotactic mechanisms to bone stromal cells, which was prevented by inhibitor AG 1478. G3 expressing cells demonstrated increased CDK2 and GSK-3ß (S9P) expression, which were related to cell growth. The activity of G3 on mouse mammary tumor cell growth, migration and its effect on spontaneous metastasis to bone in an orthotopic model was modulated by up-regulating the EGFR-mediated signaling pathway. Taken together, EGFR-signaling appears to be an important pathway in versican G3-mediated breast cancer tumor invasiveness and metastasis.

Deriving the aquatic predicted no-effect concentrations (PNECs) of three chlorophenols for the Taihu Lake, China.

The Predicted No-Effect Concentration (PNEC) is a key for ecological risk assessment. In this paper, the aquatic species existing widely in the Taihu Lake were selected, and their toxicity data to 2,4-dichlorophenol (2,4-DCP), 2,4,6-trichlorophenol (2,4,6-TCP) and pentachlorophenol (PCP) were collected. The PNECs of 2,4-DCP; 2,4,6-TCP; and PCP were derived using three different approaches, i.e., the assessment factor (AF), species sensitivity distribution (SSD) as well as an eco-toxicological model (AQUATOX). As the results, PNEC(AF)s were 2.18 µg L(-1), 2.53 µg L(-1) and 0.26 µg L(-1), and PNEC(SSD)s were 77 µg L(-1), 197 µg L(-1) and 10 µg L(-1), respectively for 2,4-DCP; 2,4,6-TCP; and PCP respectively. Based on the aquatic conditions of the Taihu Lake, the derived site-specific PNEC(AQUATOX)s were 15 µg L(-1), 67 µg L(-1) and 4 µg L(-1), respectively. In general, the PNECs for three chlorophenols derived from different approaches followed the declined order of PNEC(SSD) > PNEC(AQUATOX) > PNEC(AF). The ratios of PNEC(AF) to PNEC(SSD) and PNEC(AQUATOX) to PNEC(SSD) for three chlorophenols were 0.013-0.028 and 0.19-0.4, respectively. It indicated that PNECs obtained using different approaches may vary and the one based on the AF was the lowest. Therefore, PNEC(AF) can be seen as overprotective. The PNEC(AQUATOX) values for three chlorophenols were less than the corresponding PNEC(SSD) values, mostly because the indirect effects were considered in the ecological model.

Construction of tunable radial basis function networks using orthogonal forward selection.

An orthogonal forward selection (OFS) algorithm based on leave-one-out (LOO) criteria is proposed for the construction of radial basis function (RBF) networks with tunable nodes. Each stage of the construction process determines an RBF node, namely, its center vector and diagonal covariance matrix, by minimizing the LOO statistics. For regression application, the LOO criterion is chosen to be the LOO mean-square error, while the LOO misclassification rate is adopted in two-class classification application. This OFS-LOO algorithm is computationally efficient, and it is capable of constructing parsimonious RBF networks that generalize well. Moreover, the proposed algorithm is fully automatic, and the user does not need to specify a termination criterion for the construction process. The effectiveness of the proposed RBF network construction procedure is demonstrated using examples taken from both regression and classification applications.

A spectrum of knock-type Doppler signals in the intracranial vessels.

BACKGROUND AND PURPOSE: Knock-type Doppler signals (KTDS) are detectable by transcranial Doppler, and it has been hypothesized that they are related to an occlusion of a small perforating artery and microvascular ischemia. However, the nature of KTDS has not been prospectively defined. We aimed at describing the spectral and power motion Doppler characteristics of KTDS and ultrasound exposure conditions that lead to their appearance. METHODS: Consecutive patients referred with symptoms of stroke or transient ischemic attacks to our cerebrovascular ultrasound laboratory were screened for the presence of KTDS. The presence of microvascular ischemia was assessed using brain MRI. RESULTS: Among 327 patients with cerebrovascular symptoms, 46 (14%) had KTDS. KTDS were found more frequently in posterior circulation vessels (55% vertebral artery, 21.5% basilar artery, and 6% posterior cerebral artery). There was no association between ultrasound identification of KTDS and the presence of brain ischemia in the distribution of any vessel (OR, 0.37; 95% CI, 0.09-1.53; P=0.171) on univariate logistic regression analyses. KTDS was not related to the presence of microvascular ischemia on brain MRI (OR, 1.12; 95% CI, 0.55-2.29; P=0.761). We described the range of spectral and power motion Doppler appearances of KTDS and experimentally demonstrated the most likely underlying mechanism being a large vessel wall movement artifact. CONCLUSIONS: Although KTDS can be distinguished from other spectral flow signals, they can be found in normal vessels, they do not seem to be associated with the vessel affected by ischemia, and they should not be overinterpreted.