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Numerical simulation of dam-break water flow over a horizontal dry bed has been performed. We have modified and verified computational techniques, including methods for determining the position of the interface and the continuum model for the surface tension force implemented in the PIFI code, as well as the OpenFOAM software with the interFoam solver and various cases of the two-parameter () model with corrections made taking into account the behavior of flows in regions of low Reynolds numbers. Calculated integral characteristics of dam-break flow were analyzed and compared with measured data. It is shown that taking into account surface tension and using an adequate turbulence model leads to deceleration of water flow and hence to a decrease in the velocity of the wave front, resulting in better agreement between the results of calculations and laboratory experiments. [ABSTRACT FROM AUTHOR]

The automated high-throughput Abbott RealTi me MTB real-time PCR assay has been recently launched for Mycobacterium tuberculosis complex (MTBC) clinical diagnosis. This study would like to evaluate its performance. We first compared its diagnostic performance with the Roche Cobas TaqMan MTB assay on 214 clinical respiratory specimens. Prospective analysis of a total 520 specimens was then performed to further evaluate the Abbott assay. The Abbott assay showed a lower limit of detection at 22.5 AFB/ml, which was more sensitive than the Cobas assay (167.5 AFB/ml). The two assays demonstrated a significant difference in diagnostic performance (McNemar's test; P = 0.0034), in which the Abbott assay presented significantly higher area under curve (AUC) than the Cobas assay (1.000 vs 0.880; P = 0.0002). The Abbott assay demonstrated extremely low PCR inhibition on clinical respiratory specimens. The automated Abbott assay required only very short manual handling time (0.5 h), which could help to improve the laboratory management. In the prospective analysis, the overall estimates for sensitivity and specificity of the Abbott assay were both 100 % among smear-positive specimens, whereas the smear-negative specimens were 96.7 and 96.1 %, respectively. No cross-reactivity with non-tuberculosis mycobacterial species was observed. The superiority in sensitivity of the Abbott assay for detecting MTBC in smear-negative specimens could further minimize the risk in MTBC false-negative detection. The new Abbott RealTi me MTB assay has good diagnostic performance which can be a useful diagnostic tool for rapid MTBC detection in clinical laboratories. [ABSTRACT FROM AUTHOR]

Background/Objectives:Chronic kidney diseases are associated with changes in cardiometabolic risk (CMR) factors in which body composition parameters have been used as sensitive predictors. This study aimed to explore the associations of anthropometric indicators, body fat (BF), body mass index (BMI) and waist circumference (WC) with estimated glomerular filtration rate (eGFR) in an adult healthy Chinese population.Subjects/Methods:A cross-sectional study was conducted for the subjects undergoing annual health examinations. The associations of subjects with body composition parameters were analyzed using the cutoff values of BMI, BF and WC in accordance with the criteria for Asian or Taiwanese population by gender.Results:A total of 3473 subjects, aged 30-45 years, who received physical examinations in 2007 were analyzed. The levels of CMR factors were significantly higher in males than in females. eGFR was negatively associated with BMI but positively related to BF. The additional roles of BMI and WC were observed in the subjects who were categorized according to BF. Females with normal weight obese were associated with increased eGFR, whereas a higher eGFR was found in males with low/normal BF and BMI or normal WC.Conclusions:Our data provided evidence that anthropometric parameters were associated with changes of eGFR in relatively healthy adults. Higher eGFR was observed in females with normal weight obese in whom hyperfiltration may be suspected, and this finding deserves further studies. [ABSTRACT FROM AUTHOR]

Background:Interferon (IFN)-based therapies could eradicate hepatitis C (HCV) and reduce the risk of hepatocellular carcinoma (HCC). However, HCC could still happen after sustained virological response (SVR). We aimed to develop a simple scoring system to predict the risk of HCC development among HCV patients after antiviral therapies.Methods:From 1999 to 2009, 1879 patients with biopsy-proven HCV infection treated with IFN-based therapies were analyzed.Results:Multivariable analysis showed old age (adjusted HR (aHR)=1.73, 95% CI=1.13-2.65 for aged 60-69 and aHR=2.20, 95% CI=1.43-3.37 for aged 70), Male gender (aHR=1.74, 95% CI=1.26-2.41), platelet count <150 × 109/l (HR=1.91, 95% CI=1.27-2.86), α-fetoprotein 20 ng ml−1 (HR=2.23, 95% CI=1.58-3.14), high fibrotic stage (HR=3.32, 95% CI=2.10-5.22), HCV genotype 1b (HR=1.53, 95% CI=1.10-2.14), and non SVR (HR=2.40, 95% CI=1.70-3.38) were independent risk factors for HCC. Regression coefficients were used to build up a risk score and the accuracy was evaluated by using the area under the receiver operating characteristic curve (AUC). Three groups as low-, intermediate-, and high-risk are classified based on the risk scores. One hundred sixty patients (12.78%) in the derivation and 82 patients (13.08%) in the validation cohort developed HCC with AUC of 79.4%, sensitivity of 84.38%, and specificity of 60.66%. In the validation cohort, the 5-year HCC incidence was 1.81%, 12.92%, and 29.95% in low-, intermediate-, and high-risk groups, with hazard ratios 4.49 in intermediate- and 16.14 in high-risk group respectively. The risk reduction of HCC is greatest in patients with SVR, with a 5-year and 10-year risk reduction of 28.91% and 27.99% respectively.Conclusion:The risk scoring system is accurate in predicting HCC development for HCV patients after antiviral therapies. [ABSTRACT FROM AUTHOR]

Higenamine mediates cardiotonic, vascular relaxation and bronchodilator effects. The relaxation effects and the mechanism of action of higenamine on the rat corpus cavernosum (CC) were assessed to investigate the effect of higenamine on penile erection. Strips of CC and aorta were used in organ baths for isometric tension studies. Tension was measured with isometric force transducers, and muscle relaxation was expressed as the percent decrease in precontraction induced by phenylephrine (PE). The relaxation reactions were investigated in an endothelial-denuded group and groups pretreated with N(G)-nitro-L-arginine methyl ester (NO synthesis inhibitor), propranolol (β-receptor blocker), indomethacin (COX inhibitor), glibenclamide (K+ATP channel inhibitor), 4-aminopyridine (membrane potential-dependent potassium channel inhibitor) and methylene blue (guanylyl cyclase inhibitor) for 30 min. Intracavernous pressure (ICP) was assessed in rats after the intravenous administration of higenamine, and changes in guanosine 3′,5′-cyclic monophosphate and adenosine 3′,5′-cyclic monophosphate (cAMP) concentrations were measured on the basis of the higenamine concentration. Also, the combined reaction of higenamine and the phosphodiesterase type-5 (PDE-5) inhibitors was assessed. Higenamine induced relaxation of the CC and the aortic strips precontracted with PE in a dose-dependent manner. The CC was significantly more relaxed than the aortic rings in response to the same higenamine concentration (P<0.05). The CC relaxation reaction was suppressed by the β-receptor blocker propranolol. The cAMP concentration increased gradually with increased higenamine concentration (P<0.05). The ICP also increased with increased higenamine concentration in vivo (P<0.05). In the group pretreated with 10−7 M higenamine, the relaxation reaction of CC induced by the PDE-5 inhibitor increased significantly, compared with CC exposed to the PDE-5 inhibitor but not pretreated with higenamine (P<0.05). In conclusion, higenamine induced relaxation of the rat CC in a dose-dependent manner. The effect may be mediated through β-adrenoceptors. The results suggest that higenamine may be valuable as a new lead compound for treating erectile dysfunction. [ABSTRACT FROM AUTHOR]

Background:The sigma-2 receptor has been identified as a biomarker of proliferating cells in solid tumours. In the present study, we studied the mechanisms of sigma-2 ligand-induced cell death in the mouse breast cancer cell line EMT-6 and the human melanoma cell line MDA-MB-435.Methods:EMT-6 and MDA-MB-435 cells were treated with sigma-2 ligands. The modulation of multiple signaling pathways of cell death was evaluated.Results:Three sigma-2 ligands (WC-26, SV119 and RHM-138) induced DNA fragmentation, caspase-3 activation and PARP-1 cleavage. The caspase inhibitor Z-VAD-FMK partially blocked DNA fragmentation and cytotoxicity caused by these compounds. These data suggest that sigma-2 ligand-induced apoptosis and caspase activation are partially responsible for the cell death. WC-26 and siramesine induced formation of vacuoles in the cells. WC-26, SV119, RHM-138 and siramesine increased the synthesis and processing of microtubule-associated protein light chain 3, an autophagosome marker, and decreased the expression levels of the downstream effectors of mammalian target of rapamycin (mTOR), p70S6K and 4EBP1, suggesting that sigma-2 ligands induce autophagy, probably by inhibition of the mTOR pathway. All four sigma-2 ligands decreased the expression of cyclin D1 in a time-dependent manner. In addition, WC-26 and SV119 mainly decreased cyclin B1, E2 and phosphorylation of retinoblastoma protein (pRb); RHM-138 mainly decreased cyclin E2; and 10 μM siramesine mainly decreased cyclin B1 and pRb. These data suggest that sigma-2 ligands also impair cell-cycle progression in multiple phases of the cell cycle.Conclusion:Sigma-2 ligands induce cell death by multiple signalling pathways. [ABSTRACT FROM AUTHOR]

Existence of humoral immunity has been previously demonstrated in malignant ascitic fluids. However, only a limited number of immunogenic tumor-associated antigens (TAAs) were identified, and few of which are associated with ovarian cancer. Here, we identified salt-inducible kinase 3 (SIK3) as a TAA through screening of a random peptide library in the phage display system. Overexpression of SIK3 markedly promoted cell proliferation, attenuated p21Waf/Cip1 and p27Kip expressions in low-grade OVCAR3 cells, and permitted the cells to grow in mice. Decrease in SIK3 expression in high-grade SK-OV3 cells consistently demonstrated its tumorigenic potency by modulating the protein levels of cell cycle regulators. When the expressions of SIK3 and CA125 were compared in cancer tissues, immunohistochemical (IHC) studies indicated that cytoplasm-localized SIK3 was highly expressed in 55% of the ovarian cancer samples. In contrast, it was rarely detected in adenomyosis, leiomyoma and normal ovary tissues, showing its higher specificity (97%) to CA125 (65%) in ovarian cancer. Moreover, experiments using pharmacological inhibitors to block SIK3-induced p21Waf/Cip1 expression revealed that activation of c-Src and phosphoinositide-3-kinase were critically required for its biological activity, suggesting that they are the downstream signaling mediators of SIK3. These data were further supported by IHC studies, showing coexpression of c-Src with SIK3 in 85% of the ovarian tumor samples stained positive for SIK3. Collectively, our findings indicate that SIK3 is a novel ovarian TAA. Overexpression of SIK3 promotes G1/S cell cycle progression, bestows survival advantages to cancer cells for growth and correlates the clinicopathological conditions of patients with ovarian cancer. [ABSTRACT FROM AUTHOR]

Activation of peroxisome proliferator-activated receptor (PPAR) δ by GW501516, a specific PPARδ ligand, significantly inhibited interleukin (IL)-1β-induced proliferation and migration of vascular smooth muscle cells (VSMCs). This effect of GW501516 was dependent on transforming growth factor-β, and was mediated through the up-regulation of IL-1 receptor antagonist. The inhibitory effect of GW501516 on VSMC proliferation was associated with cell cycle arrest at the G1 to S phase transition, which was accompanied by the induction of p21 and p53 along with decreased cyclin-dependent kinase 4 expression. Inhibition of cell migration by GW501516 was associated with the down-regulation of matrix metalloproteinase (MMP)-2 and MMP-9 in IL-1β-treated VSMCs. Inhibition of extracellular signal-regulated kinase significantly reduced the GW501516-mediated inhibition of IL-1β-stimulated VSMC proliferation. These results suggest that PPARδ plays an important role in the pathophysiology of diseases associated with the proliferation and migration of VSMCs. [ABSTRACT FROM AUTHOR]

The clinical utility of therapeutic drug monitoring in tuberculosis has not been adequately evaluated by controlled clinical trials. To examine the relationship between slow culture conversion and peak plasma rifampicin level (Cmax-rfm) in a case-control study, patients with persistence of positive sputum smear despite at least 8 weeks of directly observed treatment with standard pyrazinamide-containing regimens were enrolled prospectively in government chest clinics from 16 December 2005 to 15 November 2006. Patients with multidrug-resistant tuberculosis, human immunodeficiency virus infection, or poor treatment adherence were excluded. Cases referred to patients with persistence of positive culture whereas controls had negative culture despite positive smear. Blood was checked at 2 and 4 hours post-dosing to capture Cmax-rfm. A cohort of 88 patients was identified. After excluding 16 patients, there were 36 controls and 36 cases. None had symptoms of malabsorption. Cmax-rfm was below 6 mg/l among 47% of controls and 44% of cases. Univariate and multiple logistic regression analyses showed no significant association between slow culture conversion and Cmax-rfm after logarithmic transformation. Thus, there is probably no association between Cmax-rfm and slow culture conversion. [ABSTRACT FROM AUTHOR]

A mathematical model of a spherical diffusion flame with heat losses and with allowance for incomplete combustion is proposed. The effect of heat losses and mass flow rate of the fuel on the degree of combustion incompleteness and flame radius and temperature is considered theoretically. A diffusion microflame with a single-stage mechanism of the chemical reaction is numerically modeled. In contrast to previous activities, the model proposed does not involve the assumption of low heat losses. A comparison of results obtained with available published data shows that the model considered offers an adequate description of the basic features of combustion of the diffusion microflame. [ABSTRACT FROM AUTHOR]

This study investigates the reliability of flip chip ball grid array (FCBGA) components with three types of solder materials: eutectic solder with a composition Sn63Pb37 and the lead-free solders SnAg3.0Cu0.5 and SnAg4.0Cu0.5. Two substrate-side solder mask (S/M) opening sizes, 0.4 mm and 0.525 mm, were used. Both the monotonic and cyclic mechanical four-point bend tests are conducted for the reliability assessment. It is found that the FCBGA components with SnAg3.0Cu0.5 solder have the best durability during the cyclic bend test, yet the eutectic solder is the strongest during the monotonic bend test. Besides, the FCBGA components with 0.525-mm S/M opening have around 3 times more life cycles than those with the 0.4-mm S/M opening in the cyclic bend test. It is also noteworthy that the lead-free solder materials have much variation in the failed cycles during the cyclic test. Moreover, the failure locations for those components with 0.4-mm S/M openings are found to be at the interface between the package side metal pad and the solder ball, and those with an S/M opening of 0.525 mm are observed to be failed mostly at the interface between the printed circuit board (PCB) side metal pad and the solder ball. [ABSTRACT FROM AUTHOR]

Over-expression of aldose reductase (AR) has been observed in many cancer cells. To clarify the role of AR in tumor cells, we investigated the pathways mediating expression of the AR gene induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoter. In A549 human lung adenocarcinoma cells, TPA elicited a dose- and time-dependent increase in AR mRNA level with an elevated enzyme activity. The TPA-induced increase in mRNA level and promoter activity of the AR gene was significantly attenuated in the presence of an inhibitor of protein kinase C, tyrosine kinase, or nuclear factor ?B (NF-?B). TPA augmented the NF-?B-dependent gene transcription, indicating the involvement of NF-?B in this regulation. Accumulation of TPA-treated cells in S phase was almost completely abolished in the presence of ethyl 1-benzyl-3-hydroxy-2(5H)-oxopyrrole-4-carboxylate, an AR inhibitor. Taken together, TPA augmented the promoter activity of the AR gene via the activation of protein kinase and NF-?B. The inhibition of AR may assist in the chemotherapy of malignant tumors by suppressing the rapid growth of cancer cells. [ABSTRACT FROM AUTHOR]

Sepsis induces lymphocyte apoptosis and prevention of lymphocyte death may improve the chances of surviving this disorder. We compared the efficacy of a selective caspase-3 inhibitor to a polycaspase inhibitor and to caspase-3-/- mice. Both inhibitors prevented lymphocyte apoptosis and improved survival. Caspase-3-/- mice shared a decreased, but not total, block of apoptosis. The polycaspase inhibitor caused a very substantial decrease in bacteremia. Caspase inhibitors did not benefit RAG-1-/- mice, which had a >tenfold increase in bacteremia compared to controls. Adoptive transfer of T cells that overexpressed the anti-apoptotic protein Bcl-2 increased survival. T cells stimulated with anti-CD3 and anti-CD28 produced increased interleukin 2 and interferon γ by 6 h. Thus, caspase inhibitors enhance immunity by preventing lymphocyte apoptosis and lymphocytes act rapidly, within 24 h, to control infection. [ABSTRACT FROM AUTHOR]

The aortic input impedance is simulated by an asymmetric T-tube model loaded with complex loads. A geometric tapering is incorporated to represent the vasculature, assuming a triangular distribution of the wave transmission paths. Parametric analyses using physiological data demonstrate that the predicted impedance and reflection coefficient spectrum (RCS) closely mimic the experimental data. The simulation also reveals several significant features. As diameter tapering can minimise the presence and influence of wave reflections, the impedance modulus stays relatively constant with two distinct minima. The frequency of first minimum of impedance modulus is evidence of the tube elasticity and load compliance in the lower extremity, and the frequency of second minimum is evidence of those in the upper extremity. The high-frequency portion of the impedance modulus is affected by the tube elasticity, but not by the load compliance. The impedance spectrum at higher frequencies shows no notable fluctuations corresponding to a decrease in blood or wall viscosity. Furthermore, the low-frequency range in RCS is dominated by the longer lower body tube, and the high-frequency range by the shorter upper body tube. This geometrically tapered T-tube is considered a more natural model for the description of the systemic arterial system. [ABSTRACT FROM AUTHOR]