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In bathymetric Airborne LiDAR (Light Detection And Ranging) for the measurement of various water depths, the echo of the laser signal is amplified by an amplifier circuit, the water surface is usually saturated, which results in a serious effect on the bottom echo signal. Therefore, this paper designs a LiDAR echo signal detection timing control system. The system adopts the STMicroelectronics32 (STM32) controller as the gated signal generator; acts on the photomultiplier tube (PMT) photoelectric conversion circuit; and adjusts the amplitude, frequency, period, and duty cycle of the gating trigger signal to achieve timing control, thus allowing the system to directly avoid the reception of overly strong surface echo signals and increasing the accuracy of the experimental results. The system combines PMT adjustable voltage control gain technology applies the weak underwater echo signal that is amplified to facilitate subsequent collection. In the actual measurement, using STM32 instead of the traditional signal generator, which can reduce the power consumption and load capacity of the system. The experimental results show that the system can amplify the underwater signal by at least 6-fold while avoiding the effect of the surface echo signal. [ABSTRACT FROM AUTHOR]

The amount of drug remaining after previous doses, or drug accumulation, is closely related to drug efficacy and safety. An accurate calculation of the accumulation index or ratio (R(ac)) is crucial for dose finding. However, in drug accumulation studies little consensus exists with regard to experimental design or data analysis. We conducted a systematic review of the literature to produce a detailed profile of drug accumulation studies of the last 30 years (1980-2011). Ninety-six articles comprising 122 studies were analyzed. A typical drug accumulation study enrolled 10 to 20 subjects randomly assigned into treatment groups of 1 or 2 dose levels to observe pharmacokinetic behaviors. The median washout period between single and multiple dosing was 7 days, and the dose interval was 1-2 elimination half-lives in non- or one-compartmental models. Generally, the number of repeated times of administration for multiple dosing was 7-14, and the median number of sampling time points was 11. Eight different methods were used to calculate R(ac). The most frequently used method, in 72.9% of the studies, was to set R(ac) equal to the ratio of the area under a plasma concentration-time curve (AUC) during a dosage interval at steady state to the AUC of a dosage interval after the first dose, i.e., R(ac) = AUC(0-τ,ss) / AUC(0-τ,1). The values of R(ac) in the included studies ranged from 0.85 to 18.8, and 68.03% were <2. We suggest that sample size estimation for an accumulation study should be similar to that of a bioequivalence study, and in most studies, 18-24 subjects will be needed. Appropriate calculation methods for R(ac) should be selected based on the experimental design and data characteristics. The crucial values for non-, weak, moderate, and strong accumulation can be set at R(ac) < 1.2, 1.2 ≤ R(ac) < 2, 2 ≤ R(ac) < 5, and R(ac) ≥ 5, respectively. Accumulations studies should also give more regard to drug metabolism and increased accumulation in kidney or liver damaged patients.

Hepatitis B x antigen, or HBxAg, contributes importantly to the pathogenesis of hepatocellular carcinoma (HCC). Given that HBxAg constitutively activates beta-catenin and that upregulated ErbB-2 promotes beta-catenin signaling in other tumor types, experiments were designed to ask whether HBxAg was associated with upregulated expression of ErbB-2. When HBxAg positive and negative HepG2 cells were subjected to proteomics analysis, ErbB-2 was shown to be upregulated in HepG2X but not control cells. ErbB-2 was also strongly upregulated in HB infected liver, and weakly in some HCC nodules, where it correlated with HBxAg expression. Among tumor bearing patients, strong ErbB-2 staining in the liver was associated with dysplasia, and a shorter survival after tumor diagnosis. This implies that elevated ErbB-2 is an early marker of HCC. Treatment of HepG2X cells with ErbB-2 specific siRNA not only reduced ErbB-2 expression, but also reduced the expression of beta-catenin, suggesting that ErbB-2 contributed to the stabilization of beta-catenin. ErbB-2 specific siRNA also partially blocked the ability of HBxAg to promote DNA synthesis and growth of HepG2 cells. These results suggest that ErbB-2/beta-catenin up-regulation contributes importantly to the mechanism of HBxAg mediated hepatocellular growth.

Intrahepatic expression of hepatitis B x antigen (HBxAg) is associated with the development of hepatocellular carcinoma (HCC), perhaps through trans-activation of selected cellular genes. When this was examined by PowerBlot analysis, upregulated levels of beta-catenin and several known beta-catenin effectors were observed in HBxAg-positive compared with HBxAg-negative HepG2 cells. When HBxAg was introduced into Hep3B cells, upregulated expression of wild-type beta-catenin was observed. This was also observed in Hep3B cells overexpressing the HBxAg upregulated gene, URG11. Upregulated expression of URG11 and beta-catenin correlated with HBxAg trans-activation function. Transient transfection assays with fragments of the beta-catenin promoter showed that it was activated by both HBxAg and URG11 and inhibited by URG11-specific small inhibitory RNA. The latter also inhibited the growth of Hep3BX cells in a serum-free medium, which correlated with depressed levels of beta-catenin. Activation of beta-catenin effector genes was observed in cells stably expressing HBxAg or overexpressing URG11 compared with control cells transfected with the pTOPFLASH reporter plasmid. Extensive costaining between HBxAg, URG11, and beta-catenin was observed in infected liver and HCC nodules, suggesting a close relationship in vivo. In conclusion, wild-type beta-catenin is activated by HBxAg, in part, through the upregulated expression of the HBxAg effector URG11. URG11 stimulates the beta-catenin promoter and hepatocellular growth and survival. These observations also suggest that URG11 may be a regulatory element in the beta-catenin signaling pathway and may be a target for chemoprevention of HCC.

Gadd45a, a p53- and BRCA1-regulated stress protein, has been implicated in the maintenance of genomic fidelity, probably through its roles in the control of cell cycle checkpoint and apoptosis. However, the mechanism(s) by which Gadd45a is involved in the induction of apoptosis remains unclear. We show here that inducible expression of Gadd45a protein causes dissociation of Bim, a Bcl2 family member, from microtubule-associated components and translocation to mitochondria. The Bim accumulation in mitochondria enhances interaction of Bim with Bcl-2, relieves Bax from Bcl-2-bound complexes, and subsequently results in release of cytochrome c into the cytoplasm. Suppression of endogenous Bim greatly inhibits Gadd45a induction of apoptosis. Interestingly, Gadd45a interacts with elongation factor 1alpha (EF-1alpha), a microtubule-severing protein that plays an important role in maintaining cytoskeletal stability, and inhibits EF-1alpha-mediated microtubule bundling, indicating that the interaction of Gadd45a with EF-1alpha disrupts cytoskeletal stability. A mutant form of Gadd45a harboring a deletion of EF-1alpha-binding domain fails to inhibit microtubule stability and to induce Bim translocation to mitochondria. Furthermore, coexpression of EF-1alpha antagonizes Gadd45a's property of suppressing cell growth and inducing apoptosis. These findings identify a novel link that connects stress protein Gadd45a to the apoptotic machinery and address the importance of cytoskeletal stability in apoptotic response to DNA damage.

The hepatitis B virus (HBV)-encoded X antigen (HBxAg) may contribute to the development of hepatocellular carcinoma (HCC) through the upregulated expression of selected cellular genes. To identify these genes, RNAs isolated from HBxAg-positive and -negative HepG2 cells were compared by PCR select cDNA subtraction. One gene overexpressed in HBxAg-positive cells by Northern and Western blotting is the ribosomal protein S15a. The S15a mRNA is 535 base pairs, encoding a protein 130 amino acids long with a molecular weight of 14.3 kDa. S15a expression was upregulated in HBV-infected livers, where it costained with HBxAg. Overexpression of S15a stimulated cell growth, colony formation in soft agar, and tumor formation in SCID mice. Hence, HBxAg upregulated the expression of S15a, the latter of which participates in the development of HCC, perhaps by altering the integrity of translation., (Copyright 2004 Wiley-Liss, Inc.)

Hepatitis B x antigen (HB x Ag) is a trans-activating protein that may be involved in hepatocarcinogenesis, although few natural effectors of HB x Ag that participate in this process have been identified. To identify additional effectors, whole cell RNA isolated from HB x Ag-positive and HB x Ag-negative HepG2 cells were compared by polymerase chain reaction select cDNA subtraction, and one clone, upregulated gene, clone 11 (URG11), was chosen for further characterization. Elevated levels of URG11 mRNA and protein were observed in HB x Ag-positive compared to HB x Ag-negative HepG2 cells. Costaining was observed in infected liver (P < 0.01). URG11 stimulated cell growth in culture (P < 0.01), anchorage-independent growth in soft agar (P < 0.001), and accelerated tumor formation (P < 0.01), and yielded larger tumors (P < 0.02) in SCID mice injected subcutaneously with HepG2 cells. These data suggest that URG11 is a natural effector of HB x Ag that may promote the development of hepatocellular carcinoma.