Design of AUVs based on 3D coils positioning and distributed base station control for nuclear spent fuel pools

An underwater magnetic induction positioning and communication system and an energy-efficient distributed control algorithm for underwater base stations are proposed in this paper. The positioning and communication system consists of a number of base stations and an Autonomous Underwater Vehicle (AUV) equipped with three-axis source coils respectively. The AUV receives this signal and based on its amplitude and phase information is able to locate the AUV and communicate with the base station. Due to the short positioning distance of magnetic induction positioning technology, a large number of base stations need to be installed underwater, which puts high demands on the control of the base stations. In this paper, an energy-efficient distributed control algorithm for underwater base stations is proposed to enable the AUV to meet the operational requirements while minimizing the total energy consumption of the base station. According to the simulation results, the design solves the problem that traditional underwater positioning and communication equipment cannot work stably for long periods of time in a high radiated environment, with a positioning error of no more than 10 cm within a preset operating range, and the algorithm proposed in this paper is able to reduce energy wastage by about 20%

Pivotal Role of Fatty Acid Synthase in c-MYC Driven Hepatocarcinogenesis

Hepatocellular carcinoma (HCC) is a deadly form of liver malignancy with limited treatment options. Amplification and/or overexpression of c-MYC is one of the most frequent genetic events in human HCC. The mammalian target of Rapamycin Complex 1 (mTORC1) is a major functional axis regulating various aspects of cellular growth and metabolism. Recently, we demonstrated that mTORC1 is necessary for c-Myc driven hepatocarcinogenesis as well as for HCC cell growth in vitro. Among the pivotal downstream effectors of mTORC1, upregulation of Fatty Acid Synthase (FASN) and its mediated de novo lipogenesis is a hallmark of human HCC. Here, we investigated the importance of FASN on c-Myc-dependent hepatocarcinogenesis using in vitro and in vivo approaches. In mouse and human HCC cells, we found that FASN suppression by either gene silencing or soluble inhibitors more effectively suppressed proliferation and induced apoptosis in the presence of high c-MYC expression. In c-Myc/Myeloid cell leukemia 1 (MCL1) mouse liver tumor lesions, FASN expression was markedly upregulated. Most importantly, genetic ablation of Fasn profoundly delayed (without abolishing) c-Myc/MCL1 induced HCC formation. Liver tumors developing in c-Myc/MCL1 mice depleted of Fasn showed a reduction in proliferation and an increase in apoptosis when compared with corresponding lesions from c-Myc/MCL1 mice with an intact Fasn gene. In human HCC samples, a significant correlation between the levels of c-MYC transcriptional activity and the expression of FASN mRNA was detected. Altogether, our study indicates that FASN is an important effector downstream of mTORC1 in c-MYC induced HCC. Targeting FASN may be helpful for the treatment of human HCC, at least in the tumor subset displaying c-MYC amplification or activation

Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade

<div><p>Previous data indicate that Tankyrase inhibitors exert anti-growth functions in many cancer cell lines due to their ability to inactivate the YAP protooncogene. In the present manuscript, we investigated the effect of Tankyrase inhibitors on the growth of hepatocellular carcinoma (HCC) cell lines and the molecular mechanisms involved. For this purpose, we performed cell proliferation assay by colony-forming ability in seven human HCC cells subjected to XAV-939 and G007-LK Tankyrase inhibitors. Noticeably, the two Tankyrase inhibitors suppressed the HCC cell growth in a dose-dependent manner. Furthermore, we found that Tankyrase inhibitors synergized with MEK and AKT inhibitors to suppress HCC cell proliferation. At the molecular level, Tankyrase inhibitors significantly decreased YAP protein levels, reduced the expression of YAP target genes, and inhibited YAP/TEAD luciferase reporter activity. In addition, Tankyrase inhibitors administration was accompanied by upregulation of Angiomotin-like 1 (AMOTL1) and Angiomotin-like 2 (AMOTL2) proteins, two major negative regulators of YAP. Altogether, the present data indicate that XAV-939 and G007-LK Tankyrase inhibitors could suppress proliferation of hepatocellular carcinoma cells and downregulate YAP/TAZ by stabilizing AMOTL1 and AMOTL2 proteins, thus representing new potential anticancer drugs against hepatocellular carcinoma.</p></div

G007-LK synergizes with U0126 or MK-2206 to inhibit HCC cell growth.

<p>Cell proliferation (A and B) and apoptosis (C and D) assays of HLE (A and C) and SNU-449 (B and D) cells treated with G007-LK, U0126 or MK-2206, either alone or in combination for 48 hours. Tukey-Kramer test: p<0.05 (a) vs. DMSO; (b) vs. 20μM G007-LK alone; (c) vs. 25μM U0126 alone; (d) vs. 5μM MK-2206 alone; (e) vs. G007-LK+U0126. Experiments were repeated three times in triplicate.</p

YAP expression in human HCC cell lines.

<p>Total YAP, phosphorylated (p-)YAP as well as nuclear YAP (n-YAP) protein levels were analyzed in a panel of 7 human HCC cell lines by Western blotting. β-actin and GAPDH were used as loading controls for total cell lysate. Histone H3 and β-tubulin were used as controls for nuclear and cytoplasmic extraction, respectively. The experiments were repeated twice.</p

Tankyrase inhibitors suppress TEAD-luciferase activity in HCC cell lines.

<p>Relative TEAD reporter activity in SNU-449 and HLE HCC cells upon XAV-939 and G007-LK treatment is shown. Student’s t-test: (a) p<0.05 vs. DMSO; (b) p<0.01 vs. DMSO. Experiments were repeated three times.</p

XAV-939 synergizes with U0126 and MK-2206 to inhibit HCC cell growth.

<p>Cell proliferation (A and B) and apoptosis (C and D) assays of HLE (A and C) and SNU-449 (B and D) cells treated with XAV-939, U0126 or MK-2206, either alone or in combination, for 48 hours. Tukey-Kramer test: p<0.05 (a) vs. DMSO; (b) vs. 20μM XAV-939 alone; (c) vs. 25μM U0126 alone; (d) vs. 5μM MK-2206 alone; (e) vs. XAV-939+U0126. Experiments were repeated three times in triplicate.</p

Tankyrase inhibitors reduce YAP protein levels and increase AMOTL1 and AMOTL2 protein expression in HCC cell lines.

<p>Western blot analysis of YAP, AMOTL1, and AMOTL2 in SNU-449 and HLE HCC cells upon XAV-939 or G007-LK treatment. β-actin and GAPDH were used as loading controls. Experiments were repeated twice.</p

Identification of a Potential Regulatory Variant for Colorectal Cancer Risk Mapping to Chromosome 5q31.1: A Post-GWAS Study

<div><p>Large-scale genome-wide association studies (GWAS) have established chromosome 5q31.1 as a susceptibility locus for colorectal cancer (CRC), which was still lack of causal genetic variants. We searched potentially regulatory single nucleotide polymorphisms (SNPs) in the overlap region between linkage disequilibrium (LD) block of 5q31.1 and regulatory elements predicted by histone modifications, then tested their association with CRC via a case-control study. Among three candidate common variants, we found rs17716310 conferred significantly (heterozygous model: OR = 1.273, 95% confidence interval (95%CI) = 1.016–1.595, <i>P</i> = 0.036) and marginally (dominant model: OR = 1.238, 95%CI = 1.000–1.532, <i>P</i> = 0.050) increase risk for CRC in a Chinese population including 695 cases and 709 controls. This variation was suggested to be regulatory altering the activity of enhancer that control <i>PITX1</i> expression. Using epigenetic information such as chromatin immunoprecipitation-sequencing (ChIP-seq) data might help researchers to interpret the results of GWAS and locate causal variants for diseases in post-GWAS era.</p></div

Characteristics of studies included in the meta-analyses.

<p>*: The dose of mushroom consumption in each category was calculated based on the average intake of mushroom per day in Japan.</p><p>Abbreviations: CC: case-control; NOS: Newsastle-Ottawa Scale; BMI: body mass index; OC: oral contraceptive; HRT: hormone replacement therapy.</p