Supplemental Figure 1S. Individual Study Results from GWAS Meta-Analysis and Replication Studies for Selected SNPs.
Supplemental Table 1S. Sequenome Primer Design for 43 SNPs included in Our Replications Studies. Supplemental Table 2S. Results from NPC GWAS Meta-Analysis.
PDF file, 2015K, Table S1. MMPs and PKCs primer pairs and PCR conditions for RT-PCR. Table S2. MMPs and PKCs primer pairs and PCR conditions for ChIP assay. Table S3. Antibodies for Western blot analysis. Figure S1. The remaining subset of human cancer cell lines without enhancement of cell migration activity after TSA treatment. Figure S2. Validation of HDACi-enhanced cell migration with treatments of 6 different HDACi. Figure S3. HDACi treatments of HCC and lung cancer cells enhance in vivo experimental metastasis. Figure S4. Treatment of HDACi modulated MMPs and PKCs expressions. Figure S5. The combination treatments of HDACi with MMPi or PKCi repress HDACi-enhanced migration activity. Figure S6. The effects of HDACi and PKCi on tumorigenesis, toxicity and tumor-progressive protein expressions in vivo. Figure S7. Suppressive effects of tumorigenesis and metastasis in liver metastasis model of TSA/Tam and TSA/Cur treated mice.
Single chamber solid oxide fuel cell (SC-SOFC) is different from the conventional solid oxide fuel cell with dual gas chamber structure. Both cathode and anode of SC-SOFC are exposed to the only one gas chamber. Mixed gas containing fuel and oxidant is fed during operation and it can generate electric energy by the selectively catalytic activities of cathode and anode. SC-SOFC has many particular advatages, such as more simple structure, eliminating the need for sealing and easy stacking etc. In this paper, the recent research advances of SC-SOFC are reviewed, including brief introduction of operational principle of SC-SOFC, the selection of key materials for SC-SOFC, the discussion of main influencing factors on SC-SOFC, as well as the design and test of micro-stack (battery) system. The investigation results on SC-SOFC of our research group are highlighted, including composite cathode, oxide anode with Ni modification, and some novel designs for SC-SOFC micro stacks, such as star-type and array-type stacks, and so on. Finally, an outlook about the potential applications of SC-SOFC is given according to the analysis of its merits and drawbacks.
Tornados are one of the most common natural disasters, but their occurrence can be sudden and unpredictable. For trains operating in the areas where tornadoes frequently happen, the operation safety is challenged. Tornado generator was recently proposed as a method of numerical investigation of tornado-like vortex flows. This paper presents a numerical approach for the simulation of train passing through a tornado-like vortex on realistic scale. It is found that the tornado-like vortex causes appearance of localized regions of a negative pressure on the train and transient variations of the aerodynamic loads acting on the train. As a result, the tornado-like vortex causes swings on the lateral force, and subsequently on the rolling moment, which affect the passenger comfort and operation safety of the train. The method presented herein can be further applied to the study of train behavior and real time response while encountering tornadoes of different types and strength, which is significant for evaluating the operation safety of high-speed trains.
Arising from the epithelial cells in nasopharynx, nasopharyngeal carcinoma (NPC) is highly prevalent in Southeastern China, including Hong Kong and Taiwan. Genetic and environmental factors play important role in NPC susceptibility. Genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms (SNPs) located in major histocompatibility complex (MHC) region with strong evidence for association with NPC. Recently, combination of GWAS and expression quantitative trait loci (eQTL) datasets, transcriptome-wide association study (TWAS) was used to identify novel associations in transcriptome level. In this study, we conducted TWAS in NPC using two in house GWAS datasets and GTEx eQTL datasets from public domain. Most of the significant results were located in chromosome six MHC region. Our analysis identified significant TWAS genes that explain the most of the GWAS signals : HLA-A, GABBR1 and HLA-F genes with P values of 5.08E-13, 5.78E-09 and 2.30E-08, respectively. One of the novel genes, ZNRD1 (P = 8.22 E-08), was known to be involved in the tumorigenesis of esophageal cancer and liver cancer. Further analysis should be needed to understand the mechanisms between ZNRD1 association in NPC. Citation Format: Wen-Hui Su, Fu-Chun Chan. Transcriptome-wide association study analysis of nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1594.
Abstract In the tumorigenesis process, miRNAs could act as oncogenes or tumor suppressor genes in the cancer cells by regulating miRNA target genes. Nasopharyngeal carcinoma (NPC) associated Epstein-Barr virus (EBV) can also influence the occurrence of NPC through its miRNAs. In this study, we used the next generation sequencing technology to analysis host-viral miRNA profiles in 24 NPC and 5 adjacent normal tissues. In average, 10.62% of mappable reads mapped to EBV genome in NPC tissue. Most of the small RNAs in NPC tissues which mapped to EBV genome were miRNAs (95.51%), rest of them were EBERs (1.80%) and v-snoRNA1 (2.68%). The percentages of EBV miRNA in total human and EBV mature miRNA reads were ranged from 4% to 51% (average 29.61%). For EBV miRNAs, the expression level of BART10-3p and BART9-3p were the top two in NPC tumors. BART20-5p, BART19-3p and BART21-5p were correlated to tumor stage. On the other hand, there were 11 and 34 human miRNAs differentially up- and down-regulated in NPC tissue, respectively. The present research provides the first evidence obtained through direct sequencing to systematically and comprehensively describe the expression of EBV and human miRNAs in NPC tissue. Citation Format: Wen-Hui Su, Jia-Hao Zhang, Kai-Ping Chang. Analysis of host-Epstein-Barr virus microRNA expression in nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4425. doi:10.1158/1538-7445.AM2017-4425
A Mo-Si-B-O alloy was obtained by spark plasma sintering (SPS) using fine Mo-62Si-5B (at.%) alloy powder (with a D-50 size of 2.21 mu m). The SPS Mo-Si-B-O pseudo alloy consisted of fine MoSi2/Mo5Si3/MoB/SiO2 microstructure and showed better oxidation resistance than the coarsened microstructure. The SiO2 that was preformed during SPS and the fine microstructure reduced the incubation stage of formation of continuously protective borosilicate layer, which is beneficial to the oxidation resistance. A "Mechanical locking" mechanism for the borosilicate layer by spilling of the pre-formed SiO2 decreased cracks in the borosilicate-substrate interface, increased interface strength and integrity of the borosilicate layer.
IMPORTANCE The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation.OBJECTIVE To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases.DATA SOURCES Genomewide association studies (GWAS) published up to January 15, 2015.STUDY SELECTION GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available.DATA EXTRACTION AND SYNTHESIS Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.MAIN OUTCOMES AND MEASURES Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation.RESULTS Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]).CONCLUSIONS AND RELEVANCE It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
Recent studies have revealed that the inflammatory process plays a role in the pathogenesis of osteoarthritis (OA). The S100 family and receptor for advanced glycation end products (RAGE) participate in regulating inflammation, even in the production of matrix metalloproteinases (MMPs). MMP-1 degrades cartilage, which may result in OA development. Moreover, polymorphisms in RAGE, S100A8, and MMP-1 have a marked effect on ligand binding and transcription regulating. In this study, we investigated the potential genetic contribution of the RAGE, S100A8, and MMP-1 genes to OA. We performed a matched case-control association study and genotyped OA patients and healthy controls, who were analyzed by polymerase chain reaction-restriction fragment length polymorphism assays. A total of 207 patients were diagnosed with knee OA and underwent total knee replacement. The control group included 207 individuals who had standard X-rays of the knee joints to confirm K/L < 2 and were matched by age and gender. Single-nucleotide polymorphisms in RAGE (-429T/C, -374T/A, and 557G/A), S100A8 (rs3795391A/G), and MMP-1 (-1607 1G/2G, -755G/T, and -519A/G) were evaluated. RAGE -374T/A, S100A8 rs3795391A/G, MMP-1 -1607 1G/2G, -755G/T, and -519A/G showed no significant difference between OA patients and healthy controls. RAGE -429T/C and 557G/A showed a significant association between OA patients and healthy controls (P = 0.016 and 0.047, respectively). In haplotype analyses, no RAGE and MMP-1 haplotypes showed associations with OA. Our results suggest that the investigated polymorphism in the RAGE gene play a role in OA in the Han Chinese population.
(1-xwt%) La0.6PrSr0.4NiO4 - (xwt%) Ce0.8Pr0.2O2 (x = 0, 10, 20, 30, 40, 50), abbreviated as LPSN-xCPO, were prepared and used as composite cathode for intermediate temperature solid oxide fuel cell (IT-SOFC). XRD result suggested that no chemical reaction occurred between LPSN and CPO after sintering at 1200 degrees C for 4 h. Electrical conductivity of LPSN-xCPO decreased with x. LPSN-40CPO exhibited the best performance on cathode impedance spectra under open-circuit condition. At 700 degrees C, Exchange current density of LPSN-40CPO and LPSN was 50.1 and 15.8 mA cm(-2), respectively, and the polarization resistance R-P of LPSN-40CPO was 0.22 Omega cm(2), which is about one-eighth of that of LPSN. The OCV of the cell with LPSN-40CPO as cathode was about 0.78 V, and the maximum of power density was about 88 mW cm(-2). LPSN-40CPO can be a promise candidate for cathode in IT-SOFC. (C) 2014 Elsevier B.V. All rights reserved.
Large thermal mismatch between GdBaCo2O5+delta (GBCO) oxide and solid electrolytes remains a challenge for its application as a cathode of solid oxide fuel cells (SOFCs). To avoid sharp discontinuities in composition, a functionally graded GBCO cathode is developed, which consists of an inner layer with high electrochemical activity and good thermal compatibility to electrolyte, and an outer layer with high electrical conductivity for current collection. Impedance spectra results reveal that the graded GBCO cathode shows a reduced polarization resistance and more importantly, an improved thermal stability during thermal cycling test. The present work confirms the advantage of graded GBCO cathode that is more robust and reliable for practical application. (C) 2014 Elsevier Ltd. All rights reserved.
In this paper, a series of Sm0.5Sr0.5CoO3-Sm0.2Ce0.8O1.9 (SSC-SDC) composite with different ratios were prepared and characterized as oxygen electrodes for solid oxide electrolysis cells (SOECs). Yttria-stabilized zirconia (YSZ) was selected as the electrolyte with a SDC barrier layer to avoid detrimental solid state interaction between SSC and YSZ. At 850 degrees C, the impedance spectra showed that the optimum SDC content in the composite electrode was found to be about 30wt.%, which showed a much lower area specific resistance of 0.03cm(2). The electrochemical performances of a Ni-YSZ hydrogen electrode supported YSZ membrane SOEC with the SSC-SDC73 oxygen electrode were also measured at 750-850 degrees C. The hydrogen production rate calculated from the Faraday's law was 327mLcm(-2)h(-1) at 850 degrees C at an electrolysis voltage of 1.3V with a steam concentration of approximate to 40%, which indicated that the SSC-SDC73 was a promising oxygen electrode candidate for high temperature electrolysis cells.
In this study, we will report our investigation for La0.75Sr0.25Cr0.5Mn0.5O3-delta (LSCrM) based anodes impregnated with solutions of cobalt (Co) nitrate. A YSZ supported SOFC with pure LSCrM anode and La0.7Sr0.3MnO3 (LSM) cathode exhibits the maximum power density (P-max) of 58.7 and 5.2 mW cm(-2) at 850 degrees C in dry H-2 and dry CH4. After the modification of anode with Co nitrate, the P-max reaches 196.2 mW cm(-2) in dry H-2 and 28.5 mW cm(-2) in dry CH4, about 3.34 times and 5.48 times increase, respectively. These results indicate that Co is also a potential catalyst for LSCrM anode. Moreover, the effect of impregnation amount of catalyst on the cell performance is also evaluated in this study. Copyright (C) 2014, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.
A novel method for fabricating Ni(NO3)(2) solution impregnated YSZ (YSZ: Yttria Stabilized Zirconia) anodes for solid oxide fuel cells (SOFCs) is presented. In order to reduce the impregnation cycles and increase the reliability of the YSZ membrane, a YSZ support with a porosity of similar to 60% is soaked in a saturated Ni(NO3)(2) solution with an increased temperature of 80 degrees C. The impregnated anode is dried in a vacuum drying device without heating, resulting in a flower-like Ni(NO3)(2)center dot 6H(2)O crystal. The formed porous structure is likely to facilitate the impregnating process and considered to be the key to success of the impregnation process with saturated solution. After heating at 700 degrees C, a novel needle-shaped NiO is presented, which exhibits some advantages including fast preparation, high connectivity, large specific surface area and high operational stability (i.e. high aggregation resistance). For the purpose of comparison, Ni(NO3)(2) solution impregnated YSZ anodes prepared through the conventional impregnation process are also characterized under the same conditions. (C) 2014 Elsevier B.V. All rights reserved.
The electrolyte material Ce0.85Sm0.15O1.92 (SDC) powders are synthesized by glycine nitrate processes and BaCe0.83Y0.17O3-delta (BCY) powders are synthesized by sol gel processes, respectively. Then SDC BCY composite electrolytes are prepared by mixing SDC and BCY. The SDC and BCY powders are mixed in the weight ratio of 95:5, 90:10 and 85:15 and named as 5395, SB90 and SB85, respectively. The electrical properties of SDC and SDC BCY composites are investigated. The experimental results show that SDC BCY composites exhibit the excellent conductivity and could significantly enhance the fuel cell performances. The behavior that SDC BCY composites display hybrid proton and oxygen ion conduction is substantiated. Among these electrolytes, the maximum power density reaches as high as 159 mW cm(-2) for the fuel cell based on SB90 composite electrolyte at 600 degrees C. Copyright (C) 2014, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.
It is common to observe the clustering of chronic hepatitis B surface antigen (HBsAg) carriers in families. Intra-familial transmission of hepatitis B virus (HBV) could be the reason for the familial clustering of HBsAg carriers. Additionally, genetic and gender factors have been reported to be involved. We conducted a three-stage genome-wide association study to identify genetic factors associated with chronic HBV susceptibility. A total of 1,065 male controls and 1,623 male HBsAg carriers were included. The whole-genome genotyping was done on Illumina HumanHap550 beadchips in 304 healthy controls and HumanHap610 beadchips in 321 cases. We found that rs9277535 (HLA-DPB1, P = 4.87x10(-14)), rs9276370 (HLA-DQA2, P = 1.9x10(-12)), rs7756516 and rs7453920 (HLA-DQB2, P = 1.48610(-11) and P = 6.66x10(-15) respectively) were significantly associated with persistent HBV infection. A novel SNP rs9366816 near HLA-DPA3 also showed significant association (P = 2.58x10(-10)). The "T-T-G-G-T" haplotype of the five SNPs further signified their association with the disease (P = 1.48x10(-12); OR = 1.49). The "T-T" haplotype composed of rs7756516 and rs9276370 was more prevalent in severe disease subgroups and associated with non-sustained therapeutic response (P = 0.0262). The "G-C" haplotype was associated with sustained therapeutic response (P = 0.0132; OR = 2.49). We confirmed that HLA-DPB1, HLA-DQA2 and HLA-DQB2 loci were associated with persistent HBV infection in male Taiwan Han-Chinese. In addition, the HLA-DQA2 and -DQB2 complex was associated with clinical progression and therapeutic response.
Abstract How prebiotic metabolic pathways could have formed is an essential question for the origins of life on early Earth. From the abiogenetic point of view, the emergence of primordial metabolism may be postulated as a continuum from Earth's geochemical processes to chemoautotrophic biochemical procedures on mineral surfaces. In the present study, we examined in detail the reversible amination of α-ketoglutarate on UV-irradiated ZnS particles under variable reaction conditions such as pH, temperature, hole scavenger species and concentrations, and different amino acids. It was observed that the reductive amination of α-ketoglutarate and the oxidative amination of glutamate were both effectively performed on ZnS surfaces in the presence and absence of a hole scavenger, respectively. Accordingly, a photocatalytic mechanism was proposed. The reversible photochemical reaction was more efficient under basic conditions but independent of temperature in the range of 30–60 °C. SO32− was more effective than S2− as the hole scavenger. Finally, we extended the glutamate dehydrogenase-like chemistry to a set of other α-amino acids and their corresponding α-oxo acids and found that hydrophobic amino acid side chains were more conducive to the reversible redox reactions. Since the experimental conditions are believed to have been prevalent in shallow water hydrothermal vent systems of early Earth, the results of this work not only suggest that the ZnS-assisted photochemical reaction can regulate the redox equilibrium between α-amino acids and α-oxo acids, but also provide a model of how prebiotic metabolic homoeostasis could have been developed and regulated. These findings can advance our understanding of the establishment of archaic non-enzymatic metabolic systems and the origins of autotrophy.