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Chuang Zhang,1,2,* Ruoxi Yu,1,2,* Zhi Li,1,2 Huicong Song,1,2 Dan Zang,1,2 Mingming Deng,1 Yibo Fan,1,2 Yunpeng Liu,1,2 Ye Zhang,1,2 Xiujuan Qu1,21Key Laboratory of Anticancer Drugs and Biotherapy, the First Hospital of China Medical University, Shenyang, Liaoning, 110001, People’s Republic of China; 2Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, People’s Republic of China *These authors contributed equally tothis work Purpose: The chr1p/19q co-deletion is a favorable prognostic factor in patients with lower grade glioma. The aim of this study was to reveal key genes for prognosis and establish prognostic gene signatures based on genes encoded by chr1p/19q.Materials and methods: The data was downloaded from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA) and Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between lower grade glioma tissue and normal brain were identified. The univariate COX regression, robust likelihood-base survival analysis (rbsurv) and multivariate COX regression analysis were used to establish the 4-gene-signature based on the DEGs. The receiver operating characteristic (ROC) curve and the Kaplan-Mere curve were used to verify the prediction accuracy of the signature. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were also performed to explore the reasons for good prognosis in patients with chr1p/19q deletion.Results: A total of 1346 DEGs were identified between lower grade glioma samples and normal brain samples in GSE16011, including 56 up-regulated mRNAs located on chr1p and 20 up-regulated mRNAs located on chr19q. We established a 4-gene-signature that was significantly associated with survival based on the 76 gene. The AUC of the 4-gene-signature for 5-year OS in TCGA and CGGA was 0.837 and 0.876, respectively, which was superior compared to other parameters such as chr1p/19q co-deletion, IDH mutant, WHO grade and histology type, especially in chr1p/19q non-co-deletion patients. GSEA and KEGG analysis suggested that the prolongation of chr1p/19q in patients could be associated with cell cycle and DNA mismatch repairing.Conclusions: We established a robust 4-gene-signature based on the chr1p/19q and we explored the potential function of these newly identified survival-associated genes by bioinformatics analysis. The 4-gene from the signature are promising molecular targets to be used in the future.Keywords: lower grade glioma, prognostic signature, 1p/19q co-deletion, rbsurv

Deng Zang,1,2 Chao Niu,1 Haji Akber Aisa1 1Key Laboratory of Plant Resources and Chemistry in Arid Regions, State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China; 2University of Chinese Academy of Sciences, Beijing 100049, China Background: Melanogenesis, or the biosynthesis of melanin, plays a critical role in the pigmentation of skin, hair, and eyes. Reduced melanogenesis may lead to depigmentation conditions such as vitiligo. Psoralen, a furocoumarin derivative, is closely associated with melanogenesis, and its derivative 8-methoxypsoralen is used in psoralen and ultraviolet A therapy for pigmentation disorders. In a previous study, we synthesized a new series of amine derivatives of furocoumarin, of which 5-(morpholinomethyl)-3-phenyl-7H-furo[3,2-g]chromen-7-one (encoded as D206008) showed a remarkable melanogenic effect in B16 murine cells.Methods: In this study, we examined the effects of D206008 on the melanogenesis-related pathways in B16 cells. D206008 increased melanin production and tyrosinase (TYR) activity, as well as the mRNA and protein expression levels of the melanogenic enzymes TYR, TRP-1 and TRP-2, and the melanogenesis-related transcription factor microphthalmia-associated transcription factor (MITF) in a dose-dependent (0–100 µM) and time-dependent (0–48 hours) manner.Results: Mechanistically, D206008 inhibited β-catenin degradation by enhancing the phosphorylation of Akt and glycogen synthase kinase-3β (GSK-3β), which increased the accumulation of β-catenin in the cytoplasm. Nuclear translocation of β-catenin also increased in response to D206008 treatment.Conclusion: Taken together, these data indicate that D206008 promotes melanin synthesis by stimulating the nuclear translocation of β-catenin, which activates MITF transcription and eventually melanogenesis. Keywords: amine derivatives of furocoumarin, melanogenesis, Akt/GSK-3β/β-catenin

CHEP'12 Talk Structured Storage - Concepts - Technologies ATLAS DDM Use Cases - Storage facility - Data intensive analytics Operational Experiences - Software - Hardware Conclusions

The DDM Tracer Service is aimed to trace and monitor the atlas file operations on the Worldwide LHC Computing Grid. The volume of traces has increased significantly since the service started in 2009. Now there are about ~5 million trace messages every day and peaks of greater than 250Hz, with peak rates continuing to climb, which gives the current service structure a big challenge. Analysis of large datasets based on on-demand queries to the relational database management system (RDBMS), i.e. Oracle, can be problematic, and have a significant effect on the database's performance. Consequently, We have investigated some new high availability technologies like messaging infrastructure, specifically ActiveMQ, and key-value stores. The advantages of key value store technology are that they are distributed and have high scalability; also their write performances are usually much better than RDBMS, all of which are very useful for the Tracer service. Indexes and distributed counters have been also tested to improve query performance and provided almost real time results. In this talk, the design principles, architecture and main characteristics of Tracer monitoring framework will be described and examples of its usage will be presented.

A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients’ lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology., National Institutes of Health (U.S.) (Grant U54HG003067), National Institutes of Health (U.S.) (Grant U54HG003273), National Institutes of Health (U.S.) (Grant U54HG003079), National Institutes of Health (U.S.) (Grant U24CA126543), National Institutes of Health (U.S.) (Grant U24CA126544), National Institutes of Health (U.S.) (Grant U24CA126546), National Institutes of Health (U.S.) (Grant U24CA126551), National Institutes of Health (U.S.) (Grant U24CA126554), National Institutes of Health (U.S.) (Grant U24CA126561), National Institutes of Health (U.S.) (Grant U24CA126563), National Institutes of Health (U.S.) (Grant U24CA143882), National Institutes of Health (U.S.) (Grant U24CA143731), National Institutes of Health (U.S.) (Grant U24CA143835), National Institutes of Health (U.S.) (Grant U24CA143845), National Institutes of Health (U.S.) (Grant U24CA143858), National Institutes of Health (U.S.) (Grant U24CA144025), National Institutes of Health (U.S.) (Grant U24CA143866), National Institutes of Health (U.S.) (Grant U24CA143867), National Institutes of Health (U.S.) (Grant U24CA143848), National Institutes of Health (U.S.) (Grant U24CA143843), National Institutes of Health (U.S.) (Grant R21CA135877)