A Survey on IT-Techniques for a Dynamic Emergency Management in Large Infrastructures

This deliverable is a survey on the IT techniques that are relevant to the three use cases of the project EMILI. It describes the state-of-the-art in four complementary IT areas: Data cleansing, supervisory control and data acquisition, wireless sensor networks and complex event processing. Even though the deliverable’s authors have tried to avoid a too technical language and have tried to explain every concept referred to, the deliverable might seem rather technical to readers so far little familiar with the techniques it describes

MLOS: An Infrastructure for Automated Software Performance Engineering

Developing modern systems software is a complex task that combines business logic programming and Software Performance Engineering (SPE). The later is an experimental and labor-intensive activity focused on optimizing the system for a given hardware, software, and workload (hw/sw/wl) context. Today's SPE is performed during build/release phases by specialized teams, and cursed by: 1) lack of standardized and automated tools, 2) significant repeated work as hw/sw/wl context changes, 3) fragility induced by a "one-size-fit-all" tuning (where improvements on one workload or component may impact others). The net result: despite costly investments, system software is often outside its optimal operating point - anecdotally leaving 30% to 40% of performance on the table. The recent developments in Data Science (DS) hints at an opportunity: combining DS tooling and methodologies with a new developer experience to transform the practice of SPE. In this paper we present: MLOS, an ML-powered infrastructure and methodology to democratize and automate Software Performance Engineering. MLOS enables continuous, instance-level, robust, and trackable systems optimization. MLOS is being developed and employed within Microsoft to optimize SQL Server performance. Early results indicated that component-level optimizations can lead to 20%-90% improvements when custom-tuning for a specific hw/sw/wl, hinting at a significant opportunity. However, several research challenges remain that will require community involvement. To this end, we are in the process of open-sourcing the MLOS core infrastructure, and we are engaging with academic institutions to create an educational program around Software 2.0 and MLOS ideas.Comment: 4 pages, DEEM 202

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10−8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction

Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction

The known breast cancer (BC) susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1,LSP1 and 2q35 confer increased risks of BC for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of three additional SNPs, rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11 and rs10941679 at 5p12 and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased BC risk for BRCA2 carriers (per-allele Hazard Ratio (HR)=1.10, 95%CI:1.03-1.18, p=0.006 and HR=1.09, 95%CI:1.01-1.19, p=0.03, respectively). Neither SNP was associated with BC risk for BRCA1 carriers and rs6504950 was not associated with BC for either BRCA1 or BRCA2 carriers. Of the nine polymorphisms investigated, seven were associated with BC for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, p-values:7×10−11-0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (p=0.0049, 0.03 respectively). All risk associated polymorphisms appear to interact multiplicatively on BC risk for mutation carriers. Based on the joint genotype distribution of the seven risk associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e. between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing BC by age 80, compared with 42-50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences may be sufficient to influence the clinical management of mutation carriers

DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

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