Old Techniques for New Join Algorithms: A Case Study in RDF Processing

Recently there has been significant interest around designing specialized RDF engines, as traditional query processing mechanisms incur orders of magnitude performance gaps on many RDF workloads. At the same time researchers have released new worst-case optimal join algorithms which can be asymptotically better than the join algorithms in traditional engines. In this paper we apply worst-case optimal join algorithms to a standard RDF workload, the LUBM benchmark, for the first time. We do so using two worst-case optimal engines: (1) LogicBlox, a commercial database engine, and (2) EmptyHeaded, our prototype research engine with enhanced worst-case optimal join algorithms. We show that without any added optimizations both LogicBlox and EmptyHeaded outperform two state-of-the-art specialized RDF engines, RDF-3X and TripleBit, by up to 6x on cyclic join queries-the queries where traditional optimizers are suboptimal. On the remaining, less complex queries in the LUBM benchmark, we show that three classic query optimization techniques enable EmptyHeaded to compete with RDF engines, even when there is no asymptotic advantage to the worst-case optimal approach. We validate that our design has merit as EmptyHeaded outperforms MonetDB by three orders of magnitude and LogicBlox by two orders of magnitude, while remaining within an order of magnitude of RDF-3X and TripleBit

Hedgehog-EGFR cooperation response genes determine the oncogenic phenotype of basal cell carcinoma and tumour-initiating pancreatic cancer cells

Inhibition of Hedgehog (HH)/GLI signalling in cancer is a promising therapeutic approach. Interactions between HH/GLI and other oncogenic pathways affect the strength and tumourigenicity of HH/GLI. Cooperation of HH/GLI with epidermal growth factor receptor (EGFR) signalling promotes transformation and cancer cell proliferation in vitro. However, the in vivo relevance of HH-EGFR signal integration and the critical downstream mediators are largely undefined. In this report we show that genetic and pharmacologic inhibition of EGFR signalling reduces tumour growth in mouse models of HH/GLI driven basal cell carcinoma (BCC). We describe HH-EGFR cooperation response genes including SOX2, SOX9, JUN, CXCR4 and FGF19 that are synergistically activated by HH-EGFR signal integration and required for in vivo growth of BCC cells and tumour-initiating pancreatic cancer cells. The data validate EGFR signalling as drug target in HH/GLI driven cancers and shed light on the molecular processes controlled by HH-EGFR signal cooperation, providing new therapeutic strategies based on combined targeting of HH-EGFR signalling and selected downstream target genes. © 2012 EMBO Molecular Medicine

The Metastasis-Associated Anterior Gradient 2 Protein Is Correlated with Poor Survival of Breast Cancer Patients

The secreted metastasis-inducing protein, human anterior gradient 2 (AGR2), has been independently reported to be associated with either a reduced or an increased survival of different groups of patients with breast cancer. We now aim to analyze the expression of AGR2 in a third completely independent group of patients using a specific AGR2 monoclonal antibody (mAb). Primary tumors from a group of 315 patients suffering from operable (stage I and II) breast cancer with 20-years follow-up were immunocytochemically stained with a specific mAb to AGR2 and associations with prognostic factors and patient survival were analyzed. The mAb specifically recognized AGR2 in Western blots, and positive staining for AGR2 was significantly associated with involved lymph nodes and staining for estrogen receptor α, progesterone receptor, and the metastasis-inducing proteins osteopontin, S100P, and S100A4. After 20 years of follow-up, only 26% of patients with AGR2-positive carcinomas survived compared with 96% of those with AGR2 negative carcinomas, with the highly significant difference in median survival times of 68 and >216 months, respectively (P < 0.0001). Cox’s multivariate regression analysis showed that staining for AGR2 was one of the most significant independent prognostic indicators, with a corrected relative risk of 9.4. The presence of AGR2 in the primary tumor is therefore a possible prognostic indicator of poor patient outcome in breast cancer