Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer

A fluorescence in situ hybridisation (FISH) assay has been used to screen for ETV1 gene rearrangements in a cohort of 429 prostate cancers from patients who had been diagnosed by trans-urethral resection of the prostate. The presence of ETV1 gene alterations (found in 23 cases, 5.4%) was correlated with higher Gleason Score (P=0.001), PSA level at diagnosis (P=<0.0001) and clinical stage (P=0.017) but was not linked to poorer survival. We found that the six previously characterised translocation partners of ETV1 only accounted for 34% of ETV1 re-arrangements (eight out of 23) in this series, with fusion to the androgen-repressed gene C15orf21 representing the commonest event (four out of 23). In 5'-RACE experiments on RNA extracted from formalin-fixed tissue we identified the androgen-upregulated gene ACSL3 as a new 5'-translocation partner of ETV1. These studies report a novel fusion partner for ETV1 and highlight the considerable heterogeneity of ETV1 gene rearrangements in human prostate cancer.

Chronology of the site of Grotte du Renne, Arcy-sur-Cure, France: implications for Neanderthal symbolic behaviour

Higham et al (2010) published a large series of new dates from the key French Palaeolithic site of the Grotte du Renne at Arcy-sur-Cure. The site is important because it is one of only two sites in Europe in which Châtelperronian lithic remains co-occur with Neanderthal human remains. A large series of dates from the Mousterian, Châtelperronian, Aurignacian and Gravettian levels of the site was obtained. The 14C results showed great variability, which Higham et al (2010) interpreted as most likely to be due to mixing of archaeological material in the site. In contrast, Caron et al (2011) suggested that the site stratigraphy is well preserved and that the problem with the variability in the radiocarbon ages was due to unremoved contamination in the dated bone. In this paper we address their critique of the original Higham et al (2010) paper

Prognostic significance of combining VEGFA, FLT1 and KDR mRNA expression in lung cancer

Angiogenesis is important in cancer progression. Promising results in clinical trials have indicated that targeting vascular epidermal growth factor (VEGF) signaling may prolong lung cancer patient survival. In particular, various studies have implicated VEGFA as a potential prognostic marker in lung cancer, although prognostication using the expression of VEGF receptors (VEGFRs), such as fms-related tyrosine kinase 1 (FLT1; also known as VEGFR1) and kinase insert domain receptor (KDR; also known as VEGFR2), has produced varied results in different lung cancer studies. The present study aimed to investigate the prognostic significance of these three factors, alone or in combination. mRNA expression data were extracted from four independent lung cancer cohorts totaling 583 patients, and the association between mRNA expression and survival was investigated by performing statistical analyses. When VEGFA, FLT1 and KDR expression were considered alone, only VEGFA demonstrated a significant association with patient survival consistently across all four datasets (P<0.05). Patients with a high expression of VEGFA and one of the two receptors were associated with significantly worse survival than patients expressing low levels of VEGFA and the particular receptor (P<0.05). Notably, patients with a high level expression of all three genes in their tumor specimens were associated with a significantly shorter survival time compared with patients exhibiting a low level expression of one, two or all three genes (P<0.05). The results indicate that a high level of VEGFA expression and its receptors may be required for cancer progression. Therefore, these three factors should be considered together as a prognostic indicator for lung cancer patients.

Exploiting Significance of Computations for Energy-Constrained Approximate Computing

Approximate execution is a viable technique for environments with energy constraints, provided that applications are given the mechanisms to produce outputs of the highest possible quality within the available energy budget. This paper introduces a framework for energy-constrained execution with controlled and graceful quality loss. A simple programming model allows developers to structure the computation in different tasks, and to express the relative importance of these tasks for the quality of the end result. For non-significant tasks, the developer can also supply less costly, approximate versions. The target energy consumption for a given execution is specified when the application is launched. A significance-aware runtime system employs an application-specific analytical energy model to decide how many cores to use for the execution, the operating frequency for these cores, as well as the degree of task approximation, so as to maximize the quality of the output while meeting the user-specified energy constraints. Evaluation on a dual-socket 16-core Intel platform using 9 benchmark kernels shows that the proposed framework picks the optimal configuration with high accuracy. Also, a comparison with loop perforation (a well-known compile-time approximation technique), shows that the proposed framework results in significantly higher quality for the same energy budget.

Expression of proteins associated with hypoxia and Wnt pathway activation is of prognostic significance in hepatocellular carcinoma

In the development and progression of hepatocellular carcinoma, tumor hypoxia plays an important role, as does activation of the Wnt pathway. The aim of this study was to characterize the expression and interrelationship between hypoxia and Wnt-pathway-associated proteins as prognostic factors for hepatocellular carcinoma. Expression of HIF-1α, CA-IX, E-cadherin, β-catenin, and Ki-67 was assessed by immunohistochemistry in 179 primary hepatocellular carcinoma cases. Univariate and multivariate analyses were performed to assess the relationship between the clinicopathological factors, protein expression, overall survival (OS), and recurrence-free survival (RFS). By univariate analysis, tumor stage, size, satellitosis, and vascular invasion were confirmed as prognostic factors for worse OS and RFS. High expression of HIF-1α, CA-IX, β-catenin, Ki-67, and E-cadherin was observed in 60, 15, 64, 8, and 64 % of tumors, respectively, and this was significantly associated with poor OS. CA-IX, HIF-1α, and E-cadherin were independent predictors of poor prognosis. We stratified 169 patients into four groups according to the expression level of hypoxia and Wnt pathway markers. The group with high expression of both hypoxia and Wnt-pathway-associated proteins showed worst OS. The poor survival of this group was also significant in patients with early stage disease and tumor size of less than 5 cm (p < 0.05). We identified a subgroup of hepatocellular carcinoma patients with high expression of both hypoxia and Wnt pathway proteins and found this predictive of poor survival. The therapeutic options for this group might need to be revisited.