Unexpected earthquake hazard revealed by Holocene rupture on the Kenchreai Fault (central Greece): Implications for weak sub-fault shear zones

High-resolution elevation models, palaeoseismic trenching, and Quaternary dating demonstrate that the Kenchreai Fault in the eastern Gulf of Corinth (Greece) has ruptured in the Holocene. Along with the adjacent Pisia and Heraion Faults (which ruptured in 1981), our results indicate the presence of closely-spaced and parallel normal faults that are simultaneously active, but at different rates. Such a configuration allows us to address one of the major questions in understanding the earthquake cycle, specifically what controls the distribution of interseismic strain accumulation? Our results imply that the interseismic loading and subsequent earthquakes on these faults are governed by weak shear zones in the underlying ductile crust. In addition, the identification of significant earthquake slip on a fault that does not dominate the late Quaternary geomorphology or vertical coastal motions in the region provides an important lesson in earthquake hazard assessment.This work forms part of the NERCand ESRC-funded project ‘Earthquakes Without Frontiers’, and was partly funded by the NERC grant ‘Looking Inside the Continents from Space’

Prognostic relevance of MMP-2 (72-kD collagenase IV) in gastric cancer

The association of MMP-2 (matrix metalloproteinase 2, 72-kD collagenase IV) with invasive and metastatic capacity of tumor cells has implicated a potential role in the prognosis for cancer patients. However, no larger study has been done to prove this hypothesis. The present study was therefore designed to investigate the prognostic impact of MMP-2 in a prospective series of 203 gastric cancer patients. MMP-2 expression was measured immunohistochemically and scored semiquantitatively (score 0-3) in carcinoma cells, and results were correlated with clinicopathological tumor parameters and parameters of the urokinase-type plasminogen activator (uPA) system. Survival analyses were done using the Kaplan-Meier method (log-rank statistics) and multivariate Cox analysis. Significant correlations were found for MMP-2 and Lauren's classification, M stage and proteases/inhibitors of the uPA system in the primary tumor. Kaplan-Meier analysis revealed an association of increasing MMP-2 expression with worse prognosis. This was especially seen in patients with a parallel high expression of uPA receptor. However, differences in survival probabilities between low and high MMP-2 levels were not significant. In a separate analysis of diffuse-type cancers, MMP-2 was significantly associated with disease-free (p = 0.0056) and overall survival (p = 0.0426). Multivariately, MMP-2 was not an independent parameter. Our results demonstrate that there is an association of immunohistochemical detection of MMP-2 with prognosis of cancer patients. For diffuse gastric cancers, it is a significant prognostic parameter, however, not of independent impact. The study further suggests that consideration of interrelated tumor-associated proteases like uPA receptor in combination with MMP-2 may improve its prognostic power

Dilatant normal faulting in jointed cohesive rocks: a physical model study

Dilatant faults often form in rocks containing pre-existing joints, but the effects of joints on fault segment linkage and fracture connectivity are not well understood. We present an analogue modeling study using cohesive powder with pre-formed joint sets in the upper layer, varying the angle between joints and a rigid basement fault. We analyze interpreted map-view photographs at maximum displacement for damage zone width, number of connected joints, number of secondary fractures, degree of segmentation and area fraction of massively dilatant fractures. Particle imaging velocimetry provides insight into the deformation history of the experiments and illustrates the localization pattern of fault segments. Results show that with increasing angle between joint-set and basement-fault strike the number of secondary fractures and the number of connected joints increase, while the area fraction of massively dilatant fractures shows only a minor increase. Models without pre-existing joints show far lower area fractions of massively dilatant fractures while forming distinctly more secondary fractures

Disruption and pseudoautosomal localization of the major histocompatibility complex in monotremes

The characterization and chromosomal mapping of major histocompatibility complex (MHC)-containing BAC clones from platypus and the short-beaked echidna reveals new insights into the evolution of both the mammalian MHC and monotreme sex chromosomes

Evolution of a highly dilatant fault zone in the grabens of Canyonlands National Park, Utah, USA - Integrating fieldwork, ground-penetrating radar and airborne imagery analysis

Abstract. The grabens of Canyonlands National Park are a young and active system of sub-parallel, arcuate grabens, whose evolution is the result of salt movement in the subsurface and a slight regional tilt of the faulted strata. We present results of ground-penetrating radar (GPR) surveys in combination with field observations and analysis of high-resolution airborne imagery. GPR data show intense faulting of the Quaternary sediments at the flat graben floors, implying a more complex fault structure than visible at the surface. Direct measurements of heave and throw at several locations to infer fault dips at depth, combined with observations of primary joint surfaces in the upper 100 m, suggest a highly dilatant fault geometry. Sinkholes observed in the field as well as in airborne imagery give insights in local dilatancy and show where water and sediments are transported underground. Based on correlations of paleosols observed in outcrops and GPR profiles, we argue that either the grabens in Canyonlands National Park are older than previously assumed or that sedimentation rates were much higher in the Pleistocene. This is the final version of the article. It first appeared from Copernicus Publications via http://dx.doi.org/10.5194/se-6-839-2015 The supplement related to this article is available online at http://dx.doi.org/10.5194/se-6-839-2015-supplemen

Immunotherapy of Peritoneal Carcinomatosis with the Antibody Catumaxomab in Colon, Gastric, or Pancreatic Cancer: An Open-Label, Multicenter, Phase I/II Trial

Background: Peritoneal carcinomatosis (PC) is common in gastrointestinal (GI) cancer and there is no effective standard treatment. We investigated the tolerability and maximum tolerated dose (MTD) of the trifunctional antibody catumaxomab in patients with PC. Methods: In this open-label, phase I/II clinical trial, patients with epithelial cell adhesion molecule (EpCAM)-positive PC from GI cancer received 4 sequential intraperitoneal catumaxomab infusions: day 0: 10 mu g; day 3: 10 or 20 mu g; day 7: 30, 50, or 100 mu g; and day 10: 50, 100, or 200 mu g. Dose escalation was guided by dose-limiting toxicities. Results: The MTD was 10, 20, 50, and 200 mu g on days 0, 3, 7, and 10, respectively. Catumaxomab had an acceptable safety profile: Most common treatment-related adverse events (at the MTD) were fever, vomiting, and abdominal pain. At final examination, 11/17 evaluable patients (65%) were progression free: 1 patient had a complete and 3 a partial response. Median overall survival from the time of diagnosis of PC was 502 days. Conclusions: Intraperitoneal catumaxomab is a promising option for the treatment of PC from GI cancer

Loss of genes implicated in gastric function during platypus evolution

Several genes implicated in food digestion have been deleted or inactivated in platypus. This loss perhaps explains the anatomical and physiological differences in the gastrointestinal tract between monotremes and other vertebrates and provides insights into platypus genome evolution

Relative timing of uplift along the Zagros Mountain Front Flexure (Kurdistan Region of Iraq): Constrained by geomorphic indices and landscape evolution modeling

The Mountain Front Flexure marks a dominant topographic step in the frontal part of the Zagros Fold–Thrust Belt. It is characterized by numerous active anticlines atop of a basement fault. So far, little is known about the relative activity of the anticlines, about their evolution, or about how crustal deformation migrates over time. We assessed the relative landscape maturity of three along-strike anticlines (from SE to NW: Harir, Perat, and Akre) located on the hanging wall of the Mountain Front Flexure in the Kurdistan Region of Iraq to identify the most active structures and to gain insights into the evolution of the fold–thrust belt. Landscape maturity was evaluated using geomorphic indices such as hypsometric curves, hypsometric integral, surface roughness, and surface index. Subsequently, numerical landscape evolution models were run to estimate the relative time difference between the onset of growth of the anticlines, using the present-day topography of the Harir Anticline as a base model. A stream power equation was used to introduce fluvial erosion, and a hillslope diffusion equation was applied to account for colluvial sediment transport. For different time steps of model evolution, we calculated the geomorphic indices generated from the base model. While Akre Anticline shows deeply incised valleys and advanced erosion, Harir and Perat anticlines have relatively smoother surfaces and are supposedly younger than the Akre Anticline. The landscape maturity level decreases from NW to SE. A comparison of the geomorphic indices of the model output to those of the present-day topography of Perat and Akre anticlines revealed that it would take the Harir Anticline about 80–100 and 160–200&thinsp;kyr to reach the maturity level of the Perat and Akre anticlines, respectively, assuming erosion under constant conditions and constant rock uplift rates along the three anticlines. Since the factors controlling geomorphology (lithology, structural setting, and climate) are similar for all three anticlines, and under the assumption of constant growth and erosion conditions, we infer that uplift of the Akre Anticline started 160–200&thinsp;kyr before that of the Harir Anticline, with the Perat Anticline showing an intermediate age. A NW-ward propagation of the Harir Anticline itself implies that the uplift has been independent within different segments. Our method of estimating the relative age difference can be applied to many other anticlines in the Mountain Front Flexure region to construct a model of temporal evolution of this belt.</p

Overexpression of piRNA pathway genes in epithelial ovarian cancer

The importance of the Piwi-interacting RNA (piRNA) pathway for germ cell maintenance, genome integrity, DNA methylation and retrotransposon control raises possible roles of this pathway in cancer. Indeed aberrant expression of human PIWI orthologs and Maelstrom has been observed in various cancers. In this study we explored the expression and function of piRNA pathway genes in human ovarian cancer, based on our recent work, which showed widespread expression of piRNA pathway genes in the mammalian. Our work shows that PIWIL1 and MAEL expression is significantly increased in malignant EOC (n = 25) compared to benign tumor tissues (n = 19) and normal ovarian tissue (n = 8). The expression of PIWIL3 is lower in malignant and benign tissues when compared to normal ovary. Sequencing of PIWIL1 transcript revealed that in many tumors deletion of exon 17 leads to the introduction of a premature stop codon in the PIWI domain, likely due to a splicing error. In situ hybridization on tumor sections revealed that L1, PIWIL1, 2 and MAEL are specifically expressed in epithelial cells (cancerous cells) of EOC. Furthermore, PIWIL2 and MAEL are co-expressed in the stromal cells adjacent to tumor cells. Since PIWIL1 and MAEL are up regulated in malignant EOC and expressed in the epithelial cells, we investigated if these two genes affect invasiveness of ovarian cancer cell lines that do not normally express these genes. PIWIL1 and MAEL were transiently over expressed in the ovarian cancer cell line SKOV3, followed by real-time measurements of cell invasiveness. Surprisingly both PIWIL1 and MAEL over expression decreased the invasiveness of SKOV3 cells. Our findings support a growing body of evidence that shows that genes in this pathway are upregulated in cancer. In ovarian cancer we show for the first time that Piwil1 transcript may often be abnormal result in non functional product. In contrast to what has been observed in other cell types, we found that PIWIL1 and MAEL have a repressive effect on cell invasiveness.Shu Ly Lim, Carmela Ricciardelli, Martin K. Oehler, Izza M. D. De Arao Tan, Darryl Russell, Frank Grützne