Issues with fracturing ice during an ice drilling project in Greenland (EastGRIP)

Drilling an ice core through an ice sheet (typically 2000 to 3000 m thick) is a technical challenge that nonetheless generates valuable and unique information on palaeo-climate and ice dynamics. As technically the drilling cannot be done in one run, the core has to be fractured approximately every 3 m to retrieve core sections from the bore hole. This fracture process is initiated by breaking the core with core-catchers which also clamp the engaged core in the drill head while the whole drill is then pulled up with the winch motor. This standard procedure is known to become difficult and requires extremely high pulling forces (Wilhelms et al. 2007), in the very deep part of the drill procedure, close to the bedrock of the ice sheet, especially when the ice material becomes warm (approximately -2°C) due to the geothermal heat released from the bedrock. Recently, during the EastGRIP (East Greenland Ice coring Project) drilling we observed a similar issue with breaking off cored sections only with extremely high pulling forces, but started from approximately 1800 m of depth, where the temperature is still very cold (approximately -20°C). This has not been observed at other ice drilling sites. As dependencies of fracture behaviour on crystal orientation and grain size are known (Schulson & Duval 2009) for ice, we thus examined the microstructure in the ice samples close to and at the core breaks. First preliminary results suggest that these so far unexperienced difficulties are due to the profoundly different c-axes orientation distribution (CPO) in the EastGRIP ice core. In contrast to other deep ice cores which have been drilled on ice domes or ice divides, EastGRIP is located in an ice stream. This location means that the deformation geometry (kinematics) is completely different, resulting in a different CPO (girdle pattern instead of single maximum pattern). Evidence regarding additional grain-size dependence will hopefully help to refine the fracturing procedure, which is possible due to a rather strong grain size layering observed in natural ice formed by snow precipitation. --------------------- Wilhelms, F.; Sheldon, S. G.; Hamann, I. & Kipfstuhl, S. Implications for and findings from deep ice core drillings - An example: The ultimate tensile strength of ice at high strain rates. Physics and Chemistry of Ice (The proceedings of the International Conference on the Physics and Chemistry of Ice held at Bremerhaven, Germany on 23-28 July 2006), 2007, 635-639 Schulson, E. M. & Duval, P. Creep and Fracture of Ice. Cambridge University Press, 2009, 40

An explorative analysis of ERCC1-19q13 copy number aberrations in a chemonaive stage III colorectal cancer cohort

BACKGROUND: Platinum-based chemotherapy has long been used in the treatment of a variety of cancers and functions by inducing DNA damage. ERCC1 and ERCC4 are involved in the removal of this damage and have previously been implicated in resistance to platinum compounds. The aim of the current investigation is to determine the presence, frequency and prognostic impact of ERCC1 or ERCC4 gene copy number alterations in colorectal cancer (CRC). METHODS: Fluorescent in situ hybridization probes directed at ERCC1 and ERCC4 with relevant reference probes were constructed. Probes were tested in a CRC cell line panel and in tumor sections from 152 stage III CRC chemonaive patients. Relationships between biomarker status and clinical endpoints (overall survival, time to recurrence, and local recurrence in rectal cancer) were analyzed by survival statistics. RESULTS: ERCC1-19q13 copy number alterations were observed in a single cell line metaphase (HT29). In patient material, ERCC1-19q13 copy number gains (ERCC1-19q13/CEN-2 ≥ 1.5) were detected in 27.0% of specimens, whereas ERCC1-19q13 deletions (ERCC1-19q13/CEN-2 < 0.8) were only detected in 1.3%. ERCC1-19q13 gain was significantly associated with longer survival (multivariate analysis, HR: 0.45, 95% CI: 0.20-1.00, p = 0.049) in patients with colon tumors, but not rectal tumors. No ERCC4 aberrations were detected and scoring was discontinued after 50 patients. CONCLUSIONS: ERCC1-19q13 copy number gains occur frequently in stage III CRC and influences survival in patients with colon tumors. Future studies will investigate the effect of ERCC1-19q13 aberrations in a platinum-treated patient population with the aim of developing a predictive biomarker profile for oxaliplatin sensitivity in CRC

Mechanisms of topoisomerase I (<em>TOP1</em>) gene copy number increase in a stage III colorectal cancer patient cohort

BACKGROUND: Topoisomerase I (Top1) is the target of Top1 inhibitor chemotherapy. The TOP1 gene, located at 20q12-q13.1, is frequently detected at elevated copy numbers in colorectal cancer (CRC). The present study explores the mechanism, frequency and prognostic impact of TOP1 gene aberrations in stage III CRC and how these can be detected by fluorescent in situ hybridization (FISH). METHODS: Nine CRC cell line metaphase spreads were analyzed by FISH with a TOP1 probe in combination with a reference probe covering either the centromeric region of chromosome 20 (CEN-20) or chromosome 2 (CEN-2). Tissue sections from 154 chemonaive stage III CRC patients, previously studied with TOP1/CEN-20, were analyzed with TOP1/CEN-2. Relationships between biomarker status and overall survival (OS), time to recurrence (TTR) in CRC and time to local recurrence (LR; rectal cancer only) were determined. RESULTS: TOP1 aberrations were observed in four cell line metaphases. In all cell lines CEN-2 was found to reflect chromosomal ploidy levels and therefore the TOP1/CEN-2 probe combination was selected to identify TOP1 gene gains (TOP1/CEN-2≥1.5). One hundred and three patients (68.2%) had TOP1 gain, of which 15 patients (14.6%) harbored an amplification (TOP1/CEN-20≥2.0). TOP1 gene gain did not have any association with clinical endpoints, whereas TOP1 amplification showed a non-significant trend towards longer TTR (multivariate HR: 0.50, p = 0.08). Once amplified cases were segregated from other cases of gene gain, non-amplified gene increases (TOP1/CEN-2≥1.5 and TOP1/CEN-20<2.0) showed a trend towards shorter TTR (univariate HR: 1.57, p = 0.07). CONCLUSIONS: TOP1 gene copy number increase occurs frequently in stage III CRC in a mechanism that often includes CEN-20. Using CEN-2 as a measurement for tumor ploidy levels, we were able to discriminate between different mechanisms of gene gain, which appeared to differ in prognostic impact. TOP1 FISH guidelines have been updated