Poor survival outcomes in HER2 positive breast cancer patients with low grade, node negative tumours

We present a retrospective analysis on a cohort of low-grade, node-negative patients showing that human epidermal growth factor receptor 2 (HER2) status significantly affects the survival in this otherwise very good prognostic group. Our results provide support for the use of adjuvant trastuzumab in patients who are typically classified as having very good prognosis, not routinely offered standard chemotherapy, and who as such do not fit current UK prescribing guidelines for trastuzumab

A Measurement of Photon Production in Electron Avalanches in CF4

This paper presents a measurement of the ratio of photon to electron production and the scintillation spectrum in a popular gas for time pro jection chambers, carbon tetrafluoride (CF4), over the range of 200 to 800 nm; the ratio is measured to be 0.34+/-0.04. This result is of particular importance for a new generation of dark matter time projection chambers with directional sensitivity which use CF4 as a fill gas.Comment: 19 pages, including appendix. 8 figure

Phosphorylated c-Src in the nucleus is associated with improved patient outcome in ER-positive breast cancer

Elevated c-Src protein expression has been shown in breast cancer and <i>in vitro</i> evidence suggests a role in endocrine resistance. To investigate whether c-Src is involved in endocrine resistance, we examined the expression of both total and activated c-Src in human breast cancer specimens from a cohort of oestrogen receptor (ER)-positive tamoxifen-treated breast cancer patients. Tissue microarray technology was employed to analyse 262 tumour specimens taken before tamoxifen treatment. Immunohistochemistry using total c-Src and activated c-Src antibodies was performed. Kaplan–Meier survival curves were constructed and log-rank test were performed. High level of nuclear activated Src was significantly associated with improved overall survival (<i>P</i>=0.047) and lower recurrence rates on tamoxifen (<i>P</i>=0.02). Improved patient outcome was only seen with activated Src in the nucleus. Nuclear activated Src expression was significantly associated with node-negative disease and a lower NPI (<i>P</i><0.05). On subgroup analysis, only ER-positive/progesterone receptor (PgR)-positive tumours were associated with improved survival (<i>P</i>=0.004). This shows that c-Src activity is increased in breast cancer and that activated Src within the nucleus of ER-positive tumours predicts an improved outcome. In ER/PgR-positive disease, activated Src kinase does not appear to be involved in <i>de novo</i> endocrine resistance. Further study is required in ER-negative breast cancer as this may represent a cohort in which it is associated with poor outcome

CERN West Area neutrino facility beam line alignment

This papers describes the alignment of the West Area Neutrino Beam Line at CERN to the two neutrino experiments CHORUS and NOMAD. The T9 neutrino (n) target position and the position of the magnetic horn were optimised using the secondary muon intensity profiles from the muon pits in the shielding. In the experiments the improved geometry provides a better centred beam (< 5 cm) and a measured increase in the n flux of 8%

Constraints on Low-Mass WIMP Interactions on 19F from PICASSO

Recent results from the PICASSO dark matter search experiment at SNOLAB are reported. These results were obtained using a subset of 10 detectors with a total target mass of 0.72 kg of 19F and an exposure of 114 kgd. The low backgrounds in PICASSO allow recoil energy thresholds as low as 1.7 keV to be obtained which results in an increased sensitivity to interactions from Weakly Interacting Massive Particles (WIMPs) with masses below 10 GeV/c^2. No dark matter signal was found. Best exclusion limits in the spin dependent sector were obtained for WIMP masses of 20 GeV/c^2 with a cross section on protons of sigma_p^SD = 0.032 pb (90% C.L.). In the spin independent sector close to the low mass region of 7 GeV/c2 favoured by CoGeNT and DAMA/LIBRA, cross sections larger than sigma_p^SI = 1.41x10^-4 pb (90% C.L.) are excluded.Comment: 23 pages, 7 figures, to be published in Phys. Lett.

Quantification of Rapid Myosin Regulatory Light Chain Phosphorylation Using High-Throughput In-Cell Western Assays: Comparison to Western Immunoblots

Quantification of phospho-proteins (PPs) is crucial when studying cellular signaling pathways. Western immunoblotting (WB) is commonly used for the measurement of relative levels of signaling intermediates in experimental samples. However, WB is in general a labour-intensive and low-throughput technique. Because of variability in protein yield and phospho-signal preservation during protein harvesting, and potential loss of antigen during protein transfer, WB provides only semi-quantitative data. By comparison, the "in-cell western" (ICW) technique has high-throughput capacity and requires less extensive sample preparation. Thus, we compared the ICW technique to WB for measuring phosphorylated myosin regulatory light chain (PMLC(20)) in primary cultures of uterine myocytes to assess their relative specificity, sensitivity, precision, and quantification of biologically relevant responses.ICWs are cell-based microplate assays for quantification of protein targets in their cellular context. ICWs utilize a two-channel infrared (IR) scanner (Odyssey(R)) to quantify signals arising from near-infrared (NIR) fluorophores conjugated to secondary antibodies. One channel is dedicated to measuring the protein of interest and the second is used for data normalization of the signal in each well of the microplate. Using uterine myocytes, we assessed oxytocin (OT)-stimulated MLC(20) phosphorylation measured by ICW and WB, both using NIR fluorescence. ICW and WB data were comparable regarding signal linearity, signal specificity, and time course of phosphorylation response to OT.ICW and WB yield comparable biological data. The advantages of ICW over WB are its high-throughput capacity, improved precision, and reduced sample preparation requirements. ICW might provide better sensitivity and precision with low-quantity samples or for protocols requiring large numbers of samples. These features make the ICW technique an excellent tool for the study of phosphorylation endpoints. However, the drawbacks of ICW include the need for a cell culture format and the lack of utility where protein purification, concentration or stoichiometric analyses are required

The ZEPLIN-III dark matter detector: instrument design, manufacture and commissioning

We present details of the technical design and manufacture of the ZEPLIN-III dark matter experiment. ZEPLIN-III is a two-phase xenon detector which measures both the scintillation light and the ionisation charge generated in the liquid by interacting particles and radiation. The instrument design is driven by both the physics requirements and by the technology requirements surrounding the use of liquid xenon. These include considerations of key performance parameters, such as the efficiency of scintillation light collection, restrictions placed on the use of materials to control the inherent radioactivity levels, attainment of high vacuum levels and chemical contamination control. The successful solution has involved a number of novel design and manufacturing features which will be of specific use to future generations of direct dark matter search experiments as they struggle with similar and progressively more demanding requirements.Comment: 25 pages, 19 figures. Submitted to Astropart. Phys. Some figures down sampled to reduce siz