A methodology for the capture and analysis of hybrid data: a case study of program debugging

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The novel mTOR inhibitor RAD001 (Everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells

Background/Aim: Tumors exhibiting constitutively activated PI(3) K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3) K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients. Copyright (c) 2007 S. Karger AG, Basel

Pulse-shape discrimination and energy resolution of a liquid-argon scintillator with xenon doping

Liquid-argon scintillation detectors are used in fundamental physics experiments and are being considered for security applications. Previous studies have suggested that the addition of small amounts of xenon dopant improves performance in light or signal yield, energy resolution, and particle discrimination. In this study, we investigate the detector response for xenon dopant concentrations from 9 +/- 5 ppm to 1100 +/- 500 ppm xenon (by weight) in 6 steps. The 3.14-liter detector uses tetraphenyl butadiene (TPB) wavelength shifter with dual photomultiplier tubes and is operated in single-phase mode. Gamma-ray-interaction signal yield of 4.0 +/- 0.1 photoelectrons/keV improved to 5.0 +/- 0.1 photoelectrons/keV with dopant. Energy resolution at 662 keV improved from (4.4 +/- 0.2)% ({\sigma}) to (3.5 +/- 0.2)% ({\sigma}) with dopant. Pulse-shape discrimination performance degraded greatly at the first addition of dopant, slightly improved with additional additions, then rapidly improved near the end of our dopant range, with performance becoming slightly better than pure argon at the highest tested dopant concentration. Some evidence of reduced neutron scintillation efficiency with increasing dopant concentration was observed. Finally, the waveform shape outside the TPB region is discussed, suggesting that the contribution to the waveform from xenon-produced light is primarily in the last portion of the slow component

Defining freshwater as a natural resource: a framework linking water use to the area of protection natural resources

© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: While many examples have shown unsustainable use of freshwater resources, existing LCIA methods for water use do not comprehensively address impacts to natural resources for future generations. This framework aims to (1) define freshwater resource as an item to protect within the Area of Protection (AoP) natural resources, (2) identify relevant impact pathways affecting freshwater resources, and (3) outline methodological choices for impact characterization model development. Methods: Considering the current scope of the AoP natural resources, the complex nature of freshwater resources and its important dimensions to safeguard safe future supply, a definition of freshwater resource is proposed, including water quality aspects. In order to clearly define what is to be protected, the freshwater resource is put in perspective through the lens of the three main safeguard subjects defined by Dewulf et al. (2015). In addition, an extensive literature review identifies a wide range of possible impact pathways to freshwater resources, establishing the link between different inventory elementary flows (water consumption, emissions, and land use) and their potential to cause long-term freshwater depletion or degradation. Results and discussion: Freshwater as a resource has a particular status in LCA resource assessment. First, it exists in the form of three types of resources: flow, fund, or stock. Then, in addition to being a resource for human economic activities (e.g., hydropower), it is above all a non-substitutable support for life that can be affected by both consumption (source function) and pollution (sink function). Therefore, both types of elementary flows (water consumption and emissions) should be linked to a damage indicator for freshwater as a resource. Land use is also identified as a potential stressor to freshwater resources by altering runoff, infiltration, and erosion processes as well as evapotranspiration. It is suggested to use the concept of recovery period to operationalize this framework: when the recovery period lasts longer than a given period of time, impacts are considered to be irreversible and fall into the concern of freshwater resources protection (i.e., affecting future generations), while short-term impacts effect the AoP ecosystem quality and human health directly. It is shown that it is relevant to include this concept in the impact assessment stage in order to discriminate the long-term from the short-term impacts, as some dynamic fate models already do. Conclusions: This framework provides a solid basis for the consistent development of future LCIA methods for freshwater resources, thereby capturing the potential long-term impacts that could warn decision makers about potential safe water supply issues in the future

A Study of the Residual 39Ar Content in Argon from Underground Sources

The discovery of argon from underground sources with significantly less 39Ar than atmospheric argon was an important step in the development of direct-detection dark matter experiments using argon as the active target. We report on the design and operation of a low background detector with a single phase liquid argon target that was built to study the 39Ar content of the underground argon. Underground argon from the Kinder Morgan CO2 plant in Cortez, Colorado was determined to have less than 0.65% of the 39Ar activity in atmospheric argon.Comment: 21 pages, 10 figure

Measurement of the Total Active 8B Solar Neutrino Flux at the Sudbury Neutrino Observatory with Enhanced Neutral Current Sensitivity

The Sudbury Neutrino Observatory (SNO) has precisely determined the total active (nu_x) 8B solar neutrino flux without assumptions about the energy dependence of the nu_e survival probability. The measurements were made with dissolved NaCl in the heavy water to enhance the sensitivity and signature for neutral-current interactions. The flux is found to be 5.21 +/- 0.27 (stat) +/- 0.38 (syst) x10^6 cm^{-2}s^{-1}, in agreement with previous measurements and standard solar models. A global analysis of these and other solar and reactor neutrino results yields Delta m^{2} = 7.1^{+1.2}_{-0.6}x10^{-5} ev^2 and theta = 32.5^{+2.4}_{-2.3} degrees. Maximal mixing is rejected at the equivalent of 5.4 standard deviations.Comment: Submitted to Phys. Rev. Let

A Search for Neutrinos from the Solar hep Reaction and the Diffuse Supernova Neutrino Background with the Sudbury Neutrino Observatory

A search has been made for neutrinos from the hep reaction in the Sun and from the diffus

SMAD4 is a predictive marker for 5-fluorouracil-based chemotherapy in patients with colorectal cancer

The gene for the transducer of transforming growth factor-beta/bone morphogenetic protein signalling SMAD4, a potential suppressor of colorectal carcinogenesis, is located at the chromosomal region 18q21. In order to evaluate the clinical relevance of SMAD4 deletion, gene copy alterations were determined by copy dosage using real-time quantitative PCR in 202 colorectal tumour biopsies from a previous randomised study of adjuvant chemotherapy. Patients with normal SMAD4 diploidy turned out to have a three-fold higher benefit of 5-fluorouracil-based adjuvant chemotherapy with a border line significance (overall survival: 3.23, P=0.056; disease-free survival: 2.89, P=0.045). These data are consistent with the previous observation that patients whose cancer had retention of the 18q21 region had a significantly higher benefit from 5-fluorouracil-based therapy. Moreover, these results may provide a refinement at the gene level of the clinical relevance of 18q21 deletion, thereby suggesting SMAD4 as a predictive marker in colorectal cancer. This data also indicate that integrity of this component of the transforming growth factor-beta/bone morphogenetic protein signalling pathway may be a critical factor for benefit of chemotherapy in patients with colorectal cancer