Technical design and performance of the NEMO3 detector

The development of the NEMO3 detector, which is now running in the Frejus Underground Laboratory (L.S.M. Laboratoire Souterrain de Modane), was begun more than ten years ago. The NEMO3 detector uses a tracking-calorimeter technique in order to investigate double beta decay processes for several isotopes. The technical description of the detector is followed by the presentation of its performance.Comment: Preprint submitted to Nucl. Instrum. Methods A Corresponding author: Corinne Augier ([email protected]

Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour cell line

BACKGROUND: Many tumours undergo disregulation of polyamine homeostasis and upregulation of ornithine decarboxylase (ODC) activity, which can promote carcinogenesis. In animal models of colon carcinogenesis, inhibition of ODC activity by difluoromethylornithine (DFMO) has been shown to reduce the number and size of colon adenomas and carcinomas. Indole-3-carbinol (I3C) has shown promising chemopreventive activity against a range of human tumour cell types, but little is known about the effect of this agent on colon cell lines. Here, we investigated whether inhibition of ODC by I3C could contribute to a chemopreventive effect in colon cell lines. METHODS: Cell cycle progression and induction of apoptosis were assessed by flow cytometry. Ornithine decarboxylase activity was determined by liberation of CO(2 )from (14)C-labelled substrate, and polyamine levels were measured by HPLC. RESULTS: I3C inhibited proliferation of the human colon tumour cell lines HT29 and SW480, and of the normal tissue-derived HCEC line, and at higher concentrations induced apoptosis in SW480 cells. The agent also caused a decrease in ODC activity in a dose-dependent manner. While administration of exogenous putrescine reversed the growth-inhibitory effect of DFMO, it did not reverse the growth-inhibition following an I3C treatment, and in the case of the SW480 cell line, the effect was actually enhanced. In this cell line, combination treatment caused a slight increase in the proportion of cells in the G(2)/M phase of the cell cycle, and increased the proportion of cells undergoing necrosis, but did not predispose cells to apoptosis. Indole-3-carbinol also caused an increase in intracellular spermine levels, which was not modulated by putrescine co-administration. CONCLUSION: While indole-3-carbinol decreased ornithine decarboxylase activity in the colon cell lines, it appears unlikely that this constitutes a major mechanism by which the agent exerts its antiproliferative effect, although accumulation of spermine may cause cytotoxicity and contribute to cell death. The precise mechanism by which putrescine enhances the growth inhibitory effect of the agent remains to be elucidated, but does result in cells undergoing necrosis, possibly following accumulation in the G(2)/M phase of the cell cycle

Alteration assemblages in Martian meteorites: implications for near-surface processes

The SNC (Shergotty-Nakhla-Chassigny) meteorites have recorded interactions between martian crustal fluids and the parent igneous rocks. The resultant secondary minerals – which comprise up to 1 vol.% of the meteorites – provide information about the timing and nature of hydrous activity and atmospheric processes on Mars. We suggest that the most plausible models for secondary mineral formation involve the evaporation of low temperature (25 – 150 °C) brines. This is consistent with the simple mineralogy of these assemblages – Fe-Mg-Ca carbonates, anhydrite, gypsum, halite, clays – and the chemical fractionation of Ca-to Mg-rich carbonate in ALH84001 "rosettes". Longer-lived, and higher temperature, hydrothermal systems would have caused more silicate alteration than is seen and probably more complex mineral assemblages. Experimental and phase equilibria data on carbonate compositions similar to those present in the SNCs imply low temperatures of formation with cooling taking place over a short period of time (e.g. days). The ALH84001 carbonate also probably shows the effects of partial vapourisation and dehydration related to an impact event post-dating the initial precipitation. This shock event may have led to the formation of sulphide and some magnetite in the Fe-rich outer parts of the rosettes. Radiometric dating (K-Ar, Rb-Sr) of the secondary mineral assemblages in one of the nakhlites (Lafayette) suggests that they formed between 0 and 670 Myr, and certainly long after the crystallisation of the host igneous rocks. Crystallisation of ALH84001 carbonate took place 0.5 Gyr after the parent rock. These age ranges and the other research on these assemblages suggest that environmental conditions conducive to near-surface liquid water have been present on Mars periodically over the last 1 Gyr. This fluid activity cannot have been continuous over geological time because in that case much more silicate alteration would have taken place in the meteorite parent rocks and the soluble salts would probably not have been preserved. The secondary minerals could have been precipitated from brines with seawater-like composition, high bicarbonate contents and a weakly acidic nature. The co-existence of siderite (Fe-carbonate) and clays in the nakhlites suggests that the pCO2 level in equilibrium with the parent brine may have been 50 mbar or more. The brines could have originated as flood waters which percolated through the top few hundred meters of the crust, releasing cations from the surrounding parent rocks. The high sulphur and chlorine concentrations of the martian soil have most likely resulted from aeolian redistribution of such aqueously-deposited salts and from reaction of the martian surface with volcanic acid volatiles. The volume of carbonates in meteorites provides a minimum crustal abundance and is equivalent to 50–250 mbar of CO2 being trapped in the uppermost 200–1000 m of the martian crust. Large fractionations in 18O between igneous silicate in the meteorites and the secondary minerals (30) require formation of the latter below temperatures at which silicate-carbonate equilibration could have taken place (400°C) and have been taken to suggest low temperatures (e.g. 150°C) of precipitation from a hydrous fluid

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Overexpression of caveolin-1 and -2 in cell lines and in human samples of inflammatory breast cancer

Inflammatory breast cancer (IBC) is the most aggressive form of locally advanced breast cancer (LABC). The IBC phenotype is characterized by an infiltrative growth pattern, increased (lymph)angiogenesis and the propensity to invade dermal lymphatics. In pancreatic cancer, interactions between caveolin-1 and RhoC GTPase, a key molecule in causing the IBC phenotype, regulate tumour cell motility and invasion. In this study we sought to investigate the role of caveolin-1 and -2 in IBC cell lines and in human IBC samples.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44235/1/10549_2005_Article_9002.pd

Pluto's lower atmosphere and pressure evolution from ground-based stellar occultations, 1988-2016

Context. The tenuous nitrogen (N2) atmosphere on Pluto undergoes strong seasonal effects due to high obliquity and orbital eccentricity, and has recently (July 2015) been observed by the New Horizons spacecraft. Aims. The main goals of this study are (i) to construct a well calibrated record of the seasonal evolution of surface pressure on Pluto and (ii) to constrain the structure of the lower atmosphere using a central flash observed in 2015. Methods. Eleven stellar occultations by Pluto observed between 2002 and 2016 are used to retrieve atmospheric profiles (density, pressure, temperature) between altitude levels of ~5 and ~380 km (i.e. pressures from ~ 10 μbar to 10 nbar). Results. (i) Pressure has suffered a monotonic increase from 1988 to 2016, that is compared to a seasonal volatile transport model, from which tight constraints on a combination of albedo and emissivity of N2 ice are derived. (ii) A central flash observed on 2015 June 29 is consistent with New Horizons REX profiles, provided that (a) large diurnal temperature variations (not expected by current models) occur over Sputnik Planitia; and/or (b) hazes with tangential optical depth of ~0.3 are present at 4–7 km altitude levels; and/or (c) the nominal REX density values are overestimated by an implausibly large factor of ~20%; and/or (d) higher terrains block part of the flash in the Charon facing hemisphere

Perioperative events influence cancer recurrence risk after surgery.

Surgery is a mainstay treatment for patients with solid tumours. However, despite surgical resection with a curative intent and numerous advances in the effectiveness of (neo)adjuvant therapies, metastatic disease remains common and carries a high risk of mortality. The biological perturbations that accompany the surgical stress response and the pharmacological effects of anaesthetic drugs, paradoxically, might also promote disease recurrence or the progression of metastatic disease. When cancer cells persist after surgery, either locally or at undiagnosed distant sites, neuroendocrine, immune, and metabolic pathways activated in response to surgery and/or anaesthesia might promote their survival and proliferation. A consequence of this effect is that minimal residual disease might then escape equilibrium and progress to metastatic disease. Herein, we discuss the most promising proposals for the refinement of perioperative care that might address these challenges. We outline the rationale and early evidence for the adaptation of anaesthetic techniques and the strategic use of anti-adrenergic, anti-inflammatory, and/or antithrombotic therapies. Many of these strategies are currently under evaluation in large-cohort trials and hold promise as affordable, readily available interventions that will improve the postoperative recurrence-free survival of patients with cancer