Exposure to Morphine and Cocaine Modify the Transcriptomic Landscape in Zebrafish Embryos

Morphine and other opioid analgesics are the drugs of election to treat moderate-to-severe pain, and they elicit their actions by binding to the opioid receptors. Cocaine is a potent inhibitor of dopamine, serotonin, and noradrenaline reuptake, as it blocks DAT, the dopamine transporter, causing an increase in the local concentration of these neurotransmitters in the synaptic cleft. The molecular effects of these drugs have been studied in specific brain areas or nuclei, but the systemic effects in the whole organism have not been comprehensively analyzed. This study aims to analyze the transcriptomic changes elicited by morphine (10 uM) and cocaine (15 uM) in zebrafish embryos. An RNAseq assay was performed with tissues extracts from zebrafish embryos treated from 5 hpf (hours post fertilization) to 72 hpf, and the most representative deregulated genes were experimentally validated by qPCR. We have found changes in the expression of genes related to lipid metabolism, chemokine receptor ligands, visual system, hemoglobins, and metabolic detoxification pathways. Besides, morphine and cocaine modified the global DNA methylation pattern in zebrafish embryos, which would explain the changes in gene expression elicited by these two drugs of abuse.post-print3160 K

Planck 2013 results. XI. All-sky model of thermal dust emission

This paper presents an all-sky model of dust emission from the Planck 353, 545, and 857?GHz, and IRAS 100 µm data. Using a modified blackbody fit to the data we present all-sky maps of the dust optical depth, temperature, and spectral index over the 353–3000?GHz range. This model is a good representation of the IRAS and Planck data at 5' between 353 and 3000?GHz (850 and 100 µm). It shows variations of the order of 30% compared with the widely-used model of Finkbeiner, Davis, and Schlegel. The Planck data allow us to estimate the dust temperature uniformly over the whole sky, down to an angular resolution of 5', providing an improved estimate of the dust optical depth compared to previous all-sky dust model, especially in high-contrast molecular regions where the dust temperature varies strongly at small scales in response to dust evolution, extinction, and/or local production of heating photons. An increase of the dust opacity at 353?GHz, t353/NH, from the diffuse to the denser interstellar medium (ISM) is reported. It is associated with a decrease in the observed dust temperature, Tobs, that could be due at least in part to the increased dust opacity. We also report an excess of dust emission at H?i column densities lower than 1020?cm-2 that could be the signature of dust in the warm ionized medium. In the diffuse ISM at high Galactic latitude, we report an anticorrelation between t353/NH and Tobs while the dust specific luminosity, i.e., the total dust emission integrated over frequency (the radiance) per hydrogen atom, stays about constant, confirming one of the Planck Early Results obtained on selected fields. This effect is compatible with the view that, in the diffuse ISM, Tobs responds to spatial variations of the dust opacity, due to variations of dust properties, in addition to (small) variations of the radiation field strength. The implication is that in the diffuse high-latitude ISM t353 is not as reliable a tracer of dust column density as we conclude it is in molecular clouds where the correlation of t353 with dust extinction estimated using colour excess measurements on stars is strong. To estimate Galactic E(B - V) in extragalactic fields at high latitude we develop a new method based on the thermal dust radiance, instead of the dust optical depth, calibrated to E(B - V) using reddening measurements of quasars deduced from Sloan Digital Sky Survey data

Planck 2013 results. VI. High Frequency Instrument data processing

We describe the processing of the 531 billion raw data samples from the High Frequency Instrument (HFI), which we performed to produce six temperature maps from the first 473 days of Planck-HFI survey data. These maps provide an accurate rendition of the sky emission at 100, 143, 217, 353, 545, and 857GHz with an angular resolution ranging from 9.´7 to 4.´6. The detector noise per (effective) beam solid angle is respectively, 10, 6 , 12, and 39?µK in the four lowest HFI frequency channels (100-353GHz) and 13 and 14?kJy sr-1 in the 545 and 857?GHz channels. Relative to the 143?GHz channel, these two high frequency channels are calibrated to within 5% and the 353?GHz channel to the percent level. The 100 and 217?GHz channels, which together with the 143?GHz channel determine the high-multipole part of the CMB power spectrum (50 <l < 2500), are calibrated relative to 143?GHz to better than 0.2%

Planck early results. V. The low frequency instrument data processing

We describe the processing of data from the Low Frequency Instrument (LFI) used in production of the Planck Early Release Compact Source Catalogue (ERCSC). In particular, we discuss the steps involved in reducing the data from telemetry packets to cleaned, calibrated, time-ordered data (TOD) and frequency maps. Data are continuously calibrated using the modulation of the temperature of the cosmic microwave background radiation induced by the motion of the spacecraft. Noise properties are estimated from TOD from which the sky signal has been removed using a generalized least square map-making algorithm. Measured 1/f noise knee-frequencies range from ~100 mHz at 30 GHz to a few tens of mHz at 70GHz. A destriping code (Madam) is employed to combine radiometric data and pointing information into sky maps, minimizing the variance of correlated noise. Noise covariance matrices required to compute statistical uncertainties on LFI and Planck products are also produced. Main beams are estimated down to the ??10dB level using Jupiter transits, which are also used for geometrical calibration of the focal plane.Planck is too large a project to allow full acknowledgement of all contributions by individuals, institutions, industries, and funding agencies. The main entities involved in the mission operations are as follows. The European Space Agency operates the satellite via its Mission Operations Centre located at ESOC (Darmstadt, Germany) and coordinates scientific operations via the Planck Science Office located at ESAC (Madrid, Spain). Two Consortia, comprising around 50 scientific institutes within Europe, the USA, and Canada, and funded by agencies from the participating countries, developed the scientific instruments LFI and HFI, and continue to operate them via Instrument Operations Teams located in Trieste (Italy) and Orsay (France). The Consortia are also responsible for scientific processing of the acquired data. The Consortia are led by the Principal Investigators: J.L. Puget in France for HFI (funded principally by CNES and CNRS/INSU-IN2P3) and N. Mandolesi in Italy for LFI(funded principally via ASI). NASA US Planck Project, based at J.P.L. and involving scientists at many US institutions, contributes significantly to the efforts of these two Consortia. The author list for this paper has been selected by the Planck Science Team, and is composed of individuals from all of the above entities who have made multi-year contributions to the development of the mission. It does not pretend to be inclusive of all contributions. The Planck-LFI project is developed by an International Consortium lead by Italy and involving Canada, Finland, Germany, Norway, Spain, Switzerland, UK, USA. The Italian contribution to Planck is supported by the Italian Space Agency (ASI) and INAF. This work was supported by the Academy of Finland grants 121703 and 121962. We thank the DEISA Consortium (http://www.deisa.eu), co-funded through the EU FP6 project RI-031513 and the FP7 project RI-222919, for support within the DEISA Virtual Community Support Initiative. We thank CSC – IT Center for Science Ltd (Finland) for computational resources. We acknowledge financial support provided by the Spanish Ministerio de Ciencia e Innovaciõn through the Plan Nacional del Espacio y Plan Nacional de Astronomia y Astrofisica. We acknowledge The Max Planck Institute for Astrophysics Planck Analysis Centre (MPAC) is funded by the Space Agency of the German Aerospace Center (DLR) under grant 50OP0901 with resources of the German Federal Ministry of Economics and Technology, and by the Max Planck Society. This work has made use of the Planck satellite simulation package (Level-S), which is assembled by the Max Planck Institute for Astrophysics Planck Analysis Centre (MPAC) Reinecke et al. (2006). We acknowledge financial support provided by the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. Some of the results in this paper have been derived using the HEALPix package Górski et al. (2005). A description of the Planck Collaboration and a list of its members, indicating which technical or scientific activities they have been involved in, can be found at http://www.rssd.esa.int/index.php?project=PLANCK&page=Planck_Collaboration

Planck 2013 results. IX. HFI spectral response

The Planck High Frequency Instrument (HFI) spectral response was determined through a series of ground based tests conducted with the HFI focal plane in a cryogenic environment prior to launch. The main goal of the spectral transmission tests was to measure the relative spectral response (includingthe level of out-of-band signal rejection) of all HFI detectors to a known source of electromagnetic radiation individually. This was determined by measuring the interferometric output of a continuously scanned Fourier transform spectrometer with all HFI detectors. As there is no on-board spectrometer within HFI, the ground-based spectral response experiments provide the definitive data set for the relative spectral calibration of the HFI. Knowledge of the relative variations in the spectral response between HFI detectors allows for a more thorough analysis of the HFI data. The spectral response of the HFI is used in Planck data analysis and component separation, this includes extraction of CO emission observed within Planck bands, dust emission, Sunyaev-Zeldovich sources, and intensity to polarization leakage. The HFI spectral response data have also been used to provide unit conversion and colour correction analysis tools. While previous papers describe the pre-flight experiments conducted on the Planck HFI, this paper focusses on the analysis of the pre-flight spectral response measurements and the derivation of data products, e.g. band-average spectra, unit conversion coefficients, and colour correction coefficients, all with related uncertainties. Verifications of the HFI spectral response data are provided through comparisons with photometric HFI flight data. This validation includes use of HFI zodiacal emission observations to demonstrate out-of-band spectral signal rejection better than 108. The accuracy of the HFI relative spectral response data is verified through comparison with complementary flight-data based unit conversion coefficients and colour correction coefficients. These coefficients include those based upon HFI observations of CO, dust, and Sunyaev-Zeldovich emission. General agreement is observed between the ground-based spectral characterization of HFI and corresponding in-flight observations, within the quoted uncertainty of each; explanations are provided for any discrepancies

Planck intermediate results. XXXVI. Optical identification and redshifts of Planck SZ sources with telescopes at the Canary Islands observatories

Catalogs and data.-- et al.We present the results of approximately three years of observations of Planck Sunyaev-Zeldovich (SZ) sources with telescopes at the Canary Islands observatories as part of the general optical follow-up programme undertaken by the Planck Collaboration. In total, 78 SZ sources are discussed. Deep-imaging observations were obtained for most of these sources; spectroscopic observations in either in long-slit or multi-object modes were obtained for many. We effectively used 37.5 clear nights. We found optical counterparts for 73 of the 78 candidates. This sample includes 53 spectroscopic redshift determinations, 20 of them obtained with a multi-object spectroscopic mode. The sample contains new redshifts for 27 Planck clusters that were not included in the first Planck SZ source catalogue (PSZ1).The Planck Collaboration acknowledges the support of: ESA; CNES, and CNRS/INSU-IN2P3-INP (France); ASI, CNR, and INAF (Italy); NASA and DoE (USA); STFC and UKSA (UK); CSIC, MINECO, JA and RES (Spain); Tekes, AoF, and CSC (Finland); DLR and MPG (Germany); CSA (Canada); DTU Space (Denmark); SER/SSO (Switzerland); RCN (Norway); SFI (Ireland); FCT/MCTES (Portugal); ERC and PRACE (EU). A.S., R.B., H.L., and J.A.R.M. acknowledge financial support from the Spanish Ministry of Economy and Competitiveness (MINECO) under the 2011 Severo Ochoa Program MINECO SEV-2011-0187, and the Consolider-Ingenio project CSD2010-00064 (EPI: Exploring the Physics of Inflation).Peer Reviewe

Planck 2013 results. X. HFI energetic particle effects: characterization, removal, and simulation

We describe the detection, interpretation, and removal of the signal resulting from interactions of high energy particles with the Planck High Frequency Instrument (HFI). There are two types of interactions: heating of the 0.1 K bolometer plate; and glitches in each detector time stream. The transientresponses to detector glitch shapes are not simple single-pole exponential decays and fall into three families. The glitch shape for each family has been characterized empirically in flight data and these shapes have been used to remove glitches from the detector time streams. The spectrum of the count rate per unit energy is computed for each family and a correspondence is made to the location on the detector of the particle hit. Most of the detected glitches are from Galactic protons incident on the die frame supporting the micro-machined bolometric detectors. In the Planck orbit at L2, the particle flux is around 5 cm-2 s-1 and is dominated by protons incident on the spacecraft with energy >39 MeV, at a rate of typically one event per second per detector. Different categories of glitches have different signatures in the time stream. Two of the glitch types have a low amplitude component that decays over nearly 1?s. This component produces excess noise if not properly removed from the time-ordered data. We have used a glitch detection and subtraction method based on the joint fit of population templates. The application of this novel glitch subtraction method removes excess noise from the time streams. Using realistic simulations, we find that this method does not introduce signal bias into the Planck data

L. Evidence of spatial variation of the polarized thermal dust spectral energy distribution and implications for CMB B-mode analysis

Planck Collaboration.The characterization of the Galactic foregrounds has been shown to be the main obstacle in thechallenging quest to detect primordial B-modes in the polarized microwave sky. We make use of the Planck-HFI 2015 data release at high frequencies to place new constraints on the properties of the polarized thermal dust emission at high Galactic latitudes. Here, we specifically study the spatial variability of the dust polarized spectral energy distribution (SED), and its potential impact on the determination of the tensor-to-scalar ratio, r. We use the correlation ratio of the angular power spectra between the 217 and 353 GHz channels as a tracer of these potential variations, computed on different high Galactic latitude regions, ranging from 80% to 20% of the sky. The new insight from Planck data is a departure of the correlation ratio from unity that cannot be attributed to a spurious decorrelation due to the cosmic microwave background, instrumental noise, or instrumental systematics. The effect is marginally detected on each region, but the statistical combination of all the regions gives more than 99% confidence for this variation in polarized dust properties. In addition, we show that the decorrelation increases when there is a decrease in the mean column density of the region of the sky being considered, and we propose a simple power-law empirical model for this dependence, which matches what is seen in the Planck data. We explore the effect that this measured decorrelation has on simulations of the BICEP2-Keck Array/Planck analysis and show that the 2015 constraints from these data still allow a decorrelation between the dust at 150 and 353 GHz that is compatible with our measured value. Finally, using simplified models, we show that either spatial variation of the dust SED or of the dust polarization angle are able to produce decorrelations between 217 and 353 GHz data similar to the values we observe in the data.The Planck Collaboration acknowledges the support of: ESA; CNES, and CNRS/INSU-IN2P3-INP (France); ASI, CNR, and INAF (Italy); NASA and DoE (USA); STFC and UKSA (UK); CSIC, MINECO, J.A., and RES (Spain); Tekes, AoF, and CSC (Finland); DLR and MPG (Germany); CSA (Canada); DTU Space (Denmark); SER/SSO (Switzerland); RCN (Norway); SFI (Ireland); FCT/MCTES (Portugal); ERC and PRACE (EU). The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) / ERC grant agreement No. 267934.Peer Reviewe

Epidermal growth factor receptor expression is associated with poor outcome in cutaneous squamous cell carcinoma

[Background]: Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans after basal cell carcinoma, and its incidence is dramatically rising. CSCC is rarely problematic, but given its high frequency, the absolute number of complicated cases is also high. It is necessary to identify molecular markers in order to recognize those CSCCs with poor prognosis. There is controversy concerning the role of epidermal growth factor receptor (EGFR) as a marker of prognosis in CSCC. In addition, EGFR-targeted therapies have emerged in recent years and a better understanding of the role of EGFR in CSCC may be of help for some patients in predicting prognosis and guiding curative management. [Objectives]: To evaluate the role of EGFR as a prognostic factor in CSCC. [Methods]: We evaluated clinical and histopathological features, including events of poor clinical evolution, in a series of 94 cases of CSCC. We also analysed EGFR expression by immunohistochemistry, fluorescent in situ hybridization and quantitative polymerase chain reaction. [Results]: We detected EGFR in 85 cases (90%), with overexpression in 33 cases (35%), and aberrant EGFR expression in the cytoplasm in 50 cases (53%). EGFR overexpression in the primary tumours was associated with lymph node progression, tumour–nodes–metastasis stage progression and proliferation (Ki-67 staining) in CSCC. EGFR overexpression and poor grade of differentiation were the strongest independent variables defining lymph node metastasis and progression in CSCC in a logistic regression model. [Conclusions]: We demonstrate that EGFR overexpression has prognostic implications associated with lymph node metastasis and progression in CSCC.J.P.‐L. was partially supported by FEDER and MICINN (PLE2009‐119, SAF2014‐56989‐R), Instituto de Salud Carlos III (PI07/0057, PI10/00328, PIE14/00066), Junta de Castilla y León (SAN673/SA26/08, SAN126/SA66/09, SA078A09, CSI034U13, BIO/SA31/15), IBSAL (IBY15/00003), the ‘Eugenio Rodríguez Pascual’, the ‘Fundación Inbiomed’ (Instituto Oncológico Obra Social de la Caja Guipozcoa‐San Sebastian, Kutxa) and the ‘Fundación Sandra Ibarra de Solidaridad frente al Cáncer’. C.R.‐C. is funded by Q3718001E (2009‐2010) and GRS 612/A/11 (2011‐2012) and ‘the Fundación Eugenio Rodríguez Pascual’. A.C.‐M. was supported by FIS (PI07/0057) and MICINN (PLE2009‐119).Peer Reviewe

Double field of view digital sideband holography as an optimized method to measure velocity fields in a large fluid volume

Digital in-line holography is a technique that allows the measurement of the three velocity components of a three dimensional fluid flow. The application of digital in-line holography in fluid velocimetry is mainly limited by three factors: the sensor size that limits the transversal area that can be recorded, the low optical aperture that reduces the spatial resolution along the optical axis and introduces aliasing, and the noise coming from the twin image that hinders the particle position and velocity measurements. These factors do not affect in the same way when characterizing the movement of the fluid, and require different solutions. In this work we are going to show how to overcome those limitations. We applied digital sideband holography for the measurement of the particle position and velocity in a fluid volume with a cross-section twice the area allowed by the camera sensor, with magnification M = 1, and a very large the dimension along the optical axis. Digital sideband holography configuration, that keeps the simplicity of the classical in-line holographic set-up, consists of a camera, a lens and a frequency filter. This frequency filter is the key element that allows us to measure in such a large volume while maintaining spatial resolution, as well as accuracy: not only removes the twin image but also prevents the recording of unwanted frequencies that causes aliasing. We have found that the Signal to Noise Ratio depends mainly on the noise introduced by the twin image, the aliasing and the particle concentration rather than on parameters such as field of view, depth of field or the intensity of the particles. This technique is applied for the quantitative characterization of the three-dimensional flow in a lid-driven squared-sectioned cuvette. The introduction of a prism in the optical set-up allowed us to double the field of view. This is achieved by illuminating two volumes of the cuvette (22 × 22 × 100 mm3, each) with the same beam that crosses the fluid twice before reaching the camera sensor. These two fluid volumes are analyzed independently while keeping the same spatial resolution in the axial component along the whole volume than the expected for a shorter one. The experimental 3D data show a very good agreement with numerical 3D simulation, which proves the very good performance of our method