Upper limits for undetected trace species in the stratosphere of Titan

In this paper we describe a first quantitative search for several molecules in Titan's stratosphere in Cassini CIRS infrared spectra. These are: ammonia (NH3), methanol (CH3OH), formaldehyde (H2CO), and acetonitrile (CH3CN), all of which are predicted by photochemical models but only the last of which observed, and not in the infrared. We find non-detections in all cases, but derive upper limits on the abundances from low-noise observations at 25{\deg}S and 75{\deg}N. Comparing these constraints to model predictions, we conclude that CIRS is highly unlikely to see NH3 or CH3OH emissions. However, CH3CN and H2CO are closer to CIRS detectability, and we suggest ways in which the sensitivity threshold may be lowered towards this goal.Comment: 11 pages plus 6 figure file

The heterogeneous coma of comet 67P/Churyumov-Gerasimenko as seen by ROSINA: H <inf>2</inf> O, CO <inf>2</inf>, and CO from September 2014 to February 2016

Context. The ESA Rosetta mission has been investigating the environment of comet 67P/Churyumov-Gerasimenko (67P) since August 2014. Among the experiments on board the spacecraft, the ROSINA experiment (Rosetta Orbiter Spectrometer for Ion and Neutral Analysis) includes two mass spectrometers to analyse the composition of neutrals and ions and a COmet Pressure Sensor (COPS) to monitor the density and velocity of neutrals in the coma. Aims. We study heterogeneities in the coma during three periods starting in October 2014 (summer in the northern hemisphere) and ending in February 2016 (end of winter in the northern hemisphere). We provide a detailed description of the main volatiles dynamics (H2O, CO2, CO) and their abundance ratios. Methods. We analysed and compared the data of the Reflectron-Type Time-Of-Flight (RTOF) mass spectrometer with data from both the Double Focusing Mass Spectrometer (DFMS) and COPS during the comet escort phase. This comparison has demonstrated that the observations performed with each ROSINA sensor are indeed consistent. Furthermore, we used a Direct Simulation Monte Carlo (DSMC) model to compare modelled densitites with in situ detections. Results. Our analysis shows how the active regions of the main volatiles evolve with the seasons with a variability mostly driven by the illumination conditions; this is the case except for an unexpected dichotomy suggesting the presence of a dust layer containing water deposited in the northern hemisphere during previous perihelions hiding the presence of CO2. The influence of various parameters is investigated in detail: distance to the comet, heliocentric distance, longitude and latitude of sub-satellite point, local time, and phase angle

Altitude dependence of nightside Martian suprathermal electron depletions as revealed by MAVEN observations

The MAVEN (Mars Atmosphere and Volatile EvolutioN) spacecraft is providing new detailed observations of the Martian ionosphere thanks to its unique orbital coverage and instrument suite. During most periapsis passages on the nightside ionosphere suprathermal electron depletions were detected. A simple criterion was implemented to identify the 1742 depletions observed from 16 November 2014 to 28 February 2015. A statistical analysis reveals that the main ion and electron populations within the depletions are surprisingly constant in time and altitude. Absorption by CO2 is the main loss process for suprathermal electrons, and electrons that strongly peaked around 6 eV are resulting from this interaction. The observation of depletions appears however highly dependent on altitude. Depletions are mainly located above strong crustal magnetic sources above 170 km, whereas the depletions observed for the first time below 170 km are globally scattered onto the Martian surface with no particular dependence on crustal fields

Spin-orbit inclinations of the exoplanetary systems HAT-P-8, HAT-P-9, HAT-P-16 and HAT-P-23

We report the measurement of the spin-orbit angle of the extra-solar planets HAT-P-8 b, HAT-P-9 b, HAT-P-16 b and HAT-P-23 b, thanks to spectroscopic observations performed at the Observatoire de Haute-Provence with the SOPHIE spectrograph on the 1.93-m telescope. Radial velocity measurements of the Rossiter-McLaughlin effect show the detection of an apparent prograde, aligned orbit for all systems. The projected spin-orbit angles are found to be lambda=-17 deg (+9.2,-11.5), -16 deg (8), -10 deg (16), +15 deg (22) for HAT-P-8, HAT-P-9, HAT-P-16 and HAT-P-23 respectively, with corresponding projected rotational velocities of 14.5 (0.8), 12.5 (1.8), 3.9 (0.8), and 7.8 (1.6) km/s. These new results increase to 37 the number of accurately measured spin-orbit angles in transiting extrasolar systems. We conclude by drawing a tentative picture of the global behaviour of orbital alignement, involving the complexity and diversity of possible mechanisms.Comment: accepted in A&

Minimal to no transfer of certolizumab pegol into breast milk: Results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study

Background Women with chronic inflammatory diseases face uncertainty regarding the safety of biologics during breast feeding. CRADLE was the first industry-sponsored study to evaluate certolizumab pegol (CZP) concentrations in human breast milk and estimate average daily infant dose (ADID) of maternal CZP. Methods CRADLE (NCT02154425) was a pharmacokinetic study of lactating mothers receiving CZP. After ≥3 CZP doses, breast milk samples were collected across one dosing period (14 days for 200 mg every 2 weeks [Q2W]; 28 days for 400 mg every 4 weeks [Q4W]). Optimal analytical methods were developed to determine CZP and polyethylene glycol (PEG) levels in breast milk. ADID and relative infant dose (RID) were estimated. Safety events in mothers and infants were assessed. Results 19 CZP-Treated mothers were screened; 17 entered the sampling period: 16 on 200 mg Q2W, 1 on 400 mg Q4W. 77/137 (56%) breast milk samples had no measurable CZP. For 4/17 mothers, all samples were below the lower limit of quantification (LLOQ). Estimated ADID was 0-0.0104 mg/kg/day; median RID: 0.15%. PEG was undetectable in 134/137 samples (results could not be determined in three samples). Infants of CZP-exposed mothers had a safety profile consistent with that of unexposed similar-Age infants. Conclusion When quantifiable, CZP concentrations were <3× LLOQ (<1% plasma concentration observed with therapeutic dose), indicating no/minimal CZP transfer from plasma to breast milk. RID was 0.15% of maternal dose; <10% is considered unlikely to be of clinical concern. No PEG transfer was observed. CZP absorption by infants via breast milk is unlikely due to its low oral bioavailability and Fc-Â-free molecular structure. These findings are reassuring and support continuation of CZP treatment during breast feeding. Trial registration number NCT02154425; Results

The Effect of DNA-Dependent Protein Kinase on Adeno-Associated Virus Replication

BACKGROUND: DNA-dependent protein kinase (DNA-PK) is a DNA repair enzyme and plays an important role in determining the molecular fate of the rAAV genome. However, the effect this cellular enzyme on rAAV DNA replication remains elusive. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we characterized the roles of DNA-PK on recombinant adeno-associated virus DNA replication. Inhibition of DNA-PK by a DNA-PK inhibitor or siRNA targeting DNA-PKcs significantly decreased replication of AAV in MO59K and 293 cells. Southern blot analysis showed that replicated rAAV DNA formed head-to-head or tail-to-tail junctions. The head-to-tail junction was low or undetectable suggesting AAV-ITR self-priming is the major mechanism for rAAV DNA replication. In an in vitro replication assay, anti-Ku80 antibody strongly inhibited rAAV replication, while anti-Ku70 antibody moderately decreased rAAV replication. Similarly, when Ku heterodimer (Ku70/80) was depleted, less replicated rAAV DNA were detected. Finally, we showed that AAV-ITRs directly interacted with Ku proteins. CONCLUSION/SIGNIFICANCE: Collectively, our results showed that that DNA-PK enhances rAAV replication through the interaction of Ku proteins and AAV-ITRs

SERENA:Particle Instrument Suite for Determining the Sun-Mercury Interaction from BepiColombo

International audienceThe ESA-JAXA BepiColombo mission to Mercury will provide simultaneous measurements from two spacecraft, offering an unprecedented opportunity to investigate magnetospheric and exospheric particle dynamics at Mercury as well as their interactions with solar wind, solar radiation, and interplanetary dust. The particle instrument suite SERENA (Search for Exospheric Refilling and Emitted Natural Abundances) is flying in space on-board the BepiColombo Mercury Planetary Orbiter (MPO) and is the only instrument for ion and neutral particle detection aboard the MPO. It comprises four independent sensors: ELENA for neutral particle flow detection, Strofio for neutral gas detection, PICAM for planetary ions observations, and MIPA, mostly for solar wind ion measurements. SERENA is managed by a System Control Unit located inside the ELENA box. In the present paper the scientific goals of this suite are described, and then the four units are detailed, as well as their major features and calibration results. Finally, the SERENA operational activities are shown during the orbital path around Mercury, with also some reference to the activities planned during the long cruise phase