A cancer rainbow mouse for visualizing the functional genomics of oncogenic clonal expansion.

Field cancerization is a premalignant process marked by clones of oncogenic mutations spreading through the epithelium. The timescales of intestinal field cancerization can be variable and the mechanisms driving the rapid spread of oncogenic clones are unknown. Here we use a Cancer rainbow (Crainbow) modelling system for fluorescently barcoding somatic mutations and directly visualizing the clonal expansion and spread of oncogenes. Crainbow shows that mutations of ß-catenin (Ctnnb1) within the intestinal stem cell results in widespread expansion of oncogenes during perinatal development but not in adults. In contrast, mutations that extrinsically disrupt the stem cell microenvironment can spread in adult intestine without delay. We observe the rapid spread of premalignant clones in Crainbow mice expressing oncogenic Rspondin-3 (RSPO3), which occurs by increasing crypt fission and inhibiting crypt fixation. Crainbow modelling provides insight into how somatic mutations rapidly spread and a plausible mechanism for predetermining the intratumor heterogeneity found in colon cancers

Atmospheric phase correction using CARMA-PACS: high angular resolution observations of the FU Orionis star PP 13S*

We present 0".15 resolution observations of the 227 GHz continuum emission from the circumstellar disk around the FU Orionis star PP 13S*. The data were obtained with the Combined Array for Research in Millimeter-wave Astronomy (CARMA) Paired Antenna Calibration System (C-PACS), which measures and corrects the atmospheric delay fluctuations on the longest baselines of the array in order to improve the sensitivity and angular resolution of the observations. A description of the C-PACS technique and the data reduction procedures are presented. C-PACS was applied to CARMA observations of PP 13S*, which led to a factor of 1.6 increase in the observed peak flux of the source, a 36% reduction in the noise of the image, and a 52% decrease in the measured size of the source major axis. The calibrated complex visibilities were fitted with a theoretical disk model to constrain the disk surface density. The total disk mass from the best-fit model corresponds to 0.06 M_⊙, which is larger than the median mass of a disk around a classical T Tauri star. The disk is optically thick at a wavelength of 1.3 mm for orbital radii less than 48 AU. At larger radii, the inferred surface density of the PP 13S* disk is an order of magnitude lower than that needed to develop a gravitational instability

Modeling and characterization of the SPIDER half-wave plate

Spider is a balloon-borne array of six telescopes that will observe the Cosmic Microwave Background. The 2624 antenna-coupled bolometers in the instrument will make a polarization map of the CMB with approximately one-half degree resolution at 145 GHz. Polarization modulation is achieved via a cryogenic sapphire half-wave plate (HWP) skyward of the primary optic. We have measured millimeter-wave transmission spectra of the sapphire at room and cryogenic temperatures. The spectra are consistent with our physical optics model, and the data gives excellent measurements of the indices of A-cut sapphire. We have also taken preliminary spectra of the integrated HWP, optical system, and detectors in the prototype Spider receiver. We calculate the variation in response of the HWP between observing the CMB and foreground spectra, and estimate that it should not limit the Spider constraints on inflation

The AROME-WMED reanalyses of the first special observation period of the Hydrological cycle in the Mediterranean experiment (HyMeX)

To study key processes of the water cycle, two special observation periods (SOPs) of the Hydrological cycle in the Mediterranean experiment (HyMeX) took place during autumn 2012 and winter 2013. The first SOP aimed to study high precipitation systems and flash flooding in the Mediterranean area. The AROME-WMED (western Mediterranean) model (Fourrié et al., 2015) is a dedicated version of the mesoscale Numerical Weather Prediction (NWP) AROME-France model, which covers the western Mediterranean basin providing the HyMeX operational center with daily real-time analyses and forecasts. These products allowed for adequate decision-making for the field campaign observation deployment and the instrument operation. Shortly after the end of the campaign, a first reanalysis with more observations was performed with the first SOP operational software. An ensuing comprehensive second reanalysis of the first SOP, which included field research observations (not assimilated in real time) and some reprocessed observation datasets, was made with AROME-WMED. Moreover, a more recent version of the AROME model was used with updated background error statistics for the assimilation process. This paper depicts the main differences between the real-time version and the benefits brought by HyMeX reanalyses with AROME-WMED. The first reanalysis used 9 % additional data and the second one 24 % more compared to the real-time version. The second reanalysis is found to be closer to observations than the previous AROME-WMED analyses. The second reanalysis forecast errors of surface parameters are reduced up to the 18 and 24 h forecast range. In the middle and upper troposphere, fields are also improved up to the 48 h forecast range when compared to radiosondes. Integrated water vapor comparisons indicate a positive benefit for at least 24 h. Precipitation forecasts are found to be improved with the second reanalysis for a threshold up to 10 mm (24 h)-1. For higher thresholds, the frequency bias is degraded. Finally, improvement brought by the second reanalysis is illustrated with the Intensive Observation Period (IOP8) associated with heavy precipitation over eastern Spain and southern France

Follow-up observations at 16 and 33 GHz of extragalactic sources from WMAP 3-year data: I - Spectral properties

We present follow-up observations of 97 point sources from the Wilkinson Microwave Anisotropy Probe (WMAP) 3-year data, contained within the New Extragalactic WMAP Point Source (NEWPS) catalogue between declinations of -4 and +60 degrees; the sources form a flux-density-limited sample complete to 1.1 Jy (approximately 5 sigma) at 33 GHz. Our observations were made at 16 GHz using the Arcminute Microkelvin Imager (AMI) and at 33 GHz with the Very Small Array (VSA). 94 of the sources have reliable, simultaneous -- typically a few minutes apart -- observations with both telescopes. The spectra between 13.9 and 33.75 GHz are very different from those of bright sources at low frequency: 44 per cent have rising spectra (alpha < 0.0), where flux density is proportional to frequency^-alpha, and 93 per cent have spectra with alpha < 0.5; the median spectral index is 0.04. For the brighter sources, the agreement between VSA and WMAP 33-GHz flux densities averaged over sources is very good. However, for the fainter sources, the VSA tends to measure lower values for the flux densities than WMAP. We suggest that the main cause of this effect is Eddington bias arising from variability.Comment: 12 pages, 13 figures, submitted to MNRA

Constraining Inflation

Slow roll reconstruction is derived from the Hamilton-Jacobi formulation of inflationary dynamics. It automatically includes information from sub-leading terms in slow roll, and facilitatesthe inclusion of priors based on the duration on inflation. We show that at low inflationary scales the Hamilton-Jacobi equations simplify considerably. We provide a new classification scheme for inflationary models, based solely on the number of parameters needed to specify the potential, and provide forecasts for likely bounds on the slow roll parameters from future datasets. A minimal running of the spectral index, induced solely by the first two slow roll parameters (\epsilon and \eta) appears to be effectively undetectable by realistic Cosmic Microwave Background experiments. However, we show that the ability to detect this signal increases with the lever arm in comoving wavenumber, and we conjecture that high redshift 21 cm data may allow tests of second order consistency conditions on inflation. Finally, we point out that the second order corrections to the spectral index are correlated with the inflationary scale, and thus the amplitude of the CMB B-mode.Comment: 32 pages. v

Pointing control for the SPIDER balloon-borne telescope

We present the technology and control methods developed for the pointing system of the SPIDER experiment. SPIDER is a balloon-borne polarimeter designed to detect the imprint of primordial gravitational waves in the polarization of the Cosmic Microwave Background radiation. We describe the two main components of the telescope's azimuth drive: the reaction wheel and the motorized pivot. A 13 kHz PI control loop runs on a digital signal processor, with feedback from fibre optic rate gyroscopes. This system can control azimuthal speed with < 0.02 deg/s RMS error. To control elevation, SPIDER uses stepper-motor-driven linear actuators to rotate the cryostat, which houses the optical instruments, relative to the outer frame. With the velocity in each axis controlled in this way, higher-level control loops on the onboard flight computers can implement the pointing and scanning observation modes required for the experiment. We have accomplished the non-trivial task of scanning a 5000 lb payload sinusoidally in azimuth at a peak acceleration of 0.8 deg/s$^2$, and a peak speed of 6 deg/s. We can do so while reliably achieving sub-arcminute pointing control accuracy.Comment: 20 pages, 12 figures, Presented at SPIE Ground-based and Airborne Telescopes V, June 23, 2014. To be published in Proceedings of SPIE Volume 914

DNA Methylation Analysis of Chromosome 21 Gene Promoters at Single Base Pair and Single Allele Resolution

Differential DNA methylation is an essential epigenetic signal for gene regulation, development, and disease processes. We mapped DNA methylation patterns of 190 gene promoter regions on chromosome 21 using bisulfite conversion and subclone sequencing in five human cell types. A total of 28,626 subclones were sequenced at high accuracy using (long-read) Sanger sequencing resulting in the measurement of the DNA methylation state of 580427 CpG sites. Our results show that average DNA methylation levels are distributed bimodally with enrichment of highly methylated and unmethylated sequences, both for amplicons and individual subclones, which represent single alleles from individual cells. Within CpG-rich sequences, DNA methylation was found to be anti-correlated with CpG dinucleotide density and GC content, and methylated CpGs are more likely to be flanked by AT-rich sequences. We observed over-representation of CpG sites in distances of 9, 18, and 27 bps in highly methylated amplicons. However, DNA sequence alone is not sufficient to predict an amplicon's DNA methylation status, since 43% of all amplicons are differentially methylated between the cell types studied here. DNA methylation in promoter regions is strongly correlated with the absence of gene expression and low levels of activating epigenetic marks like H3K4 methylation and H3K9 and K14 acetylation. Utilizing the single base pair and single allele resolution of our data, we found that i) amplicons from different parts of a CpG island frequently differ in their DNA methylation level, ii) methylation levels of individual cells in one tissue are very similar, and iii) methylation patterns follow a relaxed site-specific distribution. Furthermore, iv) we identified three cases of allele-specific DNA methylation on chromosome 21. Our data shed new light on the nature of methylation patterns in human cells, the sequence dependence of DNA methylation, and its function as epigenetic signal in gene regulation. Further, we illustrate genotype–epigenotype interactions by showing novel examples of allele-specific methylation