Gene-environment interactions in the causation and prevention of neural tube defects

The aim of the work described in this thesis is to investigate the mechanisms underlying neural tube defects (NTDs), birth defects of the developing central nervous system. The study makes use of mouse models of NTDs, and particularly focuses on the interaction between nutritional factors and genetic risk factors in determining susceptibility to NTDs. In humans some NTDs are preventable by folic acid supplementation, but this is not fully effective so investigation of alternative strategies was a key focus. The efficacy of oral nucleotide and/or inositol supplementation was evaluated for prevention of NTDs in the curly tail (Grhl3 hypomorph) mouse, a model for Folic acid-resistant NTDs. Metabolic effects were investigated by mass spectrometry methods for analysis of folate one-carbon metabolism (FOCM) and nucleotide, nucleoside and nucleobase pools. Genetic factors influencing FOCM in curly tail embryos were investigated, focussing on expression of Mthfd1L, which encodes an enzyme of mitochondrial FOCM. Effects on downstream metabolites and the potential for rescue by supplementation with one-carbon donors was evaluated, together with mass spectrometry based analysis of the treatment. The effect of caffeine on neural tube closure was investigated in several mouse strains to test the hypothesis that caffeine may be a risk factor for NTDs. Caffeine did not interfere with neurulation, and was in fact found to prevent spina bifida in curly tail mice. This prevention was accompanied by changes in embryonic FOCM, and cellular effects were analysed. The cellular basis for prevention of NTDs by folic acid was investigate in the Splotch (Pax3 mutant) mouse. Proliferation was investigated in the cranial neuroepithelium of Splotch mutant and wild-type embryos, under standard and folic acid supplemented conditions. The molecular basis of NTDs was investigated with a focus on abnormal Sonic Hedgehog signalling and disrupted dorso-ventral patterning as potentially contributing to NTDs in Splotch mutants

Planck 2015 results: XXV. Diffuse low-frequency Galactic foregrounds

We discuss the Galactic foreground emission between 20 and 100 GHz based on observations by Planck and WMAP. The total intensity in this part of the spectrum is dominated by free-free and spinning dust emission, whereas the polarized intensity is dominated by synchrotron emission. The Commander component-separation tool has been used to separate the various astrophysical processes in total intensity. Comparison with radio recombination line templates verifies the recovery of the free-free emission along the Galactic plane. Comparison of the high-latitude Hα emission with our free-free map shows residuals that correlate with dust optical depth, consistent with a fraction (≈30%) of Hα having been scattered by high-latitude dust. We highlight a number of diffuse spinning dust morphological features at high latitude. There is substantial spatial variation in the spinning dust spectrum, with the emission peak (in Iν) ranging from below 20 GHz to more than 50 GHz. There is a strong tendency for the spinning dust component near many prominent H ii regions to have a higher peak frequency, suggesting that this increase in peak frequency is associated with dust in the photo-dissociation regions around the nebulae. The emissivity of spinning dust in these diffuse regions is of the same order as previous detections in the literature. Over the entire sky, the Commander solution finds more anomalous microwave emission (AME) than the WMAP component maps, at the expense of synchrotron and free-free emission. This can be explained by the difficulty in separating multiple broadband components with a limited number of frequency maps. Future surveys, particularly at 5–20 GHz, will greatly improve the separation by constraining the synchrotron spectrum. We combine Planck and WMAP data to make the highest signal-to-noise ratio maps yet of the intensity of the all-sky polarized synchrotron emission at frequencies above a few GHz. Most of the high-latitude polarized emission is associated with distinct large-scale loops and spurs, and we re-discuss their structure. We argue that nearly all the emission at 40deg > l > −90deg is part of the Loop I structure, and show that the emission extends much further in to the southern Galactic hemisphere than previously recognised, giving Loop I an ovoid rather than circular outline. However, it does not continue as far as the “Fermi bubble/microwave haze”, making it less probable that these are part of the same structure. We identify a number of new faint features in the polarized sky, including a dearth of polarized synchrotron emission directly correlated with a narrow, roughly 20deg long filament seen in Hα at high Galactic latitude. Finally, we look for evidence of polarized AME, however many AME regions are significantly contaminated by polarized synchrotron emission, and we find a 2σ upper limit of 1.6% in the Perseus region

Planck 2015 results:X. Diffuse component separation: Foreground maps

Planck has mapped the microwave sky in temperature over nine frequency bands between 30 and 857 GHz and in polarization over seven frequency bands between 30 and 353 GHz in polarization. In this paper we consider the problem of diffuse astrophysical component separation, and process these maps within a Bayesian framework to derive an internally consistent set of full-sky astrophysical component maps. Component separation dedicated to cosmic microwave background (CMB) reconstruction is described in a companion paper. For the temperature analysis, we combine the Planck observations with the 9-yr Wilkinson Microwave Anisotropy Probe (WMAP) sky maps and the Haslam et al. 408 MHz map, to derive a joint model of CMB, synchrotron, free-free, spinning dust, CO, line emission in the 94 and 100 GHz channels, and thermal dust emission. Full-sky maps are provided for each component, with an angular resolution varying between 7.́5 and 1deg. Global parameters (monopoles, dipoles, relative calibration, and bandpass errors) are fitted jointly with the sky model, and best-fit values are tabulated. For polarization, the model includes CMB, synchrotron, and thermal dust emission. These models provide excellent fits to the observed data, with rms temperature residuals smaller than 4μK over 93% of the sky for all Planck frequencies up to 353 GHz, and fractional errors smaller than 1% in the remaining 7% of the sky. The main limitations of the temperature model at the lower frequencies are internal degeneracies among the spinning dust, free-free, and synchrotron components; additional observations from external low-frequency experiments will be essential to break these degeneracies. The main limitations of the temperature model at the higher frequencies are uncertainties in the 545 and 857 GHz calibration and zero-points. For polarization, the main outstanding issues are instrumental systematics in the 100–353 GHz bands on large angular scales in the form of temperature-to-polarization leakage, uncertainties in the analogue-to-digital conversion, and corrections for the very long time constant of the bolometer detectors, all of which are expected to improve in the near future

Predicting the response of a submillimeter bolometer to cosmic rays

Bolometers designed to detect. submillimeter radiation also respond to cosmic, gamma, and x rays. Because detectors cannot be fully shielded from such energy sources, it is necessary to understand the effect of a photon or cosmic-ray particle being absorbed. The resulting signal (known as a glitch) can then be removed from raw data. We present measurements using an Americium-241 gamma radiation source to irradiate a prototype bolometer for the High Frequency Instrument in the Planck Surveyor satellite. Our measurements showed no variation in response depending on where the radiation was absorbed, demonstrating that the bolometer absorber and thermistor thermalize quickly. The bolometer has previously been fully characterized both electrically and optically. We find that using optically measured time constants underestimates the time taken for the detector to recover from a radiation absorption event. However, a full thermal model for the bolometer, with parameters taken from electrical and optical measurements, provides accurate time constants. Slight deviations from the model were seen at high energies; these can be accounted for by use of an extended model

The Simons Observatory: Science goals and forecasts

The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial configuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping ≈ 10% of the sky to a white noise level of 2 μK-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of σ(r)=0.003. The large aperture telescope will map ≈ 40% of the sky at arcminute angular resolution to an expected white noise level of 6 μK-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources

First characterization of a superconducting filter-bank spectrometer for hyper-spectral microwave atmospheric sounding with transition edge sensor readout

We describe the design, fabrication, integration and characterization of a prototype superconducting filter bank with transition edge sensor readout designed to explore millimetre-wave detection at frequencies in the range 40 to 65 GHz. Results indicate highly uniform filter channel placement in frequency and high overall detection efficiency. The route to a full atmospheric sounding instrument in this frequency range is discussed.Centre for Earth Observing Instrumentation UK (CEOI

Optical Characterisation of a Camera module Developed for Ultra-low NEP TES Detector Arrays at FIR Wavelengths

Here we report on the optical design and on the spectral-spatial characterisation of a small 16 pixel camera. The prototype uses TES detectors with NEPs ~10-16 W/Hz0.5 which have been fabricated with near identical optical coupling structures to mimic their much lower NEP counterparts (~10-19 W/Hz0.5). This modification, which is achieved through changing only the pixel thermal conductance, G, has allowed us to perform spectral/spatial cryogenic testing using a 100mK ADR to view room temperature thermal sources. The measurements show a flat spectral response across the waveband and minimal side lobe structure in the antenna patterns down to 30dB

Use of High Sensitivity Bolometers for Astronomy: Planck High Frequency Instrument

The Planck satellite is dedicated to the measurement of the anisotropy of the Cosmic Microwave Background (CMB) with unprecedented sensitivity and angular resolution. It is a project of the European Space Agency based on a wide international collaboration, including United States and Canadian laboratories. The detectors of its High Frequency Instrument (HFI) are bolometers cooled down to 100 mK. Their sensitivity will be limited by the photon noise of the CMB itself at low frequencies, and of the instrument background at high frequencies. The requirements on the measurement chain are directly related to the strategy of observation used for the satellite. This impacts the bolometer design as well as other elements: The cooling system must present outstanding temperature stability, and the amplification chain must show a flat noise spectrum down to very low frequencies

Performance of horn-coupled transition edge sensors for L- and S-band optical detection on the SAFARI instrument

We describe the geometry, architecture, dark- and optical performance of ultra-low-noise transition edge sensors as THz detectors for the SAFARI instrument. The TESs are fabricated from superconducting Mo/Au bilayers coupled to impedance-matched superconducting ß-phase Ta thin-film absorbers. The detectors have phonon-limited dark noise equivalent powers of order 0.5 - 1.0 aW/$\sqrt{Hz}$ and saturation powers of order 20 - 40 fW. The low temperature test configuration incorporating micro-machined backshorts is also described, and construction and typical performance characteristics for the optical load are shown. We report preliminary measurements of the optical performance of these TESs for two SAFARI bands; L-band at 110 - 210 µm and S-band 34 - 60 µm .European Space AgencyThis is the final version of the article. It first appeared from SPIE via http://dx.doi.org/10.1117/12.223274

A strained silicon cold electron bolometer using Schottky contacts

We describe optical characterisation of a strained silicon cold electron bolometer (CEB), operating on a 350 mK stage, designed for absorption of millimetre-wave radiation. The silicon cold electron bolometer utilises Schottky contacts between a superconductor and an n++ doped silicon island to detect changes in the temperature of the charge carriers in the silicon, due to variations in absorbed radiation. By using strained silicon as the absorber, we decrease the electron-phonon coupling in the device and increase the responsivity to incoming power. The strained silicon absorber is coupled to a planar aluminium twin-slot antenna designed to couple to 160 GHz and that serves as the superconducting contacts. From the measured optical responsivity and spectral response, we calculate a maximum optical efficiency of 50% for radiation coupled into the device by the planar antenna and an overall noise equivalent power, referred to absorbed optical power, of 1.1×10−16 W Hz−1/2 when the detector is observing a 300 K source through a 4 K throughput limiting aperture. Even though this optical system is not optimized, we measure a system noise equivalent temperature difference of 6 mK Hz−1/2. We measure the noise of the device using a cross-correlation of time stream data, measured simultaneously with two junction field-effect transistor amplifiers, with a base correlated noise level of 300 pV Hz−1/2 and find that the total noise is consistent with a combination of photon noise, current shot noise, and electron-phonon thermal noise