School of Physics - Research Publications
Now showing items 1-12 of 1058
RNA sequencing reveals sexually dimorphic gene expression before gonadal differentiation in chicken and allows comprehensive annotation of the W-chromosome
BACKGROUND: Birds have a ZZ male: ZW female sex chromosome system and while the Z-linked DMRT1 gene is necessary for testis development, the exact mechanism of sex determination in birds remains unsolved. This is partly due to the poor annotation of the W chromosome, which is speculated to carry a female determinant. Few genes have been mapped to the W and little is known of their expression. RESULTS: We used RNA-seq to produce a comprehensive profile of gene expression in chicken blastoderms and embryonic gonads prior to sexual differentiation. We found robust sexually dimorphic gene expression in both tissues pre-dating gonadogenesis, including sex-linked and autosomal genes. This supports the hypothesis that sexual differentiation at the molecular level is at least partly cell autonomous in birds. Different sets of genes were sexually dimorphic in the two tissues, indicating that molecular sexual differentiation is tissue specific. Further analyses allowed the assembly of full-length transcripts for 26 W chromosome genes, providing a view of the W transcriptome in embryonic tissues. This is the first extensive analysis of W-linked genes and their expression profiles in early avian embryos. CONCLUSION: Sexual differentiation at the molecular level is established in chicken early in embryogenesis, before gonadal sex differentiation. We find that the W chromosome is more transcriptionally active than previously thought, expand the number of known genes to 26 and present complete coding sequences for these W genes. This includes two novel W-linked sequences and three small RNAs reassigned to the W from the Un_Random chromosome.
Structure of a photosynthetic reaction centre determined by serial femtosecond crystallography
(NATURE PUBLISHING GROUP, 2013-12-01)
Serial femtosecond crystallography is an X-ray free-electron-laser-based method with considerable potential to have an impact on challenging problems in structural biology. Here we present X-ray diffraction data recorded from microcrystals of the Blastochloris viridis photosynthetic reaction centre to 2.8 Å resolution and determine its serial femtosecond crystallography structure to 3.5 Å resolution. Although every microcrystal is exposed to a dose of 33 MGy, no signs of X-ray-induced radiation damage are visible in this integral membrane protein structure.
Cell-Type-Specific Transcriptional Profiles of the Dimorphic Pathogen Penicillium marneffei Reflect Distinct Reproductive, Morphological, and Environmental Demands
(GENETICS SOCIETY AMERICA, 2013-11-01)
Penicillium marneffei is an opportunistic human pathogen endemic to Southeast Asia. At 25° P. marneffei grows in a filamentous hyphal form and can undergo asexual development (conidiation) to produce spores (conidia), the infectious agent. At 37° P. marneffei grows in the pathogenic yeast cell form that replicates by fission. Switching between these growth forms, known as dimorphic switching, is dependent on temperature. To understand the process of dimorphic switching and the physiological capacity of the different cell types, two microarray-based profiling experiments covering approximately 42% of the genome were performed. The first experiment compared cells from the hyphal, yeast, and conidiation phases to identify "phase or cell-state-specific" gene expression. The second experiment examined gene expression during the dimorphic switch from one morphological state to another. The data identified a variety of differentially expressed genes that have been organized into metabolic clusters based on predicted function and expression patterns. In particular, C-14 sterol reductase-encoding gene ergM of the ergosterol biosynthesis pathway showed high-level expression throughout yeast morphogenesis compared to hyphal. Deletion of ergM resulted in severe growth defects with increased sensitivity to azole-type antifungal agents but not amphotericin B. The data defined gene classes based on spatio-temporal expression such as those expressed early in the dimorphic switch but not in the terminal cell types and those expressed late. Such classifications have been helpful in linking a given gene of interest to its expression pattern throughout the P. marneffei dimorphic life cycle and its likely role in pathogenicity.
Surface code implementation of block code state distillation
(NATURE PUBLISHING GROUP, 2013-06-05)
State distillation is the process of taking a number of imperfect copies of a particular quantum state and producing fewer better copies. Until recently, the lowest overhead method of distilling states produced a single improved [formula: see text] state given 15 input copies. New block code state distillation methods can produce k improved [formula: see text] states given 3k + 8 input copies, potentially significantly reducing the overhead associated with state distillation. We construct an explicit surface code implementation of block code state distillation and quantitatively compare the overhead of this approach to the old. We find that, using the best available techniques, for parameters of practical interest, block code state distillation does not always lead to lower overhead, and, when it does, the overhead reduction is typically less than a factor of three.
Ab initio calculation of valley splitting in monolayer delta-doped phosphorus in silicon
: The differences in energy between electronic bands due to valley splitting are of paramount importance in interpreting transport spectroscopy experiments on state-of-the-art quantum devices defined by scanning tunnelling microscope lithography. Using vasp, we develop a plane-wave density functional theory description of systems which is size limited due to computational tractability. Nonetheless, we provide valuable data for the benchmarking of empirical modelling techniques more capable of extending this discussion to confined disordered systems or actual devices. We then develop a less resource-intensive alternative via localised basis functions in siesta, retaining the physics of the plane-wave description, and extend this model beyond the capability of plane-wave methods to determine the ab initio valley splitting of well-isolated δ-layers. In obtaining an agreement between plane-wave and localised methods, we show that valley splitting has been overestimated in previous ab initio calculations by more than 50%.
Reconfigurable, Defect-Free, Ultrahigh-Q Photonic Crystal Microcavities for Sensing
(MDPI AG, 2013-03-01)
We propose a new approach for creating reconfigurable high-Q cavities in defect-free photonic crystal slabs (PCSs). The approach relies on selective air-hole infiltration in otherwise defect-free PCSs. We show that using this method we can design ultrahigh-Q microcavities, with Q~10(6). Numerical calculations indicate a large number of high-Q modes with high sensitivity, which are ideal for simultaneous, multi-parameter refractive index-based sensing.
Statistical analysis of an RNA titration series evaluates microarray precision and sensitivity on a whole-array basis
BACKGROUND: Concerns are often raised about the accuracy of microarray technologies and the degree of cross-platform agreement, but there are yet no methods which can unambiguously evaluate precision and sensitivity for these technologies on a whole-array basis. RESULTS: A methodology is described for evaluating the precision and sensitivity of whole-genome gene expression technologies such as microarrays. The method consists of an easy-to-construct titration series of RNA samples and an associated statistical analysis using non-linear regression. The method evaluates the precision and responsiveness of each microarray platform on a whole-array basis, i.e., using all the probes, without the need to match probes across platforms. An experiment is conducted to assess and compare four widely used microarray platforms. All four platforms are shown to have satisfactory precision but the commercial platforms are superior for resolving differential expression for genes at lower expression levels. The effective precision of the two-color platforms is improved by allowing for probe-specific dye-effects in the statistical model. The methodology is used to compare three data extraction algorithms for the Affymetrix platforms, demonstrating poor performance for the commonly used proprietary algorithm relative to the other algorithms. For probes which can be matched across platforms, the cross-platform variability is decomposed into within-platform and between-platform components, showing that platform disagreement is almost entirely systematic rather than due to measurement variability. CONCLUSION: The results demonstrate good precision and sensitivity for all the platforms, but highlight the need for improved probe annotation. They quantify the extent to which cross-platform measures can be expected to be less accurate than within-platform comparisons for predicting disease progression or outcome.
High efficiency coherent optical memory with warm rubidium vapour
(NATURE PUBLISHING GROUP, 2011-02-01)
By harnessing aspects of quantum mechanics, communication and information processing could be radically transformed. Promising forms of quantum information technology include optical quantum cryptographic systems and computing using photons for quantum logic operations. As with current information processing systems, some form of memory will be required. Quantum repeaters, which are required for long distance quantum key distribution, require quantum optical memory as do deterministic logic gates for optical quantum computing. Here, we present results from a coherent optical memory based on warm rubidium vapour and show 87% efficient recall of light pulses, the highest efficiency measured to date for any coherent optical memory suitable for quantum information applications. We also show storage and recall of up to 20 pulses from our system. These results show that simple warm atomic vapour systems have clear potential as a platform for quantum memory.
Improved count rate corrections for highest data quality with PILATUS detectors
The PILATUS detector system is widely used for X-ray experiments at third-generation synchrotrons. It is based on a hybrid technology combining a pixelated silicon sensor with a CMOS readout chip. Its single-photon-counting capability ensures precise and noise-free measurements. The counting mechanism introduces a short dead-time after each hit, which becomes significant for rates above 10(6) photons s(-1) pixel(-1). The resulting loss in the number of counted photons is corrected for by applying corresponding rate correction factors. This article presents the results of a Monte Carlo simulation which computes the correction factors taking into account the detector settings as well as the time structure of the X-ray beam at the synchrotron. The results of the simulation show good agreement with experimentally determined correction factors for various detector settings at different synchrotrons. The application of accurate rate correction factors improves the X-ray data quality acquired at high photon fluxes. Furthermore, it is shown that the use of fast detector settings in combination with an optimized time structure of the X-ray beam allows for measurements up to rates of 10(7) photons s(-1) pixel(-1).
Micrometre resolution of a charge integrating microstrip detector with single photon sensitivity
(INT UNION CRYSTALLOGRAPHY, 2012-05-01)
A synchrotron beam has been used to test the spatial resolution of a single-photon-resolving integrating readout-chip coupled to a 320 µm-thick silicon strip sensor with a dedicated readout system. Charge interpolation methods have yielded a spatial resolution of σ(x) ≃ 1.8 µm for a 20 µm-pitch strip.
ChIP-seq analysis reveals distinct H3K27me3 profiles that correlate with transcriptional activity
(OXFORD UNIV PRESS, 2011-09-01)
Transcriptional control is dependent on a vast network of epigenetic modifications. One epigenetic mark of particular interest is tri-methylation of lysine 27 on histone H3 (H3K27me3), which is catalysed and maintained by Polycomb Repressive Complex 2 (PRC2). Although this histone mark is studied widely, the precise relationship between its local pattern of enrichment and regulation of gene expression is currently unclear. We have used ChIP-seq to generate genome-wide maps of H3K27me3 enrichment, and have identified three enrichment profiles with distinct regulatory consequences. First, a broad domain of H3K27me3 enrichment across the body of genes corresponds to the canonical view of H3K27me3 as inhibitory to transcription. Second, a peak of enrichment around the transcription start site (TSS) is commonly associated with 'bivalent' genes, where H3K4me3 also marks the TSS. Finally and most surprisingly, we identified an enrichment profile with a peak in the promoter of genes that is associated with active transcription. Genes with each of these three profiles were found in different proportions in each of the cell types studied. The data analysis techniques developed here will be useful for the identification of common enrichment profiles for other histone modifications that have important consequences for transcriptional regulation.
Megapixel imaging of (micro)nutrients in mature barley grains
(OXFORD UNIV PRESS, 2011-01-01)
Understanding the accumulation and distribution of essential nutrients in cereals is of primary importance for improving the nutritional quality of this staple food. While recent studies have improved the understanding of micronutrient loading into the barley grain, a detailed characterization of the distribution of micronutrients within the grain is still lacking. High-definition synchrotron X-ray fluorescence was used to investigate the distribution and association of essential elements in barley grain at the micro scale. Micronutrient distribution within the scutellum and the embryo was shown to be highly variable between elements in relation to various morphological features. In the rest of the grain, the distribution of some elements such as Cu and Zn was not limited to the aleurone layer but extended into the endosperm. This pattern of distribution was less marked in the case of Fe and, in particular, Mn. A significant difference in element distribution was also found between the ventral and dorsal part of the grains. The correlation between the elements was not consistent between and within tissues, indicating that the transport and storage of elements is highly regulated. The complexity of the spatial distribution and associations has important implications for improving the nutritional content of cereal crops such as barley.