Ferric ion phases in Mössbauer spectra of “oxidized” and “reduced” CV3 chondrites.

Accepted versio

Fe-rich pentlandite in Allende bulk samples and separates: Mössbauer spectroscopy analysis.

Published versio

Vertical leakage mechanism in GaN on Si high electron mobility transistor buffer layers

Control of leakage currents in the buffer layers of GaN based transistors on Si substrates is vital for the demonstration of high performance devices. Here, we show that the growth conditions during the metal organic chemical vapour deposition growth of the graded AlGaN strain relief layers (SRLs) can significantly influence the vertical leakage. Using scanning capacitance microscopy, secondary ion mass spectrometry, and transmission electron microscopy, we investigate the origins of leakage paths and show that they result from the preferential incorporation of oxygen impurities on the side wall facets of the inverted hexagonal pyramidal pits which can occur during the growth of the graded AlGaN SRL. We also show that when 2D growth of the AlGaN SRL is maintained a significant increase in the breakdown voltage can be achieved even in much thinner buffer layer structures. These results demonstrate the importance of controlling the morphology of the high electron mobility transistor buffer layer as even at a very low density the leakage paths identified would provide leakage paths in large area devices.This work was funded by the Engineering and Physical Sciences Research Council under Grant Code Nos. EP/K014471/1 and EP/N01202X/1 and the European Research Council under the European Community's Seventh Framework Programme Grant Agreement No. 279361 (MACONS)

Geocoding rural addresses in a community contaminated by PFOA: a comparison of methods

BACKGROUND: Location is often an important component of exposure assessment, and positional errors in geocoding may result in exposure misclassification. In rural areas, successful geocoding to a street address is limited by rural route boxes. Communities have assigned physical street addresses to rural route boxes as part of E911 readdressing projects for improved emergency response. Our study compared automated and E911 methods for recovering and geocoding valid street addresses and assessed the impact of positional errors on exposure classification. METHODS: The current study is a secondary analysis of existing data that included 135 addresses self-reported by participants of a rural community study who were exposed via public drinking water to perfluorooctanoate (PFOA) released from a DuPont facility in Parkersburg, West Virginia. We converted pre-E911 to post-E911 addresses using two methods: automated ZP4 address-correction software with the U.S. Postal Service LACS database and E911 data provided by Wood County, West Virginia. Addresses were geocoded using TeleAtlas, an online commercial service, and ArcView with StreetMap Premium North America NAVTEQ 2008 enhanced street dataset. We calculated positional errors using GPS measurements collected at each address and assessed exposure based on geocoded location in relation to public water pipes. RESULTS: The county E911 data converted 89% of the eligible addresses compared to 35% by ZP4 LACS. ArcView/NAVTEQ geocoded more addresses (n = 130) and with smaller median distance between geocodes and GPS coordinates (39 meters) than TeleAtlas (n = 85, 188 meters). Without E911 address conversion, 25% of the geocodes would have been more than 1000 meters from the true location. Positional errors in TeleAtlas geocoding resulted in exposure misclassification of seven addresses whereas ArcView/NAVTEQ methods did not misclassify any addresses. CONCLUSIONS: Although the study was limited by small numbers, our results suggest that the use of county E911 data in rural areas increases the rate of successful geocoding. Furthermore, positional accuracy of rural addresses in the study area appears to vary by geocoding method. In a large epidemiological study investigating the health effects of PFOA-contaminated public drinking water, this could potentially result in exposure misclassification if addresses are incorrectly geocoded to a street segment not serviced by public water

Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Orton et al.BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) activated Extracellular-signal Regulated Kinase (ERK) pathway is a critical cell signalling pathway that relays the signal for a cell to proliferate from the plasma membrane to the nucleus. Deregulation of the EGFR/ERK pathway due to alterations affecting the expression or function of a number of pathway components has long been associated with numerous forms of cancer. Under normal conditions, Epidermal Growth Factor (EGF) stimulates a rapid but transient activation of ERK as the signal is rapidly shutdown. Whereas, under cancerous mutation conditions the ERK signal cannot be shutdown and is sustained resulting in the constitutive activation of ERK and continual cell proliferation. In this study, we have used computational modelling techniques to investigate what effects various cancerous alterations have on the signalling flow through the ERK pathway. RESULTS: We have generated a new model of the EGFR activated ERK pathway, which was verified by our own experimental data. We then altered our model to represent various cancerous situations such as Ras, B-Raf and EGFR mutations, as well as EGFR overexpression. Analysis of the models showed that different cancerous situations resulted in different signalling patterns through the ERK pathway, especially when compared to the normal EGF signal pattern. Our model predicts that cancerous EGFR mutation and overexpression signals almost exclusively via the Rap1 pathway, predicting that this pathway is the best target for drugs. Furthermore, our model also highlights the importance of receptor degradation in normal and cancerous EGFR signalling, and suggests that receptor degradation is a key difference between the signalling from the EGF and Nerve Growth Factor (NGF) receptors. CONCLUSION: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems.This work was funded by the Department of Trade and Industry (DTI), under their Bioscience Beacon project programme. AG was funded by an industrial PhD studentship from Scottish Enterprise and Cyclacel

Tycho Brahe's 1572 supernova as a standard type Ia explosion revealed from its light echo spectrum

Type Ia supernovae (SNe Ia) are thermonuclear explosions of white dwarf stars in close binary systems. They play an important role as cosmological distance indicators and have led to the discovery of the accelerated expansion of the Universe. Among the most important unsolved questions are how the explosion actually proceeds and whether accretion occurs from a companion or via the merging of two white dwarfs. Tycho Brahe's supernova of 1572 (SN 1572) is thought to be one of the best candidates for a SN Ia in the Milky Way. The proximity of the SN 1572 remnant has allowed detailed studies, such as the possible identification of the binary companion, and provides a unique opportunity to test theories of the explosion mechanism and the nature of the progenitor. The determination of the yet unknown exact spectroscopic type of SN 1572 is crucial to relate these results to the diverse population of SNe Ia. Here we report an optical spectrum of Tycho Brahe's supernova near maximum brightness, obtained from a scattered-light echo more than four centuries after the direct light of the explosion swept past Earth. We find that SN 1572 belongs to the majority class of normal SNe Ia. The presence of a strong Ca II IR feature at velocities exceeding 20,000 km/s, which is similar to the previously observed polarized features in other SNe Ia, suggests asphericity in SN 1572.Comment: 15 pages, 3 figures - accepted for publication in Natur

Explicit BCJ Numerators from Pure Spinors

We derive local kinematic numerators for gauge theory tree amplitudes which manifestly satisfy Jacobi identities analogous to color factors. They naturally emerge from the low energy limit of superstring amplitudes computed with the pure spinor formalism. The manifestation of the color--kinematics duality is a consequence of the superstring computation involving no more than (n-2)! kinematic factors for the full color dressed n-point amplitude. The bosonic part of these results describe gluon scattering independent on the number of supersymmetries and captures any N^kMHV helicity configuration after dimensional reduction to D=4 dimensions.Comment: 32 pages, harvma

ERK1/2 signaling dominates over RhoA signaling in regulating early changes in RNA expression induced by endothelin-1 in neonatal rat cardiomyocytes

Cardiomyocyte hypertrophy is associated with changes in gene expression. Extracellular signal-regulated kinases 1/2 (ERK1/2) and RhoA [activated by hypertrophic agonists (e.g. endothelin-1)] regulate gene expression and are implicated in the response, but their relative significance in regulating the cardiomyocyte transcriptome is unknown. Our aim was to establish the significance of ERK1/2 and/or RhoA in the early cardiomyocyte transcriptomic response to endothelin-1.Cardiomyocytes were exposed to endothelin-1 (1 h) with/without PD184352 (to inhibit ERK1/2) or C3 transferase (C3T, to inhibit RhoA). RNA expression was analyzed using microarrays and qPCR. ERK1/2 signaling positively regulated approximately 65% of the early gene expression response to ET-1 with a small (approximately 2%) negative effect, whereas RhoA signaling positively regulated approximately 10% of the early gene expression response to ET-1 with a greater (approximately 14%) negative contribution. Of RNAs non-responsive to endothelin-1, 66 or 448 were regulated by PD184352 or C3T, respectively, indicating that RhoA had a more significant effect on baseline RNA expression. mRNAs upregulated by endothelin-1 encoded a number of receptor ligands (e.g. Ereg, Areg, Hbegf) and transcription factors (e.g. Abra/Srf) that potentially propagate the response.ERK1/2 dominates over RhoA in the early transcriptomic response to endothelin-1. RhoA plays a major role in maintaining baseline RNA expression but, with upregulation of Abra/Srf by endothelin-1, RhoA may regulate changes in RNA expression over longer times. Our data identify ERK1/2 as a more significant node than RhoA in regulating the early stages of cardiomyocyte hypertrophy

Errors in chromosome segregation during oogenesis and early embryogenesis

Errors in chromosome segregation occurring during human oogenesis and early embryogenesis are very common. Meiotic chromosome development during oogenesis is subdivided into three distinct phases. The crucial events, including meiotic chromosome pairing and recombination, take place from around 11 weeks until birth. Oogenesis is then arrested until ovulation, when the first meiotic division takes place, with the second meiotic division not completed until after fertilization. It is generally accepted that most aneuploid fetal conditions, such as trisomy 21 Down syndrome, are due to maternal chromosome segregation errors. The underlying reasons are not yet fully understood. It is also clear that superimposed on the maternal meiotic chromosome segregation errors, there are a large number of mitotic errors taking place post-zygotically during the first few cell divisions in the embryo. In this chapter, we summarise current knowledge of errors in chromosome segregation during oogenesis and early embryogenesis, with special reference to the clinical implications for successful assisted reproduction