Limitation of fixed nitrogen and deepening of the carbonate-compensation depth through the Hirnantian at Dob's Linn, Scotland

This study was funded by University of Washington Department of Earth and Space Sciences Harry Wheeler Scholarship and Jody Bourgeois Graduate Student Support Fund granted to MCK. Stephen Hillier acknowledges support of the Scottish Government's Rural and Environment Science and Analytical Services Division (RESAS).The late Ordovician is characterized by dramatic changes in global climate concurrent with a major mass extinction and possible changes in ocean redox. To further refine our understanding of these events, we present nitrogen and carbon isotope and abundance data from the Ordovician-Silurian (O-S) Global Boundary Stratotype Section and Point at Dob's Linn, Scotland. We show that this section experienced post-depositional ammonium migration from the organic-rich to the organic-poor horizons. However, our data suggest that isotopic fractionations from ammonium substitution into illitic clay minerals are small and can be corrected. Reconstructed primary nitrogen isotope ratios indicate that unlike in tropical continental shelf sections that were transiently enriched in nitrate during the Hirnantian glaciation, the sub-tropical continental slope setting at Dob's Linn experienced persistent limitation of fixed nitrogen across the O-S boundary. Shallow subpolar settings appear to be the only environment that shows persistent nitrate availability at that time. This pattern suggests that spatial trends in marine nitrate concentrations – which are observed in the modern ocean as a result of latitudinal temperature gradients – were already established during the Paleozoic. While the average marine O2 chemocline depth may have deepened during the Hirnantian glaciation, it probably did not lead to global ventilation of the deep ocean, which may have been delayed until the Carboniferous. Furthermore, carbonate data from this and other sections suggest a deepening of the carbonate compensation depth (CCD) during the Hirnantian. This observation indicates that Pacific-style responses of the CCD to glacial/interglacial periods were operational across the O-S boundary, and that the expansion of abiotic carbonate deposition and preservation beyond the shelf break could have in-part mediated changes to surface CO2 during these extreme changes in climate.PostprintPeer reviewe

Novel genotoxins that target estrogen receptor- and androgen receptor- positive cancers : identification of DNA adducts, pharmacokinetics, and mechanism

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005.Vita.Includes bibliographical references.We have designed and synthesized novel molecules capable of selectively killing tumor cells that aberrantly express steroid hormone receptors. Many human breast cancers express high levels of the estrogen receptor (ER), and most prostate cancers express the androgen receptor (AR). We reasoned that the potential genotoxic effect of DNA adducts would be increased in target cells if these adducts were camouflaged by their association with receptor proteins. This association could shield the DNA adducts from repair proteins and thus increase the toxicity towards a tumor cell. Furthermore, these hormone receptors are transcription factors and an interaction between the protein and the DNA adduct could disrupt cellular signaling events, thus leading to further toxicity. We have synthesized bifunctional agents that contain an aniline mustard linked to ligands for tumor specific hormone receptors. To target ER(+) breast cancers, an aniline mustard was linked to estradiol at the 7[alpha] position (E2-7[alpha]), and to target AR(+) prostate cancer, the aniline mustard was linked to estradien-3-one at the 11[beta] position (11[beta]). Competitive binding experiments show that E2-7[alpha] and 11[beta] compete well with the natural ligands for the ER and AR, respectively. Clonal survival studies have shown that hormone receptor expressing malignant cell lines are more sensitive to our compounds than a corresponding receptor deficient line. [¹⁴C]-E2-7[alpha] and [¹⁴C]- 11[beta] have been formulated in Cremophor-EL and exhibit good bioavailability and stability when injected into mice intraperitoneally. E2-7[alpha] inhibits the growth of ER(+) HeLa cells and 11[beta] inhibits the growth of AR(+) LNCaP cells, both in xenograft mouse models.(cont.) The compounds are well tolerated by mice after the therapeutic regimens. Stable DNA adducts have been isolated and detected by electrospray mass spectrometry and accelerator mass spectrometry has provided us with a means of quantifying the number of DNA adducts formed in vivo. E2-7[alpha] DNA adducts are repaired, in part, by nucleotide excision repair but the adducts persist longer in ER(+) cells than in ER(-) ones. Melphalan adducts, however, are repaired with equal rates in both cell lines. This result provides evidence in support of the repair shielding hypothesis and suggests that it may be a contributing mechanism to the increased toxicity observed for the ER(+) cell line in the clonal survival study.by Shawn M. Hillier.Ph.D

Debris-flow release processes investigated through the analysis of multi-temporal LiDAR datasets in north-western Iceland

Debris flows are fast‐moving gravity flows of poorly sorted rock and soil, mixed and saturated with water. Debris‐flow initiation has been studied using empirical and experimental modelling, but the geomorphic changes, indicative of different triggering processes, are difficult to constrain with field observations only. We identify signatures to distinguish two different debris‐flow release styles by integrating high‐resolution multi‐temporal remote sensing datasets and morphometric analysis. We analyse debris flows sourced above the town of Ísafjörður (Iceland). Two debris‐flow triggering processes were previously hypothesized for this site: (i) slope failure, characterised by landslides evolving into debris flows, and (ii) the fire‐hose effect, in which debris accumulated in pre‐existing, steep‐sided bedrock passages is transported by a surge of water. It is unknown which process dominates and determines the local risk. To investigate this question, we compare airborne LiDAR elevation models and aerial photographs collected in 2007 with similar data from 2013. We find that two new debris‐flow tracks were created by slope failures. These are characterised by steep sliding surfaces and lateral leveed channels. Slope failure also occurred in two large, recently active tracks, creating the preparatory conditions for the fire‐hose effect to mobilise existing debris. These tracks show alternating zones of fill and scour along their length, and debris stored below the source‐area at rest angles >35°. Our approach allows us to identify and quantify the morphological changes produced by slope failure release process, which generated the preparatory conditions for the fire‐hose effect. As debris flows are rarely observed in action and morphological changes induced by them are difficult to detect and monitor, the same approach could be applied to other landscapes to understand debris‐flow initiation in absence of other monitoring information, and can improve the identification of zones at risk in inhabited areas near hillslopes with potential for debris flows

Superconductivity and the upper critical field in the chiral noncentrosymmetric superconductor NbRh2B2

NbRh2B2 crystallises in a chiral noncentrosymmetric structure and exhibits bulk type-II superconductivity below 7.46(5) K. Here we show that the temperature dependence of the upper critical field deviates from the behaviour expected for both Werthamer-Helfand-Hohenberg and the Ginzburg-Landau models and that μ0Hc2 (0) ~ 18 T exceeds the Pauli paramagnetic limit, μ0HP = 13.9 T. We explore the reasons for this enhancement. Transverse-field muon spectroscopy measurements suggest that the superconducting gap is either s-wave or (s + s)-wave, a the pressure dependence of Tc reveals the superconducting gap is primarily s- wave in character. The magnetic penetration depth lambda(0) = 595(5) nm. Heat capacity measurements reveal the presence of a multigap (s + s)-wave superconducting order parameter and moderate electron-phonon coupling

Redefining and interrogating pedagogical practices

Lockdowns and the rapid pivot to remote teaching disrupted much of Australasian higher education and has given us impetus to rethink educational design and practice. Overnight, some educators found themselves thrown into remote teaching, while for others, their courses were already designed with blended and online learning in mind. Universities with large face-to-face cohorts have tended to rely upon traditional teaching and assessment modes, with some variation across faculties and departments. Long before the pandemic, learners had been choosing flexible, online teaching and learning modes with dedicated online providers with programmes purposefully designed to leverage online technologies over the traditional on-campus experiences. Many across the higher education sector have recognised this as an opportune time to reflect on just how far education has shifted from a teacher-centred to a learner-centred approach, and how technology may enable or hinder that process

A systematic review of the validity, reliability, and feasibility of measurement tools used to assess the physical activity and sedentary behaviour of pre-school aged children

Physical activity (PA) and sedentary behaviour (SB) of pre-school aged children are associated with important health and developmental outcomes. Accurate measurement of these behaviours in young children is critical for research and practice in this area. The aim of this review was to examine the validity, reliability, and feasibility of measurement tools used to assess PA and SB of pre-school aged children. Searches of electronic databases, and manual searching, were conducted to identify articles that examined the measurement properties (validity, reliability or feasibility) of measurement tools used to examine PA and/or SB of pre-school aged children (3–7 years old). Following screening, data were extracted and risk of bias assessment completed on all included articles. A total of 69 articles, describing 75 individual studies were included. Studies assessed measurement tools for PA (n = 27), SB (n = 5), and both PA and SB (n = 43). Outcome measures of PA and SB differed between studies (e.g. moderate to vigorous activity, step count, posture allocation). Most studies examined the measurement properties of one measurement tool only (n = 65). Measurement tools examined included: calorimetry, direct observation, combined heart rate and accelerometry, heart rate monitors, accelerometers, pedometers, and proxy report (parent, carer or teacher reported) measures (questionnaires or diaries). Studies most frequently assessed the validity (criterion and convergent) (n = 65), face and content validity (n = 2), test-retest reliability (n = 10) and intra-instrument reliability (n = 1) of the measurement tools. Feasibility data was abstracted from 41 studies. Multiple measurement tools used to measure PA and SB in pre-school aged children showed some degree of validity, reliability and feasibility, but often for different purposes. Accelerometers, including the Actigraph (in particular GT3X versions), Actical, ActivPAL and Fitbit (Flex and Zip), and proxy reported measurement tools used in combination may be useful for a range of outcome measures, to measure intensity alongside contextual information

Molards as an indicator of permafrost degradation and landslide processes

Molards have been defined in the past as conical mounds of debris that can form part of a landslide's deposits. We present the first conclusive evidence that molards in permafrost terrains are cones of loose debris that result from thawing of frozen blocks of ice-rich sediments mobilised by a landslide, and hence propose a rigorous definition of this landform in permafrost environments. We show that molards can be used as an indicator of permafrost degradation, and that their morphometry and spatial distribution give valuable insights into landslide dynamics in permafrost environments. We demonstrate that molards are readily recognisable not only in the field, but also in remote sensing data; surveys of historic aerial imagery allow the recognition of relict molards, which can be used as an indicator of current and past permafrost conditions. The triggering of landslides as a result of permafrost degradation will arguably occur more often as global atmospheric temperatures increase, so molards should be added to our armoury for tracking climate change, as well as helping us to understand landslide-related hazards. Finally, we have also identified candidate molards on Mars, so molards can inform about landscape evolution on Earth and other planetary bodies

Debris-flow release processes investigated through the analysis of multi-temporal LiDAR datasets in north-western Iceland

Debris flows are fast-moving gravity flows of poorly sorted rock and soil, mixed and saturated with water. Debris-flow initiation has been studied using empirical and experimental modelling, but the geomorphic changes, indicative of different triggering processes, are difficult to constrain with field observations only. We identify signatures to distinguish two different debris-flow release styles by integrating high-resolution multi temporal remote sensing datasets and morphometric analysis. We analyse debris flows sourced above the town of Ísafjörður (Iceland). Two debris-flow triggering processes were previously hypothesized for this site: (i) slope failure, characterised by landslides evolving into debris flows, and (ii) the fire-hose effect, in which debris accumulated in pre-existing, steep-sided bedrock passages is transported by a surge of water. It is unknown which process dominates and determines the local risk. To investigate this question, we compare airborne LiDAR elevation models and aerial photographs collected in 2007 with similar data from 2013. We find that two new debris-flow tracks were created by slope failures. These are characterised by steep sliding surfaces and lateral leveed channels. Slope failure also occurred in two large, recently active tracks, creating the preparatory conditions for the fire-hose effect to mobilise existing debris. These tracks show alternating zones of fill and scour along their length, and debris stored below the source-area at rest angles >35°. Our approach allows us to identify and quantify the morphological changes produced by slope failure release process, which generated the preparatory conditions for the fire-hose effect. As debris flows are rarely observed in action and morphological changes induced by them are difficult to detect and monitor, the same approach could be applied to other landscapes to understand debris-flow initiation in absence of other monitoring information, and can improve the identification of zones at risk in inhabited areas near hillslopes with potential for debris flows