Message in a bottle : a tale of two Triassic temnospondyl (labyrinthodont) femora from Tasmania

In 1997 the senior author, while exploring the antique shops of Hobart, found in Suffolk Park Antiques an intriguing small, nineteenth-century, clear glass bottle. Labelled as "message in a bottle", it did indeed contain a note on a slip, cut from a visiting card, together with a wafer-thin, sub-triangular piece of dark, porous material (pl. 1). The handwritten note read "section shaft humerus labryinthodont, sandstone quarry, Hobart, 1856, Tas Museum".A further annotation, written at right angles to the preceding note, appears to read "Pro R.S.T 1898-9". Pro R.S.T. is an abbreviated reference to the Papers and Proceedings of the Royal Society of Tasmania, 1898-99. This issue of the journal included a short note by WH. Twelvetrees and WF. Petterd describing and illustrating two labyrinthodont bones from Tasmania lodged in the Tasmanian Museum and Art Gallery (TMAG) collection. Here we trace the history of the two temnospondyl (labyrinthodont) bones, review the significance of these specimens and propose an explanation as to how part of one specimen came to be in the Suffolk Park Antiques sho

Microflow of fluorescently labelled red blood cells in tumours expressing single isoforms of VEGF and their response to VEGF-R tyrosine kinase inhibition

In this work we studied the functional differences between the microcirculation of murine tumours that only express single isoforms of vascular endothelial growth factor-A (VEGF), VEGF120 and VEGF188, and the effect of VEGF receptor tyrosine kinase (VEGF-R TK) inhibition on their functional response to the vascular disrupting agent, combretastatin A-4 phosphate (CA-4-P). We used measurement of fluorescently- labelled red blood cell (RBC) velocities in tumour microvessels to study this functional response. RBC velocity for control VEGF120-expressing tumours was over 50% slower than for control VEGF188- expressing tumours, which may be due to the immature and haemorrhagic vasculature of the VEGF120 tumour. After chronic treatment with a VEGF-R tyrosine kinase inhibitor, SU5416, RBC velocities in VEGF120 tumours were significantly increased compared to control VEGF120 tumours, and similar to velocities in both VEGF188 treatment groups. Control and SU5416 treated VEGF188 tumours were not different from each other. Treatment of VEGF120 tumours with SU5416 reduced their vascular response to CA-4-P to a similar level to the VEGF188 tumours. Differential expression of VEGF isoforms not only affected vascular function in untreated tumours but also impacted on response to a vascular disrupting drug, CA-4-P, alone and in combination with an anti-angiogenic approach involving VEGF-R TK inhibition. Analysis of RBC velocities is a useful tool in measuring functional responses to vascular targeted treatments

Proglacial icings as indicators of glacier thermal regime : ice thickness changes and icing occurrence in Svalbard

Proglacial icings (also known as naled or aufeis) are frequently observed in the forefields of polar glaciers. Their formation has been ascribed to the refreezing of upwelling groundwater that has originated from subglacial melt, and thus the presence of icings has been used as evidence of polythermal glacier regime. We provide an updated analysis of icing occurrence in Svalbard and test the utility of icings as an indicator of thermal regime by comparing icing presence with: (1) mean glacier thickness, as a proxy for present thermal regime; and (2) evidence of past surge activity, which is an indicator of past thermal regime. A total of 279 icings were identified from TopoSvalbard imagery covering the period 2008-2012, of which 143 corresponded to icings identified by Bukowska-Jania and Szafraniec (2005) from aerial photographs from 1990. Only 46% of icings observed in 2008-2012 were found to occur at glaciers with thicknesses consistent with a polythermal regime, meaning a large proportion were associated with glaciers predicted to be of a cold or transitional thermal regime. As a result, icing presence alone may be an unsuitable indicator of glacier regime. We further found that, of the 279 glaciers with icings, 63% of cold-based glaciers and 64% of transitional glaciers were associated with evidence of surge activity. We therefore suggest that proglacial icing formation in Svalbard may reflect historical (rather than present) thermal regime, and that icings possibly originate from groundwater effusion from subglacial taliks that persist for decades following glacier thinning and associated regime change

Self-regulated learning: a literature review. [Wider Benefits of Learning Research Report No. 33]

Within the framework of risk and resilience, this report focuses on changes in wellbeing from middle childhood to early adolescence. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigate trajectories and drivers of change across psychological, behavioural, social and subjective school wellbeing. We also examine those children who have a large number of risks in their lives, identifying those factors which may help protect their wellbeing. Findings suggest that the course of wellbeing for the individual child is varied and complex. Factors either support or undermine changes in wellbeing, but while some appear universal for both high- and low-risk children, others are differentiated by risk level and/or gender. Nonetheless, a few key factors are highlighted, including the importance of children?s environments ? in terms of their relationships with parents, friends and school ? as well as their experiences and capabilities in terms of attainment and SEN, rather than their social background and where they live

A potential nitrergic mechanism of action for indomethacin, but not of other COX inhibitors: relevance to indomethacin-sensitive headaches

Non-steroidal anti-inflammatory drugs (NSAIDs) that act as cyclo-oxygenase (COX) inhibitors are commonly used in the treatment of a range of headache disorders, although their mechanism of action is unclear. Indomethacin is of particular interest given its very special effect in some primary headaches. Here the in vivo technique of intravital microscopy in rats has been utilised as a model of trigeminovascular nociception to study the potential mechanism of action of indomethacin. Dural vascular changes were produced using electrical (neurogenic) dural vasodilation (NDV), calcitonin gene-related peptide (CGRP) induced dural vasodilation and nitric oxide (NO) induced dural vasodilation using NO donors. In each of these settings the effect of intravenously administered indomethacin (5 mg kg−1), naproxen (30 mg kg−1) and ibuprofen (30 mg kg−1) was tested. All of the tested drugs significantly inhibited NDV (between 30 and 52%). Whilst none of them was able to inhibit CGRP-induced dural vasodilation, only indomethacin reduced NO induced dural vasodilation (35 ± 7%, 10 min post administration). We conclude NSAIDs inhibit release of CGRP after NDV without an effect on CGRP directly. Further we describe a differentiating effect of indomethacin inhibiting nitric oxide induced dural vasodilation that is potentially relevant to understanding its unique action in disorders such as paroxysmal hemicrania and hemicrania continua

The nature of localization in graphene under quantum Hall conditions

Particle localization is an essential ingredient in quantum Hall physics [1,2]. In conventional high mobility two-dimensional electron systems Coulomb interactions were shown to compete with disorder and to play a central role in particle localization [3]. Here we address the nature of localization in graphene where the carrier mobility, quantifying the disorder, is two to four orders of magnitude smaller [4,5,6,7,8,9,10]. We image the electronic density of states and the localized state spectrum of a graphene flake in the quantum Hall regime with a scanning single electron transistor [11]. Our microscopic approach provides direct insight into the nature of localization. Surprisingly, despite strong disorder, our findings indicate that localization in graphene is not dominated by single particle physics, but rather by a competition between the underlying disorder potential and the repulsive Coulomb interaction responsible for screening.Comment: 18 pages, including 5 figure

Hyperpolarized Long-T1 Silicon Nanoparticles for Magnetic Resonance Imaging

Silicon nanoparticles are experimentally investigated as a potential hyperpolarized, targetable MRI imaging agent. Nuclear T_1 times at room temperature for a variety of Si nanoparticles are found to be remarkably long (10^2 to 10^4 s) - roughly consistent with predictions of a core-shell diffusion model - allowing them to be transported, administered and imaged on practical time scales without significant loss of polarization. We also report surface functionalization of Si nanoparticles, comparable to approaches used in other biologically targeted nanoparticle systems.Comment: supporting material here: http://marcuslab.harvard.edu/Aptekar_hyper1_sup.pd

Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss

Genome-wide analyses have identified thousands of long noncoding RNAs (lncRNAs). Malat1 (metastasis-associated lung adenocarcinoma transcript 1) is among the most abundant lncRNAs whose expression is altered in numerous cancers. Here we report that genetic loss or systemic knockdown of Malat1 using antisense oligonucleotides (ASOs) in the MMTV (mouse mammary tumor virus)-PyMT mouse mammary carcinoma model results in slower tumor growth accompanied by significant differentiation into cystic tumors and a reduction in metastasis. Furthermore, Malat1 loss results in a reduction of branching morphogenesis in MMTV-PyMT- and Her2/neu-amplified tumor organoids, increased cell adhesion, and loss of migration. At the molecular level, Malat1 knockdown results in alterations in gene expression and changes in splicing patterns of genes involved in differentiation and protumorigenic signaling pathways. Together, these data demonstrate for the first time a functional role of Malat1 in regulating critical processes in mammary cancer pathogenesis. Thus, Malat1 represents an exciting therapeutic target, and Malat1 ASOs represent a potential therapy for inhibiting breast cancer progression

Observation of Electron-Hole Puddles in Graphene Using a Scanning Single Electron Transistor

The electronic density of states of graphene is equivalent to that of relativistic electrons. In the absence of disorder or external doping the Fermi energy lies at the Dirac point where the density of states vanishes. Although transport measurements at high carrier densities indicate rather high mobilities, many questions pertaining to disorder remain unanswered. In particular, it has been argued theoretically, that when the average carrier density is zero, the inescapable presence of disorder will lead to electron and hole puddles with equal probability. In this work, we use a scanning single electron transistor to image the carrier density landscape of graphene in the vicinity of the neutrality point. Our results clearly show the electron-hole puddles expected theoretically. In addition, our measurement technique enables to determine locally the density of states in graphene. In contrast to previously studied massive two dimensional electron systems, the kinetic contribution to the density of states accounts quantitatively for the measured signal. Our results suggests that exchange and correlation effects are either weak or have canceling contributions.Comment: 13 pages, 5 figure