Natural age dispersion arising from the analysis of broken crystals, part I. Theoretical basis and implications for the apatite (U-Th)/He thermochronometer

Over the last decade major progress has been made in developing both the theoretical and practical aspects of apatite (U-Th)/He thermochronometry and it is now standard practice, and generally seen as best practice, to analyse single grain aliquots. These individual prismatic crystals are often broken and are fragments of larger crystals that have broken during mineral separation along the weak basal cleavage in apatite. This is clearly indicated by the common occurrence of only 1 or no clear crystal terminations present on separated apatite grains, and evidence of freshly broken ends when grains are viewed using a scanning electron microscope. This matters because if the 4He distribution within the whole grain is not homogeneous, because of partial loss due to thermal diffusion for example, then the fragments will all yield ages different from each other and from the whole grain age. Here we use a numerical model with a finite cylinder geometry to approximate 4He ingrowth and thermal diffusion within hexagonal prismatic apatite crystals. This is used to quantify the amount and patterns of inherent, natural age dispersion that arises from analysing broken crystals. A series of systematic numerical experiments were conducted to explore and quantify the pattern and behaviour of this source of dispersion using a set of 5 simple thermal histories that represent a range of plausible geological scenarios. In addition some more complex numerical experiments were run to investigate the pattern and behaviour of grain dispersion seen in several real data sets. The results indicate that natural dispersion of a set of single fragment ages (defined as the range divided by the mean) arising from fragmentation alone varies from c. 7% even for rapid (c. 10 ∘C/Ma), monotonic cooling to over 50% for protracted, complex histories that cause significant diffusional loss of 4He. The magnitude of dispersion arising from fragmentation scales with the grain cylindrical radius, and is of a similar magnitude to dispersion expected from differences in absolute grain size alone (spherical equivalent radii of 40 to 150 μm). This source of dispersion is significant compared with typical analytical uncertainties on individual grain analyses (c. 6%) and standard deviations on multiple grain analyses from a single sample (c. 10-20%). Where there is a significant difference in the U and Th concentration of individual grains (eU), the effect of radiation damage accumulation on 4He diffusivity (assessed using the RDAAM model of Flowers et al. (2009)) is the primary cause of dispersion for samples that have experienced a protracted thermal history, and can cause dispersion in excess of 100% for realistic ranges of eU conentration (i.e. 5-100 ppm). Expected natural dispersion arising from the combined effects of reasonable variations in grain size (radii 40-125 μm), eU concentration (5-150 ppm) and fragmentation would typically exceed 100% for complex thermal histories. In addition to adding a significant component of natural dispersion to analyses, the effect of fragmentation also acts to decouple and corrupt expected correlations between grain ages and absolute grain size and to a lesser extent between grain age and effective uranium concentration (eU). Considering fragmentation explicitly as a source of dispersion and analysing how the different sources of natural dispersion all interact with each other provides a quantitative framework for understanding patterns of dispersion that otherwise appear chaotic. An important outcome of these numerical experiments is that they demonstrate that the pattern of age dispersion arising from fragmentation mimics the pattern of 4He distribution within the whole grains, thus providing an important source of information about the thermal history of the sample. We suggest that if the primary focus of a study is to extract the thermal history information from (U-Th)/He analyses then sampling and analytical strategies should aim to maximise the natural dispersion of grain ages, not minimise it, and should aim to analyse circa 20-30 grains from each sample. The key observations and conclusions drawn here are directly applicable to other thermochronometers, such as the apatite, rutile and titanite U-Pb systems, where the diffusion domain is approximated by the physical grain size

Surface pinning of fluctuating charge order: an "extraordinary" surface phase transition

We study the mean-field theory of charge-density wave (CDW) order in a layered system, including the effect of the long-range Coulomb interaction and of screening by uncondensed electrons. We particularly focus on the conditions necessary for an ``extraordinary'' transition, in which the surface orders at a higher temperature, and is more likely to be commensurate, than the bulk. We interpret recent experiments on NaCCOC as indicating the presence of commensurate CDW at the surface that is not present in the bulk. More generally, we show that poor screening of the Coulomb interaction tends to stabilize incommensurate order, possibly explaining why the CDW order in LSCO and NbSe2 remains incommensurate to T -> 0, despite the small magnitude of the incommensurability.Comment: 9 pages, no figures, 31 references; 1 new figure and minor editing of the tex

Structured evaluation of virtual environments for special-needs education

This paper describes the development of a structured approach to evaluate experiential and communication virtual learning environments (VLEs) designed specifically for use in the education of children with severe learning difficulties at the Shepherd special needs school in Nottingham, UK. Constructivist learning theory was used as a basis for the production of an evaluation framework, used to evaluate the design of three VLEs and how they were used by students with respect to this learning theory. From an observational field study of student-teacher pairs using the VLEs, 18 behaviour categories were identified as relevant to five of the seven constructivist principles defined by Jonassen (1994). Analysis of student-teacher behaviour was used to provide support for, or against, the constructivist principles. The results show that the three VLEs meet the constructivist principles in very different ways and recommendations for design modifications are put forward

Quantitative sensory testing in children with sickle cell disease: additional insights and future possibilities.

Quantitative sensory testing (QST) is used in a variety of pain disorders to characterize pain and predict prognosis and response to specific therapies. In this study, we aimed to confirm results in the literature documenting altered QST thresholds in sickle cell disease (SCD) and assess the test-retest reliability of results over time. Fifty-seven SCD and 60 control subjects aged 8-20 years underwent heat and cold detection and pain threshold testing using a Medoc TSAII. Participants were tested at baseline and 3 months; SCD subjects were additionally tested at 6 months. An important facet of our study was the development and use of a novel QST modelling approach, allowing us to model all data together across modalities. We have not demonstrated significant differences in thermal thresholds between subjects with SCD and controls. Thermal thresholds were consistent over a 3- to 6-month period. Subjects on whom hydroxycarbamide (HC) was initiated shortly before or after baseline testing (new HC users) exhibited progressive decreases in thermal sensitivity from baseline to 6 months, suggesting that thermal testing may be sensitive to effective therapy to prevent vasoocclusive pain. These findings inform the use of QST as an endpoint in the evaluation of preventative pain therapies

Radiative Corrections to W and Quark Propagators in the Resonance Region

We discuss radiative corrections to W and quark propagators in the resonance region, |s-M^2| \lsim M*Gamma. We show that conventional mass renormalization, when applied to photonic or gluonic corrections, leads in next to leading order (NLO) to contributions proportional to [M*Gamma/(s-M^2)]^n, (n=1,2...), i.e. to a non-convergent series in the resonance region, a difficulty that affects all unstable particles coupled to massless quanta. A solution of this problem, based on the concepts of pole mass and width, is presented. It elucidates the issue of renormalization of amplitudes involving unstable particles and automatically circumvents the problem of apparent on-shell singularities. The roles of the Fried-Yennie gauge and the Pinch Technique prescription are discussed. Because of special properties of the photonic and gluonic contributions, and in contrast with the Z case, the gauge dependence of the conventional on-shell definition of mass is unbounded in NLO. The evaluations of the width in the conventional and pole formulations are compared and shown to agree in NLO but not beyond.Comment: 19 pages, 7 figures, LaTeX (uses epsfig). Slight rewording of the abstract and one of the sentences of the text. Minor misprints corrected. To appear in Phys. Rev.

TBLR1 regulates the expression of nuclear hormone receptor co-repressors

BACKGROUND: Transcription is regulated by a complex interaction of activators and repressors. The effectors of repression are large multimeric complexes which contain both the repressor proteins that bind to transcription factors and a number of co-repressors that actually mediate transcriptional silencing either by inhibiting the basal transcription machinery or by recruiting chromatin-modifying enzymes. RESULTS: TBLR1 [GenBank: NM024665] is a co-repressor of nuclear hormone transcription factors. A single highly conserved gene encodes a small family of protein molecules. Different isoforms are produced by differential exon utilization. Although the ORF of the predominant form contains only 1545 bp, the human gene occupies ~200 kb of genomic DNA on chromosome 3q and contains 16 exons. The genomic sequence overlaps with the putative DC42 [GenBank: NM030921] locus. The murine homologue is structurally similar and is also located on Chromosome 3. TBLR1 is closely related (79% homology at the mRNA level) to TBL1X and TBL1Y, which are located on Chromosomes X and Y. The expression of TBLR1 overlaps but is distinct from that of TBL1. An alternatively spliced form of TBLR1 has been demonstrated in human material and it too has an unique pattern of expression. TBLR1 and the homologous genes interact with proteins that regulate the nuclear hormone receptor family of transcription factors. In resting cells TBLR1 is primarily cytoplasmic but after perturbation the protein translocates to the nucleus. TBLR1 co-precipitates with SMRT, a co-repressor of nuclear hormone receptors, and co-precipitates in complexes immunoprecipitated by antiserum to HDAC3. Cells engineered to over express either TBLR1 or N- and C-terminal deletion variants, have elevated levels of endogenous N-CoR. Co-transfection of TBLR1 and SMRT results in increased expression of SMRT. This co-repressor undergoes ubiquitin-mediated degradation and we suggest that the stabilization of the co-repressors by TBLR1 occurs because of a novel mechanism that protects them from degradation. Transient over expression of TBLR1 produces growth arrest. CONCLUSION: TBLR1 is a multifunctional co-repressor of transcription. The structure of this family of molecules is highly conserved and closely related co-repressors have been found in all eukaryotic organisms. Regulation of co-repressor expression and the consequent alterations in transcriptional silencing play an important role in the regulation of differentiation

High-throughput screening in larval zebrafish identifies novel potent sedative-hypnotics

BACKGROUND: Many general anesthetics were discovered empirically, but primary screens to find new sedative-hypnotics in drug libraries have not used animals, limiting the types of drugs discovered. The authors hypothesized that a sedative-hypnotic screening approach using zebrafish larvae responses to sensory stimuli would perform comparably to standard assays, and efficiently identify new active compounds. METHODS: The authors developed a binary outcome photomotor response assay for zebrafish larvae using a computerized system that tracked individual motions of up to 96 animals simultaneously. The assay was validated against tadpole loss of righting reflexes, using sedative-hypnotics of widely varying potencies that affect various molecular targets. A total of 374 representative compounds from a larger library were screened in zebrafish larvae for hypnotic activity at 10 µM. Molecular mechanisms of hits were explored in anesthetic-sensitive ion channels using electrophysiology, or in zebrafish using a specific reversal agent. RESULTS: Zebrafish larvae assays required far less drug, time, and effort than tadpoles. In validation experiments, zebrafish and tadpole screening for hypnotic activity agreed 100% (n = 11; P = 0.002), and potencies were very similar (Pearson correlation, r > 0.999). Two reversible and potent sedative-hypnotics were discovered in the library subset. CMLD003237 (EC50, ~11 µM) weakly modulated γ-aminobutyric acid type A receptors and inhibited neuronal nicotinic receptors. CMLD006025 (EC50, ~13 µM) inhibited both N-methyl-D-aspartate and neuronal nicotinic receptors. CONCLUSIONS: Photomotor response assays in zebrafish larvae are a mechanism-independent platform for high-throughput screening to identify novel sedative-hypnotics. The variety of chemotypes producing hypnosis is likely much larger than currently known.This work was supported by grants from Shanghai Jiaotong University School of Medicine, Shanghai, China, and the Chinese Medical Association, Beijing, China (both to Dr. Yang). The Department of Anesthesia, Critical Care and Pain Medicine of Massachusetts General Hospital, Boston, Massachusetts, supported this work through a Research Scholars Award and an Innovation Grant (both to Dr. Forman). Contributions to this research from the Boston University Center for Molecular Discovery, Boston, Massachusetts (to Drs. Porco, Brown, Schaus, and Xu, and to Mr. Trilles), were supported by a grant from the National Institutes of Health, Bethesda, Maryland (grant No. R24 GM111625). (Shanghai Jiaotong University School of Medicine, Shanghai, China; Chinese Medical Association, Beijing, China; Department of Anesthesia, Critical Care and Pain Medicine of Massachusetts General Hospital, Boston, Massachusetts; R24 GM111625 - National Institutes of Health, Bethesda, Maryland)Accepted manuscript2019-09-0

Eruption of kimberlite magmas: physical volcanology, geomorphology and age of the youngest kimberlitic volcanoes known on earth (the Upper Pleistocene/ Holocene Igwisi Hills volcanoes, Tanzania)

The Igwisi Hills volcanoes (IHV), Tanzania, are unique and important in preserving extra-crater lavas and pyroclastic edifices. They provide critical insights into the eruptive behaviour of kimberlite magmas that are not available at other known kimberlite volcanoes. Cosmogenic 3He dating of olivine crystals from IHV lavas and palaeomagnetic analyses indicates that they are Upper Pleistocene to Holocene in age. This makes them the youngest known kimberlite bodies on Earth by >30 Ma and may indicate a new phase of kimberlite volcanism on the Tanzania craton. Geological mapping, Global Positioning System surveying and field investigations reveal that each volcano comprises partially eroded pyroclastic edifices, craters and lavas. The volcanoes stand 102 to 106 Pa s) for kimberlite, attributed to degassing and in-vent cooling. Each volcano is inferred to be the result of a small-volume, short-lived (days to weeks) monogenetic eruption. The eruptive processes of each Igwisi volcano were broadly similar and developed through three phases: (1) fallout of lithic-bearing pyroclastic rocks during explosive excavation of craters and conduits; (2) fallout of juvenile lapilli from unsteady eruption columns and the construction of pyroclastic edifices around the vent; and (3) effusion of degassed viscous magma as lava flows. These processes are similar to those observed for other small-volume monogenetic eruptions (e.g. of basaltic magma)

Thomas Graham Brown (1882–1965): Behind the Scenes at the Cardiff Institute of Physiology

Thomas Graham Brown undertook seminal experiments on the neural control of locomotion between 1910 and 1915. Although elected to the Royal Society in 1927, his locomotion research was largely ignored until the 1960s when it was championed and extended by the distinguished neuroscientist, Anders Lundberg. Puzzlingly, Graham Brown's published research stopped in the 1920s and he became renowned as a mountaineer. In this article, we review his life and multifaceted career, including his active neurological service in WWI. We outline events behind the scenes during his tenure at Cardiff's Institute of Physiology in Wales, UK, including an interview with his technician, Terrence J. Surman, who worked in this institute for over half a century