The Norse waterways of West Mainland Orkney, Scotland

This study was funded by BA/Leverhulme Small Research Grants 2017-18 Round.Norse place-names for farms, individual landscape features and general landscape areas are ubiquitous throughout the Orkney Islands. These have an origin during the mediaeval period AD790–1350 when Orkney was ruled by Scandinavian earls. The oldest referenced maps for the parish of Harray (West Mainland, Orkney) suggests that in the past significant waterways crossed wetlands extending between the Loch of Harray and Houseby in an area associated with the earldom power base at Birsay. Subsequent drainage projects, changes in climate and sea level have since resulted in the loss of the waterways. An investigation of the wetlands using geophysical and geological analysis provided a reconstruction of the palaeo-environments. Comparison with place-names of significance allowed interpretation of possible routeways along navigable waters by shallow-draught Viking-Age vessels. The results allow for re-drawing the map of Norse Orkney and postulation of produce transfer corridors from estates in the south to the power centre at Birsay.PostprintPeer reviewe

Tunable light and drug induced depletion of target proteins

Biological processes in development and disease are controlled by the abundance, localization and modification of cellular proteins. We have developed versatile tools based on recombinant E3 ubiquitin ligases that are controlled by light or drug induced heterodimerization for nanobody or DARPin targeted depletion of endogenous proteins in cells and organisms. We use this rapid, tunable and reversible protein depletion for functional studies of essential proteins like PCNA in DNA repair and to investigate the role of CED-3 in apoptosis during Caenorhabditis elegans development. These independent tools can be combined for spatial and temporal depletion of different sets of proteins, can help to distinguish immediate cellular responses from long-term adaptation effects and can facilitate the exploration of complex networks

Dialogue Act Modeling for Automatic Tagging and Recognition of Conversational Speech

We describe a statistical approach for modeling dialogue acts in conversational speech, i.e., speech-act-like units such as Statement, Question, Backchannel, Agreement, Disagreement, and Apology. Our model detects and predicts dialogue acts based on lexical, collocational, and prosodic cues, as well as on the discourse coherence of the dialogue act sequence. The dialogue model is based on treating the discourse structure of a conversation as a hidden Markov model and the individual dialogue acts as observations emanating from the model states. Constraints on the likely sequence of dialogue acts are modeled via a dialogue act n-gram. The statistical dialogue grammar is combined with word n-grams, decision trees, and neural networks modeling the idiosyncratic lexical and prosodic manifestations of each dialogue act. We develop a probabilistic integration of speech recognition with dialogue modeling, to improve both speech recognition and dialogue act classification accuracy. Models are trained and evaluated using a large hand-labeled database of 1,155 conversations from the Switchboard corpus of spontaneous human-to-human telephone speech. We achieved good dialogue act labeling accuracy (65% based on errorful, automatically recognized words and prosody, and 71% based on word transcripts, compared to a chance baseline accuracy of 35% and human accuracy of 84%) and a small reduction in word recognition error.Comment: 35 pages, 5 figures. Changes in copy editing (note title spelling changed

Transduction of a dominant-negative H-Ras into human eosinophils attenuates extracellular signal-regulated kinase activation and interleukin-5-mediated cell viability

Inhibition of eosinophil apoptosis by exposure to interleukin-5 (IL-5) is associated with the development of tissue eosinophilia and may contribute to the inflammation characteristic of asthma. Analysis of the signaling events associated with this process has been hampered by the inability to efficiently manipulate eosinophils by the introduction of active or inhibitory effector molecules. Evidence is provided, using a dominantnegative N17 H-Ras protein (dn-H-Ras) and MEK inhibitor U0126, that activation of the Ras-Raf-MEK-ERK pathway plays a determining role in the prolongation of eosinophil survival by IL-5. For these studies, a small region of the human immunodeficiency virus Tat protein, a protein transduction domain known to enter mammalian cells efficiently, was fused to the N-terminus of dn-H-Ras. The Tat-dn-HRas protein generated from this construct transduced isolated human blood eosinophils at more than 95% efficiency. When Tat-dn-H-Ras-transduced eosinophils were treated with IL-5, they exhibited a time- and dosage-dependent reduction in extracellular regulated kinase 1 and 2 activation and an inhibition of p90 Rsk1 phosphorylation and IL-5-mediated eosinophil survival in vitro. In contrast, Tat-dn-H-Ras did not inhibit CD11b upregulation or STAT5 tyrosine phosphorylation. These data demonstrate that Tat dominant-negative protein transduction can serve as an important and novel tool in studying primary myeloid cell signal transduction in primary leukocytes and can implicate the Ras-Raf-MEK-ERK pathway in IL-5-initiated eosinophil survival

The Role of Dietary Sugars and De novo Lipogenesis in Non-Alcoholic Fatty Liver Disease

Dietary sugar consumption, in particular sugar-sweetened beverages and the monosaccharide fructose, has been linked to the incidence and severity of non-alcoholic fatty liver disease (NAFLD). Intervention studies in both animals and humans have shown large doses of fructose to be particularly lipogenic. While fructose does stimulate de novo lipogenesis (DNL), stable isotope tracer studies in humans demonstrate quantitatively that the lipogenic effect of fructose is not mediated exclusively by its provision of excess substrates for DNL. The deleterious metabolic effects of high fructose loads appear to be a consequence of altered transcriptional regulatory networks impacting intracellular macronutrient metabolism and altering signaling and inflammatory processes. Uric acid generated by fructose metabolism may also contribute to or exacerbate these effects. Here we review data from human and animal intervention and stable isotope tracer studies relevant to the role of dietary sugars on NAFLD development and progression, in the context of typical sugar consumption patterns and dietary recommendations worldwide. We conclude that the use of hypercaloric, supraphysiological doses in intervention trials has been a major confounding factor and whether or not dietary sugars, including fructose, at typically consumed population levels, effect hepatic lipogenesis and NAFLD pathogenesis in humans independently of excess energy remains unresolved

Measurement error in a multi-level analysis of air pollution and health: a simulation study.

BACKGROUND: Spatio-temporal models are increasingly being used to predict exposure to ambient outdoor air pollution at high spatial resolution for inclusion in epidemiological analyses of air pollution and health. Measurement error in these predictions can nevertheless have impacts on health effect estimation. Using statistical simulation we aim to investigate the effects of such error within a multi-level model analysis of long and short-term pollutant exposure and health. METHODS: Our study was based on a theoretical sample of 1000 geographical sites within Greater London. Simulations of "true" site-specific daily mean and 5-year mean NO2 and PM10 concentrations, incorporating both temporal variation and spatial covariance, were informed by an analysis of daily measurements over the period 2009-2013 from fixed location urban background monitors in the London area. In the context of a multi-level single-pollutant Poisson regression analysis of mortality, we investigated scenarios in which we specified: the Pearson correlation between modelled and "true" data and the ratio of their variances (model versus "true") and assumed these parameters were the same spatially and temporally. RESULTS: In general, health effect estimates associated with both long and short-term exposure were biased towards the null with the level of bias increasing to over 60% as the correlation coefficient decreased from 0.9 to 0.5 and the variance ratio increased from 0.5 to 2. However, for a combination of high correlation (0.9) and small variance ratio (0.5) non-trivial bias (> 25%) away from the null was observed. Standard errors of health effect estimates, though unaffected by changes in the correlation coefficient, appeared to be attenuated for variance ratios > 1 but inflated for variance ratios < 1. CONCLUSION: While our findings suggest that in most cases modelling errors result in attenuation of the effect estimate towards the null, in some situations a non-trivial bias away from the null may occur. The magnitude and direction of bias appears to depend on the relationship between modelled and "true" data in terms of their correlation and the ratio of their variances. These factors should be taken into account when assessing the validity of modelled air pollution predictions for use in complex epidemiological models

Mindfulness-based cognitive therapy for residual depressive symptoms

Objectives. Mindfulness-based cognitive therapy (MBCT) is a new group-based intervention for prevention of relapse in recurrent depression which has not been scientifically evaluated regarding its clinical effectiveness for ameliorating residual depressive symptoms following a depressive episode. The aim of this study was to assess the efficacy of MBCT in reducing residual depressive symptoms in psychiatric outpatients with recurrent depression, and to particularly explore the effects of mindfulness techniques on rumination. Design. The design of this study was a mixed model complex design. Design 1 consisted of a consecutive series of patients. They were assigned to either MBCT or TAU. The independent variables were time and group allocation, and dependent variables were Beck Depression Inventory (BDI) and Rumination Scale. In Design 2, the TAU group proceeded to complete an MBCT group, and the BDI and Rumination Scale results of the two groups were collapsed. Method. Nineteen patients with residual depressive symptoms following a depressive episode, and who were attending outpatient clinic, were assigned to either MBCT or treatment as usual (TAU), with the TAU group then proceeding to complete an MBCT group. Depressive and ruminative symptoms were assessed before, during, and after treatment, and at one-month follow-up. Results. A significant reduction in depressive symptoms was found at the end of MBCT, with a further reduction at one-month follow-up. A trend towards a reduction in rumination scores was also observed. Conclusions. Group MBCT has a marked effect on residual depressive symptoms, which may be mediated through the mindfulness-based cognitive approach toward

BRAF V600E-Positive Multisite Langerhans Cell Histiocytosis in a Preterm Neonate

Hemorrhagic pustules with a “blueberry muffin” appearance accompanied by respiratory failure in a neonate present a challenging differential diagnosis that includes infections and neoplasms. We present a case of multiorgan, multisite Langerhans cell histiocytosis (LCH), positive for the oncogenic BRAF V600E mutation, in a preterm neonate. Infants with LCH pose a diagnostic challenge due to their heterogeneous presentations. This case is unusual in that the newborn presented with severe multiorgan involvement. Due to the rare incidence, wide spectrum of clinical manifestations, and high mortality rate, clinicians must maintain a high index of suspicion for LCH

The Iowa Homemaker vol.26, no.6

Extracurricular Activities Provide Training, Tony DeLay, page 2 Home Service Program for Young America, Doris Adams, page 3 The Home Economist in Business, Beth Bailey McLean, page 4 How to Become a Career Girl, Frances Kerekes, page 6 Clubs Combine as Future Homemakers of America, Barbara Bates, page 7 1947 Vicky Turns the Page of Fashion, Ann Fuhs, page 8 Christmas Lighting, Ann Rozeboom, page 9 Homemaking is a Challenging Career, Martha Coover, page 10 Good Professional Attitude, Mary Elizabeth Lush, page 11 Alum Head Product Testing Program, Lydia Cooley, page 12 Keeping Up With Today, Joyce Edgar, page 14 Festival Book Aids Party Planning, Luanne Madsen, page 1