Hydrographic Surveying in the Great Lakes During the Nineteenth Century

This paper reviews the development of hydrographic surveys in the Great Lakes during the 19th century. It traces the work of the early Admiralty surveyors and of the U.S. Corps of Engineers through to the formation of the Canadian Hydrographic Service and describes some of the methods used and the hardships faced by the early surveyors

Modelling stratospheric polar ozone using objective analysis

We have studied the development of the austral ozone hole using a 3-D spectral chemical transport model at R15 resolution for the period 15th September to 15th October, 1991. The model is driven by objectively analyzed wind fields obtained from the Canadian Meteorological Center and uses the chemical module developed by Kaminski (1992). Although extensive processing of NO(y) and Cl(x) occurs within the model, the ozone hole that develops appears shallow and ephemeral. Analysis of the results indicate that the meridional transport of ozone is sufficient to overwhelm the substantial chemical depletion that does occur. We suggest that the low resolution objectively analyzed data used is unable to capture the essential isolated nature of the vortex

Optical evidence of surface state suppression in Bi based topological insulators

A key challenge in condensed matter research is the optimization of topological insulator (TI) compounds for the study and future application of their unique surface states. Truly insulating bulk states would allow the exploitation of predicted surface state properties, such as protection from backscattering, dissipationless spin-polarized currents, and the emergence of novel particles. Towards this end, major progress was recently made with the introduction of highly resistive Bi$_2$Te$_2$Se, in which surface state conductance and quantum oscillations are observed at low temperatures. Nevertheless, an unresolved and pivotal question remains: while room temperature ARPES studies reveal clear evidence of TI surface states, their observation in transport experiments is limited to low temperatures. A better understanding of this surface state suppression at elevated temperatures is of fundamental interest, and crucial for pushing the boundary of device applications towards room-temperature operation. In this work, we simultaneously measure TI bulk and surface states via temperature dependent optical spectroscopy, in conjunction with transport and ARPES measurements. We find evidence of coherent surface state transport at low temperatures, and propose that phonon mediated coupling between bulk and surface states suppresses surface conductance as temperature rises.Comment: 13 pages, 10 figure

New evidence on Allyn Young's style and influence as a teacher

This paper publishes the hitherto unpublished correspondence between Allyn Abbott Young's biographer Charles Blitch and 17 of Young's former students or associates. Together with related biographical and archival material, the paper shows the way in which this adds to our knowledge of Young's considerable influence as a teacher upon some of the twentieth century's greatest economists. The correspondents are as follows: James W Angell, Colin Clark, Arthur H Cole, Lauchlin Currie, Melvin G de Chazeau, Eleanor Lansing Dulles, Howard S Ellis, Frank W Fetter, Earl J Hamilton, Seymour S Harris, Richard S Howey, Nicholas Kaldor, Melvin M Knight, Bertil Ohlin, Geoffrey Shepherd, Overton H Taylor, and Gilbert Walker

FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis

Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials

Functional and proteomic analysis of a full thickness filaggrin-deficient skin organoid model

Background: Atopic eczema is an itchy inflammatory disorder characterised by skin barrier dysfunction. Loss-of-function mutations in the gene encoding filaggrin (FLG) are a major risk factor, but the mechanisms by which filaggrin haploinsufficiency leads to atopic inflammation remain incompletely understood. Skin as an organ that can be modelled using primary cells in vitro provides the opportunity for selected genetic effects to be investigated in detail. Methods: Primary human keratinocytes and donor-matched primary fibroblasts from healthy individuals were used to create skin organoid models with and without siRNA-mediated knockdown of FLG. Biological replicate sets of organoids were assessed using histological, functional and biochemical measurements. Results: FLG knockdown leads to subtle changes in histology and ultrastructure including a reduction in thickness of the stratum corneum and smaller, less numerous keratohyalin granules. Immature organoids showed some limited evidence of barrier impairment with FLG knockdown, but the mature organoids showed no difference in transepidermal water loss, water content or dye penetration. There was no difference in epidermal ceramide content. Mass spectrometry proteomic analysis detected &gt;8000 proteins per sample. Gene ontology and pathway analyses identified an increase in transcriptional and translational activity but a reduction in proteins contributing to terminal differentiation, including caspase 14, dermokine, AKT1 and TGF-beta-1. Aspects of innate and adaptive immunity were represented in both the up-regulated and down-regulated protein groups, as was the term ‘axon guidance’. Conclusions: This work provides further evidence for keratinocyte-specific mechanisms contributing to immune and neurological, as well as structural, aspects of skin barrier dysfunction. Individuals with filaggrin deficiency may derive benefit from future therapies targeting keratinocyte-immune crosstalk and neurogenic pruritus