Activation of the E-cadherin/catenin complex in human MCF-7 breast cancer cells by all-trans-retinoic acid.

All-trans-retinoic acid (RA), like insulin-like growth factor I (IGF-I) and tamoxifen, inhibit invasion of human MCF-7/6 mammary cancer cells in vitro. For tamoxifen and for IGF-I, activation of the invasion-suppressor function of the E-cadherin/catenin complex was shown to be the most probable mechanism of the anti-invasive action. We did a series of experiments to determine whether the anti-invasive effect of RA also implicated the invasion-suppressor E-cadherin/catenin complex. Human MCF-7/6 mammary and HCT-8/R1 colon cancer cells, both with a dysfunctional E-cadherin/catenin complex, were treated with RA and the function of the complex was evaluated through Ca(2+)-dependent fast aggregation. Fast aggregation of both MCF-7/6 and HCT-8/R1 cells was induced by 1 microM RA. This effect was abolished by antibodies against E-cadherin. RA-induced fast aggregation was not sensitive to cycloheximide, tyrosine kinase inhibitors or antibodies against IGF-I or against the IGF-I receptor. RA did not stimulate IGF-I receptor phosphorylation or alter the E-cadherin/catenin complex, as evidenced by immunoprecipitation. RA up-regulates the function of the invasion-suppressor complex E-cadherin/catenin. Its action mechanism is different from that of IGF-I. RA may act as an anti-invasive agent with unique mechanisms of action

Insulin-like growth factor I activates the invasion suppressor function of E-cadherin in MCF-7 human mammary carcinoma cells in vitro.

The calcium-dependent cell-cell adhesion molecule E-cadherin has been shown to counteract invasion of epithelial neoplastic cells. Using three monoclonal antibodies, we have demonstrated the presence of E-cadherin at the surface of human MCF-7/6 mammary carcinoma cells by indirect immunofluorescence coupled to flow cytometry and by immunocytochemistry. Nevertheless, MCF-7/6 cells failed to aggregate in a medium containing 1.25 mM CaCl2, and they were invasive after confrontation with embryonic chick heart fragments in organ culture. Treatment of MCF-7/6 cells with 0.5 microgram ml-1 insulin-like growth factor I (IGF-I) led to homotypic aggregation within 5 to 10 min and inhibited invasion in vitro during at least 8 days. The effect of IGF-I on cellular aggregation was insensitive to cycloheximide. However, monoclonal antibodies that interfered with the function of either the IGF-I receptor (alpha IR3) or E-cadherin (HECD-1, MB2) blocked the effect of IGF-I on aggregation. The effects of IGF-I on aggregation and on invasion could be mimicked by 1 microgram ml-1 insulin, but not by 0.5 microgram ml-1 IGF-II. The insulin effects were presumably not mediated by the IGF-I receptor, since they could not be blocked by an antibody against this receptor (alpha IR3). Our results indicate that IGF-I activates the invasion suppressor role of E-cadherin in MCF-7/6 cells

Response of AGATA Segmented HPGe Detectors to Gamma Rays up to 15.1 MeV

The response of AGATA segmented HPGe detectors to gamma rays in the energy range 2-15 MeV was measured. The 15.1 MeV gamma rays were produced using the reaction d(11B,ng)12C at Ebeam = 19.1 MeV, while gamma-rays between 2 to 9 MeV were produced using an Am-Be-Fe radioactive source. The energy resolution and linearity were studied and the energy-to-pulse-height conversion resulted to be linear within 0.05%. Experimental interaction multiplicity distributions are discussed and compared with the results of Geant4 simulations. It is shown that the application of gamma-ray tracking allows a suppression of background radiation following neutron capture by Ge nuclei. Finally the Doppler correction for the 15.1 MeV gamma line, performed using the position information extracted with Pulse-shape Analysis, is discussed.Comment: 10 pages, 11 figure

A Regularized Discrete Laminate Parametrization Technique with Applications to Wing-Box Design Optimization

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97055/1/AIAA2012-1519.pd

Deathscapes of Settler Colonialism : The necro-settlement of Stoney Creek, Ontario, Canada

This is the Accepted Manuscript of an article published by Taylor & Francis Group in annals of Association of American Geographers on 23 January 2018, available online https://doi.org/10.1080/24694452.2017.1406327. The Accepted Manuscript is under embargo until 23 January 2019.This article considers the influence of burials and memorials to colonial soldiers from an earlier era on contemporary social and cultural landscapes in Canada. Through the example of a landscape centered on Smith’s Knoll, a burial ground for war dead from the British-American War of 1812, it explores the process of necro-settlement: the strengthening of settler colonial claims to land based on the development of complex, meaningladen landscapes of dead and memory. This article consists of three parts: The first situates geographical studies of deathscapes alongside theories about settler colonialism through intersecting discourses of land use. The second includes a settler colonial microhistorical geography of Smith’s Knoll and the local deathscape that surrounds it. The third section draws on this case study to reveal new perspectives on the role of burial and memorial in settler colonial place-making and the erasure of Indigenous histories and peoples.Peer reviewedFinal Accepted Versio

Identification of high-spin proton configurations in Ba 136 and Ba 137

19 pags., 11 figs., 3 tabs.The high-spin structures of Ba136 and Ba137 are investigated after multinucleon-transfer (MNT) and fusion-evaporation reactions. Ba136 is populated in a Xe136+U238 MNT reaction employing the high-resolution Advanced GAmma Tracking Array (AGATA) coupled to the magnetic spectrometer PRISMA at the Laboratori Nazionali di Legnaro, Italy, and in two Be9+Te130 fusion-evaporation reactions using the High-efficiency Observatory for γ-Ray Unique Spectroscopy (HORUS) at the FN tandem accelerator of the University of Cologne, Germany. Furthermore, both isotopes are populated in an elusive reaction channel in the B11+Te130 fusion-evaporation reaction utilizing the HORUS γ-ray array. The level scheme above the Jπ=10+ isomer in Ba136 is revised and extended up to an excitation energy of approximately 5.5 MeV. From the results of angular-correlation measurements, the Ex=3707- and Ex=4920-keV states are identified as the bandheads of positive- and negative-parity cascades. While the high-spin regimes of both Te132 and Xe134 are characterized by high-energy 12+→10+ transitions, the Ba136E2 ground-state band is interrupted by negative-parity states only a few hundred keV above the Jπ=10+ isomer. Furthermore, spins are established for several hitherto unassigned high-spin states in Ba137. The new results close a gap along the high-spin structure of N<82 Ba isotopes. Experimental results are compared to large-scale shell-model calculations employing the GCN50:82, Realistic SM, PQM130, and SN100PN interactions. The calculations suggest that the bandheads of the positive-parity bands in both isotopes are predominantly of proton character.Furthermore, we express our thanks to Dr. E. Teruya and Dr. N. Yoshinaga from Saitama University, Japan, for providing the results of their shellmodel calculation with the PQM130 interaction. The research leading to these results has received funding from the German BMBF under Contracts No. 05P15PKFN9 TP1 and No. 05P18PKFN9 TP1, from the European Union Seventh Framework Programme FP7/2007-2013 under Grant Agreement No. 262010 - ENSAR, from the Spanish Ministerio de Ciencia e Innovación under Contract No. FPA2011-29854- C04, from the Spanish Ministerio de Economía y Competitividad under Contract No. FPA2014-57196-C5, and from the UK Science and Technology Facilities Council (STFC). L.K. and A.V. thank the Bonn-Cologne Graduate School of Physics and Astronomy (BCGS) for financial support. One of the authors (A. Gadea) has been supported by the Generalitat Valenciana, Spain, under Grant No. PROMETEOII/2014/019, and EU under the FEDER program

Older adult experience of care and staffing on hospital and community wards: a cross-sectional study

BACKGROUND: Recent major concerns about the quality of healthcare delivered to older adults have been linked to inadequate staffing and a lack of patient-centred care. Patient experience is a key component of quality care - yet there has been little research on whether and how staffing levels and staffing types affect satisfaction amongst older adult hospital inpatients. This study aimed to evaluate the association between registered nurse and healthcare assistant staffing levels and satisfaction with care amongst older adult hospital inpatients, and to test whether any positive effect of higher staffing levels is mediated by staff feeling they have more time to care for patients. METHODS: Survey data from 4928 inpatients aged 65 years and older and 2237 medical and nursing staff from 123 acute and community medical wards in England, United Kingdom (UK) was collected through the Royal College of Psychiatrist's Elder Care Quality Mark. The cross-sectional association between staffing ratios and older adult patient satisfaction, and mediation by staff perceived time to care, was evaluated using multi-level modelling, adjusted for ward type and with a random effect for ward identity. RESULTS: Higher numbers of patients per healthcare assistant were associated with poorer patient satisfaction (adjusted β = - 0.32, 95% CI - 0.55 to 0.10, p < 0.01), and this was found to be partially mediated by all ward staff reporting less time to care for patients (adjusted β = - 0.10, bias-corrected 95% CI - 1.16 to - 0.02). By contrast, in both unadjusted and adjusted models, the number of patients per registered nurse was not associated with patient satisfaction. CONCLUSIONS: Older adult hospital patients may particularly value the type of care provided by healthcare assistants, such as basic personal care and supportive communication. Additionally, higher availability of healthcare assistants may contribute to all ward staff feeling more able to spend time with patients. However, high availability of registered nurses has been shown in other research to be vital for ensuring quality and safety of patient care. Future research should seek to identify the ideal balance of registered nurses and healthcare assistants for optimising a range of outcomes amongst older adult patients

Study of Isomeric States in ^{198,200,202,206}Pb and ²⁰⁶Hg Populated in Fragmentation Reactions

Isomeric states in isotopes in the vicinity of doubly-magic 208Pb were populated following reactions of a relativistic 208Pb primary beam impinging on a 9Be fragmentation target. Secondary beams of 198;200;202;206Pb and 206Hg were isotopically separated and implanted in a passive stopper positioned in the focal plane of the GSI Fragment Separator. Delayed γ rays were detected with the Advanced GAmma Tracking Array (AGATA). Decay schemes were re-evaluated and interpreted with shell-model calculations. The momentum-dependent population of isomeric states in the two-nucleon hole nuclei 206Pb/206Hg was found to differ from the population of multi neutron-hole isomeric states in 198;200;202Pb

Isospin dependence of electromagnetic transition strengths among an isobaric triplet

Electric quadrupole matrix elements, M, for the J=2→0, ΔT=0, T=1 transitions across the A=46 isobaric multiplet Cr-V-Ti have been measured at GSI with the FRS-LYCCA-AGATA setup. This allows direct insight into the isospin purity of the states of interest by testing the linearity of M with respect to T. Pairs of nuclei in the T=1 triplet were studied using identical reaction mechanisms in order to control systematic errors. The M values were obtained with two different methodologies: (i) a relativistic Coulomb excitation experiment was performed for Cr and Ti; (ii) a “stretched target” technique was adopted here, for the first time, for lifetime measurements in V and Ti. A constant value of M across the triplet has been observed. Shell-model calculations performed within the fp shell fail to reproduce this unexpected trend, pointing towards the need of a wider valence space. This result is confirmed by the good agreement with experimental data achieved with an interaction which allows excitations from the underlying sd shell. A test of the linearity rule for all published data on complete T=1 isospin triplets is presented.Peer Reviewe