963 research outputs found
Interest of colchicine for the treatment of cystic fibrosis patients. Preliminary report.
Cystic fibrosis (CF) lung disease is characterized by persistent inflammation. Antiinflammatory drugs, such as corticosteroids and ibuprofen, have proved to slow the decline of pulmonary function although their use is limited because of frequent adverse events. We hypothesized that colchicine could be an alternative treatment because of its antiinflammatory properties and upregulatory effect on cystic fibrosis transmembrane regulator (CFTR) closely related proteins. We herein present results obtained in an open study of eight CF children treated with colchicine for at least 6 months. Clinical status was better in all patients and respiratory function tests significantly improved in five. Median duration of antibiotherapy decreased significantly. These preliminary results support our hypothesis of a beneficial effect of colchicine in CF patients and stress the need for a controlled therapeutic trial
Gene expression profiling identifies activated growth factor signaling in poor prognosis (Luminal-B) estrogen receptor positive breast cancer
BACKGROUND: Within estrogen receptor-positive breast cancer (ER+ BC), the expression levels of proliferation-related genes can define two clinically distinct molecular subtypes. When treated with adjuvant tamoxifen, those ER+ BCs that are lowly proliferative have a good prognosis (luminal-A subtype), however the clinical outcome of those that are highly proliferative is poor (luminal-B subtype). METHODS: To investigate the biological basis for these observations, gene set enrichment analysis (GSEA) was performed using microarray data from 246 ER+ BC samples from women treated with adjuvant tamoxifen monotherapy. To create an in vitro model of growth factor (GF) signaling activation, MCF-7 cells were treated with heregulin (HRG), an HER3 ligand. RESULTS: We found that a gene set linked to GF signaling was significantly enriched in the luminal-B tumors, despite only 10% of samples over-expressing HER2 by immunohistochemistry. To determine the biological significance of this observation, MCF-7 cells were treated with HRG. These cells displayed phosphorylation of HER2/3 and downstream ERK and S6. Treatment with HRG overcame tamoxifen-induced cell cycle arrest with higher S-phase fraction and increased anchorage independent colony formation. Gene expression profiles of MCF-7 cells treated with HRG confirmed enrichment of the GF signaling gene set and a similar proliferative signature observed in human ER+ BCs resistant to tamoxifen. CONCLUSION: These data demonstrate that activation of GF signaling pathways, independent of HER2 over-expression, could be contributing to the poor prognosis of the luminal-B ER+ BC subtype.Journal Articleinfo:eu-repo/semantics/publishe
Reconstructing past terrace fields in the Pyrenees: Insights into land management and settlement from the Bronze Age to the Early Modern era at Vilalta (1650 masl, Cerdagne, France)
© Trustees of Boston University 2015. The building of a solar power station at Thémis, at 1650 masl on the south-facing slope of the Carlit massif in the eastern Pyrenees, led to an archaeological evaluation from April-June 2009. This evaluation covered a surface of 10 ha that included a medieval village as well as the surrounding agricultural land in terraces. Non-destructive archaeological methods were used for the village. A detailed study of the 6 ha of terraces began with a fieldwalking survey, mapping every visible feature, followed by systematic trial trenches. Fifty-five trenches, 11 in the village and 44 in the fields, were opened. The stratigraphies were then compared with a series of 22 radiocarbon dates and eight relative dates provided by ceramic typologies. This combination of surface and buried evidence supported our preliminary hypothesis about the dynamics of the slope. The results suggest the existence of agrarian features beginning in the Bronze Age and reveal that the field patterns were frequently transformed, both in the Medieval and Early Modern periods. The transformations in the terrace fields after the village was abandoned are as interesting as those during occupation because, contrary to the idea of a fixed, unchanging landscape after the end of the Middle Ages, they challenge the idea that mountain zones are marginal spaces by nature, or were marginalized later.Peer Reviewe
On the Three-dimensional Central Moment Lattice Boltzmann Method
A three-dimensional (3D) lattice Boltzmann method based on central moments is
derived. Two main elements are the local attractors in the collision term and
the source terms representing the effect of external and/or self-consistent
internal forces. For suitable choices of the orthogonal moment basis for the
three-dimensional, twenty seven velocity (D3Q27), and, its subset, fifteen
velocity (D3Q15) lattice models, attractors are expressed in terms of
factorization of lower order moments as suggested in an earlier work; the
corresponding source terms are specified to correctly influence lower order
hydrodynamic fields, while avoiding aliasing effects for higher order moments.
These are achieved by successively matching the corresponding continuous and
discrete central moments at various orders, with the final expressions written
in terms of raw moments via a transformation based on the binomial theorem.
Furthermore, to alleviate the discrete effects with the source terms, they are
treated to be temporally semi-implicit and second-order, with the implicitness
subsequently removed by means of a transformation. As a result, the approach is
frame-invariant by construction and its emergent dynamics describing fully 3D
fluid motion in the presence of force fields is Galilean invariant. Numerical
experiments for a set of benchmark problems demonstrate its accuracy.Comment: 55 pages, 8 figure
Zero temperature phases of the frustrated J1-J2 antiferromagnetic spin-1/2 Heisenberg model on a simple cubic lattice
At zero temperature magnetic phases of the quantum spin-1/2 Heisenberg
antiferromagnet on a simple cubic lattice with competing first and second
neighbor exchanges (J1 and J2) is investigated using the non-linear spin wave
theory. We find existence of two phases: a two sublattice Neel phase for small
J2 (AF), and a collinear antiferromagnetic phase at large J2 (CAF). We obtain
the sublattice magnetizations and ground state energies for the two phases and
find that there exists a first order phase transition from the AF-phase to the
CAF-phase at the critical transition point, pc = 0.28. Our results for the
value of pc are in excellent agreement with results from Monte-Carlo
simulations and variational spin wave theory. We also show that the quartic 1/S
corrections due spin-wave interactions enhance the sublattice magnetization in
both the phases which causes the intermediate paramagnetic phase predicted from
linear spin wave theory to disappear.Comment: 19 pages, 4 figures, Fig. 1b modified, Appendix B text modifie
SUMO chain formation is required for response to replication arrest in S. pombe
SUMO is a ubiquitin-like protein that is post-translationally attached to one or more lysine residues on target proteins. Despite having only 18% sequence identity with ubiquitin, SUMO contains the conserved betabetaalphabetabetaalphabeta fold present in ubiquitin. However, SUMO differs from ubiquitin in having an extended N-terminus. In S. pombe the N-terminus of SUMO/Pmt3 is significantly longer than those of SUMO in S. cerevisiae, human and Drosophila. Here we investigate the role of this N-terminal region. We have used two dimensional gel electrophoresis to demonstrate that S. pombe SUMO/Pmt3 is phosphorylated, and that this occurs on serine residues at the extreme N-terminus of the protein. Mutation of these residues (in pmt3-1) results in a dramatic reduction in both the levels of high Mr SUMO-containing species and of total SUMO/Pmt3, indicating that phosphorylation of SUMO/Pmt3 is required for its stability. Despite the significant reduction in high Mr SUMO-containing species, pmt3-1 cells do not display an aberrant cell morphology or sensitivity to genotoxins or stress. Additionally, we demonstrate that two lysine residues in the N-terminus of S. pombe SUMO/Pmt3 (K14 and K30) can act as acceptor sites for SUMO chain formation in vitro. Inability to form SUMO chains results in aberrant cell and nuclear morphologies, including stretched and fragmented chromatin. SUMO chain mutants are sensitive to the DNA synthesis inhibitor, hydroxyurea (HU), but not to other genotoxins, such as UV, MMS or CPT. This implies a role for SUMO chains in the response to replication arrest in S. pomb
Eocene intra-plate shortening responsible for the rise of a faunal pathway in the northeastern Caribbean realm
Intriguing latest Eocene land-faunal dispersals between South America and the Greater Antilles (northern Caribbean) has inspired the hypothesis of the GAARlandia (Greater Antilles Aves Ridge) land bridge. This landbridge, however, should have crossed the Caribbean oceanic plate, and the geological evolution of its rise and demise, or its geodynamic forcing, remain unknown. Here we present the results of a land-sea survey from the northeast Caribbean plate, combined with chronostratigraphic data, revealing a regional episode of mid to late Eocene, trench-normal, E-W shortening and crustal thickening by ∼25%. This shortening led to a regional late Eocene–early Oligocene hiatus in the sedimentary record revealing the location of an emerged land (the Greater Antilles-Northern Lesser Antilles, or GrANoLA, landmass), consistent with the GAARlandia hypothesis. Subsequent submergence is explained by combined trench-parallel extension and thermal relaxation following a shift of arc magmatism, expressed by a regional early Miocene transgression. We tentatively link the NE Caribbean intra-plate shortening to a well-known absolute and relative North American and Caribbean plate motion change, which may provide focus for the search of the remaining connection between ‘GrANoLA’ land and South America, through the Aves Ridge or Lesser Antilles island arc. Our study highlights the how regional geodynamic evolution may have driven paleogeographic change that is still reflected in current biology
Prehistory of Transit Searches
Nowadays the more powerful method to detect extrasolar planets is the transit
method. We review the planet transits which were anticipated, searched, and the
first ones which were observed all through history. Indeed transits of planets
in front of their star were first investigated and studied in the solar system.
The first observations of sunspots were sometimes mistaken for transits of
unknown planets. The first scientific observation and study of a transit in the
solar system was the observation of Mercury transit by Pierre Gassendi in 1631.
Because observations of Venus transits could give a way to determine the
distance Sun-Earth, transits of Venus were overwhelmingly observed. Some
objects which actually do not exist were searched by their hypothetical
transits on the Sun, as some examples a Venus satellite and an infra-mercurial
planet. We evoke the possibly first use of the hypothesis of an exoplanet
transit to explain some periodic variations of the luminosity of a star, namely
the star Algol, during the eighteen century. Then we review the predictions of
detection of exoplanets by their transits, those predictions being sometimes
ancient, and made by astronomers as well as popular science writers. However,
these very interesting predictions were never published in peer-reviewed
journals specialized in astronomical discoveries and results. A possible
transit of the planet beta Pic b was observed in 1981. Shall we see another
transit expected for the same planet during 2018? Today, some studies of
transits which are connected to hypothetical extraterrestrial civilisations are
published in astronomical refereed journals. Some studies which would be
classified not long ago as science fiction are now considered as scientific
ones.Comment: Submiited to Handbook of Exoplanets (Springer
Variational Principles for Stellar Structure
The four equations of stellar structure are reformulated as two alternate
pairs of variational principles. Different thermodynamic representations lead
to the same hydromechanical equations, but the thermal equations require, not
the entropy, but the temperature as the thermal field variable. Our treatment
emphasizes the hydrostatic energy and the entropy production rate of luminosity
produced and transported. The conceptual and calculational advantages of
integral over differential formulations of stellar structure are discussed
along with the difficulties in describing stellar chemical evolution by
variational principles.Comment: 28 pages, LaTeX, requires AASTeX, 1 PostScript figure, revisions:
erratum; accepted by Astrophysical Journa
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