Early stages of LDL oxidation: apolipoprotein B structural changes monitored by infrared spectroscopy.

Changes in the conformation of apoliprotein B-100 in the early stages of copper-mediated low density lipoprotein oxidation have been monitored by infrared spectroscopy. During the lag phase no variation in structure is observed, indicating that copper binding to the protein does not significantly affect its structure. In the propagation phase, while hydroperoxides are formed but the protein is not modified, no changes in secondary structure are observed, but the thermal profile of the band corresponding to alpha-helix is displaced in frequency, indicating changes in tertiary structure associated with this conformation but not with beta-sheet components. When aldehyde formation starts, a decrease of approximately 3% in the area of bands corresponding to alpha-helix and beta-sheet is produced, concomitantly with an increase in beta-turns and unordered structure. The two bands corresponding to beta-turns vary as well under these conditions, indicating changes in these structures. Also at this stage the thermal profile shows variations in frequency for the bands corresponding to both alpha-helix and beta-sheet.The results are consistent with the hypothesis that as soon as the polyunsaturated fatty acids from the particle core are modified, this change is reflected at the surface, in the alpha-helical components contacting the monolayer.Fil: Chehin, Rosana Nieves. Consejo Superior de Investigaciones Científicas; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad del País Vasco; EspañaFil: Rengel, David. Consejo Superior de Investigaciones Científicas; España. Universidad del País Vasco; EspañaFil: Milicua, José Carlos G.. Universidad del País Vasco; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Goñi, Félix M.. Universidad del País Vasco; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Arrondo JL. Consejo Superior de Investigaciones Científicas; España. Universidad del País Vasco; EspañaFil: Pifat, Greta. Rudjer Bošković Institute; Croaci

Chinese–Spanish neural machine translation enhanced with character and word bitmap fonts

Recently, machine translation systems based on neural networks have reached state-of-the-art results for some pairs of languages (e.g., German–English). In this paper, we are investigating the performance of neural machine translation in Chinese–Spanish, which is a challenging language pair. Given that the meaning of a Chinese word can be related to its graphical representation, this work aims to enhance neural machine translation by using as input a combination of: words or characters and their corresponding bitmap fonts. The fact of performing the interpretation of every word or character as a bitmap font generates more informed vectorial representations. Best results are obtained when using words plus their bitmap fonts obtaining an improvement (over a competitive neural MT baseline system) of almost six BLEU, five METEOR points and ranked coherently better in the human evaluation.Peer ReviewedPostprint (published version

Starvation and desiccation tolerance in Drosophila melanogaster: differences between European, North African and Afrotropical populations

International audienc

Measuring Slepton Masses and Mixings at the LHC

Flavor physics may help us understand theories beyond the standard model. In the context of supersymmetry, if we can measure the masses and mixings of sleptons and squarks, we may learn something about supersymmetry and supersymmetry breaking. Here we consider a hybrid gauge-gravity supersymmetric model in which the observed masses and mixings of the standard model leptons are explained by a U(1) x U(1) flavor symmetry. In the supersymmetric sector, the charged sleptons have reasonably large flavor mixings, and the lightest is metastable. As a result, supersymmetric events are characterized not by missing energy, but by heavy metastable charged particles. Many supersymmetric events are therefore fully reconstructible, and we can reconstruct most of the charged sleptons by working up the long supersymmetric decay chains. We obtain promising results for both masses and mixings, and conclude that, given a favorable model, precise measurements at the LHC may help shed light not only on new physics, but also on the standard model flavor parameters.Comment: 24 pages; v2: fixed a typo in our computer program that led to some miscalculated branching ratios, various clarifications and minor improvements, conclusions unchanged, published versio

Deuteronomy and Numbers

Four light isotopes - D, ^3He, ^4He and ^7Li - were produced by nuclear reactions a few seconds after the big bang. New measurements of ^3He in the ISM by Gloeckler and Geiss and of deuterium in high redshift hydrogen clouds by Tytler and his collaborators provide further confirmation of big-bang nucleosynthesis and new insight about the density of ordinary matter (baryons).Comment: 6 pages LaTeX with 1 eps Figur

Boundary operators in minimal Liouville gravity and matrix models

We interpret the matrix boundaries of the one matrix model (1MM) recently constructed by two of the authors as an outcome of a relation among FZZT branes. In the double scaling limit, the 1MM is described by the (2,2p+1) minimal Liouville gravity. These matrix operators are shown to create a boundary with matter boundary conditions given by the Cardy states. We also demonstrate a recursion relation among the matrix disc correlator with two different boundaries. This construction is then extended to the two matrix model and the disc correlator with two boundaries is compared with the Liouville boundary two point functions. In addition, the realization within the matrix model of several symmetries among FZZT branes is discussed.Comment: 26 page

Mixture models for distance sampling detection functions

Funding: EPSRC DTGWe present a new class of models for the detection function in distance sampling surveys of wildlife populations, based on finite mixtures of simple parametric key functions such as the half-normal. The models share many of the features of the widely-used “key function plus series adjustment” (K+A) formulation: they are flexible, produce plausible shapes with a small number of parameters, allow incorporation of covariates in addition to distance and can be fitted using maximum likelihood. One important advantage over the K+A approach is that the mixtures are automatically monotonic non-increasing and non-negative, so constrained optimization is not required to ensure distance sampling assumptions are honoured. We compare the mixture formulation to the K+A approach using simulations to evaluate its applicability in a wide set of challenging situations. We also re-analyze four previously problematic real-world case studies. We find mixtures outperform K+A methods in many cases, particularly spiked line transect data (i.e., where detectability drops rapidly at small distances) and larger sample sizes. We recommend that current standard model selection methods for distance sampling detection functions are extended to include mixture models in the candidate set.Publisher PDFPeer reviewe

Antitumor activity of the ERK inhibitor SCH772984 [corrected] against BRAF mutant, NRAS mutant and wild-type melanoma.

BackgroundIn melanoma, dysregulation of the MAPK pathway, usually via BRAF(V600) or NRAS(Q61) somatic mutations, leads to constitutive ERK signaling. While BRAF inhibitors are initially effective for BRAF-mutant melanoma, no FDA-approved targeted therapies exist for BRAF-inhibitor-resistant BRAF(V600), NRAS mutant, or wild-type melanoma.MethodsThe 50% inhibitory concentration (IC50) of SCH772984, a novel inhibitor of ERK1/2, was determined in a panel of 50 melanoma cell lines. Effects on MAPK and AKT signaling by western blotting and cell cycle by flow cytometry were determined.ResultsSensitivity fell into three groups: sensitive, 50% inhibitory concentration (IC50) < 1 μM; intermediately sensitive, IC50 1-2 μM; and resistant, >2 μM. Fifteen of 21 (71%) BRAF mutants, including 4 with innate vemurafenib resistance, were sensitive to SCH772984. All three (100%) BRAF/NRAS double mutants, 11 of 14 (78%) NRAS mutants and 5 of 7 (71%) wild-type melanomas were sensitive. Among BRAF(V600) mutants with in vitro acquired resistance to vemurafenib, those with MAPK pathway reactivation as the mechanism of resistance were sensitive to SCH772984. SCH772984 caused G1 arrest and induced apoptosis.ConclusionsCombining vemurafenib and SCH722984 in BRAF mutant melanoma was synergistic in a majority of cell lines and significantly delayed the onset of acquired resistance in long term in vitro assays. Therefore, SCH772984 may be clinically applicable as a treatment for non-BRAF mutant melanoma or in BRAF-mutant melanoma with innate or acquired resistance, alone or in combination with BRAF inhibitors