Identificacion of differentially expressed proteins in acute coronary syndromes

Comunicaciones a congreso

Cardiac safety of adjuvant pegylated liposomal doxorubicin with concurrent trastuzumab: a randomized phase II trial

Background The cardiac safety of trastuzumab concurrent with pegylated liposomal doxorubicin (PLD) in an adjuvant breast cancer treatment regimen is unknown. Patients and methods Women with resected node-positive or intermediate-risk node-negative HER2 overexpressing breast cancer and baseline left ventricular ejection fraction (LVEF) ≥55% were randomized (1:2) to doxorubicin 60 mg/m2 (A)+cyclophosphamide 600 mg/m2 (C) every 21 days (q21d) for four cycles or PLD 35 mg/m2+C q21d+trastuzumab 2 mg/kg weekly (H) for 12 weeks. Both groups then received paclitaxel (Taxol, T) 80 mg/m2 with H for 12 weeks followed by H to complete 1 year. The primary end point was cardiac event rate or inability to administer 1 year of trastuzumab. Results Of 181 randomized patients, 179 underwent cardiac analysis. The incidence of cardiac toxicity or inability to administer trastuzumab due to cardiotoxicity was 18.6% [n=11; 95% confidence interval (CI) 9.7% to 30.9%] with A+C → T+H and 4.2% (n=5; 95% CI 1.4% to 9.5%) with PLD+C+H → T+H (P=0.0036). All events, except one, were asymptomatic systolic dysfunction or mildly symptomatic heart failure. Mean absolute LVEF reduction at cycle 8 was greater with doxorubicin (5.6% versus 2.1%; P=0.0014). Conclusion PLD+C+H → T+H is feasible and results in lower early cardiotoxicity rates compared with A+C → T+

Search based software engineering: Trends, techniques and applications

© ACM, 2012. This is the author's version of the work. It is posted here by permission of ACM for your personal use. Not for redistribution. The definitive version is available from the link below.In the past five years there has been a dramatic increase in work on Search-Based Software Engineering (SBSE), an approach to Software Engineering (SE) in which Search-Based Optimization (SBO) algorithms are used to address problems in SE. SBSE has been applied to problems throughout the SE lifecycle, from requirements and project planning to maintenance and reengineering. The approach is attractive because it offers a suite of adaptive automated and semiautomated solutions in situations typified by large complex problem spaces with multiple competing and conflicting objectives. This article provides a review and classification of literature on SBSE. The work identifies research trends and relationships between the techniques applied and the applications to which they have been applied and highlights gaps in the literature and avenues for further research.EPSRC and E

Discovery of new globular clusters in the Sagittarius dwarf galaxy

© ESO 2021. Published by EDP Sciences. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1051/0004-6361/202140395Context. Globular clusters (GCs) are witnesses of the past accretion events onto the Milky Way. In particular, the GCs of the Sagittarius (Sgr) dwarf galaxy are important probes of an on-going merger. Aims. Our main goal is to search for new GC members of this dwarf galaxy using the VISTA Variables in the Via Lactea Extended Survey (VVVX) near-infrared database combined with the Gaia Early Data Release 3 (EDR3) optical database. Methods. We investigated all VVVX-enabled discoveries of GC candidates in a region covering about 180 sq. deg. toward the bulge and the Sgr dwarf galaxy. We used multiband point-spread function photometry to obtain deep color-magnitude diagrams (CMDs) and luminosity functions (LFs) for all GC candidates, complemented by accurate Gaia-EDR3 proper motions (PMs) to select Sgr members and variability information to select RR Lyrae which are potential GC members. Results. After applying a strict PM cut to discard foreground bulge and disk stars, the CMDs and LFs for some of the GC candidates exhibit well defined red giant branches and red clump giant star peaks. We selected the best Sgr GCs, estimating their distances, reddenings, and associated RR Lyrae. Conclusions. We discover 12 new Sgr GC members, more than doubling the number of GCs known in this dwarf galaxy. In addition, there are 11 other GC candidates identified that are uncertain, awaiting better data for confirmation.Peer reviewedFinal Accepted Versio

Protective effect of stromal Dickkopf-3 in prostate cancer: opposing roles for TGFBI and ECM-1

Aberrant transforming growth factor–β (TGF-β) signaling is a hallmark of the stromal microenvironment in cancer. Dickkopf-3 (Dkk-3), shown to inhibit TGF-β signaling, is downregulated in prostate cancer and upregulated in the stroma in benign prostatic hyperplasia, but the function of stromal Dkk-3 is unclear. Here we show that DKK3 silencing in WPMY-1 prostate stromal cells increases TGF-β signaling activity and that stromal cellconditioned media inhibit prostate cancer cell invasion in a Dkk-3-dependent manner. DKK3 silencing increased the level of the cell-adhesion regulator TGF-β–induced protein (TGFBI) in stromal and epithelial cell-conditioned media, and recombinant TGFBI increased prostate cancer cell invasion. Reduced expression of Dkk-3 in patient tumors was associated with increased expression of TGFBI. DKK3 silencing reduced the level of extracellular matrix protein-1 (ECM-1) in prostate stromal cell-conditioned media but increased it in epithelial cell-conditioned media, and recombinant ECM-1 inhibited TGFBI-induced prostate cancer cell invasion. Increased ECM1 and DKK3 mRNA expression in prostate tumors was associated with increased relapse-free survival. These observations are consistent with a model in which the loss of Dkk-3 in prostate cancer leads to increased secretion of TGFBI and ECM-1, which have tumor-promoting and tumor-protective roles, respectively. Determining how the balance between the opposing roles of extracellular factors influences prostate carcinogenesis will be key to developing therapies that target the tumor microenvironment

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

E17K substitution in AKT1 in prostate cancer

Background:The phosphatidylinositol 3-kinase (PI3K)-AKT pathway is activated in many cancers. Mutational hotspots in AKT1 and in the regulatory and catalytic subunits of PI3K have been detected in multiple tumour types. In AKT1, the E17K substitution leads to a PI3K-independent activation of AKT1.Methods:A mutational profiling of AKT1 and of the mutational hotspots in PIK3CA and PIK3R1 was carried out in samples from primary and recurrent prostate tumours.Results:We show that, in prostate cancer, AKT1(E17K) had a prevalence of 1.4%. The mutation seemed to be associated with a favourable clinical course but it was not associated with a specific tumour growth pattern. Activating mutations in PIK3CA or PIK3R1 were not found in prostate cancer.Conclusion:The E17K substitution in AKT1 is rare in prostate cancer. It seems associated with a favourable clinical outcome but not with a specific histology of the tumo

Nitrogen deposition in Spain : modeled patterns and threatened habitats within the Natura 2000 network

The Mediterranean Basin presents an extraordinary biological richness but very little information is available on the threat that air pollution, and in particular reactive nitrogen (N), can pose to biodiversity and ecosystem functioning. This study represents the first approach to assess the risk of N enrichment effects on Spanish ecosystems. The suitability of EMEP and CHIMERE air quality model systems as tools to identify those areas where effects of atmospheric N deposition could be occurring was tested. For this analysis, wet deposition of NO₃− and NH₄+ estimated with EMEP and CHIMERE model systems were compared with measured data for the period 2005-2008 obtained from different monitoring networks in Spain. Wet N deposition was acceptably predicted by both models, showing better results for oxidized than for reduced nitrogen, particularly when using CHIMERE. Both models estimated higher wet deposition values in northern and northeastern Spain, and decreasing along a NE-SW axis. Total (wet + dry) nitrogen deposition in 2008 reached maxima values of 19.4 and 23.0 kg N ha¯¹ year¯¹ using EMEP and CHIMERE models respectively. Total N deposition was used to estimate the exceedance of N empirical critical loads in the Natura 2000 network. Grassland habitats proved to be the most threatened group, particularly in the northern alpine area, pointing out that biodiversity conservation in these protected areas could be endangered by N deposition. Other valuable mountain ecosystems can be also threatened, indicating the need to extend atmospheric deposition monitoring networks to higher altitudes in Spain

Latitude does not influence cavity entrance orientation of South American avian excavators

In the Northern Hemisphere, several avian cavity excavators (e.g., woodpeckers) orient their cavities increasingly toward the equator as latitude increases (i.e., farther north), and it is proposed that they do so to take advantage of incident solar radiation at their nests. If latitude is a key driver of cavity orientations globally, this pattern should extend to the Southern Hemisphere. Here, we test the prediction that cavities are oriented increasingly northward at higher (i.e., colder) latitudes in the Southern Hemisphere and describe the preferred entrance direction(s) of 1501 cavities excavated by 25 avian species (n = 22 Picidae, 2 Trogonidae, 1 Furnariidae) across 12 terrestrial ecoregions (15°S ? 55°S) in South America. We used Bayesian projected normal mixed-effects models for circular data to examine the influence of latitude, and potential confounding factors, on cavity orientation. Also, a probability model selection procedure was used to simultaneously examine multiple orientation hypotheses in each ecoregion, to explore underlying cavity-orientation patterns. Contrary to predictions, and patterns from the Northern Hemisphere, birds did not orient their cavities more toward the equator with increasing latitude, suggesting that latitude may not be an important underlying selective force shaping excavation behavior in South America. Moreover, unimodal cavity-entrance orientations were not frequent among the ecoregions analyzed (infour ecoregions), whereas bimodal (in five ecoregions) or uniform (in three ecoregions) werealso common, although many of these patterns were not very sharp. Our results highlight the need to include data from under-studied biotas and regions to improve inferences at macroecology scales. Furthermore, we suggest a re-analysis of Northern Hemisphere cavity orientation patterns using a multimodel approach, and a more comprehensive assessment of the role of environmental factors as drivers of cavity orientation at different spatial scales in both hemispheres.Fil: Ojeda, Valeria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Schaaf, Alejandro Alberto. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; ArgentinaFil: Altamirano, Tatiana Edith. University of British Columbia; CanadáFil: Bonaparte, Eugenia Bianca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Bragagnolo, Laura Araceli. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Chazarreta, L.. Secretaría de Ambiente y Desarrallo Sustentable de la Nación; ArgentinaFil: Cockle, Kristina Louise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Dias, R.. Universidade do Brasília; BrasilFil: Di Sallo, Facundo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Ibarra, T.. Pontificia Universidad Católica de Chile; ChileFil: Ippi, Silvina Graciela. Universidad Nacional del Comahue. Centro Regional Universitario Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Jauregui, Adrian. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Área Zoología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Jimenez, Jaime E.. Universidad de Magallanes; ChileFil: Lammertink, J. Martjan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Lopez, F.. Universidad Nacional de La Pampa; ArgentinaFil: Nuñez Montellano, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; ArgentinaFil: de la Peña, Martín. No especifíca;Fil: Rivera, Luis Osvaldo. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; ArgentinaFil: Vivanco, Constanza Guadalupe. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; ArgentinaFil: Santillán, Miguel. Museo de Historia Natural de La Pampa; ArgentinaFil: Soto, G.. Cornell University; Estados UnidosFil: Vergara, P.. Universidad de Santiago de Chile; ChileFil: Politi, Natalia. University of North Texas; Estados Unido