1,166 research outputs found

    Negative skin friction on piles: a simplified analysis and prediction procedure

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    In order to describe the interaction between a single pile and a consolidating soil a stress transfer approach at the interface is proposed. The non-linear, plastic character of the shear stress acting on the pile shaft and the adequate modelling of unloading and cyclic behaviour are properly incorporated through a ‘shooting’ solution procedure of the equilibrium equations. The whole problem is formulated in dimensionless terms both for external uniform loading conditions and for changes in piezometric levels. The formulation and the computational procedure developed are fairly general and may accommodate arbitrary layering and complicated loading sequences. In many practical situations the whole length of the shaft-soil interface has reached a limiting shear stress state except for a narrow zone around the neutral point. It is then possible to derive analytical solutions for the main design parameters. Their usefulness has been checked through several well-documented case records.Peer Reviewe

    A constitutive model for partially saturated soils

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    The Paper presents a constitutive model for describing the stress-strain behaviour of partially saturated soils. The model is formulated within the framework of hardening plasticity using two imdependent sets of stress variables: the excess of total stress over air pressure and the suction. The model is able to represent, in a consistent and unified manner, many of the fundamental features of the behaviour of partially saturated soils which had been treated separately by previously proposed models. On reaching saturation, the model becomes a conventional critical state model. Because experimental evidence is still limited, the model has been kept as simple as possible in order to provide a basic framework from which extensions are possible. Tbe mode1 is intended for partially saturated soils which are slightly or moderately expansive. After formulating the model for isotropic and biaxial stress states, typical predictions are described and compared, in a qualitative way, with characteristic trends of the behaviour of partially saturated soils. Afterwards, the results of a number of suction-controlled laboratory tests on compacted kaolin and a sandy clay are used to evaluate the ability of the model to reproduce, quantitatively, observed behaviour. The agreement between observed and computed results is considered satisfactory and confirms the possibilities of reproducing the most important features of partially saturated soil behaviour using a simple general framework.Peer Reviewe

    What is the status of immunotherapy in thyroid neoplasms?

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    Immunotherapy; Thyroid neoplasms; Tumor mutational burdenInmunoterapia; Neoplasias de la tiroides; Carga mutacional tumoralImmunoteràpia; Neoplàsies de les tiroides; Càrrega mutacional tumoralImmunotherapy has changed the treatment of patients with advanced cancer, with different phase III trials showing durable responses across different histologies. This review focuses on the preclinical and clinical evidence of potential predictive biomarkers of response and efficacy of immunotherapy in thyroid neoplasms. Programmed death-ligand 1 (PD-L1) staining by immunohistochemistry has shown higher expression in anaplastic thyroid cancer (ATC) compared to other subtypes. The tumor mutational burden in thyroid neoplasms is low but seems to be higher in ATC. Immune infiltrates in the tumor microenvironment (TME) differ between the different thyroid neoplasm subtypes. In general, differentiated thyroid cancer (DTC) has a higher number of tumor-associated lymphocytes and regulatory T cells (Tregs), while ATC and medullary thyroid cancer (MTC) display a high density of tumor-associated macrophages (TAMs). Nevertheless, results from clinical trials with immunotherapy as monotherapy or combinations have shown limited efficacy. Further investigation into new strategies aside from anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4)/programmed death 1 (PD-1)/PD-L1 antibodies, validation of predictive biomarkers, and better population selection for clinical trials in thyroid neoplasms is more than needed in the near future

    A Role for Pre-mRNA-PROCESSING PROTEIN 40C in the Control of Growth, Development, and Stress Tolerance in Arabidopsis thaliana

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    Because of their sessile nature, plants have adopted varied strategies for growing and reproducing in an ever-changing environment. Control of mRNA levels and pre-mRNA alternative splicing are key regulatory layers that contribute to adjust and synchronize plant growth and development with environmental changes. Transcription and alternative splicing are thought to be tightly linked and coordinated, at least in part, through a network of transcriptional and splicing regulatory factors that interact with the carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II. One of the proteins that has been shown to play such a role in yeast and mammals is pre-mRNA-PROCESSING PROTEIN 40 (PRP40, also known as CA150, or TCERG1). In plants, members of the PRP40 family have been identified and shown to interact with the CTD of RNA Pol II, but their biological functions remain unknown. Here, we studied the role of AtPRP40C, in Arabidopsis thaliana growth, development and stress tolerance, as well as its impact on the global regulation of gene expression programs. We found that the prp40c knockout mutants display a late-flowering phenotype under long day conditions, associated with minor alterations in red light signaling. An RNA-seq based transcriptome analysis revealed differentially expressed genes related to biotic stress responses and also differentially expressed as well as differentially spliced genes associated with abiotic stress responses. Indeed, the characterization of stress responses in prp40c mutants revealed an increased sensitivity to salt stress and an enhanced tolerance to Pseudomonas syringae pv. maculicola (Psm) infections. This constitutes the most thorough analysis of the transcriptome of a prp40 mutant in any organism, as well as the first characterization of the molecular and physiological roles of a member of the PRP40 protein family in plants. Our results suggest that PRP40C is an important factor linking the regulation of gene expression programs to the modulation of plant growth, development, and stress responses.Fil: Hernando, Carlos Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: García Hourquet, Mariano. Fundación Instituto Leloir; ArgentinaFil: de Leone, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Careno, Daniel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Iserte, Javier Alonso. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Mora Garcia, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Yanovsky, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

    Manual de identidad de marca y campaña de relanzamiento por redes sociales para Sabergeek

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    Este proyecto profesional se centró en SaberGeek, una página de entretenimiento e información en Facebook e Instagram que busca generar una comunidad de fans alrededor del contenido Geek y Gamer. Ante el potencial de esta página nace la oportunidad de realizar un trabajo de rebranding y creación de un manual de marca y plan de comunicación para relanzamiento en redes, cambiando desde el símbolo de representación, logotipo, además de la estética de los post (publicaciones) y tono de comunicación, proponiendo un nuevo diseño de ideas innovadoras para captar la atención de su público y fidelizar a los seguidores existentes. Esto con la finalidad de caracterizar y destacar este medio de contenidos, darle un sentido de originalidad a partir de su propia esencia y alinear su propuesta de comunicación al objetivo de crear una comunidad en sus propias redes.This professional project focused on SaberGeek, an entertainment and information page on Facebook and Instagram that seeks to generate a community of fans around Geek and Gamer content. Given the potential of this page, the opportunity arises to carry out a rebranding work and creation of a brand manual and communication plan for relaunching in networks, changing from the representation symbol, logo, in addition to the aesthetics of the post (publications) and communication tone, proposing a new design of innovative ideas to capture the attention of your audience and retain existing followers. This in order to characterize and highlight this content medium, give it a sense of originality based on its own essence and align its communication proposal with the objective of creating a community in its own networks

    Safety and efficacy of asciminib treatment in chronic myeloid leukemia patients in real-life clinical practice

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    Chronic myeloid leukemia; Asciminib; TreatmentLeucemia mieloide crónica; Asciminib; TratamientoLeucèmia mieloide crònica; Asciminib; TractamentDespite the excellent overall survival (OS) of chronic myeloid leukemia (CML) patients, a significant proportion will fail currently available tyrosine-kinase inhibitors (TKIs) due to resistance or intolerance. Intolerant patients are usually managed successfully with alternative second-generation tyrosine-kinase inhibitors (2GTKIs). However, more than half of the patients will eventually discontinue second-line treatment due to loss of response or toxicity. Ponatinib is an effective drug in the setting of resistance to 2GTKIs, however with life-threatening side effects and varying responses. Asciminib is a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor that potently and specifically inhibits BCR-ABL1 via binding to a pocket distinct from the ATP binding site of the kinase. Asciminib has the potential to overcome resistance to prior TKIs, and also offers the possibility of dual inhibition of BCR-ABL1 in combination with ATP-binding TKIs. Asciminib has been evaluated in a phase I study in patients with Ph-positive leukemia failing prior TKIs, with promising results. Our aim is to share the first data on the use of asciminib in CML patients in clinical practice, allowed by Novartis under a managed-access program (MAP)

    Shade delays flowering in Medicago sativa

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    Shade intolerant plants respond to the decrease in the red (R) to far-red light (FR) ratio (R:FR) occurring under shade by elongating stems and petioles and re-positioning leaves, in a race to out-compete neighbors for the sunlight resource. In some annual species, these shade-avoidance responses (SAS) are accompanied by the early induction of flowering. Anticipated flowering is viewed as a strategy to set seeds before the resources become severely limiting. Little is known about the molecular mechanisms of SAS in perennial forage crops like alfalfa (Medicago sativa). To study SAS in alfalfa, we exposed alfalfa plants to simulated shade by supplementing with FR. Low R:FR produced a classical SAS, such as increased internode and petiole length but, unexpectedly, delayed flowering. To understand the molecular mechanisms involved in uncoupling SAS from early flowering, we used a transcriptomic approach. SAS were likely mediated by increased expression of msPIF3 and msHB2 in low R:FR. Constitutive expression of these genes in Arabidopsis led to SAS, including early flowering, strongly suggesting their roles are conserved. Delayed flowering was likely to be mediated by the downregulation of msSPL3, which promotes flowering in both Arabidopsis and alfalfa. Shade-delayed flowering in alfalfa may be important to extend the vegetative phase under sub-optimal light conditions and thus assure the accumulation of reserves necessary to resume growth after the next season. This article is protected by copyright. All rights reserved.Fil: Lorenzo, Christian Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Iserte, Javier Alonso. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Sanchez Lamas, Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Antonietti, Mariana Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Garcia Gagliardi, Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Hernando, Carlos Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Dezar, Carlos Alberto Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Agrobiotecnología de Rosario; ArgentinaFil: Vazquez, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Agrobiotecnología de Rosario; ArgentinaFil: Casal, Jorge José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Yanovsky, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Cerdan, Pablo Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

    Senegalese sole transcriptomic profiles in response to different betanodavirus RGNNV/SJNNV reassortant strains

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    Betanodaviruses are the causative agents of viral nervous necrosis (VNN), a disease that has been reported in more than 40 marine and freshwater fish species worldwide, including Senegalese sole (Solea senegalensis). Based on the variable region T4 (RNA2), betanodaviruses have been classified into 4 genotypes: striped jack nervous necrosis virus (SJNNV), tiger puffer nervous necrosis virus (TPNNV), redspotted grouper nervous necrosis virus (RGNNV), and barfin flounder nervous necrosis virus (BFNNV). Reassortant isolates combining genomic segments from the SJNNV and RGNNV genotypes have been obtained from farmed fish species. The reassortant SpSs-IAusc160.03 (wild type reassortant), with a genome consisting of RGNNV-type RNA1 and SJNNV-type RNA2 segments, is more suited for infecting sole than the parental genotypes, causing 100% mortality by bath challenges. Furthermore, compared with the parental SJNNV genotype, this reassortant strain presents two aminoacidic substitutions (positions 247 and 270) at the extreme C-terminal of the capsid protein, which are involved in host specificity. In the current study, the RNA-Seq technology has been used to determine changes in Senegalese sole transcriptome after infection with the wild type and a less virulent recombinant (rSs160.03247+270) with mutations at aminoacids 247 (serine to alanine) and 270 (serine to asparagine), provoking a 40% decreased mortality. Animals (5 g weight) were distributed into two groups to be intramuscularly injected with the above described viral strains (2x105 TCID50/fish). A negative control group (L15-injected) was also established. Head kidney and nervous tissues (eye+brain) were sampled at 48 post-inoculation. A total of 633 genes were differentially expressed (DEGs) in animals infected with the wild type isolate (358 up-regulated and 49 down-regulated in head kidney; 206 up-regulated and 20 down-regulated in eye+brain), whereas only 393 genes were differentially expressed in animals infected with the mutated isolate (129 up-regulated and 10 down-regulated in head-kidney; 28 up-regulated and 226 down-regulated in eye+brain). The results obtained indicate a 37.9% decrease in the number of DEGs after infection with the mutated reassortant, as well as an inversion in the proportion of genes up/down-regulated in nervous tissue of these animals. In addition, the expression patterns of genes coding for proteins involved in the IFN type I pathway were different in both group of animals. Thus, genes coding for proteins acting as mediators of IFN type I expression (MDA5, LGP2, IRF3, IRF7) and IFN-stimulated genes (ISG15, Mx, PKR, IFI6, IFI35, IFI44, IFIT-1, among others) were up-regulated in animals infected with the wild type reassortant, whereas no-differential expression of these genes was observed in animals infected with the mutated isolate. The different transcriptomic profiles obtained could help to better understand NNV pathogenesis in Senegalese sole, setting up the importance as virulence determinants of aminoacids at positions 247 and 270 within the RNA2 segment. Furthermore, the results obtained permit to identify DEGs that could be used to develop new strategies to control this infectious disease, which has reached high relevance in the aquaculture sector.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

    Evaluación de rendimiento del sistema de ficheros paralelo Expand Ad-Hoc en MareNostrum 4

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    Durante los últimos años las aplicaciones utilizadas en el campo de la ciencia están evolucionando hacia el análisis masivo de datos a través de workflows debido al crecimiento de áreas como la Inteligencia Artificial y el big data. Sin embargo, el mayor cuello de botella cuando se ejecutan este tipo de aplicaciones se encuentra en las operaciones de E/S. Para tratar de solventar este problema se está desarrollando el sistema de ficheros paralelo Expand Ad-Hoc. Permite crear particiones virtuales ad-hoc para incrementar el rendimiento de E/S en entornos de supercomputación. El objetivo de este trabajo es presentar una evaluación de este sistema de ficheros sobre el supercomputador MareNostrum 4. En la evaluación de Expand Ad-Hoc llevada a cabo en MareNostrum 4, se ha podido comprobar que su rendimiento y escalabilidad es globalmente superior al del sistema de ficheros paralelo GPFS
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