Anderson And Belnap's Minimal Positive Logic With Minimal Negation

Our question is: can we embed minimal negation in implicative logics weaker than I→? Previous results show how to define minimal negation in the positive fragment of the logic of relevance R and in contractionless intuitionistic logic. Is it possible to endow weaker positive logics with minimal negation? This paper prooves that minimal negation can be embedded in even such a weak system as Anderson and Belnap’s minimal positive logic

Time for change: a new training programme for morpho-molecular pathologists?

The evolution of cellular pathology as a specialty has always been driven by technological developments and the clinical relevance of incorporating novel investigations into diagnostic practice. In recent years, the molecular characterisation of cancer has become of crucial relevance in patient treatment both for predictive testing and subclassification of certain tumours. Much of this has become possible due to the availability of next-generation sequencing technologies and the whole-genome sequencing of tumours is now being rolled out into clinical practice in England via the 100 000 Genome Project. The effective integration of cellular pathology reporting and genomic characterisation is crucial to ensure the morphological and genomic data are interpreted in the relevant context, though despite this, in many UK centres molecular testing is entirely detached from cellular pathology departments. The CM-Path initiative recognises there is a genomics knowledge and skills gap within cellular pathology that needs to be bridged through an upskilling of the current workforce and a redesign of pathology training. Bridging this gap will allow the development of an integrated 'morphomolecular pathology' specialty, which can maintain the relevance of cellular pathology at the centre of cancer patient management and allow the pathology community to continue to be a major influence in cancer discovery as well as playing a driving role in the delivery of precision medicine approaches. Here, several alternative models of pathology training, designed to address this challenge, are presented and appraised

Programming Skeletal Muscle Metabolic Flexibility in Offspring of Male Rats in Response to Maternal Consumption of Slow Digesting Carbohydrates during Pregnancy

Skeletal muscle plays a relevant role in metabolic flexibility and fuel usage and the associated muscle metabolic inflexibility due to high-fat diets contributing to obesity and type 2 diabetes. Previous research from our group indicates that a high-fat and rapid-digesting carbohydrate diet during pregnancy promotes an excessive adipogenesis and also increases the risk of non-alcoholic fatty liver disease in the offspring. This effect can be counteracted by diets containing carbohydrates with similar glycemic load but lower digestion rates. To address the role of the skeletal muscle in these experimental settings, pregnant rats were fed high-fat diets containing carbohydrates with similar glycemic load but different digestion rates, a high fat containing rapid-digesting carbohydrates diet (HF/RD diet) or a high fat containing slow-digesting carbohydrates diet (HF/SD diet). After weaning, male offspring were fed a standard diet for 3 weeks (weaning) or 10 weeks (adolescence) and the impact of the maternal HF/RD and HF/SD diets on the metabolism, signaling pathways and muscle transcriptome was analyzed. The HF/SD offspring displayed better muscle features compared with the HF/RD group, showing a higher muscle mass, myosin content and differentiation markers that translated into a greater grip strength. In the HF/SD group, metabolic changes such as a higher expression of fatty acids (FAT/CD36) and glucose (GLUT4) transporters, an enhanced glycogen content, as well as changes in regulatory enzymes such as muscle pyruvate kinase and pyruvate dehydrogenase kinase 4 were found, supporting an increased muscle metabolic flexibility and improved muscle performance. The analysis of signaling pathways was consistent with a better insulin sensitivity in the muscle of the HF/SD group. Furthermore, increased expression of genes involved in pathways leading to muscle differentiation, muscle mass regulation, extracellular matrix content and insulin sensitivity were detected in the HF/SD group when compared with HF/RD animals. In the HF/SD group, the upregulation of the ElaV1/HuR gene could be one of the main regulators in the positive effects of the diet in early programming on the offspring. The long-lasting programming effects of the HF/SD diet during pregnancy may depend on a coordinated gene regulation, modulation of signaling pathways and metabolic flexibility that lead to an improved muscle functionality. The dietary early programming associated to HF/SD diet has synergic and positive crosstalk effects in several tissues, mainly muscle, liver and adipose tissue, contributing to maintain the whole body homeostasis in the offspring.European Union’s Seventh Framework Programme (FP7/2007–2013

Más mercado, menos Estado: el financiamiento de los posgrados en Argentina

Las dinámicas público-privadas de la educación superior en Argentina muestran la convivencia de dos modalidades diferentes de financiamiento de la educación superior. En el grado, las universidades públicas no cobran aranceles, son completamente sostenidas por el estado. En el posgrado tanto universidades públicas como privadas tienen como principio rector el autofinanciamiento, entendiendo esto como la cobertura de los costos mediante el cobro de aranceles y matrículas de las carreras de dicho nivel. El presente estudio, de carácter explora-torio, presenta el primer relevamiento sistemático de aranceles de carreras de posgrado de instituciones públicas y privadas en Argentina. El análisis de la información recabada muestra diversas situaciones, tales como la variabilidad de aranceles de las carreras de posgrado por sector, tipo de carrera y área disciplinar y la posible existencia de subsidios cruzados tanto en el sector público como en el privado.Public-private dynamics in Argentine higher education show the coexistence of two different funding modalities. At the undergraduate level, public universities do not charge tuition fees, they are fully subsidized by the national government. At the postgraduate level, both the public and private institutions have to self-fund their programs. In other words, postgraduate programs have to cover their costs through tuition fees. This exploratory study presents the first systematic data survey of postgraduate program prices in Argentine public and private institutions. The analysis shows a diversity of situations, such as the price variability of postgraduate programs by sector, type of program, and disciplinary area. Also, the study indicates the possibility of cross subsidies in both the public and the private sectors.Dossier: Justicia social, educación y equida

Computationally Guided Design of a Readily Assembled Phosphite- Thioether Ligand for a Broad Range of Pd-Catalyzed Asymmetric Allylic Substitutions

A modular approach employing indene as common starting material, has enabled the straightforward preparation in three reaction steps of P-thioether ligands for the Pd-catalyzed asymmetric allylic substitution. The analysis of a starting library of P-thioether ligands based on rational design and theoretical calculations has led to the discovery of an optimized anthracenethiol derivative with excellent behavior in the reaction of choice. Improving most approaches reported to date, this ligand presents a broad substrate and nucleophile scope. Excellent enantioselectivities have been achieved for a range of linear and cyclic allylic substrates using a large number of C-, N-, and O-nucleophiles (40 compounds in total). The species responsible for the catalytic activity have been further investigated by NMR in order to clearly establish the origin of the enantioselectivity. The resulting products have been derivatized by means of ring-closing metathesis or Pauson–Khand reactions to further prove the synthetic versatility of the methodology for preparing enantiopure complex structures

Determinación de los coeficientes de control de flujo en un tramo acotado de la ruta glucolítica

The Flux Control Theory has been applied successfully to the study of the regulation of metabolism. There have been described several methods for the determination of the flux control coefficients in different metabolic pathways. In this work, we describe an experimental method for the determination of these coefficients in the earlier glycolytic steps in rat-kidney cortex, their change caused by AMP and the possible application to the study of the metabolic importance of the substrate cycle established between fructose 6-phosphate and fructose             1,6-bisphosphate.La Teoría de Control de Flujo ha demostrado ser útil en el estudio de la regulación del metabolismo. Han sido descritos varios métodos para la determinación de los coeficientes de control de flujo en diferentes rutas metabólicas. En este trabajo describimos un método experimental para la determinación de estos coeficientes en las primeras etapas de las glucolisis en corteza renal de rata, su modificación en presencia de AMP y la posible aplicación al estudio de la importancia metabólica del ciclo de sustrato establecido entre fructosa 6-fosfato y fructosa 1,6-bisfosfato

Determinación de los coeficientes de control de flujo en un tramo acotado de la ruta glucolítica

La Teoría de Control de Flujo ha demostrado ser útil en el estudio de la regulación del metabolismo. Han sido descritos varios métodos para la determinación de los coeficientes de control de flujo en diferentes rutas metabólicas. En este trabajo describimos un método experimental para la determinación de estos coeficientes en las primeras etapas de las glucolisis en corteza renal de rata, su modificación en presencia de AMP y la posible aplicación al estudio de la importancia metabólica del ciclo de sustrato establecido entre fructosa 6-fosfato y fructosa 1,6- bisfosfato.The Flux Control Theory has been applied successfully to the study of the regulation of metabolismo There have been described several methods for the determination of the flux control coefficients in different metabolic pathways. In this work, we describe an experimental method for the determination of these coefficients in the earlier glycolytic steps in rat-kidney cortex, their change caused by AMP and the possible application to the study of the metabolic importance of the substrate cycle established between fructose 6-phosphate and fructose 1,6- bisphosphate

A blocking monoclonal antibody to CCL24 alleviates liver fibrosis and inflammation in experimental models of liver damage

Background & Aims: C-C motif chemokine ligand 24 (CCL24) is a chemokine that regulates inflammatory and fibrotic activities through its receptor, C-C motif chemokine receptor (CCR3). The aim of the study was to evaluate the involvement of the CCL24-CCR3 axis in liver fibrosis and inflammation and to assess the potential of its blockade, by a monoclonal anti-CCL24 antibody, as a therapeutic strategy for non-alcoholic steatohepatitis (NASH) and liver fibrosis. Methods: Expression of CCL24 and CCR3 was evaluated in liver biopsies and blood samples. CCL24 involvement in NAFLD/NASH pathogenesis was assessed in Ccl24 knockout mouse using the methionine-choline deficient (MCD) diet experimental model. Antifibrotic and anti-inflammatory effects of CM-101 were tested in the MCD and STAM mouse models and in the thioacetamide (TAA) model in rats. Liver enzymes, liver morphology, histology and collagen deposition, as well as fibrosis- and inflammation-related protein expression were assessed. Activation of hepatic stellate cells (HSCs) was evaluated in the human LX2 cell line. Results: Patients with NASH and advanced NAFLD exhibited significant expression of both CCL24 and CCR3 in liver and blood samples. In the experimental MCD-diet model, Ccl24 knockout mice showed an attenuated liver damage response compared to wild-type mice, exhibiting reduced histological NAFLD activity scores and fibrosis, as well as lower levels of liver enzymes. Blocking CCL24 using CM-101 robustly reduced liver damage in 3 experimental animal models (MCD, STAM and TAA), as demonstrated by attenuation of liver fibrosis and NAFLD activity score. Furthermore, blocking CCL24 by CM-101 significantly inhibited CCL24-induced HSC motility, α-SMA expression and pro-collagen I secretion. Conclusion: Our results reveal that blocking CCL24 significantly attenuates liver fibrosis and inflammation and may have a potential therapeutic effect in patients with NASH and/or liver fibrosis. Lay summary: CCL24 is a chemokine that regulates inflammation and fibrosis. It was found to be significantly expressed in patients with non-alcoholic steatohepatitis, in whom it regulates profibrotic processes in the liver. Herein, we show that blockade of CCL24 using a monoclonal antibody robustly attenuated liver fibrosis and inflammation in animal models, thus suggesting a potential therapeutic role for an anti-CCL24 agent