En este libro se analizan las relaciones sociales entre el linaje Malvezzi y el Colegio de España en Bolonia. La aparentemente extraña simbiosis entre una familia de la oligarquía urbana y un colegio ...secular universitario se explica en el contexto de creación de facciones favorables a las Casas de Austria y de Valois, que polarizaron la vida política italiana. Así, el colegio, partícipe de las estructuras administrativas de la monarquía, se incorporó a un circuito hispanófilo creado en Bolonia y liderado precisamente por la familia Malvezzi. El objetivo de estas redes de afinidad era la promoción social de sus líderes masculinos a través del servicio político y militar a los monarcas españoles. Desde los precedentes en el reino de Nápoles, se avanza hacia la articulación de un partido filo-Habsburgo en Bolonia que extendió su influencia más allá de la ciudad, y que contó con el Colegio de España y con varios de sus colegiales a lo largo del siglo XVI. De esta forma, se integran los fundamentos del poder local
de los Malvezzi dentro de las redes filoespañolas italianas, combinando las escalas urbana, regional e internacional. Un estudio que se apoya en el Análisis de Redes para poder interpretar adecuadamente la participación del colegio y los intereses personales de cada uno de los líderes italianos involucrados. Por último, se abordan las cuestiones relativas al capital simbólico, tratando de desgranar los puntos fundamentales del relato hispanófilo elaborado por la familia Malvezzi y la colaboración del Colegio de España en dicha empresa ideológica. Esta contribución no solo amplía el conocimiento del fenómeno de las facciones filoespañolas en la Italia del Renacimiento, sino que también permite interpretar el rol que jugó un colegio universitario en una ciudad en la que, a diferencia de Roma, Nápoles o Milán, no había centros de referencia de la Monarquía Hispánica. Texto de la editorial.
•Holidays affect electricity load greatly, causing inaccurate forecasts.•This effect varies widely among holidays, special days and adjacent days.•Wide and detailed classification of each special day ...can reduce forecasting error.•The proper methodology eliminates the analisys effort needed for classification.•An automatic classification can outperform an expert-level classification.
Electricity demand presents a repetitive pattern following daily, weekly and seasonal patterns. However, factors like temperature or social events tend to disrupt these patterns introducing outlying data that is difficult to forecast. This paper introduces a new methodology to classify special days without any prior knowledge of the database. Simple classification of special days into two or three categories is insufficient as the consumers’ behavior has many shades on these days. However, classifying special days in a wide range of categories required a deep understanding of the consumers’ behavior on different days and periods of the year. The methodology proposed describes an algorithm to automate this classification starting from a simple day-of-the-week classification and branching into as many categories as needed to fit a real database. Categories with similar profiles are merged to avoid overfitting and actual outliers are detected to ensure that no false categories are created. The methodology is developed using data from 2010 to 2017 and tested in three different systems. The benchmark used is the classification used by the Transmission System Operator in Spain and the test show that the proposed methodology provides more accurate results without the need of an expert to develop the classification.
Abstract Epidemiological data indicate that 5.8% of cancer deaths world-wide are attributable to alcohol consumption. The risk of cancer is higher in tissues in closest contact on ingestion of ...alcohol, such as the oral cavity, pharynx and esophagus. However, since ethanol is not mutagenic and the carcinogenic metabolite of ethanol (acetaldehyde) is mostly produced in the liver, it is not clear why alcohol use preferentially exerts a local carcinogenic effect. It is well known that ethanol causes cell death at the concentrations present in alcoholic beverages; however, this effect may have been overlooked because dead cells cannot give rise to cancer. Here I discuss that the cytotoxic effect of ethanol on the cells lining the oral cavity, pharynx and esophagus activates the division of the stem cells located in deeper layers of the mucosa to replace the dead cells. Every time stem cells divide, they become exposed to unavoidable errors associated with cell division (e.g., mutations arising during DNA replication and chromosomal alterations occurring during mitosis) and also become highly vulnerable to the genotoxic activity of DNA-damaging agents (e.g., acetaldehyde and tobacco carcinogens). Alcohol consumption may increase the risk of developing cancer of the oral cavity, pharynx and esophagus by promoting the accumulation of cell divisions in the stem cells that maintain these tissues in homeostasis. Understanding the mechanisms of carcinogenicity of alcohol is important to reinforce the epidemiological evidence and to raise public awareness of the strong link between alcohol consumption and cancer.
The exceptional hybridization properties of peptide nucleic acids (PNAs) coupled with the ease of their synthesis has made this artificial nucleic acid mimetic a desirable platform for diagnostics, ...therapeutics and supramolecular engineering. PNA backbone modifications have been extensively explored to finetune physicochemical properties and for conjugation of functional molecules. Here, we detail the synthesis of a universal γ‐propargyl‐PNA backbone from serine, and its acylation with the four DNA canonical nucleobases. The availability of serine as d or l enantiomer provide simple accesses to PNA oligomers for hybridization with natural oligonucleotides or for orthogonal hybridization circuitry. We show that late‐stage conjugation enables optimization of the physicochemical properties. This approach is appealing due to its orthogonality to Fmoc‐SPPS, its flexibility and ease for introducing diversity by on‐resin copper(I)‐catalyzed azide‐alkyne cycloaddition (CuAAC). We exemplified the utility of these novel monomers with PNA based hybridization chain reactions (HCRs).
Since the 2008 economic recession, state intervention in the real estate sector has strengthened. This article explains how housing financialization was reignited in Spain following key policy ...reforms in 2013. We argue that Spanish authorities managed to strategically recreate a finance-friendly environment to attract global investors. They combined financial policies, other deregulatory reforms and neoliberal measures in a coordinated manner we call a policy package. Our analysis provides evidence of the legal and political arrangements at various state levels that effectively facilitated the reanimation of a new cycle of housing financialization which caused rising inflation in prices and distress in tenants' rights. This approach contributes to the understanding of how state-led actions foster a spatial fix to overcome financial crises by granting global speculative funds extraordinary benefits. In addition, we show how this process occurred with poor democratic accountability and was also confronted by various forms of social contestation.
B-cell lymphoproliferative disorders exhibit a diverse spectrum of diagnostic entities with heterogeneous behaviour. Multiple efforts have focused on the determination of the genomic drivers of ...B-cell lymphoma subtypes. In the meantime, the aggregation of diverse tumors in pan-cancer genomic studies has become a useful tool to detect new driver genes, while enabling the comparison of mutational patterns across tumors. Here we present an integrated analysis of 354 B-cell lymphoid disorders. 112 recurrently mutated genes were discovered, of which KMT2D, CREBBP, IGLL5 and BCL2 were the most frequent, and 31 genes were putative new drivers. Mutations in CREBBP, TNFRSF14 and KMT2D predominated in follicular lymphoma, whereas those in BTG2, HTA-A and PIM1 were more frequent in diffuse large B-cell lymphoma. Additionally, we discovered 31 significantly mutated protein networks, reinforcing the role of genes such as CREBBP, EEF1A1, STAT6, GNA13 and TP53, but also pointing towards a myriad of infrequent players in lymphomagenesis. Finally, we report aberrant expression of oncogenes and tumor suppressors associated with novel noncoding mutations (DTX1 and S1PR2), and new recurrent copy number aberrations affecting immune check-point regulators (CD83, PVR) and B-cell specific genes (TNFRSF13C). Our analysis expands the number of mutational drivers of B-cell lymphoid neoplasms, and identifies several differential somatic events between disease subtypes.
From current cognitive science, some theories propose that the human mind includes two systems: a system leading quick intuitions and a system ruling slow logical reasoning. Given that the systems ...are in the mind, one might think that their existence is difficult to check. This paper presents a way to gradually confirm the hypothesis about the two systems. It adopts the conception of the two systems as presented by the theory of mental models. Moreover, following Carnap’s proposal of reduction, the paper describes two procedures to incrementally confirm the hypothesis. One of them investigates human performance at inferences in the form of Modus Tollendo Tollens. The other one investigates inferences from an exclusive disjunction having three disjuncts.
Kai kurios šiuolaikinio kognityvinio mokslo teorijos teigia, kad žmogaus prote veikia dvi sistemos: sistema, vykdanti greitą intuityvų mąstymą, bei sistema, vadovaujanti lėtam logiškam mąstymui. Būtų galima manyti, kad šių sistemų egzistavimą patikrinti sudėtinga. Šiame straipsnyje pateikiamas būdas palaipsniui patvirtinti šių dviejų sistemų egzistavimą. Pasitelkiamas dviejų sistemų, pasireiškiančių per mentalinių modelių teoriją, principas. Be to, laikantis Carnapo redukcijos idėjos, straipsnyje aprašomos dvi procedūros, kuriomis hipotezė patvirtinama palaipsniui. Viena iš jų tyrinėja, kaip žmogaus protas nagrinėja žmogaus proto veiklą darant išvedimus pagal modus tollendo tollens. Kita hipotezė tyrinėja išvedimus iš griežtosios disjunkcijos su trimis disjunktais.
Brown adipose tissue (BAT) has been also considered as the main thermogenic organ responsible of maintenance body temperature through heat production. However, a new type of thermogenic fat has been ...characterized during the last years, the beige or brite fat, that is developed from white adipose tissue (WAT) in response to different stimuli by a process known as browning. The activities of brown and beige adipocytes ameliorate metabolic disease, including obesity in mice and correlate with leanness in humans. Many genes and pathways that regulate brown and beige adipocyte biology have now been identified, providing a variety of promising therapeutic targets for metabolic disease. The hypothalamus is the main central place orchestrating the outflow signals that drive the sympathetic nerve activity to BAT and WAT, controlling heat production and energy homeostasis. Recent data have revealed new hypothalamic molecular mechanisms, such as hypothalamic AMP-activated protein kinase (AMPK), that control both thermogenesis and browning. This review provides an overview of the factors influencing BAT and WAT thermogenesis, with special focus on the integration of peripheral information on hypothalamic circuits controlling thermoregulation.
•The hypothalamus regulates brown fat thermogenesis and browning of white fat.•Hormones signal at the hypothalamus to regulate BAT and WAT through the SNS.•The AMPK(VMH)-SNS-BAT is a canonical pathway regulating energy balance.•Targeting BAT or browning of WAT might be suitable strategies to treat obesity.
AMP-activated protein kinase (AMPK) is the downstream component of a kinase cascade that acts as a gauge of cellular energy levels. Over the last few years, accumulating evidence has demonstrated ...that AMPK is also involved in the regulation of energy balance at the whole-body level by responding to hormones and nutrient signals, which leads to changes in energy homeostasis. The physiological relevance of this new role of AMPK is demonstrated by the fact that impairment of AMPK function is associated with metabolic alterations, insulin resistance, obesity, hormonal disorders and cardiovascular disease. Here, we summarize the role of AMPK in the regulation of energy homeostasis. Understanding this key enzyme and its tissue-specific regulation will provide new targets for the treatment of metabolic disorders.
ABSTRACT
Bacteria frequently cooperate by sharing secreted metabolites such as enzymes and siderophores. The expression of such ‘public good’ traits can be interdependent, and studies on laboratory ...systems have shown that trait linkage affects eco-evolutionary dynamics within bacterial communities. Here, we examine whether linkage among social traits occurs in natural habitats by examining investment levels and correlations between five public goods (biosurfactants, biofilm components, proteases, pyoverdines and toxic compounds) in 315 Pseudomonas isolates from soil and freshwater communities. Our phenotypic assays revealed that (i) social trait expression profiles varied dramatically; (ii) correlations between traits were frequent, exclusively positive and sometimes habitat-specific; and (iii) heterogeneous (specialised) trait repertoires were rarer than homogeneous (unspecialised) repertoires. Our results show that most isolates lie on a continuum between a ‘social’ type producing multiple public goods, and an ‘asocial’ type showing low investment into social traits. This segregation could reflect local adaptation to different microhabitats, or emerge from interactions between different social strategies. In the latter case, our findings suggest that the scope for competition among unspecialised isolates exceeds the scope for mutualistic exchange of different public goods between specialised isolates. Overall, our results indicate that complex interdependencies among social traits shape microbial lifestyles in nature.
Exploring the multi-dimensionality of bacterial public goods production in natural soil and freshwater Pseudomonas communities reveals that bacteria show low levels of specialisation and invest homogeneously into five social traits.
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