Neural Information Processing: between synchrony and chaos

The brain is characterized by performing many different processing tasks ranging from elaborate processes such as pattern recognition, memory or decision-making to more simple functionalities such as linear filtering in image processing. Understanding the mechanisms by which the brain is able to produce such a different range of cortical operations remains a fundamental problem in neuroscience. Some recent empirical and theoretical results support the notion that the brain is naturally poised between ordered and chaotic states. As the largest number of metastable states exists at a point near the transition, the brain therefore has access to a larger repertoire of behaviours. Consequently, it is of high interest to know which type of processing can be associated with both ordered and disordered states. Here we show an explanation of which processes are related to chaotic and synchronized states based on the study of in-silico implementation of biologically plausible neural systems. The measurements obtained reveal that synchronized cells (that can be understood as ordered states of the brain) are related to non-linear computations, while uncorrelated neural ensembles are excellent information transmission systems that are able to implement linear transformations (as the realization of convolution products) and to parallelize neural processes. From these results we propose a plausible meaning for Hebbian and non-Hebbian learning rules as those biophysical mechanisms by which the brain creates ordered or chaotic ensembles depending on the desired functionality. The measurements that we obtain from the hardware implementation of different neural systems endorse the fact that the brain is working with two different states, ordered and chaotic, with complementary functionalities that imply non-linear processing (synchronized states) and information transmission and convolution (chaotic states)

Els mitjans econòmics del Sindicat de Fora (segles XIV-XVI)

L'objectiu d'aquest article és l'estudi de les finances i dels mitjans económics del Sindicat de Fora durant els segles XIV-XVI. El Sindicat tenia dret a percehre una part alfquota dels fons monetaris de la Universilat del refine de Mallorca. pecó la percepció regular d'aquesta yunta quasi scmpre fou dificultosa i insufcient a causa del control que sobre els diners públics excrcicn cls jurats del Refine, per aixi6, el Sindicat va haver de recórrer a l'endeutament i a les contribucions dírectes -talles- per finanyar-se. En el nostre estudi provam que la facultat del Sindicat per recol lectar talles a la Part Forana fou csscncial no solament per cobrir les seves necessitals econótniques, sinó per assegusar la propia pcrvivéncia. Finalment, exposam unes breas consideracioris sobre la figura. la trajectòria i les atribucions dels síndics clavaris

Characterisation of nanobodies directed against emerging viruses

The emergence of new viral pathogens, such as SARS-CoV-2, or re-emergence of known pathogens, like CHIKV, point out the need for further understanding of the biology behind viruses, as well as the urgent need for the development of therapeutic and diagnostic tools. Nanobodies, small antigen-binding fragments derived from camelid heavy-chain antibodies, have gained attention for their use in viral research due to their wide range of applications: from the study of protein-protein interactions, uncovering of new viral targets, to the generation of new diagnostic tools or therapeutics. In paper I, we isolated a nanobody, Ty1, targeting the receptor binding domain (RBD) of SARS-CoV-2. We showed the ability of Ty1 to neutralise SARS-CoV-2 pseudotyped lentivirus potently (IC50 of 0.77 μg mL-1). The highly neutralising ability of Ty1 was likely due to its ability to bind the RBD in the ‘up’ and ‘down’ conformations, causing direct blocking to the cellular receptor and steric hindrance, respectively. Moreover, staining of SARS-CoV-2-infected cells with Ty1 confirmed its high specificity. In paper II we made use of a novel and rapid strategy to create nanobody multimers. We first functionalised the nanobodies using sortase A ligation to attach click chemistry functional groups. Then, the functionalised nanobodies were used to create C-to-C terminal bi- and tetravalent nanobody constructs by Cu-free strain-promoted azide-alkyne click chemistry (SPAAC). The bivalent and tetrameric nanobody constructs showed an increased potency with respect to the monomeric Ty1 of 150-fold and 4000-fold, respectively. This was true both for SARS-CoV-2 spike pseudotyped lentivirus and infectious SARS-CoV-2. In paper III, we generated nanobodies targeting the spike complex of CHIKV. We used a combinatory immunisation strategy with a cDNA prime followed by a protein boost. The CHIKV spike complex is formed by homotrimers of heterodimers of the E1 and E2 proteins. While E2 binds to the cellular receptor, E1 is responsible for the fusion of viral and cellular membranes, both essential steps of viral entry. We made use of a bivariate mining approach coupled to NGS and calculation of enrichment (fold difference in frequency between basal and enriched libraries) for the quick selection of nanobodies targeting either protein. We identified 12 nanobodies that detected cells infected with the 3 CHIKV lineages (ECSA, Asian and WA). Surprisingly, neutralisation of the ECSA and Asian genotypes was below 50% for all tested nanobodies, while 2 nanobodies, Dy010 and Dy059 could neutralise the WA lineage above 50% with PRNT50 values of 563 and 722 nM, respectively. Fusion to an Fc fragment produced an increase in potency of 130- and 63-fold for Dy010 and Dy059. Moreover, 4 of the nanobodies, Dy009, Dy025, Dy027 and Dy201 cross-reacted with other alphaviruses including ONNV, RRV and SFV, while one nanobody, Dy007, showed great specificity for CHIKV. These nanobodies expand the toolbox for research of this important human pathogen and could form a basis for the development of therapeutic or diagnostic tools

Sobre la comparación métrica en la poética clasicista

Este artículo analiza la teoría métrica de la época clasicista y muestra cómo puede descubrirse un cierto impulso, aunque carente de método, hacia la comparación. Esto parece una notable excepción en un período en el que los principios son homogéneos y universales.________________________________ This paper analyzes the classicist theory of meter and shows that it can be found a non-methodical impulse towards comparison. This seems a remarkable exception in a period when principles are homogeneous and universal