"Ráfagas de una campaña" (1962). Un texto recuperado de José-Miguel Ullán

During summer 1962, a 17-years old José-Miguel Ullán took part in a Literacy Campaign organized by the University Service of Labour (Servicio Universitario del Trabajo, SUT), integrated in the Spanish University Union (Sindicato Español Universitario, SEU). He worked and lived together with the people of El Almendral, a very small village next to the town of Zafarraya, in the province of Granada. Shortly after his arrival, he began to write a series of short articles, or “bursts”, sharing his impressions and experiences were published in the local newspapers Ideal during July and August 1962. These juvenile texts, the first ones known to have been signed by the author, remained lost inside the pages of a provincial daily and had never been cited when studying the works and evolution of Ullán, who then became a renowned poet from Salamanca. This paper focuses on its recovery and analysis.En el verano de 1962 José-Miguel Ullán, con 17 años, participó en una Campaña de Alfabetización que el Servicio Universitario de Trabajo (SUT), dependiente del Sindicato Español Universitario (SEU), realizó en la provincia de Granada. Trabajó y convivió con los vecinos de El Almendral, un pequeño núcleo de población anejo al municipio de Zafarraya y al poco de llegar comenzó a escribir unos breves artículos o «ráfagas» contando sus impresiones y experiencias, que fue publicando el diario granadino Ideal durante los meses de julio y agosto. Nunca se habían citado dichos textos juveniles, perdidos en las páginas de un periódico provincial, al estudiar la obra del poeta salmantino, los primeros conservados, cuya recuperación y análisis se realiza en este trabajo

Bifurcations of the normal modes of the Ne...Br2 complex

ABSTRACT: We study the classical dynamics of the rare gas-dihalogen Ne· · ·Br2 complex in its ground electronic state. By considering the dihalogen bond frozen at its equilibrium distance, the system has two degrees of freedom and its potential energy surface presents linear and T-shape isomers. We find the nonlinear normal modes of both isomers that determine the phase space structure of the system. By means of surfaces of section and applying the numerical continuation of families of periodic orbits, we detect and identify the different bifurcations suffered by the normal modes as a function of the system energy. Finally, using the Orthogonal Fast Lyapunov Indicator (OFLI), we study the evolution of the fraction of the phase space volume occupied by regular motions. Keywords: Bifurcations, Br2 complex, Orthogonal Fast Lyapunov Indicator (OFLI), Potential energy surface

Thalamic bursts modulate cortical synchrony locally to switch between states of global functional connectivity in a cognitive task

Performing a cognitive task requires going through a sequence of functionally diverse stages. Although it is typically assumed that these stages are characterized by distinct states of cortical synchrony that are triggered by sub-cortical events, little reported evidence supports this hypothesis. To test this hypothesis, we first identified cognitive stages in single-trial MEG data of an associative recognition task, showing with a novel method that each stage begins with local modulations of synchrony followed by a state of directed functional connectivity. Second, we developed the first whole-brain model that can simulate cortical synchrony throughout a task. The model suggests that the observed synchrony is caused by thalamocortical bursts at the onset of each stage, targeted at cortical synapses and interacting with the structural anatomical connectivity. These findings confirm that cognitive stages are defined by distinct states of cortical synchrony and explains the network-level mechanisms necessary for reaching stage-dependent synchrony states

Glutathione-sensitive nanoplatform for monitored intracellular delivery and controlled release of Camptothecin

[EN] We report the design, synthesis, characterization and in vitro testing of a novel nanodrug based on a covalent linking model that allows intracellular controlled release of the pharmaceutical payload. A new synthetic strategy is implemented by direct coupling of as-synthesized (pyridin-2-yldisulfanyl)alkyl carbonate derivatives of camptothecin (CPT) with thiol groups of silica hybrid nanoparticles containing a non-porous core and a mesoporous shell. Upon reaction with thiols in physiological conditions, disulfide bridge cleavage occurs, releasing the naked drug after an intramolecular cyclization mechanism. Additional incorporation of a fluorophore into particles core facilitates imaging at the subcellular level for the monitoring of uptake and delivery. Confocal microscopy experiments in HeLa cervix cancer cells confirms that nanoparticles enter the cells by endocytosis but are able to escape from endo-lysosomes and enter the cytosolic compartment to release their cargo. The incorporation to cells of L-buthionine-sulfoximine, a glutathione inhibitor allows concluding that the intracellular releasing mechanism is mainly driven by the reducing activity of this tripeptide. This camptothecin nanoplatform shows the same cytotoxic activity than the free drug and is clearly superior to those release systems depending on enzymatic hydrolysis (as determined by calculation of the IC50 ratios).This work was financially supported by "Comision Interministerial de Ciencia y Tecnologia" of Spain (projects CSD2009-00050 and MAT2012-39290-C02-02), and grants from CIBER-BBN (NanoMets Intramural Grant) "Fondo de Investigaciones Sanitarias - Instituto de Salud Carlos III" (PI080771) y "Universidad Catolica de Valencia San Vicente Martir" (PI2011-011-010). CM thanks the Spanish "Ministerio de Economia y Competitividad" for a FPU Ph.D. studentship (AP2008-02851). SSA thanks the "Universidad Catolica de Valencia San Vicente Martir" for a Ph.D. studentship.Muniesa Lajara, C.; Vicente Vilas, V.; Quesada Vilar, M.; Saez-Atienzar, S.; Blesa-Blesa, JR.; Abasolo, I.; Fernández, Y.... (2013). Glutathione-sensitive nanoplatform for monitored intracellular delivery and controlled release of Camptothecin. RSC Advances. 3(35):15121-15131. https://doi.org/10.1039/c3ra41404cS151211513133

Palbociclib Rechallenge for Hormone Receptor-Positive/HER-Negative Advanced Breast Cancer: Findings from the Phase II BioPER Trial

Hormone receptor; Advanced breast cancerCàncer de mama avançat; Receptor hormonalCáncer de mama avanzado; Receptor hormonalPurpose: To assess the efficacy and exploratory biomarkers of continuing palbociclib plus endocrine therapy (ET) beyond progression on prior palbociclib-based regimen in patients with hormone receptor–positive/HER2-negative (HR+/HER2−) advanced breast cancer (ABC). Patients and Methods: The multicenter, open-label, phase II BioPER trial included women who had experienced a progressive disease (PD) after having achieved clinical benefit on the immediately prior palbociclib plus ET regimen. Palbociclib (125 mg, 100 mg, or 75 mg daily orally for 3 weeks and 1 week off as per prior palbociclib-based regimen) plus ET of physician's choice were administered in 4-week cycles until PD or unacceptable toxicity. Coprimary endpoints were clinical benefit rate (CBR) and percentage of tumors with baseline loss of retinoblastoma (Rb) protein expression. Additional endpoints included safety and biomarker analysis. Results: Among 33 patients enrolled, CBR was 34.4% [95% confidence interval (CI), 18.6–53.2; P < 0.001] and 13.0% of tumors (95% CI, 5.2–27.5) showed loss of Rb protein expression, meeting both coprimary endpoints. Median progression-free survival was 2.6 months (95% CI, 1.8–6.7). No new safety signals were reported. A signature that included baseline mediators of therapeutic resistance to palbociclib and ET (low Rb score, high cyclin E1 score, ESR1 mutation) was independently associated with shorter median progression-free survival (HR, 22.0; 95% CI, 1.71–282.9; P = 0.018). Conclusions: Maintaining palbociclib after progression on prior palbociclib-based regimen seems to be a reasonable, investigational approach for selected patients. A composite biomarker signature predicts a subset of patients who may not derive a greater benefit from palbociclib rechallenge, warranting further validation in larger randomized controlled trials.This work was supported by Pfizer. The authors would like to thank the patients, their caregivers, and their families for participating in this study and all investigators and site personnel. The BioPER study was conceived and designed by Medica Scientia Innovation Research (MEDSIR) in collaboration with Pfizer Inc., which funded the study and provided palbociclib. J. Albanell acknowledges CIBERONC CB16/12/00241, PI21/00002, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union, Generalitat de Catalunya (2017 SGR 507)

Beam search for the longest common subsequence problem

The longest common subsequence problem is a classical string problem that concerns finding the common part of a set of strings. It has several important applications, for example, pattern recognition or computational biology. Most research efforts up to now have focused on solving this problem optimally. In comparison, only few works exist dealing with heuristic approaches. In this work we present a deterministic beam search algorithm. The results show that our algorithm outperforms classical approaches as well as recent metaheuristic approaches.Postprint (published version

Modelos y plataforma IEC 61499 adaptados al control distribuido de máquinas herramienta en sistemas de fabricación ágil

Los sistemas de fabricación han ido evolucionando para adaptarse a las cada vez más cambiantes demandas del mercado, pasando de los sistemas de fabricación en masa a los sistemas flexibles y, finalmente, a los sistemas ágiles. Estos últimos están soportados por sistemas reconfigurables, capaces de ser modificados sin parar su funcionamiento, así como por tecnologías de la información y la comunicación, por lo que pueden adaptarse muy rápidamente a cambios en la producción. Para denominar estos nuevos sistemas han surgido también términos como e-manufacturing, cloud-manufacturing, industrie 4.0. El estándar actual de referencia para el desarrollo de software de control en los sistemas de fabricación es IEC 61131, del que algunos trabajos han indicado su poca adecuación frente a los requisitos de los nuevos sistemas. Por este motivo ha surgido el más complejo IEC 61499, que define arquitecturas y modelos para un software de control distribuido y reconfigurable. La industria demanda a este estándar la capacidad para desarrollar software de control: predecible, escalable, mantenible y extensible. A este respecto, aunque ha sido objeto de múltiples trabajos por parte de la comunidad académica, a día de hoy IEC 61499 no ha adquirido esa capacidad, por lo que no es aceptado todavía por la industria. El objeto de la presente tesis es aportar propuestas que contribuyan a que el estándar alcance dicha capacidad. Con este fin, se propone el uso de metodologías y modelos de componentes software adaptados al dominio de aplicación, en particular, al control de máquinas herramienta en sistemas de fabricación ágil. Este dominio ha sido elegido por su complejidad, frente a los sencillos tipos de aplicación y casos de uso considerados en anteriores propuestas relacionadas con IEC 61499. Para establecer dichas metodologías y modelos adaptados se estudia en primer lugar el dominio indicado, determinando los principios de diseño de su software de control. Estos principios sirven de base para efectuar una revisión del estado actual del estándar. Seguidamente, se propone y modela el control distribuido de una máquina herramienta genérica, a partir del cual se establecen los modelos de bloque función y de ejecución IEC 61499 adaptados a ese dominio. Dichos modelos facilitan el establecimiento de una metodología de diseño, a la vez que permiten una implementación del estándar determinista, eficiente, escalable y que cumple restricciones de tiempo real. A la hora de verificar experimentalmente la metodología y los modelos adaptados es necesaria una plataforma de ejecución. Debido a que las plataformas IEC 61499 existentes no soportan dichos modelos se ha especificado, diseñado e implementado la plataforma COSME. A diferencia de anteriores plataformas, ésta incorpora características que hacen posible su empleo en entornos industriales. En este sentido, la plataforma COSME ha sido desarrollada dentro de un proyecto de investigación, transferencia y colaboración tecnológica entre la universidad y un grupo industrial fabricante de máquinas herramienta. Dicho proyecto ha permitido que esta plataforma, la metodología y los modelos adaptados hayan sido validados en casos de uso reales

Chronic intestinal pseudoobstruction and ophthalmoplegia in a patient with mitochondrial myopathy

A 38 year old woman having chronic intestinal pseudoobstruction associated with mitochondrial myopathy is reported. The clinical and radiographic features suggested the diagnosis of chronic intestinal pseudoobstruction. Muscular atrophy and ophthalmoplegia led to muscle biopsy, which disclosed accumulation of normal and abnormal mitochondria ('ragged red fibres'), characteristic of mitochondrial myopathy