Research into the endogamy of boolean circuits

Trabajo de Fin de Grado en Ingeniería Informática y Matemáticas, Facultad de Informática UCM, Departamento de Sistemas Informáticos y Computación, Curso 2019/2020El objetivo de este trabajo consistió en desarrollar un experimento que permita analizar múltiples tipos de circuitos booleanos y las funciones que estos computan, de manera que podamos analizar las relaciones entre ambos conceptos. En el primer capítulo, se expone una definición formal del concepto archiconocido de circuito booleano, se analiza el crecimiento doblemente exponencial del conjunto de circuitos con m bits de entrada y se dota de un orden total a dicho conjunto. En el segundo capítulo, se demuestran una serie de resultados sobre vectores con determinadas propiedades que nos permiten recorrer de manera eficiente el conjunto de circuitos booleanos que tienen determinada profundidad y anchura. Este algoritmo se ha implementado en C++ utilizando técnicas de programación concurrente y estructuras de datos adecuadas para garantizar la eficiencia del mismo. A lo largo del tercer capítulo se exponen distintas métricas para medir la endogamia de los circuitos booleanos, así como intuiciones que justifican estas definiciones. Además, se incorpora un breve cuarto capítulo que versa sobre un tipo de gramática libre de contexto particular que genera funciones booleanas y su correspondencia con los circuitos booleanos. Finalmente, este trabajo concluye con un quinto y último capítulo en el que se analizan los resultados obtenidos en este experimento y se exponen las conclusiones consecuentes.The aim of this project was to develop an experiment that allow us to analyze different kinds of boolean circuits and the functions they compute to study the relationship between both concepts. In the first chapter, a formal definition of boolean circuits is introduced, the double exponential growth of the set of circuits with m bits of input is analyzed and a total order in this set is defined. During the second chapter, some results about vectors of some kind are proved, which allow us to efficiently sweep the set of boolean circuits with fixed depth and width. This algorithm has been implemented in C++ using concurrent programming and adequate data structures to ensure its efficiency. During the third chapter, some metrics to measure the endogamy of boolean circuits are defined and some ideas beyond these definitions are added. In addition, there is a fourth brief chapter where the relationship between a special type of context-free grammar and its equivalence with our boolean circuits are discussed. To conclude, a final fifth chapter is added to analyse the results obtained in the experiment and the conclusions these results led us to.Depto. de Sistemas Informáticos y ComputaciónFac. de InformáticaTRUEunpu

Dynamic Partial Order Reduction for Checking Correctness Against Transaction Isolation Levels

Modern applications, such as social networking systems and e-commerce platforms are centered around using large-scale databases for storing and retrieving data. Accesses to the database are typically enclosed in transactions that allow computations on shared data to be isolated from other concurrent computations and resilient to failures. Modern databases trade isolation for performance. The weaker the isolation level is, the more behaviors a database is allowed to exhibit and it is up to the developer to ensure that their application can tolerate those behaviors. In this work, we propose stateless model checking algorithms for studying correctness of such applications that rely on dynamic partial order reduction. These algorithms work for a number of widely-used weak isolation levels, including Read Committed, Causal Consistency, Snapshot Isolation, and Serializability. We show that they are complete, sound and optimal, and run with polynomial memory consumption in all cases. We report on an implementation of these algorithms in the context of Java Pathfinder applied to a number of challenging applications drawn from the literature of distributed systems and databases.Comment: Submission to PLDI 202

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Plasmalemmal sodium-calcium exchanger shapes the calcium and exocytotic signals of chromaffin cells at physiological temperature

The activity of the plasmalemmal Na(+)/Ca(2+) exchanger (NCX) is highly sensitive to temperature. We took advantage of this fact to explore here the effects of the NCX blocker KB-R7943 (KBR) at 22 and 37°C on the kinetics of Ca(2+) currents (ICa), cytosolic Ca(2+) ([Ca(2+)]c) transients, and catecholamine release from bovine chromaffin cells (BCCs) stimulated with high K(+), caffeine, or histamine. At 22°C, the effects of KBR on those parameters were meager or nil. However, at 37°C whereby the NCX is moving Ca(2+) at a rate fivefold higher than at 22°C, various of the effects of KBR were pronounced, namely: 1) no effects on ICa; 2) reduction of the [Ca(2+)]c transient amplitude and slowing down of its rate of clearance; 3) blockade of the K(+)-elicited quantal release of catecholamine; 4) blockade of burst catecholamine release elicited by K(+); 5) no effect on catecholamine release elicited by short K(+) pulses (1-2 s) and blockade of the responses produced by longer K(+) pulses (3-5 s); and 6) potentiation of secretion elicited by histamine or caffeine. Furthermore, the more selective NCX blocker SEA0400 also potentiated the secretory responses to caffeine. The results suggest that at physiological temperature the NCX substantially contributes to shaping the kinetics of [Ca(2+)]c transients and the exocytotic responses elicited by Ca(2+) entry through Ca(2+) channels as well as by Ca(2+) release from the endoplasmic reticulum.We thank the continued support of Fundación Teófilo Hernando, Madrid, Spain. This work was supported by the following grants to to A. G. García: 1) SAF 2010-21795, Ministerio de Economía y Competitividad, Spain; 2) RENEVAS-RETICS-RD06/0026, Instituto de Salud Carlos III, Spain; and 3) CABICYC Bioibérica/UAM. Also by grant from Ministerio de Economía y Competitividad No. 2010-18837 (to L. G. Gandía).Peer reviewe

Rhythm and ROS: Hepatic Chronotherapeutic Features of Grape Seed Proanthocyanidin Extract Treatment in Cafeteria Diet-Fed Rats

Polyphenols play a key role in the modulation of circadian rhythms, while the cafeteria diet (CAF) is able to perturb the hepatic biological rhythm and induce important ROS production. Consequently, we aimed to elucidate whether grape seed proanthocyanidin extract (GSPE) administration recovers the CAF-induced hepatic antioxidant (AOX) misalignment and characterize the chronotherapeutic properties of GSPE. For this purpose, Fischer 344 rats were fed a standard diet (STD) or a CAF and concomitantly treated with GSPE at two time-points (ZT0 vs. ZT12). Animals were euthanized every 6 h and the diurnal rhythms of hepatic ROS-related biomarkers, hepatic metabolites, and AOX gene expression were examined. Interestingly, GSPE treatment was able to recover the diurnal rhythm lost due to the CAF. Moreover, GSPE treatment also increased the acrophase of Sod1, as well as bringing the peak closer to that of the STD group. GSPE also corrected some hepatic metabolites altered by the CAF. Importantly, the differences observed at ZT0 vs. ZT12 due to the time of GSPE administration highlight a chronotherapeutic profile on the proanthocyanin effect. Finally, GSPE could also reduce diet-induced hepatic oxidative stress not only by its ROS-scavenging properties but also by retraining the circadian rhythm of AOX enzymes

Aspectos didácticos de Ciencias de la Tierra y del Medio Ambiente. 1

Se recogen las ponencias sobre Ciencias de la Tierra y del Medio Ambiente presentadas en el 'XI Curso sobre aspectos didácticos de la Enseñanza Secundaria', organizado por el ICE de la Universidad de Zaragoza del 11 al 13 de septiembre de 1995. 'Ciencias de la Tierra y del Medio Ambiente: contenidos y actividades de campo' muestra un modelo experimentado en la docencia directa, un enfoque de las Ciencias de la Naturaleza sobre la educación ambiental que articula el currículo en torno al estudio de campo de una zona próxima. 'Educación ambiental y escuela: apuntes para la implantación de estrategias organizativas' plantea el centro educativo como un modelo de experimentación y mejora en aspectos de gestión ambiental, tales como consumo energético, residuos, etc. 'Modelos de explotación/conservación en el medio rural aragonés y su aprovechamiento didáctico' ofrece una perspectiva diferente, el enfoque de la biología aplicada a la agronomía. 'Recursos didácticos en biología para la evaluación medioambiental de nuestro entorno' propone iniciar a los alumnos en metodología y técnicas biológicas de análisis y evaluación ambiental. Por último, 'Las Ciencias de la Tierra y el Medio Ambiente' analiza el currículo de esta asignatura.AragónBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]