On the use of biased-randomized algorithms for solving non-smooth optimization problems

Soft constraints are quite common in real-life applications. For example, in freight transportation, the fleet size can be enlarged by outsourcing part of the distribution service and some deliveries to customers can be postponed as well; in inventory management, it is possible to consider stock-outs generated by unexpected demands; and in manufacturing processes and project management, it is frequent that some deadlines cannot be met due to delays in critical steps of the supply chain. However, capacity-, size-, and time-related limitations are included in many optimization problems as hard constraints, while it would be usually more realistic to consider them as soft ones, i.e., they can be violated to some extent by incurring a penalty cost. Most of the times, this penalty cost will be nonlinear and even noncontinuous, which might transform the objective function into a non-smooth one. Despite its many practical applications, non-smooth optimization problems are quite challenging, especially when the underlying optimization problem is NP-hard in nature. In this paper, we propose the use of biased-randomized algorithms as an effective methodology to cope with NP-hard and non-smooth optimization problems in many practical applications. Biased-randomized algorithms extend constructive heuristics by introducing a nonuniform randomization pattern into them. Hence, they can be used to explore promising areas of the solution space without the limitations of gradient-based approaches, which assume the existence of smooth objective functions. Moreover, biased-randomized algorithms can be easily parallelized, thus employing short computing times while exploring a large number of promising regions. This paper discusses these concepts in detail, reviews existing work in different application areas, and highlights current trends and open research lines

Integration of CLIP experiments of RNAbinding proteins: a novel approach to predict context-dependent splicing factors from transcriptomic data

Background: Splicing is a genetic process that has important implications in several diseases including cancer. Deciphering the complex rules of splicing regulation is crucial to understand and treat splicing-related diseases. Splicing factors and other RNA-binding proteins (RBPs) play a key role in the regulation of splicing. The specific binding sites of an RBP can be measured using CLIP experiments. However, to unveil which RBPs regulate a condition, it is necessary to have a priori hypotheses, as a single CLIP experiment targets a single protein. Results: In this work, we present a novel methodology to predict context-specific splicing factors from transcriptomic data. For this, we systematically collect, integrate and analyze more than 900 CLIP experiments stored in four CLIP databases: POSTAR2, CLIPdb, DoRiNA and StarBase. The analysis of these experiments shows the strong coherence between the binding sites of RBPs of similar families. Augmenting this information with expression changes, we are able to correctly predict the splicing factors that regulate splicing in two gold-standard experiments in which specific splicing factors are knocked-down. Conclusions: The methodology presented in this study allows the prediction of active splicing factors in either cancer or any other condition by only using the information of transcript expression. This approach opens a wide range of possible studies to understand the splicing regulation of different conditions. A tutorial with the source code and databases is available at https://gitlab.com/fcarazo.m/sfprediction

SeniorFit : Una aplicación móvil para el seguimiento de la adherencia a estilos de vida saludable para gente mayor

El envejecimiento progresivo de la población en los países desarrollados exige la promoción de estilos de vida saludables para fomentar el envejecimiento activo. En este trabajo se presenta una aplicación denominada SeniorFit que pretende facilitar la autoevaluación de la adherencia al estilo de vida mediante una herramienta sencilla, cómoda y fiable. La aplicación está desarrollada para móviles y permite medir de forma no intrusiva la actividad física, el pulso cardíaco y evaluar el estado de ánimo utilizando únicamente el propio móvil. Esta aplicación ha sido utilizada por un grupo de gente mayor durante 3 semanas y en condiciones libres. Los usuarios han manifestado un alto grado de satisfacción y la facilidad de su uso.Postprint (published version

Complejos de Osmio con Ligandos Carbeno N-Heterocíclicos: Preparación y Actividad Catalítica

Los metales 5d forman enlaces más fuertes que sus homólogos 4d con las moléculas típicamente implicadas en procesos catalíticos. Como resultado, los complejos de metales 5d han sido tradicionalmente usados para estudiar reacciones elementales implicadas en procesos catalizados por complejos relacionados de metales 4d. Rutenio ha sido uno de los elementos más importantes en catálisis homogénea durante la última década mientras que osmio ha sido escasamente investigado, en particular los complejos con ligandos carbeno N-heterocíclicos. A la vista de estos hechos, al inicio de la presente Memoria nos propusimos generar conocimiento en el ámbito de los complejos de osmio con ligandos NHC, mediante el estudio de reacciones elementales que fueran de interés en la química catalítica de rutenio y osmio, la caracterización de los compuestos resultantes y el descubrimiento de nuevos tipos de catalizadores, a ser posible más eficientes que los ya conocidos, para transformaciones orgánicas respetuosas con el medio ambiente. En esta Memoria se presenta la preparación y caracterización de nuevos y originales complejos catiónicos dihidruro-borilo y dihidruro-sililo de osmio(IV) estabilizados por un ligando NHC, [OsH2(BR2)(h6-p-cimeno)(IPr)]OTf y [OsH2(SiR3)(h6-p-cimeno)(IPr)]OTf, y revela una clara relación diagonal entre ellos, que se demuestra en su formación, reactividad hacia los grupos OH, estructura, comportamiento en disolución y tipo de enlace. Los complejos fenil y ciclohexilamido de osmio estabilizados con un ligando IPr pueden ser preparados vía intermedios amina y por reacción directa del catión bis(solvato) [Os(¿6-p-cimeno)(NCCH3)2(IPr)]2+ con aminas. A 100 ºC en tetrahidrofurano y en presencia de trazas de agua el ligando IPr del derivado ciclohexilamido sufre degradación, mediante la activación C¿C de un enlace isopropilo-arilo de uno de sus sustituyentes, para dar un sistema policíclico de tres anillos fusionados con un corazón Os¿NHC. El catión [Os(=CHPh)(NCCH3)4(IPr)]2+ intercambia el grupo alquilideno con propileno y etileno para dar especies etilideno y metilideno, respectivamente. La presencia de un sustituyente alquilo en el alquilideno aumenta su estabilidad. Así, mientras el primero de ellos es estable, el segundo lleva a cabo una cicloadición [2+2] con una nueva molécula de etileno para dar un intermedio metalaciclobutano, que evoluciona mediante ß-eliminación de hidrógeno y posterior eliminación reductora a un derivado ¿2-propileno. El acetonitrilo desplaza la olefina del complejo anterior, y el compuesto penta(solvato) resultante reacciona con alquinoles en alcoholes, para dar complejos alcoxialquenilcarbeno a través de intermedios alenilideno. Hemos descrito el catalizador de osmio más activo y versátil descrito hasta la fecha para la hidratación selectiva de nitrilos a amidas y el aislamiento y caracterización, mediante análisis de difracción de rayos X, de intermedios catalíticos llave Os(¿2-amidato). Los resultados presentados indican que el osmio es un elemento que debe tenerse en cuenta para el desarrollo de la metodología de préstamo de hidrógeno, dado que puede dar lugar a catalizadores más eficientes que aquellos basados en los metales tradicionales, en particular para algunas reacciones como las ¿-alquilaciones de fenilacetonitrilos y metil cetonas. En conclusión, hemos generado nuevo conocimiento mediante el estudio de reacciones estequeométricas elementales de interés en catálisis homogénea, la caracterización de compuestos nuevos y originales y el descubrimiento de catalizadores, más eficientes que los ya conocidos, para transformaciones orgánicas respetuosas con el medio ambiente

Comparison of video-based methods for respiration rhythm measurement

The aim of this work is to characterize the di erences in the respiratory rhythm obtained through three video based methods by comparing the obtained respiratory signals with the one obtained with the gold standard method in adult population. The analysed methods are an RGB camera, a depth camera and a thermal camera while the gold standard is an inductive thorax plethysmography system (Respiband system from BioSignals Plux). 21 healthy subjects where measured, performing 4 tests for each subject. The respiratory rhythm and its variability was obtained from the four respiratory signals (3 video methods and gold standard). The signal acquisition was performed with custom and proprietary algorithms. To characterize the respiratory rhythm and its variability obtained with the di erent video sources and gold standard, the instantaneous frequency, Bland-Altman plots and standard deviation of the error between video methods and the gold standard have been computed. The depth and RGB camera present high agreement with no statistical di erences between them, with errors when comparing with the gold standard in the range of mHz. The thermal camera performs poorly if compared with the two other methods, nevertheless it cannot be discarded directly because some errors produced by the subjects head movement could not be corrected. From these results we conclude that the depth and RGB camera, and their respective acquisition algorithms) can be used in controlled conditions to measure respiration rhythm and its variability. The thermal camera on the other hand, although it can not be discarded directly, performed poorly if compared with the other two methods. Further studies are needed to con rm that these methods can be used in real life conditions.Postprint (author's final draft

A photoplethysmography smartphone-based method for heart rate variability assessment: device model and breathing influences

© 2019 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/A measurement method of heart rate and heart rate variability (HRV) based on smartphone has been developed and validated. The method is based on photoplethysmography (PPG) acquired with the smartphone camera (SPPG). SPPG was compared with the electrocardiogram (ECG), used as the gold standard, and with an external PPG sensor. Twenty-three healthy subjects were measured using two different smartphone models in three different breathing conditions. The error of the first differentiation between SPPG and ECG series is minimized with the fiducial point at maximum first derivative of the SPPG. The obtained standard deviation of error (SDE) between SPPG and ECG is around 5.4 ms and it is similar to SDE between PPG and ECG. Good agreement between SPPG and ECG for NN, SDNN and RMSSD have been found but it is insufficient agreement for LF/HF. Similar levels of agreement for SPPG-ECG and PPG-ECG have been obtained for the HRV indices. Finally, the differences between smartphone models for HRV indices are slight. Therefore, the smartphone can be used for measuring accurately the following HRV indices: NN, SDNN and RMSSD.Peer ReviewedPostprint (published version

ISOGO: Functional annotation of protein-coding splice variants

The advent of RNA-seq technologies has switched the paradigm of genetic analysis from a genome to a transcriptome-based perspective. Alternative splicing generates functional diversity in genes, but the precise functions of many individual isoforms are yet to be elucidated. Gene Ontology was developed to annotate gene products according to their biological processes, molecular functions and cellular components. Despite a single gene may have several gene products, most annotations are not isoform-specifc and do not distinguish the functions of the diferent proteins originated from a single gene. Several approaches have tried to automatically annotate ontologies at the isoform level, but this has shown to be a daunting task. We have developed ISOGO (ISOform+GO function imputation), a novel algorithm to predict the function of coding isoforms based on their protein domains and their correlation of expression along 11,373 cancer patients. Combining these two sources of information outperforms previous approaches: it provides an area under precision-recall curve (AUPRC) fve times larger than previous attempts and the median AUROC of assigned functions to genes is 0.82. We tested ISOGO predictions on some genes with isoform-specifc functions (BRCA1, MADD,VAMP7 and ITSN1) and they were coherent with the literature. Besides, we examined whether the main isoform of each gene -as predicted by APPRIS- was the most likely to have the annotated gene functions and it occurs in 99.4% of the genes. We also evaluated the predictions for isoform-specifc functions provided by the CAFA3 challenge and results were also convincing. To make these results available to the scientifc community, we have deployed a web application to consult ISOGO predictions (https://biotecnun.unav. es/app/isogo). Initial data, website link, isoform-specifc GO function predictions and R code is available at https://gitlab.com/icassol/isogo

Prototipo de pulsera para la medida de ECG bajo demanda y la medida continua de la onda de pulso

El interés en la variabilidad de ritmo cardiaco (HRV) y la estimación de la presión arterial a partir del tiempo de llegada de la onda de pulso (PAT) se ha incrementado exponencialmente en los últimos años debido a los indicadores que se pueden extraer. En este trabajo se presenta un prototipo de pulsera que, sin ningún otro medio externo a esta, es capaz de medir electrocardiograma (ECG), onda de pulso y, por consiguiente el PAT, de forma no invasiva. Además, está diseñada para la realización de medidas oportunistas y pensando en la comodidad del usuario. Se presentan también los materiales y electrónica empleados para la implementación del prototipo. A partir de los resultados obtenidos se da una guía para la colocación de los sensores en la pulsera. Finalmente, los resultados indican que la calidad de las medidas realizadas es suficiente para ser utilizadas en el estudio de HRV y PAT.Postprint (updated version