Probabilistic reasoning with an enzyme-driven DNA device

We present a biomolecular probabilistic model driven by the action of a DNA toolbox made of a set of DNA templates and enzymes that is able to perform Bayesian inference. The model will take single-stranded DNA as input data, representing the presence or absence of a specific molecular signal (the evidence). The program logic uses different DNA templates and their relative concentration ratios to encode the prior probability of a disease and the conditional probability of a signal given the disease. When the input and program molecules interact, an enzyme-driven cascade of reactions (DNA polymerase extension, nicking and degradation) is triggered, producing a different pair of single-stranded DNA species. Once the system reaches equilibrium, the ratio between the output species will represent the application of Bayes? law: the conditional probability of the disease given the signal. In other words, a qualitative diagnosis plus a quantitative degree of belief in that diagno- sis. Thanks to the inherent amplification capability of this DNA toolbox, the resulting system will be able to to scale up (with longer cascades and thus more input signals) a Bayesian biosensor that we designed previously

Modelos de computación lógica con ADN

La computación molecular es una disciplina que se ocupa del diseño e implementación de dispositivos para el procesamiento de información sobre un sustrato biológico, como el ácido desoxirribonucleico (ADN), el ácido ribonucleico (ARN) o las proteínas. Desde que Watson y Crick descubrieron en los años cincuenta la estructura molecular del ADN en forma de doble hélice, se desencadenaron otros descubrimientos como las enzimas que cortan el ADN o la reacción en cadena de la polimerasa (PCR), contribuyendo más que signi�cativamente a la irrupción de la tecnología del ADN recombinante. Gracias a esta tecnología y al descenso vertiginoso de los precios de secuenciación y síntesis del ADN, la computación biomolecular pudo abandonar su concepción puramente teórica. En 1994, Leonard Adleman logró resolver un problema de computación NP-completo (El Problema del Camino de Hamilton Dirigido) utilizando únicamente moléculas de ADN. La gran capacidad de procesamiento en paralelo ofrecida por las técnicas del ADN recombinante permitió a Adleman ser capaz de resolver dicho problema en tiempo polinómico, aunque a costa de un consumo exponencial de moléculas de ADN. Utilizando algoritmos similares al de �fuerza bruta� utilizado por Adleman se logró resolver otros problemas NP-completos (por ejemplo, el de Satisfacibilidad de Fórmulas Lógicas / SAT). Pronto se comprendió que la computación con biomolecular no podía competir en velocidad ni precisión con los ordenadores de silicio, por lo que su enfoque y objetivos se centraron en la resolución de problemas biológicos con aplicación biomédica, dejando de lado la resolución de problemas clásicos de computación. Desde entonces se han propuesto diversos modelos de dispositivos biomoleculares que, de forma autónoma (sin necesidad de un bio-ingeniero realizando operaciones de laboratorio), son capaces de procesar como entrada un sustrato biológico y proporcionar una salida también en formato biológico: procesadores que aprovechan la extensión de la Polimerasa, autómatas que funcionan con enzimas de restricción o con deoxiribozimas, circuitos de hibridación competitiva. Esta tesis presenta un conjunto de modelos de dispositivos de ácidos nucleicos escalables, sensibles al tiempo y energéticamente e�cientes, capaces de implementar diversas operaciones de computación lógica aprovechando el fenómeno de la hibridación competitiva del ADN. La capacidad implícita de estos dispositivos para aplicar reglas de inferencia como modus ponens, modus tollens, resolución o el silogismo hipotético tiene un gran potencial. Entre otras funciones, permiten representar implicaciones lógicas (o reglas del tipo SI/ENTONCES), como por ejemplo, �si se da el síntoma 1 y el síntoma 2, entonces estamos ante la enfermedad A�, o �si estamos ante la enfermedad B, entonces deben manifestarse los síntomas 2 y 3�. Utilizando estos módulos lógicos como bloques básicos de construcción, se pretende desarrollar sistemas in vitro basados en sensores de ADN, capaces de trabajar de manera conjunta para detectar un conjunto de síntomas de entrada y producir un diagnóstico de salida. La reciente publicación en la revista Science de un autómata biomolecular de diagnóstico, capaz de tratar las células cancerígenas sin afectar a las células sanas, es un buen ejemplo de la relevancia cientí�ca que este tipo de autómatas tienen en la actualidad. Además de las recién mencionadas aplicaciones en el diagnóstico in vitro, los modelos presentados también tienen utilidad en el diseño de biosensores inteligentes y la construcción de bases de datos con registros en formato biomolecular que faciliten el análisis genómico. El estudio sobre el estado de la cuestión en computación biomolecular que se presenta en esta tesis está basado en un artículo recientemente publicado en la revista Current Bioinformatics. Los nuevos dispositivos presentados en la tesis forman parte de una solicitud de patente de la que la UPM es titular, y han sido presentados en congresos internacionales como Unconventional Computation 2010 en Tokio o Synthetic Biology 2010 en París

TTS evaluation campaign with a common spanish database

This paper describes the first TTS evaluation campaign designed for Spanish. Seven research institutions took part in the evaluation campaign and developed a voice from a common speech database provided by the organisation. Each participating team had a period of seven weeks to generate a voice. Next, a set of sentences were released and each team had to synthesise them within a week period. Finally, some of the synthesised test audio files were subjectively evaluated via an online test according to the following criteria: similarity to the original voice, naturalness and intelligibility. Box-plots, Wilcoxon tests and WER have been generated in order to analyse the results. Two main conclusions can be drawn: On the one hand, there is considerable margin for improvement to reach the quality level of the natural voice. On the other hand, two systems get significantly better results than the rest: one is based on statistical parametric synthesis and the other one is a concatenative system that makes use of a sinusoidal model to modify both prosody and smooth spectral joints. Therefore, it seems that some kind of spectral control is needed when building voices with a medium size database for unrestricted domains.Postprint (published version

BUCEADOR hybrid TTS for blizzard challenge 2011

This paper describes the Text-to-Speech (TTS) systems presented by the Buceador Consortium in the Blizzard Challenge 2011 evaluation campaign. The main system is a concatenative hybrid one that tries to combine the strong points of both statistical and unit selection synthesis (i.e. robustness and segmental naturalness respectively). The hybrid system has reached results significantly above average as far as similarity and naturalness are concerned, with no significant differences with most of the systems in the intelligibility task. This clearly improves the performance achieved in previous participations, and shows the validity of the hybrid approach proposed. Besides, an HMM-based system was built for the ES1 intelligibility tasks, using an HNM-based vocoder.Peer ReviewedPostprint (published version

Advanced HCI and 3D Web over Low performance Devices

This position paper presents the authors’ goals on advanced human computer interaction and 3D Web -- Previous work on speech, natural language processing and visual technologies has achieved the development of the BerbaTek language learning demonstrator, a 3D virtual tutor that supports Basque language students through spoken interaction -- Next steps consist on migrating all the system to multidevice web technologies -- This paper shows the architecture defined and the steps to be performed in the next month

Emissivity measurements conducted on intermetallic γ-TiAl-based alloys for aeronautical applications

The directional spectral emissivity of a Ti–48Al–2Nb–2Cr alloy (in at.%), 4822 alloy, and a Ti-43.5Al–4Nb–1Mo-0.1B alloy (in at.%),TNM alloy, used in the aeronautical industry, are measured between 150 and 850 °C. The differences in the emissivity values between both alloys at the lowest temperatures, indicates that the βo phase, only present in TNM, exhibit higher emissivity values. By numerical integration of the measured data, the total directional and hemispherical emissivity have been calculated. At 850 °C the total hemispherical emissivity in vacuum are nearly identical with 0.274 ± 0.006 for the 4822 alloy and 0.273 ± 0.007 for the TNM alloy. The lower emissivity change with temperature measured in TNM alloys is related with the deconvolution of βo phase by diffusion processes. Afterwards, near-normal spectral emissivity measurements are performed in both alloys during isothermal oxidation treatments at 750 °C and 850 °C for 120 h. The emissivity data reveal that the TNM alloy exhibits higher oxidation resistance especially at 750 °C. In parallel, microstructural characterization has been performed before the measurements, after the directional emissivity measurements prior to oxidation and after isothermal oxidations. The formed oxide scale is composed of four layers that coincide with those reported in the literature: an outer layer of TiO2 contiguous with a layer of Al2O3, followed by a TiO2/Al2O3 mixed layer and finally a thin layer of Nb-rich nitride. This mixed layer governs the interferential part of the alloys’ emissivity spectra, which, in combination with the background, determines the overall radiative behavior of the alloys under service conditions.This work was supported by the Education Department of Basque Government via PIBA-PUE2021_1_0022 and IT-1714-22 projects as well as a predoctoral grant (M. Sainz-Menchón: PRE-2022-1-0086). The authors thank for technical and human support provided by SGIker of UPV/EHU and European funding (ERDF and ESF) as well as R. Wartbichler for sample preparation and helpful discussions

Onset of irreversible reactions in overcharging lithium-ion cells: an experimental and modeling approach

Lithium-ion batteries are energy storage systems used in an increasing number of applications. Due to their flammable materials, their use entails risks of fire and explosion. The study of the abuse operation of these batteries before reaching the thermal runaway is a relevant research topic to prevent safety issues. There are various studies in the bibliography providing exhaustive thermal studies of the safe operating area, as well as concerning the thermal runaway. However, the onset irreversible reactions, that take place at a SOC around 110%, have not been properly analyzed. We present in this contribution an experimental study of this onset reaction measured in pouch Li-ion cells under various conditions of charge current and temperature. We also propose a lumped-parameter thermal model for the cell, which allows a detailed characterization of this exothermic reaction. The results achieved in this contributions can be a key tool to prevent overcharge accidents that may arise due to malfunctioning of the battery charger or battery management system.This work is part of the projects PID2019-111262RB-I00, funded by MCIN/AEI/10.13039/501100011033/, TED2021-132457B-I00, funded by MCIN/AEI/10.13039/501100011033/ and by the European Union NextGenerationEU/PRTR, STARDUST (774094), funded by European Union's Horizon 2020 research and innovation programme, HYBPLANT (0011-1411-2022- 000039), funded by Government of Navarre, and has also been supported by MCIN/AEI/10.13039/501100011033/ and by European Social Fund under a PhD scholarship (grant PRE2020-095314)

Temperature indicators and overtemperature detection in lithium-ion batteries based on electrochemical impedance spectroscopy

Lithium-ion batteries are the leading technology for energy storage systems due to their attractive advantages. However, the safety of lithium-ion batteries is a major concern, as their operating conditions are limited in terms of temperature, voltage and state of charge. Therefore, it is important to monitor the conditions of lithium-ion batteries to guarantee safe operation. To this end, in the present work, we analyze electrochemical impedance spectroscopy (EIS) as a tool to estimate the temperature of batteries. Overtemperature abuse tests from 25 °C to 140 °C are performed at various states of charge, and EIS measurements are obtained during the tests. The influence of temperature on cell impedance at different frequencies is analyzed and new findings are revealed. The real part of the impedance is identified to be the best indicator for cell temperature estimation by EIS. In addition, the best frequency to achieve accurate temperature monitoring, avoiding disturbances produced by state of charge variations, is proposed based on experimental results. Finally, EIS is proven to be a reliable technique for overtemperature and thermal runaway detection.This work is part of the projects PID2019-111262RB-I00, funded by MCIN/AEI/10.13039/501100011033/, TED2021-132457B-I00, funded by MCIN/AEI/10.13039/501100011033/ and by the European Union NextGenerationEU/PRTR, STARDUST (774094), funded by European Union’s Horizon 2020 research and innovation programme, HYBPLANT (0011-1411-2022- 000039), funded by Government of Navarre, and has also been supported by MCIN/AEI/10.13039/501100011033/ and by European Social Fund under a PhD scholarship (grant PRE2020-095314)