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Abstract The increasing availability of multidimensional phenotypic data in large cohorts of genotyped individuals requires efficient methods to identify genetic effects on multiple traits. Permutational multivariate analysis of variance (PERMANOVA) offers a powerful non-parametric approach. However, it relies on permutations to assess significance, which hinders the analysis of large datasets. Here, we derive the limiting null distribution of the PERMANOVA test statistic, providing a framework for the fast computation of asymptotic p values. Our asymptotic test presents controlled type I error and high power, often outperforming parametric approaches. We illustrate its applicability in the context of QTL mapping and GWAS.

An outstanding event related to the understanding of the physics of mechanical sensors occurred and was announced in 1954, exactly seventy years ago. This event was the discovery of the piezoresistive effect, which led to the development of semiconductor strain gauges with a sensitivity much higher than that obtained before in conventional metallic strain gauges. In turn, this motivated the subsequent development of the earliest micromachined silicon devices and the corresponding MEMS devices. The science and technology related to sensors has experienced noteworthy advances in the last decades, but the piezoresistive effect is still the main physical phenomenon behind many mechanical sensors, both commercial and in research models. On this 70th anniversary, this tutorial aims to explain the operating principle, subtypes, input–output characteristics, and limitations of the three main types of mechanical sensor: strain gauges, capacitive sensors, and piezoelectric sensors. These three sensor technologies are also compared with each other, highlighting the main advantages and disadvantages of each one.

Abstract Long non-coding RNAs (lncRNAs) are involved in numerous biological processes and are pivotal mediators of the immune response, yet little is known about their properties at the single-cell level. Here, we generate a multi-tissue bulk RNAseq dataset from Ebola virus (EBOV) infected and not-infected rhesus macaques and identified 3979 novel lncRNAs. To profile lncRNA expression dynamics in immune circulating single-cells during EBOV infection, we design a metric, Upsilon, to estimate cell-type specificity. Our analysis reveals that lncRNAs are expressed in fewer cells than protein-coding genes, but they are not expressed at lower levels nor are they more cell-type specific when expressed in the same number of cells. In addition, we observe that lncRNAs exhibit similar changes in expression patterns to those of protein-coding genes during EBOV infection, and are often co-expressed with known immune regulators. A few lncRNAs change expression specifically upon EBOV entry in the cell. This study sheds light on the differential features of lncRNAs and protein-coding genes and paves the way for future single-cell lncRNA studies.

High-throughput technologies have generated vast amounts of omic data. It is a consensus that the integration of diverse omics sources improves predictive models and biomarker discovery. However, managing multiple omics data poses challenges such as data heterogeneity, noise, high-dimensionality and missing data, especially in block-wise patterns. This study addresses the challenges of high dimensionality and block-wise missing data through a regularization and constrained-based approach. The methodology is implemented in the R package bwm for binary and continuous response variables, and applied to breast cancer and exposome multi-omics datasets, achieving strong performance even in scenarios with missing data present in all omics. In binary classification task, our proposed model achieves accuracy in the range of 86% to 92%, and F1 in the range of 68% to 79%. And, in regression task the correlation between true and predicted responses is in the range of 72% to 76%. However, there is a slight decline in performance metrics as the percentage of missing data increases. In scenarios where block-wise missing data affects multiple omics, the model performance actually surpasses that of scenarios where missing data is present in only one omics. One possible explanation for this might be that the other scenarios introduce a greater diversity of observation profiles, leading to a more robust model. Depending on the specific omics being studied, there is greater consistency in feature selection when comparing block-wise missing data scenarios.

This article proposes and experimentally characterizes two implementations of a novel front-end circuit for three-wire connected resistive sensors with a wire-resistance compensation. The first implementation relies on two twin diodes, whereas the second on a switch; in both cases, those devices are non-remote (i.e., they are placed at the circuit end). The two circuit proposals have a square-wave input excitation so that a constant current with the two polarities is alternatively generated. Then, depending on that polarity, the current goes through either the sensor and the wire parasitic resistances or just the parasitic resistances. This generates a square-wave bipolar output signal whose average value, which is obtained by a low-pass filter, is proportional to the sensor resistance and only depends on the mismatch between two of the three wire resistances involved. Experimental tests applied to resistances related to a Pt100 thermal sensor show a remarkable linearity. For example, the switch-based front-end circuit offers a non-linearity error lower than 0.01% full-scale span, and this is practically insensitive to both the presence and the mismatch between the wire resistances.

In this article, a novel front-end circuit for remote two-wire resistive sensors that is insensitive to the wire resistances is proposed and experimentally characterized. The circuit relies on an OpAmp-based current source with a square-wave excitation, two twin diodes in the feedback path, and a low-pass filter at the output. Using such a circuit topology, the output is a DC voltage proportional to the sensor resistance and independent of the wire resistances. A prototype was built measuring resistances that correspond to a Pt100 thermal sensor and with different values of wire resistance. The experimental results show that the output voltage is almost insensitive to both the wire resistances and their mismatch, with a relative error (with respect to the case with null parasitic resistance) in the range of 0.01–0.03% Full-Scale Span (FSS). In addition, the proposed circuit shows a remarkable linearity (around 0.01% FSS), and again this is independent of the presence and also of the mismatch of the wire resistances.

Summary: Understanding the consequences of individual transcriptome variation is fundamental to deciphering human biology and disease. We implement a statistical framework to quantify the contributions of 21 individual traits as drivers of gene expression and alternative splicing variation across 46 human tissues and 781 individuals from the Genotype-Tissue Expression project. We demonstrate that ancestry, sex, age, and BMI make additive and tissue-specific contributions to expression variability, whereas interactions are rare. Variation in splicing is dominated by ancestry and is under genetic control in most tissues, with ribosomal proteins showing a strong enrichment of tissue-shared splicing events. Our analyses reveal a systemic contribution of types 1 and 2 diabetes to tissue transcriptome variation with the strongest signal in the nerve, where histopathology image analysis identifies novel genes related to diabetic neuropathy. Our multi-tissue and multi-trait approach provides an extensive characterization of the main drivers of human transcriptome variation in health and disease.

The profiling of genetic variants affecting splicing can give insight into disease mechanisms. Here, the authors develop a pipeline for discovery of variants affecting splicing (sQTLs) and with application to the GTEx dataset they generate a catalog of human sQTLs.

In the context of a society saturated in images, convolutional neural networks (CNNs), pre-trained using from the visual information contained in many thousands of images, constitute a tool that is of great use in helping us to organize the visual heritage, thus offering a route of entry that would otherwise be impossible. One of the responsibilities of the contemporary artist is to adopt a position that will help to provide sense, to project meaning onto the accumulation of images that we are faced with. The artificial neuronal network ResNet-50 has been used in order to extract the visual characteristics of large sets of images from the internet. Textual searches have been carried out on social issues such as climate change, the COVID-19 pandemic, demonstrations around the world, and manifestations of popular culture, and the image descriptors obtained have been the input for the algorithm t-SNE. In this way, we produce large visual maps composed of thousands of images and arranged following the criteria of formal similitude, displaying the visual patterns of the archetypes of specific semantic categories. The method of filing and recovering our collective memory must have a correlation with the technological and scientific advances of our time, in order for us to progressively discover new horizons of knowledge.

Abstract Background The necessity to analyze medium-throughput data in epidemiological studies with small sample size, particularly when studying biomedical data may hinder the use of classical statistical methods. Support vector machines (SVM) models can be successfully applied in this setting because they are a powerful tool to analyze data with large number of predictors and limited sample size, especially when handling binary outcomes. However, biomedical research often involves analysis of time-to-event outcomes and has to account for censoring. Methods to handle censored data in the SVM framework can be divided into two classes: those based on support vector regression (SVR) and those based on binary classification. Methods based on SVR seem to be suboptimal to handle sparse data and yield results comparable to Cox proportional hazards model and kernel Cox regression. The limited work dedicated to assess methods based on of SVM for binary classification has been based on SVM learning using privileged information and SVM with uncertain classes. Results This paper proposes alternative methods and extensions within the binary classification framework, specifically, a conditional survival approach for weighting censored observations and a semi-supervised SVM with local invariances. Using simulation studies and some real datasets, we evaluate those two methods and compare them with a weighted SVM model, SVM extensions found in the literature, kernel Cox regression and Cox model. Conclusions Our proposed methods perform generally better under a wide variety of realistic scenarios about the structure of biomedical data. Specifically, the local invariances method using the conditional survival approach is the most robust method under different scenarios and is a good approach to consider as an alternative to other time-to-event methods. When analysing real data is a method to be considered and recommended since outperforms other methods in proportional and non-proportional scenarios and sparse data, which is something usual in biomedical data and biomarkers analysis.

Abstract Background Support vector machines (SVM) are a powerful tool to analyze data with a number of predictors approximately equal or larger than the number of observations. However, originally, application of SVM to analyze biomedical data was limited because SVM was not designed to evaluate importance of predictor variables. Creating predictor models based on only the most relevant variables is essential in biomedical research. Currently, substantial work has been done to allow assessment of variable importance in SVM models but this work has focused on SVM implemented with linear kernels. The power of SVM as a prediction model is associated with the flexibility generated by use of non-linear kernels. Moreover, SVM has been extended to model survival outcomes. This paper extends the Recursive Feature Elimination (RFE) algorithm by proposing three approaches to rank variables based on non-linear SVM and SVM for survival analysis. Results The proposed algorithms allows visualization of each one the RFE iterations, and hence, identification of the most relevant predictors of the response variable. Using simulation studies based on time-to-event outcomes and three real datasets, we evaluate the three methods, based on pseudo-samples and kernel principal component analysis, and compare them with the original SVM-RFE algorithm for non-linear kernels. The three algorithms we proposed performed generally better than the gold standard RFE for non-linear kernels, when comparing the truly most relevant variables with the variable ranks produced by each algorithm in simulation studies. Generally, the RFE-pseudo-samples outperformed the other three methods, even when variables were assumed to be correlated in all tested scenarios. Conclusions The proposed approaches can be implemented with accuracy to select variables and assess direction and strength of associations in analysis of biomedical data using SVM for categorical or time-to-event responses. Conducting variable selection and interpreting direction and strength of associations between predictors and outcomes with the proposed approaches, particularly with the RFE-pseudo-samples approach can be implemented with accuracy when analyzing biomedical data. These approaches, perform better than the classical RFE of Guyon for realistic scenarios about the structure of biomedical data.

En el contexto de una sociedad saturada de imágenes, las redes neuronales convolucionales (convolutional neural networks - CNN), preentrenadas a partir de la información visual contenida en miles y miles de imágenes, constituyen una herramienta de gran utilidad para ayudarnos a ordenar el patrimonio visual, ofreciéndonos así un punto de acceso que de otra manera sería imposible. Una de las responsabilidades del artista contemporáneo es adoptar posiciones que ayuden a dar significado, a proyectar sentido sobre la acumulación visual a la que nos enfrentamos. En este artículo pasamos a describir dos exposiciones de la artista Pilar Rosado: Revolutionary Arkive y Mnemosyne 2.0. En ellas se ha utilizado la red neuronal artificial ResNet-50 para extraer las características visuales de grandes conjuntos de imágenes y los descriptores de imagen obtenidos se han usado como entrada para el algoritmo t-SNE. Así, se han elaborado grandes mapas visuales formados por miles de imágenes ordenadas siguiendo criterios de similitud formal en los que se ponen de manifiesto los patrones visuales de los arquetipos de una determinada categoría semántica. La manera de archivar y recuperar nuestra memoria colectiva debe tener una correlación con los avances tecnológicos y científicos de nuestra época para que se nos vayan descubriendo progresivamente nuevos horizontes de conocimiento. En su práctica artística, Rosado explora, en el ámbito de la cocreación humano-máquina, cuestiones políticas que se pueden abordar desde la imagen y que implican a las tecnologías de aprendizaje automático, como la gestión de la información en los archivos visuales del futuro o la revisión de la memoria visual colectiva.

RNA levels in post-mortem tissue can differ greatly from those before death. Studying the effect of post-mortem interval on the transcriptome in 36 human tissues, Ferreira et al. find that the response to death is largely tissue-specific and develop a model to predict time since death based on RNA data.

Generative adversarial networks (GANs) provide powerful architectures for deep generative learning. GANs have enabled us to achieve an unprecedented degree of realism in the creation of synthetic images of human faces, landscapes, and buildings, among others. Not only image generation, but also image manipulation is possible with GANs. Generative deep learning models are inherently limited in their creative abilities because of a focus on learning for perfection. We investigated the potential of GAN’s latent spaces to encode human expressions, highlighting creative interest for suboptimal solutions rather than perfect reproductions, in pursuit of the artistic concept. We have trained Deep Convolutional GAN (DCGAN) and StyleGAN using a collection of portraits of detained persons, portraits of dead people who died of violent causes, and people whose portraits were taken during an orgasm. We present results which diverge from standard usage of GANs with the specific intention of producing portraits that may assist us in the representation and recognition of otherness in contemporary identity construction.

An amendment to this paper has been published and can be accessed via the original article.

A new sensor topology meant to extract figures of merit of radio-frequency analog integrated circuits (RF-ICs) was experimentally validated. Implemented in a standard 0.35 μm complementary metal-oxide-semiconductor (CMOS) technology, it comprised two blocks: a single metal-oxide-semiconductor (MOS) transistor acting as temperature transducer, which was placed near the circuit to monitor, and an active band-pass filter amplifier. For validation purposes, the temperature sensor was integrated with a tuned radio-frequency power amplifier (420 MHz) and MOS transistors acting as controllable dissipating devices. First, using the MOS dissipating devices, the performance and limitations of the different blocks that constitute the temperature sensor were characterized. Second, by using the heterodyne technique (applying two nearby tones) to the power amplifier (PA) and connecting the sensor output voltage to a low-cost AC voltmeter, the PA’s output power and its central frequency were monitored. As a result, this topology resulted in a low-cost approach, with high linearity and sensitivity, for RF-IC testing and variability monitoring.

This paper proposes a compact Thévenin model for a rectenna. This model is then applied to design a high-efficiency radio frequency harvester with a maximum power point tracker (MPPT). The rectenna under study consists of an L-matching network and a half-wave rectifier. The derived model is simpler and more compact than those suggested so far in the literature and includes explicit expressions of the Thévenin voltage (Voc) and resistance and of the power efficiency related with the parameters of the rectenna. The rectenna was implemented and characterized from −30 to −10 dBm at 808 MHz. Experimental results agree with the proposed model, showing a linear current–voltage relationship as well as a maximum efficiency at Voc/2, in particular 60% at −10 dBm, which is a remarkable value. An MPPT was also used at the rectenna output in order to automatically work at the maximum efficiency point, with an overall efficiency near 50% at −10 dBm. Further tests were performed using a nearby transmitting antenna for powering a sensor node with a power consumption of 4.2 µW.

This paper proposes a microcontroller-based measurement system to detect and confirm the presence of a subject in a chair. The system relies on a single Force Sensing Resistor (FSR), which is arranged in the seat of the chair, that undergoes a sudden resistance change when a subject/object is seated/placed over the chair. In order to distinguish between a subject and an inanimate object, the system also monitors small-signal variations of the FSR resistance caused by respiration. These resistance variations are then directly measured by a low-cost general-purpose microcontroller unit (MCU) without using either an analogue processing stage or an analogue-to-digital converter. Two versions of such a MCU-based circuit are presented: one to prove the concept of the measurement, and another with a smart wake-up (generated by the sudden resistance change) intended to reduce the energy consumption. The feasibility of the proposed measurement system is experimentally demonstrated with subjects of different weight sitting at different postures, and also with objects of different weight. The MCU-based circuit with a smart wake-up shows a standby current consumption of 800 nA, and requires an energy of 125 µJ to carry out the measurement after the wake-up.

This paper presents a microcontroller-based measurement system to detect and confirm the presence of a subject in a chair. The system relies on a single Force Sensing Resistor (FSR), which may be arranged in the seat or backrest of the chair, that undergoes a sudden resistance change when a subject/object is seated/placed over the chair. In order to distinguish between a subject and an inanimate object, the system also monitors small-signal variations of the FSR resistance caused by respiration. These resistance variations are then directly measured by a low-cost general-purpose microcontroller without using either an analogue processing stage or an analogue-to-digital converter, thus resulting in a low-cost, low-power, compact design solution.

Autonomous sensors that harvest energy from the environment usually employ a dc/dc converter to regulate the operating voltage of the energy transducer around its maximum power point (MPP). In this context, this work evaluates the efficiency of a buck converter when regulating the operating point of two low-power photovoltaic (PV) modules subjected to different irradiance levels. The buck converter operates in burst mode (BM) and is able to transfer the energy from the PV module to a storage unit through an optimal value of the inductor current. Experimental results show that an irradiance increase can cause either an increase or a decrease of the converter efficiency. This is because the higher the irradiance, the higher both the MPP voltage and current of the PV module, which involve opposite effects in terms of the converter efficiency.

This paper presents the implementation of a high-efficiency radiofrequency (RF) harvester, which consists of a rectenna and a maximum power point tracker (MPPT). The rectenna was characterized from −30 dBm to −10 dBm at 808 MHz, achieving an efficiency higher than 60% at −10 dBm. Experimental results also show that the rectenna can be well modelled as a Thévenin equivalent circuit, which allows the use of a simple ensuing MPPT. The complete RF harvester was tested, achieving an overall efficiency near 50% at −10 dBm. Further tests were performed powering a sensor node from a nearby antenna.

This paper reviews the direct connection of sensors to microcontrollers without using any analogue circuit (such as an amplifier or analogue-to-digital converter) in the signal path, thus resulting in a low-cost, lower-power sensor electronic interface. It first discusses the operating principle and explains how resistive and capacitive sensors with different topologies (i.e., single, differential and bridge type) can be directly connected to a microcontroller to build the so-called direct interface circuit. It then shows some applications of the proposed circuits using commercial devices and discusses their performance. Finally, it deals with the power consumption and proposes some design guidelines to reduce the current consumption of such circuits in active mode.

En este estudio se evalúa el rendimiento de los métodos de Bag-of-Visualterms (BOV) para la clasificación automática de imágenes digitales de la base de datos del artista Miquel Planas. Estas imágenes intervienen en la ideación y diseño de su producción escultórica. Constituye un interesante desafío dada la dificultad de la categorización de escenas cuando éstas difieren más por los contenidos semánticos que por los objetos que contienen. Hemos empleado un método de reconocimiento basado en Kernels introducido por Lazebnik, Schmid y Ponce en 2006. Los resultados son prometedores, en promedio, la puntuación del rendimiento es aproximadamente del 70%. Los experimentos sugieren que la categorización automática de imágenes basada en métodos de visión artificial puede proporcionar principios objetivos en la catalogación de imágenes y que los resultados obtenidos pueden ser aplicados en diferentes campos de la creación artística.

This paper evaluates the performance of direct interface circuits (DIC), where the sensor is directly connected to a microcontroller, when a resistive sensor subjected to dynamic changes is measured. The theoretical analysis provides guidelines for the selection of the components taking into account both the desired resolution and the bandwidth of the input signal. Such an analysis reveals that there is a trade-off between the sampling frequency and the resolution of the measurement, and this depends on the selected value of the capacitor that forms the RC circuit together with the sensor resistance. This performance is then experimentally proved with a DIC measuring a magnetoresistive sensor exposed to a magnetic field of different frequencies, amplitudes, and waveforms. A sinusoidal magnetic field up to 1 kHz can be monitored with a resolution of eight bits and a sampling frequency of around 10 kSa/s. If a higher resolution is desired, the sampling frequency has to be lower, thus limiting the bandwidth of the dynamic signal under measurement. The DIC is also applied to measure an electrocardiogram-type signal and its QRS complex is well identified, which enables the estimation, for instance, of the heart rate.

En el presente artículo se ha desarrollado un sistema capaz de categorizar de forma automática la base de datos de imágenes que sirven de punto de partida para la ideación y diseño en la producción artística del escultor M. Planas. La metodología utilizada está basada en características locales. Para la construcción de un vocabulario visual se sigue un procedimiento análogo al que se utiliza en el análisis automático de textos (modelo "Bag-of-Words"-BOW) y en el ámbito de las imágenes nos referiremos a representaciones "Bag-of-Visual Terms" (BOV). En este enfoque se analizan las imágenes como un conjunto de regiones, describiendo solamente su apariencia e ignorando su estructura espacial. Para superar los inconvenientes de polisemia y sinonimia que lleva asociados esta metodología, se utiliza el análisis probabilístico de aspectos latentes (PLSA) que detecta aspectos subyacentes en las imágenes, patrones formales. Los resultados obtenidos son prometedores y, además de la utilidad intrínseca de la categorización automática de imágenes, este método puede proporcionar al artista un punto de vista auxiliar muy interesante.