Search

Esta obra aúna en un mismo volumen el necesario estudio histórico preliminar sobre la Universidad de Irache y, simultáneamente, una base de datos fundamental para los futuros análisis de esta institución. En otras palabras, una obra que trata de completar y profundizar en torno al conocimiento y análisis que tenemos de las universidades menores, pero también de convertirse en fuente esencial y fundamental para los futuros estudios sobre una de ellas. Un punto de partida para la contextualización, pero también para la profundización en la tan necesaria «historia total» de las instituciones universitarias que señala el autor y que, tanto en Irache como en el resto de universidades menores, es incomprensible sin el análisis de uno de sus ejes fundamentales: el estudiantado, sus redes, dinámicas y prácticas sociales.

How does the brain internally represent a sequence of sensory information that jointly drives a decision-making behavior? Studies of perceptual decision-making have often assumed that sensory cortices provide noisy but otherwise veridical sensory inputs to downstream processes that accumulate and drive decisions. However, sensory processing in even the earliest sensory cortices can be systematically modified by various external and internal contexts. We recorded from neuronal populations across posterior cortex as mice performed a navigational decision-making task based on accumulating randomly timed pulses of visual evidence. Even in V1, only a small fraction of active neurons had sensory-like responses time-locked to each pulse. Here, we focus on how these ‘cue-locked’ neurons exhibited a variety of amplitude modulations from sensory to cognitive, notably by choice and accumulated evidence. These task-related modulations affected a large fraction of cue-locked neurons across posterior cortex, suggesting that future models of behavior should account for such influences.

Local antibiotic delivery using different carriers plays an important role in both infection prophylaxis and treatment. Besides dead space management, these carriers have the advantage of providing a high concentration of local antibiotics with a lower risk of systemic toxicity. Few studies have reported on systemic toxicity associated with antibiotic-impregnated carriers. The present study investigates the systemic tobramycin concentration at 24, 48 and 72 h postoperatively after using tobramycin-loaded polymethyl methacrylate (PMMA) and calcium sulfate (CS) as local antibiotic carriers. Additionally, this work assesses the renal function postoperatively for indications of acute kidney injury (AKI). Fifty-two patients were treated in 58 procedures with tobramycin and vancomycin-loaded PMMA, CS, or both. All systemic tobramycin levels were

Interactive movements of bees facilitate the division and organization of collective tasks, notably when they need to face internal or external environmental challenges. Here, we present a Bayesian and computational approach to track the movement of several honey bee, Apis mellifera, workers at colony level. We applied algorithms that combined tracking and Kernel Density Estimation (KDE), allowing measurements of entropy and Probability Distribution Function (PDF) of the motion of tracked organisms. We placed approximately 200 recently emerged and labeled bees inside an experimental colony, which consists of a mated queen, approximately 1000 bees, and a naturally occurring beehive background. Before release, labeled bees were fed for one hour with uncontaminated diets or diets containing a commercial mixture of synthetic fungicides (thiophanate-methyl and chlorothalonil). The colonies were filmed (12 min) at the 1st hour, 5th and 10th days after the bees’ release. Our results revealed that the algorithm tracked the labeled bees with great accuracy. Pesticide-contaminated colonies showed anticipated collective activities in peripheral hive areas, far from the brood area, and exhibited reduced swarm entropy and energy values when compared to uncontaminated colonies. Collectively, our approach opens novel possibilities to quantify and predict potential alterations mediated by pollutants (e.g., pesticides) at the bee colony-level.

The use of Neuropixels probes for chronic neural recordings is in its infancy and initial studies leave questions about long-term stability and probe reusability unaddressed. Here, we demonstrate a new approach for chronic Neuropixels recordings over a period of months in freely moving rats. Our approach allows multiple probes per rat and multiple cycles of probe reuse. We found that hundreds of units could be recorded for multiple months, but that yields depended systematically on anatomical position. Explanted probes displayed a small increase in noise compared to unimplanted probes, but this was insufficient to impair future single-unit recordings. We conclude that cost-effective, multi-region, and multi-probe Neuropixels recordings can be carried out with high yields over multiple months in rats or other similarly sized animals. Our methods and observations may facilitate the standardization of chronic recording from Neuropixels probes in freely moving animals.

GPER-1 is a novel membrane sited G protein-coupled estrogen receptor. Clinical studies have shown that patients suffering an estrogen receptor α (ERα)/GPER-1 positive, breast cancer have a lower survival rate than those who have developed ERα-positive/GPER-1 negative tumors. Moreover, absence of GPER-1 improves the prognosis of patients treated with tamoxifen, the most used selective estrogen receptor modulator to treat ERα-positive breast cancer. MCF-7 breast cancer cells were continuously treated with 1,000 nM tamoxifen for 7 days to investigate its effect on GPER-1 protein expression, cell proliferation and intracellular [Ca2+]i mobilization, a key signaling pathway. Breast cancer cells continuously treated with tamoxifen, exhibited a robust [Ca2+]i mobilization after stimulation with 1,000 nM tamoxifen, a response that was blunted by preincubation of cells with G15, a commercial GPER-1 antagonist. Continuously treated cells also displayed a high [Ca2+]i mobilization in response to a commercial GPER-1 agonist (G1) and to estrogen, in a magnitude that doubled the response observed in untreated cells and was almost completely abolished by G15. Proliferation of cells continuously treated with tamoxifen and stimulated with 2,000 nM tamoxifen, was also higher than that observed in untreated cells in a degree that was approximately 90% attributable to GPER-1. Finally, prolonged tamoxifen treatment did not increase ERα expression, but did overexpress the kinin B1 receptor, another GPCR, which we have previously shown is highly expressed in breast tumors and increases proliferation of breast cancer cells. Although we cannot fully extrapolate the results obtained in vitro to the patients, our results shed some light on the occurrence of drug resistance in breast cancer patients who are ERα/GPER-1 positive, have been treated with tamoxifen and display low survival rate. Overexpression of kinin B1 receptor may explain the increased proliferative response observed in breast tumors under continuous treatment with tamoxifen.

Currently, the load quantification during training and competition in all sports is important to injury prevention, design specific training sessions, and player performance enhancement. The present study aimed to describe the external load profile of amateur-level handball players and to compare the playing position and match outcome-related differences in an official 2nd Regional Division male official match. 19 handball players were monitored by WIMU PROTM electronic performance and tracking systems (EPTS) with ultrawide-band (UWB) indoor location technology. Statistical analysis was composed of a t-student independent sample test and one-way ANOVA with Bonferroni posthoc. In amateur handball, most demands are composed of aerobic intensity displacements (

Kallikrein-related peptidases (KLKs) are a family of serine proteases that when dysregulated may contribute to neuroinflammation and neurodegeneration. In the present review article, we describe what is known about their physiological and pathological roles with an emphasis on KLK6 and KLK8, two KLKs that are highly expressed in the adult central nervous system (CNS). Altered expression and activity of KLK6 have been linked to brain physiology and the development of multiple sclerosis. On the other hand, altered levels of KLK6 in the brain and serum of people affected by Alzheimer’s disease and Parkinson’s disease have been documented, pointing out to its function in amyloid metabolism and development of synucleinopathies. People who have structural genetic variants of KLK8 can suffer mental illnesses such as intellectual and learning disabilities, seizures, and autism. Increased expression of KLK8 has also been implicated in schizophrenia, bipolar disorder, and depression. Also, we discuss the possible link that exists between KLKs activity and certain viral infections that can affect the nervous system. Although little is known about the exact mechanisms that mediate KLKs function and their participation in neuroinflammatory and neurodegenerative disorders will open a new field to develop novel therapies to modulate their levels and/or activity and their harmful effects on the CNS.

registro fotográfico Aislamiento y entrevista sonora.

Neural responses of oddball tasks can be used as a physiological biomarker to evaluate the brain potential of information processing under the assumption that the differential contribution of deviant stimuli can be assessed accurately. Nevertheless, the non-stationarity of neural activity causes the brain networks to fluctuate hugely in time, deteriorating the estimation of pairwise synergies. To deal with the time variability of neural responses, we have developed a piecewise multi-subject analysis that is applied over a set of time intervals within the stationary assumption holds. To segment the whole stimulus-locked epoch into multiple temporal windows, we experimented with two approaches for piecewise segmentation of EEG recordings: a fixed time-window, at which the estimates of FC measures fulfill a given confidence level, and variable time-window, which is segmented at the change points of the time-varying classifier performance. Employing the weighted Phase Lock Index as a functional connectivity metric, we have presented the validation in a real-world EEG data, proving the effectiveness of variable time segmentation for connectivity extraction when combined with a supervised thresholding approach. Consequently, we performed a piecewise group-level analysis of electroencephalographic data that deals with non-stationary functional connectivity measures, evaluating more carefully the contribution of a link node-set in discriminating between the labeled oddball responses.

Summary: Silicon-based multi-junction (tandem) technology is one potential route to the next breakthrough for terrestrial photovoltaic conversion. Significant progress has been made in tandem solar cells. To move forward, development of tandem module technology is essential. Here, we theoretically compare five possible tandem module architectures with multiple material combinations by modeling their outdoor performance ratios around the globe. This framework aids in evaluating future module designs and technology pathways by relating lab-based efficiency to field performance and even project financing. We find that tandem performance ratios depend notably on climate conditions. In general, three-terminal and mechanically voltage-matched modules show exceptionally good outdoor performance. Furthermore, we investigate the implications of technical performance on manufacturing cost globally and find that tandems are promising in high-value markets in arid climates, where a three to five times increase in the current silicon module manufacturing cost is allowed under an optimistic scenario.

Selection of the time-window mainly affects the effectiveness of piecewise feature extraction procedures. We present an enhanced bag-of-patterns representation that allows capturing the higher-level structures of brain dynamics within a wide window range. So, we introduce augmented instance representations with extended window lengths for the short-time Common Spatial Pattern algorithm. Based on multiple-instance learning, the relevant bag-of-patterns are selected by a sparse regression to feed a bag classifier. The proposed higher-level structure representation promotes two contributions: (i) accuracy improvement of bi-conditional tasks, (ii) A better understanding of dynamic brain behavior through the learned sparse regression fits. Using a support vector machine classifier, the achieved performance on a public motor imagery dataset (left-hand and right-hand tasks) shows that the proposed framework performs very competitive results, providing robustness to the time variation of electroencephalography recordings and favoring the class separability.

In an inventory management model for perishables, depletion due to interacting with the demand is of importance, but also, damage to products is a relevant variable. This article considers that demand and sales phenomena do not always go hand-in-hand. The demand process relates to the willingness to acquire products in good condition, giving the customer the power to evaluate the quality of the product before an effective purchase takes place. We also considered the cost of disposing of unsold units, besides the conventional costs for storage and procurement. We then proposed a mathematical model to derive the Economic Order Quantity (EOQ) under specific conditions, in order to minimize the expected management cost of perishables, assuming constant demand and linearly decreasing purchase probability during the product life cycle. We proposed several random instances and validate the mathematical model using simulation. We then found the optimal parameters for the inventory policy using a third-order numerical approximation. Last, we developed a sensitivity analysis over the product life cycle to prove that the proposed model approximates to a traditional EOQ model for perishables when life cycle is sufficiently large.

The purpose of the present study was to: (a) assess centripetal force (CentF) and changes of direction (COD) in elite soccer players according to playing position (central defender, CD; lateral defender, LD; central midfielder, CM; lateral midfielder, LM; forward, FW), laterality (right-footed vs. left-footed) and field zone (central vs. lateral), and (b) analyze the relationship between anthropometric characteristics (age, weight, height, body mass and fat mass) and non-linear locomotion workload. Thirty professional soccer players (age: 26.57±5.56 years) were tracked during the 2017-2018 season during friendly, national and international matches (38 total games) using inertial measurement devices. CentF and COD were the variables extracted for analysis. A one-way ANOVA was used for playing position comparison, a t-test for laterality and field zone, and Pearson's correlation coefficient to analyze relationships between anthropometric characteristics and dependent variables. There were differences by playing position in COD (556.33-to-412.18), R20COD (484.36-to-354.81) and R60COD (48.38-to-38.61) (p < .01; ωp2 = 0.03-to-0.05; CD>CM>LD>LM = FW); in CODHIA (49.75-to-37.11), R20CODHIA (16.04-to-9.11) and R60CODHIA (10.64-to-9.11) (p < .01; ωp2 = 0.03-to-0.07; CM>FW>LM>CD = LD); in CODSPRINT (14.56-to-8.40) and R20CODSPRINT (3.29-to-1.40) (p < .01; ωp2 = 0.03-to-0.04; FW = LM = CM>CD = LD); and in CentFMAX both in clockwise (992.04-to-902.09N) and counterclockwise (999.24-to-872.61N) directions (p < .02; ωp2 = 0.02-to-0.07; FW = CD>CM = LM = LD). The highest values of counterclockwise CentF were performed by left-footed players in the central zone (p < .001; d = 0.71-to-1.44) and clockwise CentF by right-footed players (p < .001; d = 0.04-to-0.55) in the lateral field zone. Moderate correlations were found between age, body mass and high intensity/sprints COD and repeated COD ability (p < .05; r = 0.235-to-0.383). Therefore, team staff should consider anthropometric characteristics, playing position, laterality and field zone to individualize training workload related to non-linear locomotion in soccer.

Accelerometry is a recent method used to quantify workload in team sports. A rapidly increasing number of studies supports the practical implementation of accelerometry monitoring to regulate and optimize training schemes. Therefore, the purposes of this study were: (1) to reflect the current state of knowledge about accelerometry as a method of workload monitoring in invasion team sports according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, and (2) to conclude recommendations for application and scientific investigations. The Web of Science, PubMed and Scopus databases were searched for relevant published studies according to the following keywords: "accelerometry" or "accelerometer" or "microtechnology" or "inertial devices", and "load" or "workload", and "sport". Of the 1383 studies initially identified, 118 were selected for a full review. The main results indicate that the most frequent findings were (i) devices' body location: scapulae; (b) devices brand: Catapult Sports; (iii) variables: PlayerLoadTM and its variations; (iv) sports: rugby, Australian football, soccer and basketball; (v) sex: male; (vi) competition level: professional and elite; and (vii) context: separate training or competition. A great number of variables and devices from various companies make the comparability between findings difficult; unification is required. Although the most common location is at scapulae because of its optimal signal reception for time-motion analysis, new methods for multi-location skills and locomotion assessment without losing tracking accuracy should be developed.

The disturbance of wildlife by humans is a worldwide phenomenon that contributes to the loss of biodiversity. It can impact animals' behaviour and physiology, and this can lead to changes in species distribution and richness. Wildlife disturbance has mostly been assessed through direct observation. However, advances in bio-logging provide a new range of sensors that may allow measuring disturbance of animals with high precision and remotely, and reducing the effects of human observers. We used tri-axial accelerometers to identify daytime flights of roosting straw-coloured fruit bats (Eidolon helvum), which were used as a proxy for roost disturbance. This bat species roosts on trees in large numbers (often reaching hundreds of thousands of animals), making them highly vulnerable to disturbance. We captured and tagged 46 straw-coloured fruit bats with dataloggers, containing a global positioning system (GPS) and an accelerometer, in five roosts in Ghana, Burkina Faso and Zambia. Daytime roost flights were identified from accelerometer signatures and modelled against our activity in the roosts during the days of trapping, as a predictor of roost disturbance, and natural stressors (solar irradiance, precipitation and wind speed). We found that daytime roost flight probability increased during days of trapping and with increasing solar irradiance (which may reflect the search for shade to prevent overheating). Our results validate the use of accelerometers to measure roost disturbance of straw-coloured fruit bats and suggest that these devices may be very useful in conservation monitoring programs for large fruit bat species.

Unstructured clinical narratives are continuously being recorded as part of delivery of care in electronic health records, and dedicated tagging staff spend considerable effort manually assigning clinical codes for billing purposes. Despite these efforts, however, label availability and accuracy are both suboptimal. In this retrospective study, we aimed to automate the assignment of top-level International Classification of Diseases version 9 (ICD-9) codes to clinical records from human and veterinary data stores using minimal manual labor and feature curation. Automating top-level annotations could in turn enable rapid cohort identification, especially in a veterinary setting. To this end, we trained long short-term memory (LSTM) recurrent neural networks (RNNs) on 52,722 human and 89,591 veterinary records. We investigated the accuracy of both separate-domain and combined-domain models and probed model portability. We established relevant baseline classification performances by training Decision Trees (DT) and Random Forests (RF). We also investigated whether transforming the data using MetaMap Lite, a clinical natural language processing tool, affected classification performance. We showed that the LSTM-RNNs accurately classify veterinary and human text narratives into top-level categories with an average weighted macro F1 score of 0.74 and 0.68 respectively. In the "neoplasia" category, the model trained on veterinary data had a high validation accuracy in veterinary data and moderate accuracy in human data, with F1 scores of 0.91 and 0.70 respectively. Our LSTM method scored slightly higher than that of the DT and RF models. The use of LSTM-RNN models represents a scalable structure that could prove useful in cohort identification for comparative oncology studies. Digitization of human and veterinary health information will continue to be a reality, particularly in the form of unstructured narratives. Our approach is a step forward for these two domains to learn from and inform one another.

Solar trackers represent an essential tool to increase the energy production of photovoltaic modules compared to fixed systems. Unlike previous technologies where the aim is to keep the solar rays perpendicular to the surface of the module and obtain a constant output power, this paper proposes the design and evaluation of two controllers for a two-axis solar tracker, which maintains the power that is produced by photovoltaic modules at their nominal value. To achieve this, mathematical models of the dynamics of the sun, the solar energy obtained on the Earth’s surface, the two-axis tracking system in its electrical and mechanical parts, and the solar cell are developed and simulated. Two controllers are designed to be evaluated in the solar tracking system, one Proportional-Integral-Derivative and the other by Fuzzy Logic. The evaluation of the simulations shows a better performance of the controller by Fuzzy Logic; this is because it presents a shorter stabilization time, a transient of smaller amplitude, and a lower percentage of error in steady-state. The principle of operation of the solar tracking system is to promote the orientation conditions of the photovoltaic module to generate the maximum available power until reaching the nominal one. This is possible because it has a gyroscope on the surface of the module that determines its position with respect to the hour angle and altitude of the sun; a data acquisition card is developed to implement voltage and current sensors, which measure the output power it produces from the photovoltaic module throughout the day and under any weather conditions. The results of the implementation demonstrate that a Fuzzy Logic control for a two-axis solar tracker maintains the output power of the photovoltaic module at its nominal parameters during peak sun hours.

In previous studies found in the literature speed (SP), acceleration (ACC), deceleration (DEC), and impact (IMP) zones have been created according to arbitrary thresholds without considering the specific workload profile of the players (e.g., sex, competitive level, sport discipline). The use of statistical methods based on raw data could be considered as an alternative to be able to individualize these thresholds. The study purposes were to: (a) individualize SP, ACC, DEC, and IMP zones in two female professional basketball teams; (b) characterize the external workload profile of 5 vs. 5 during training sessions; and (c) compare the external workload according to the competitive level (first vs. second division). Two basketball teams were recorded during a 15-day preseason microcycle using inertial devices with ultra-wideband indoor tracking technology and microsensors. The zones of external workload variables (speed, acceleration, deceleration, impacts) were categorized through k-means clusters. Competitive level differences were analyzed with Mann–Whitney’s U test and with Cohen’s d effect size. Five zones were categorized in speed (2), deceleration (2), and impacts (p < 0.03; d = 0.21–0.56). In conclusion, k-means clustering can be considered as an optimal tool to categorize intensity zones in team sports. The individualization of external workload demands according to the competitive level is fundamental for designing training plans that optimize sports performance and reduce injury risk in sport.

The emergence of very large cohorts in genomic research has facilitated a focus on genotype-imputation strategies to power rare variant association. These strategies have benefited from improvements in imputation methods and association tests, however little attention has been paid to ways in which array design can increase rare variant association power. Therefore, we developed a novel framework to select tag SNPs using the reference panel of 26 populations from Phase 3 of the 1000 Genomes Project. We evaluate tag SNP performance via mean imputed r2 at untyped sites using leave-one-out internal validation and standard imputation methods, rather than pairwise linkage disequilibrium. Moving beyond pairwise metrics allows us to account for haplotype diversity across the genome for improve imputation accuracy and demonstrates population-specific biases from pairwise estimates. We also examine array design strategies that contrast multi-ethnic cohorts vs. single populations, and show a boost in performance for the former can be obtained by prioritizing tag SNPs that contribute information across multiple populations simultaneously. Using our framework, we demonstrate increased imputation accuracy for rare variants (frequency < 1%) by 0.5–3.1% for an array of one million sites and 0.7–7.1% for an array of 500,000 sites, depending on the population. Finally, we show how recent explosive growth in non-African populations means tag SNPs capture on average 30% fewer other variants than in African populations. The unified framework presented here will enable investigators to make informed decisions for the design of new arrays, and help empower the next phase of rare variant association for global health.

In a dynamic environment old evidence could be outdated. Here, the authors investigate the ability of rats to integrate and discount evidence provided by auditory clicks to infer a hidden, dynamic, state of the world and model the consequence of sensory noise to explain the source of errors.

Genetic loci linked to susceptibility for the common skin cancer cutaneous squamous cell carcinoma (cSCC) have been identified by genome wide association studies (GWAS). Here, the authors impute gene expression levels from GWAS data to perform a transcriptome wide association study (TWAS), identifying five novel genetic loci linked to cSCC susceptibility.

The crystal structure of the title compound, [Ni(C25H28N4)(C8H12)]·C4H8O or (MesNHC2Me)Ni(COD), which contains a bidentate N-heterocyclic carbene (NHC) ligand with mesityl aryl groups is reported. The complex at 100 K has monoclinic (P21/c) symmetry and a distorted tetrahedral geometry around the nickel center, with the cyclooctadiene ligand coordinated in a κ2,η2 fashion. The bidentate NHC ligand is not planar, with a C(carbene)—Ni—C(carbene) angle of 91.51 (12)°, resulting in the mesityl groups being on the same side of the cyclooctadiene (COD) ligand. One molecule of tetrahydrofuran (THF) is co-crystallized with the nickel complex and has positional disorder.

El presente artículo, realizado a través de un estudio de caso en una empresa del sector siderúrgico, se apoya en la revisión literaria sobre los indicadores de segundo nivel del modelo SCOR para la gestión de una cadena de suministro. Estos indicadores hacen alusión a la importancia de la planeación de los pagos a los distintos proveedores en una compañía perteneciente al sector de aceros en Barranquilla, Colombia. Para ello, se pretende conocer el impacto que generan en el orden de las finanzas corporativas estos indicadores, siendo el objetivo principal de este artículo demostrar que un buen manejo del ciclo cash to cash en la empresa objeto de estudio coadyuvará a mejorar los índices de liquidez por el impacto que estas variables tienen directamente en el flujo de caja de la compañía. Dentro de los resultados se destaca que las empresas deben garantizar la planeación financiera al momento de cubrir obligaciones que se adquieren con proveedores, permitiendo la optimización de la cadena de suministro y optimizando la labor financiera de la compañía desde la gestión logística. Se propone la optimización en la gestión de cartera para optimizar el flujo de caja de la empresa estudiada.

Abstract Background Organizations that issue guidance on breast cancer recommend the use of immunohistochemistry (IHC) for providing appropriate and precise care. However, little focus has been directed to the identification of maximum allowable turnaround times for IHC, which is necessary given the diversity of hospital settings in the world. Much less effort has been committed to the development of digital tools that allow hospital administrators to monitor service utilization histories of their patients. Methods In this retrospective cohort study, we reviewed electronic and paper medical records of all suspected breast cancer patients treated at one secondary-care hospital of the Mexican Institute of Social Security (IMSS), located in western Mexico. We then followed three years of medical history of those patients with IHC testing. Results In 2014, there were 402 breast cancer patients, of which 30 (7.4% of total) were tested for some IHC biomarker (ER, PR, HER2). The subtyping allowed doctors to adjust (56.7%) or confirm (43.3%) the initial therapeutic regimen. The average turnaround time was 56 days. Opportune IHC testing was found to be beneficial when it was available before or during the first rounds of chemotherapy. Conclusions The use of data mining tools applied to health record data revealed that there is an association between timely immunohistochemistry and improved outcomes in breast cancer patients. Based on this finding, inclusion of turnaround time in clinical guidelines is recommended. As much of the health data in the country becomes digitized, our visualization tools allow a digital dashboard of the hospital service utilization histories.

Abstract Antihistamines and glucocorticoids (GCs) are often used together in the clinic, in several inflammatory‐related situations. Even though there is no clear rationale for this drug association, the clinical practice is based on the assumption that due to their concomitant antiinflammatory effects, there should be an intrinsic benefit in their coadministration. Our group has studied the molecular interaction between the histamine H1 receptor and the glucocorticoid receptor (GR) signaling pathways, showing an enhancing effect on GC‐induced GR transcriptional activity induced by antihistamines. We hypothesize that the existence of this synergistic effect could contribute in reducing the GCs clinical doses, ineffective by itself but effective in combination with an antihistamine. This could result in a therapeutic advantage as the GC‐desired effects may be reinforced by the addition of an antihistamine and, as a consequence of the dose reduction, GC‐related adverse effects could be reduced or at least mitigated. Here we discuss the potential therapeutic applications of this cotreatment seeking to evaluate its usefulness, especially in inflammatory‐related conditions.

Abstract Glucocorticoids are among the most effective drugs to treat asthma. However, the severe adverse effects associated generate the need for its therapeutic optimization. Conversely, though histamine is undoubtedly related to asthma development, there is a lack of efficacy of antihistamines in controlling its symptoms, which prevents their clinical application. We have reported that antihistamines potentiate glucocorticoids’ responses in vitro and recent observations have indicated that the coadministration of an antihistamine and a synthetic glucocorticoid has synergistic effects on a murine model of allergic rhinitis. Here, the aim of this work is to establish if this therapeutic combination could be beneficial in a murine model of asthma. We used an allergen‐induced model of asthma (employing ovalbumin) to evaluate the effects of the synthetic glucocorticoid dexamethasone combined with the antihistamine azelastine. Our results indicate that the cotreatment with azelastine and a suboptimal dose of dexamethasone can improve allergic lung inflammation as shown by a decrease in eosinophils in bronchoalveolar lavage, fewer peribronchial and perivascular infiltrates, and mucin‐producing cells. In addition, serum levels of allergen‐specific IgE and IgG1 were also reduced, as well as the expression of lung inflammatory‐related genes IL‐4, IL‐5, Muc5AC, and Arginase I. The potentiation of dexamethasone effects by azelastine could allow to reduce the effective glucocorticoid dose needed to achieve a therapeutic effect. These findings provide first new insights into the potential benefits of glucocorticoids and antihistamines combination for the treatment of asthma and grants further research to evaluate this approach in other related inflammatory conditions.

Technical noise in experiments is unavoidable, but it introduces inaccuracies into the biological networks we infer from the data. Here, the authors introduce a diffusion-based method for denoising undirected, weighted networks, and show that it improves the performances of downstream analyses.

Abstract Background As most ancient biological samples have low levels of endogenous DNA, it is advantageous to enrich for specific genomic regions prior to sequencing. One approach—in-solution capture-enrichment—retrieves sequences of interest and reduces the fraction of microbial DNA. In this work, we implement a capture-enrichment approach targeting informative regions of the Y chromosome in six human archaeological remains excavated in the Caribbean and dated between 200 and 3000 years BP. We compare the recovery rate of Y-chromosome capture (YCC) alone, whole-genome capture followed by YCC (WGC + YCC) versus non-enriched (pre-capture) libraries. Results The six samples show different levels of initial endogenous content, with very low (

Individual choices are not made in isolation but are embedded in a series of past experiences, decisions, and outcomes. The effects of past experiences on choices, often called sequential biases, are ubiquitous in perceptual and value-based decision-making, but their neural substrates are unclear. We trained rats to choose between cued guaranteed and probabilistic rewards in a task in which outcomes on each trial were independent. Behavioral variability often reflected sequential effects, including increased willingness to take risks following risky wins, and spatial ‘win-stay/lose-shift’ biases. Recordings from lateral orbitofrontal cortex (lOFC) revealed encoding of reward history and receipt, and optogenetic inhibition of lOFC eliminated rats’ increased preference for risk following risky wins, but spared other sequential effects. Our data show that different sequential biases are neurally dissociable, and the lOFC’s role in adaptive behavior promotes learning of more abstract biases (here, biases for the risky option), but not spatial ones.

Importance: The real prevalence and clinical burden of severe neonatal jaundice are undefined due to difficulties in measuring total serum bilirubin (TSB) outside secondary and tertiary clinical centers. Objective: To assess the diagnostic performance of the point-of care Bilistick System (BS) in identifying neonatal jaundice patients requiring treatment. Design: Between April 2015 and November 2016, 1911 neonates, were recruited to participate in the study. Blood samples were simultaneously collected for the TSB determination by BS and by hospital laboratory (Lab). Data were collected and sent to the Bilimetrix headquarter in Trieste where statistical analysis was performed. Newborns with neonatal jaundice were treated with phototherapy according to each center's guidelines. Setting: 17 hospitals from Nigeria, Egypt, Indonesia, and Viet Nam. Participants: 1911 newborns were included, of which 1458 (76·3%) fulfilled the inclusion criteria. Results: TSB level measured by BS agreed (p

Protein-truncating variants (PTVs) are predicted to significantly affect a gene’s function and, thus, human traits. Here, DeBoever et al. systematically analyze PTVs in more than 300,000 individuals across 135 phenotypes and identify 27 associations between PTVs and medical conditions.

Abstract Background Our intent was to identify differences between the transcriptome of fibroblast-like synoviocytes (FLS) in oligoarticular juvenile idiopathic arthritis (JIA) before extension when compared to persistent subtype of JIA, when the two are clinically indistinguishable. Additionally, we sought to determine if differences between the transcriptomes of FLS from extended-to-be and polyarticular course JIA could be detected. Our hypothesis was that intrinsic differences in the transcriptome of the FLS from extended-to-be JIA would distinguish them from persistent oligoarticular JIA, before the course is clinically apparent. Methods Global gene expression was defined in cultured FLS from 6 controls, 12 JIA with persistent course, 7 JIA prior to extension (extended-to-be), 4 JIA with extended course and 6 polyarticular onset, using Affymetrix Human GeneChips 133plus2.0. Results Bioconductor Linear Models for Microarray Analysis revealed 22 probesets with differential expression between persistent and extended-to-be FLS at 15% FDR, however only 2 probesets distinguished extended-to-be from extended and none distinguished extended-to-be and polyarticular at 15% FDR. Differences in extended and polyarticular gene expression profiles were not detected. Confirmation of select genes was done on the RNA level by RT-qPCR and on the protein level in synovial fluid by ELISA. Conclusions The transcriptome of FLS from extended-to-be juvenile idiopathic arthritis is distinct from persistent course before a clinical distinction can be made. Additionally, the transcriptome of extended-to-be and polyarticular course, including those who have already extended, are indistinguishable. These gene expression data suggest that FLS already reflect a polyarticular behavior early in disease course, suggesting that extended-to-be may be “latent polyarticular” at onset. These differences can be used to develop early biomarkers of disease course, allowing for better-informed treatment decisions.

Summary: Family B DNA polymerases (PolBs) play a central role during replication of viral and cellular chromosomes. Here, we report the discovery of a third major group of PolBs, which we denote primer-independent PolB (piPolB), that might be a link between the previously known protein-primed and RNA/DNA-primed PolBs. PiPolBs are encoded by highly diverse mobile genetic elements, pipolins, integrated in the genomes of diverse bacteria and also present as circular plasmids in mitochondria. Biochemical characterization showed that piPolB displays efficient DNA polymerization activity that can use undamaged and damaged templates and is endowed with proofreading and strand displacement capacities. Remarkably, the protein is also capable of template-dependent de novo DNA synthesis, i.e., DNA-priming activity, thereby breaking the long-standing dogma that replicative DNA polymerases require a pre-existing primer for DNA synthesis. We suggest that piPolBs are involved in self-replication of pipolins and may also contribute to bacterial DNA damage tolerance. : Redrejo-Rodríguez et al. report and characterize a DNA polymerase group (piPolB) from the B family that can perform primer-independent DNA replication. PiPolBs are encoded by Pipolins, diverse self-replicating genetic elements that are widespread among bacterial phyla and in mitochondria. Keywords: DNA replication, translesion synthesis, primer-independent DNA synthesis, de novo DNA synthesis, family B DNA polymerase, self-replicating mobile element, DNA damage

Abstract A new study highlights the biases and inaccuracies of polygenic risk scores (PRS) when predicting disease risk in individuals from populations other than those used in their derivation. The design bias of workhorse tools used for research, particularly genotyping arrays, contributes to these distortions. To avoid further inequities in health outcomes, the inclusion of diverse populations in research, unbiased genotyping, and methods of bias reduction in PRS are critical.

Basketball is a sport in continuous evolution, being one of these key aspects of the players’ physical fitness that has an impact on the game. Therefore, this study aimed to characterize and identify the physical fitness level and profiles of basketball players according to sex. Total of 26 semi-professional basketball players were assessed (13 male, 13 female) through inertial devices in different previously validated fitness tests. T-test for independent samples and principal component analysis were used to analyze sex-related differences and to identify physical fitness profiles. The results showed differences according to sex in all physical fitness indexes (p < 0.01; d > 1.04) with higher values in males, except in accelerometer load during small-sided games (p = 0.17; d < 0.20). Four principal components were identified in male and female basketball players, being two common ([PC1] aerobic capacity and in-game physical conditioning, [PC4 male, PC3 female] unipodal jump performance) and two different profiles (male: [PC2] bipodal jump capacity and acceleration, [PC3] curvilinear displacement; female: [PC2] bipodal jump capacity and curvilinear displacement, [PC4] deceleration). In conclusion, training design must be different and individualized according to different variables, including physical fitness profiles between them. For practical applications, these results will allow knowing the advantages and weaknesses of each athlete to adapt training tasks and game systems based on the skills and capabilities of the players in basketball.

The COVID-19 pandemic forced the scientific community and the pharmaceutical industry to develop new vaccines, in an attempt to reach herd immunity and stop the SARS-CoV-2 from spreading. However, to ensure vaccination among the general population, COVID-19 vaccine intention must be measured. So far, no studies have focused on rural residents in Latin America, which represent approximately 20% of the population of this geographical region. In this study, we present the validation of a self-developed questionnaire, which was validated in a pilot study with 40 Spanish-speaking Mexican rural residents in the state of Guerrero, Mexico. In this study, we describe the chronological validation of the questionnaire, including the assessment of its internal consistency and temporal reliability, which we measured with the Cronbach’s alpha and Spearman’s rank correlation coefficient, respectively. After the psychometrical analysis, we were able to validate a 20-item questionnaire, which intends to assess vaccine intention among the rural population. Aiming to develop a comprehensive policy and vaccination strategies, we hope this instrument provides valuable insight regarding COVID-19 vaccination willingness across rural communities in Mexico and Latin America. Finally, if we want to reach worldwide herd immunity, it is important to understand rural residents’ position towards COVID-19 vaccination.

For every nine tons of produced biodiesel, there is another ton of glycerol as a byproduct. Therefore, glycerol prices dropped significantly worldwide in recent years; the more significant biodiesel production is, the more glycerol exists as a byproduct. glycerol prices also impact the biodiesel manufacturing business, as it could be sold according to its refinement grade. The primary objective of this work was to evaluate the economic potential of the production of 1,2-propanediol derived from the biodiesel produced in Colombia. A plant to produce 1,2-propanediol via catalytic hydrogenation of glycerol in a trickle-bed reactor was designed. The plant comprised a reaction scheme where non-converted excess hydrogen was recycled, and the heat generated in the reactor was recovered. The reactor effluent was sent to a separation train where 98% m/m purity 1,2-propanediol was attained. Capital and operational costs were estimated from the process simulation. The net present value (NPV) and the modified internal return rate (MIRR) of the plant were used to assess the viability of the process. Their sensitivity to key input variables was evaluated to find the viability limits of the project. The economic potential of the 1,2-propanediol was calculated in USD 1.2/kg; for the base case, the NPV and the MIRR were USD 54.805 million and 22.56%, respectively, showing that, for moderate variations in products and raw material prices, the process is economically viable.

The external workload measured in one anatomical location does not determine the total load supported by the human body. Therefore, the purpose of the present study was to characterize the multi-location external workload through PlayerLoadRT of 13 semi-professional women’s basketball players, as well as to analyze differences among anatomical locations (inter-scapulae line, lumbar region, 2× knee, 2× ankle) and laterality (left vs. right) during five tests that represent the most common movements in basketball—(a) linear locomotion, 30-15 IFT; (b) acceleration and deceleration, 16.25-m RSA (c) curvilinear locomotion, 6.75-m arc (d) jump, Abalakov test (e) small-sided game, 10’ 3 vs. 3 10 × 15-m. Statistical analysis was composed of a repeated-measures t-test and eta partial squared effect size. Regarding laterality, differences were found only in curvilinear locomotion, with a higher workload in the outer leg (p < 0.01; ηp2 = 0.33–0.63). In the vertical profile, differences among anatomical locations were found in all tests (p < 0.01; ηp2 = 0.56–0.98). The nearer location to ground contact showed higher values except between the scapulae and lumbar region during jumps (p = 0.83; ηp2 = 0.00). In conclusion, the multi-location assessment of external workload through a previously validated test battery will make it possible to understand the individual effect of external workload in each anatomical location that depends on the type of locomotion. These results should be considered when designing specific strategies for training and injury prevention.

The present study analyzed the multi-location external workload profile in basketball players using a previously validated test battery and compared the demands among anatomical locations. A basketball team comprising 13 semi-professional male players was evaluated in five tests (abilities/skills/tests): (a) aerobic, linear movement, 30-15 IFT; (b) lactic anaerobic, acceleration and deceleration, 16.25 m RSA (c) alactic anaerobic, curvilinear movement, 6.75 m arc (d) elastic, jump, Abalakov test (e) physical-conditioning, small-sided game, 10’ 3 vs.3 10 × 15 m. PlayerLoadRT was evaluated at six anatomical locations simultaneously (interscapular line, lumbar region, knees and ankles) by six WIMU PROTM inertial devices attached to the player using an ad hoc integral suit. Statistical analysis was composed of an ANOVA of repeated measures and partial eta squared effect sizes. Significant differences among anatomical locations were found in all tests with higher values in the location nearer to ground contact (p < 0.01). However, differences between lower limb locations were only found in curvilinear movements, with a higher workload in the outside leg (p < 0.01). Additionally, high between-subject variability was found in team players, especially at lower limb locations. In conclusion, multi-location evaluation in sports movements will make it possible to establish an individual external workload profile and design specific strategies for training and injury prevention programs.

In this paper, a design driven comparison between two 190 kVA industrial three-phase two-level voltage source converter (2L-VSC) designs based in silicon carbide (SiC) and silicon (Si) for 690 V grids is presented. These two designs were conceived to have the same nominal power, while switching at reasonable switching speeds and requiring the same case to ambient thermal impedance. Under these conditions, the designs were studied to detect the potential gains and limitations that a pragmatic converter design could feature when using these two technologies regarding cost, efficiency, size and weight. To achieve this, experimentally determined semiconductor characteristics were used to perform simulations, the results of which were then used to design the essential parts of the converter. These designed parts were then corroborated with manufacturers, from which physical characteristics of all designed components were obtained. The results show that the SiC based design presents substantial weight savings and an 11% system cost reduction, while preserving its traditional characteristics such as improved overall efficiency when compared to the silicon based design under the given design requirements and constraints.

At present, new data sharing technologies, such as those used in the Internet of Things (IoT) paradigm, are being extensively adopted. For this reason, intelligent security controls have become imperative. According to good practices and security information standards, particularly those regarding security in depth, several defensive layers are required to protect information assets. Within the context of IoT cyber-attacks, it is fundamental to continuously adapt new detection mechanisms for growing IoT threats, specifically for those becoming more sophisticated within mesh networks, such as identity theft and cloning. Therefore, current applications, such as Intrusion Detection Systems (IDS), Intrusion Prevention Systems (IPS), and Security Information and Event Management Systems (SIEM), are becoming inadequate for accurately handling novel security incidents, due to their signature-based detection procedures using the matching and flagging of anomalous patterns. This project focuses on a seldom-investigated identity attack—the Clone ID attack—directed at the Routing Protocol for Low Power and Lossy Networks (RPL), the underlying technology for most IoT devices. Hence, a robust Artificial Intelligence-based protection framework is proposed, in order to tackle major identity impersonation attacks, which classical applications are prone to misidentifying. On this basis, unsupervised pre-training techniques are employed to select key characteristics from RPL network samples. Then, a Dense Neural Network (DNN) is trained to maximize deep feature engineering, with the aim of improving classification results to protect against malicious counterfeiting attempts.

A simple methodology was developed to quantify penicillamine (PA) in pharmaceutical samples, using the selective interaction of the drug with Cu-modified graphene quantum dots (Cu-GQDs). The proposed strategy combines the advantages of carbon dots (over other nanoparticles) with the high affinity of PA for the proposed Cu-GQDs, resulting in a significant and selective quenching effect. Under the optimum conditions for the interaction, a linear response (in the 0.10–7.50 µmol/L PA concentration range) was observed. The highly fluorescent GQDs used were synthesized using uric acid as single precursor and then characterized by high resolution transmission electron microscopy, Raman spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, fluorescence, and absorption spectroscopy. The proposed methodology could also be extended to other compounds, further expanding the applicability of GQDs.

Abstract Background Blue corn is a cereal rich in phenolic compounds used to make blue tortillas. Tortillas are an important part of the Mexican diet. Blue corn and tortilla represent an important source of the natural antioxidants anthocyanins. However, studies on their biological activity on cancer cell lines are limited. The goal of this study was to evaluate the antioxidant and antiproliferative activity of blue corn and tortilla on different cancer cell lines. Methods Total polyphenol content, monomeric anthocyanins, and antioxidant activity by the DPPH and TBARS methods of blue corn and tortilla were determined. The anthocyanin profile of tortilla was obtained by means of HPLC–ESI-MS. The antiproliferative activity of blue corn and tortilla extract on HepG2, H-460, Hela, MCF-7 and PC-3 was evaluated by the MTT assay. Results Blue corn had higher content of total polyphenols and monomeric anthocyanins as well as lower percentage of polymeric color than tortilla; however, both showed similar antioxidant activity by DPPH. In addition, although a higher degradation of anthocyanins was observed on tortilla extract, both extracts inhibited lipid peroxidation (IC50) at a similar concentration. The anthocyanin profile showed 28 compounds which are primarily derived from cyanidin, including acylated anthocyanins and proanthocyanidins. Blue corn and tortilla extracts showed antiproliferative effects against HepG2, H-460, MCF-7 and PC-3 cells at 1000 μg/mL, however Hela cells were more sensitive at this concentration. Conclusion This is the first report to demonstrate anticancer properties in vitro of tortilla derived from blue corn, suggesting that this product has beneficial health effects. In addition, blue corn could be a potential source of nutraceuticals with anticancer activity.