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Abstract Brillouin Optical Time-Domain Analysis (BOTDA) is a widely-used distributed optical fiber sensing technology employing pulse-modulated pump waves for local information retrieval of the Brillouin gain or loss spectra. The spatial resolution of BOTDA systems is intrinsically linked to pulse duration, so high-resolution measurements demand high electronic bandwidths inversely proportional to the resolution. This paper introduces Brillouin Expanded Time-Domain Analysis (BETDA) as a modified BOTDA system, simultaneously achieving high spatial resolution and low detection bandwidth. Utilizing two optical frequency combs (OFCs) with different frequency intervals as pump and probe, local Brillouin gain spectra are recorded by their spectral beating traces in an expanded time domain. A 2-cm-long hotspot located in a 230 m single-mode fiber is successfully measured in the time domain with a detection bandwidth of less than 100 kHz using dual OFCs with tailored spectral phase, line spacing, and bandwidth.

As traditional education systems struggle to keep up with technological advances, incorporating open science into Education 5.0 is critical to addressing student skills gaps. In this study, the MAICC model is introduced, a tool designed to foster complex thinking in higher education students through the evaluation of citizen science projects. It integrates research-based learning and service learning, and helps develop critical and reflective skills by applying them to real-life settings. To assess student engagement and skills development, a mixed methods approach combining qualitative and quantitative analysis was used. Findings indicate that the MAICC model promotes complex thinking, enhances critical thinking through citizen science project evaluation, and features an emphasis on citizen science and educational technology. Discussion highlights citizen science’s important role in education and suggests future research exploring its wider application across disciplines and contexts to enhance 21st century skills.

Determining the type of kidney stones allows urologists to prescribe a treatment to avoid the recurrence of renal lithiasis. An automated in-vivo image-based classification method would be an important step towards an immediate identification of the kidney stone type required as a first phase of the diagnosis. In the literature, it was shown on ex-vivo data (i.e., in very controlled scene and image acquisition conditions) that an automated kidney stone classification is indeed feasible. This pilot study compares the kidney stone recognition performances of six shallow machine learning methods and three deep-learning architectures which were tested with in-vivo images of the four most frequent urinary calculus types acquired with an endoscope during standard ureteroscopies. This contribution details the construction of an in-vivo dataset of endoscopic images with four of the most recurrent classes in clinical practice. It also describes the design, implementation, and results of the classifiers (shallow machine learning and deep learning-based methods) of kidney stones. Even if the best results were obtained by the InceptionV3 architecture (weighted accuracy, precision, recall and F1-Score of $97\pm 03\%, 97\pm 03\%, 98\pm 04\%$ , and $98\pm 03\%$ , respectively), it is also shown that choosing an appropriate colour space and texture features allows a shallow machine learning method to approach closely the performances of the most promising deep-learning methods (the XGBoost classifier led to weighted accuracy, precision, recall and F1-Score values of $96\pm 14\%$ ).

Abstract Immigration has become a key demographic component in developed European nations. At the same time, many countries have seen an increase in immigration from non-European origins and more diversified migrant flows. In most population projections, however, immigrants are considered an almost homogenous population. This study utilizes a population microsimulation projection model (QuantMig-Mic) for 31 European countries that includes place of birth as a source of heterogeneity for components that could impact population size, age structures, and economic dependency ratios. We simulated different scenarios from 2020 to 2060 in which the birth regions of future immigrant flows were changed drastically compared to recent trends. Our results showed that major shifts in the origin of immigration flows toward Europe would impact the spatial distribution of the population in the continent and therefore—at the local level—the population size of some countries. We found that the age structure would be only marginally affected and that shifts in the composition of immigration flows would not significantly alter the increasing age dependency ratio. Moreover, even in the countries most impacted in terms of population size, no scenario led to notable changes in the total labor force participation rate or in the educational structure of the labor force.

In this work, we report on the novel employment of lithium niobate tuning forks as acoustic transducers in photoacoustic spectroscopy for gas sensing. The lithium niobate tuning fork (LiNTF) exhibits a fundamental resonance frequency of 39196.6 Hz and a quality factor Q = 5900 at atmospheric pressure. The possibility to operate the LiNTF as a photoacoustic wave detector was demonstrated targeting a water vapor absorption line falling at 7181.14 cm−1 (1.39 µm). A noise equivalent concentration of 2 ppm was reached with a signal integration time of 20 s. These preliminary results open the path towards integrated photonic devices for gas sensing with LiNTF-based detectors on lithium niobate platforms.

Food allergy (FA) is estimated to impact up to 10% of the population and is a growing health concern. FA results from a failure in the mucosal immune system to establish or maintain immunological tolerance to innocuous dietary antigens, IgE production, and the release of histamine and other mediators upon exposure to a food allergen. Of the different FAs, peanut allergy has the highest incidence of severe allergic responses, including systemic anaphylaxis. Despite the recent FDA approval of peanut oral immunotherapy and other investigational immunotherapies, a loss of protection following cessation of therapy can occur, suggesting that these therapies do not address the underlying immune response driving FA. Our lab has shown that liver-directed gene therapy with an adeno-associated virus (AAV) vector induces transgene product-specific regulatory T cells (Tregs), eradicates pre-existing pathogenic antibodies, and protects against anaphylaxis in several models, including ovalbumin induced FA. In an epicutaneous peanut allergy mouse model, the hepatic AAV co-expression of four peanut antigens Ara h1, Ara h2, Ara h3, and Ara h6 together or the single expression of Ara h3 prevented the development of a peanut allergy. Since FA patients show a reduction in Treg numbers and/or function, we believe our approach may address this unmet need.

Abstract The widespread use of digital technologies and the expansion of social networks has created new communication and meeting spaces where people and social and political actors connect with each other. This opens diverse spaces and possibilities for digital engagement in a more accessible, immediate, continuous, egalitarian, and personalized way. Digital technology facilitates learning, dissemination, and access to information, turning it into a means of communication and fueling the practice of critical thinking. In particular civic critical thinking practices improve the organization and effectiveness of civic networks and spaces for citizen participation, ultimately helping to produce responsible, conscious citizens. This study proposes a series of hypotheses based on the relationships between digital learning, critical thinking and civic participation, and tests them using the technique of structural equation modeling (SEM) with partial least squares (PLS) applied to a sample of 191 primary and secondary school students. The results indicate that digital tools have a positive impact on the development of critical thinking, and this influences citizen participation, transforming people into more engaged citizens of the world with participatory attitudes and values.

Summary: Precision oncology approaches for patients with colorectal cancer (CRC) continue to lag behind other solid cancers. Functional precision oncology—a strategy that is based on perturbing primary tumor cells from cancer patients—could provide a road forward to personalize treatment. We extend this paradigm to measuring proteome activity landscapes by acquiring quantitative phosphoproteomic data from patient-derived organoids (PDOs). We show that kinase inhibitors induce inhibitor- and patient-specific off-target effects and pathway crosstalk. Reconstruction of the kinase networks revealed that the signaling rewiring is modestly affected by mutations. We show non-genetic heterogeneity of the PDOs and upregulation of stemness and differentiation genes by kinase inhibitors. Using imaging mass-cytometry-based profiling of the primary tumors, we characterize the tumor microenvironment (TME) and determine spatial heterocellular crosstalk and tumor-immune cell interactions. Collectively, we provide a framework for inferring tumor cell intrinsic signaling and external signaling from the TME to inform precision (immuno-) oncology in CRC.

Microvibrations are mechanical oscillations caused by components such as the reaction wheels of an attitude control system of a spacecraft. These microvibrations are transferred through the spacecraft structure onto important instruments (e.g., optical instruments), causing those to produce diminished results (e.g., reduced image quality, imprecise geolocation etc.). At the present state, microvibrations in spacecraft cannot be actively controlled because their very high frequencies of up to 1000 Hz are above the control bandwidth a current attitude control system can provide. However, being able to reduce the effects of microvibrations on a space mission is becoming increasingly more critical as the envelope of future optical satellite missions expands. Furthermore, the advancements made in the performance of small satellites as well as the growing interest in laser and quantum communication call for a cost-efficient solution for managing microvibrations. This paper describes how cheap MEMS-based measurement systems have already proven that they are a potential solution. Showing high sensitivity and low-noise performance while allowing fast and easy prototyping.

Training a model to recognize human actions in videos is computationally intensive. While modern strategies employ transfer learning methods to make the process more efficient, they still face challenges regarding flexibility and efficiency. Existing solutions are limited in functionality and rely heavily on pretrained architectures, which can restrict their applicability to diverse scenarios. Our work explores knowledge distillation (KD) for enhancing the training of self-supervised video models in three aspects: improving classification accuracy, accelerating model convergence, and increasing model flexibility under regular and limited-data scenarios. We tested our method on the UCF101 dataset using differently balanced proportions: 100%, 50%, 25%, and 2%. We found that using knowledge distillation to guide the model’s training outperforms traditional training without affecting the classification accuracy and while reducing the convergence rate of model training in standard settings and a data-scarce environment. Additionally, knowledge distillation enables cross-architecture flexibility, allowing model customization for various applications: from resource-limited to high-performance scenarios.

Time-expanded phase-sensitive optical time-domain reflectometry is a distributed optical fiber sensing technology based on dual-frequency combs that allows for dynamic and high spatial resolution measurements while maintaining reduced detection requirements. Since the formalization of the technique, different experimental schemes have been satisfactorily tested, with a general performance of cm-scale spatial resolution over hundreds of meters. In this article, we present an optimized scheme with enhanced energy and spectral efficiencies that allows reaching 5 mm spatial resolution. As compared to previous experimental approaches, the presented architecture is based on a free-running dual comb setup generated through pure electro-optical phase modulation. Besides, the introduction of an optical hybrid in the detection stage allows for doubling the spatial resolution while keeping the refresh rate and the sensing range unchanged.

The development of inflammatory bowel diseases (IBD) involves the breakdown of two barriers: the epithelial barrier and the gut-vascular barrier (GVB). The destabilization of each barrier can promote initiation and progression of the disease. Interestingly, first evidence is available that both barriers are communicating through secreted factors that may accordingly serve as targets for therapeutic modulation of barrier functions. Interferon (IFN)-γ is among the major pathogenesis factors in IBD and can severely impair both barriers. In order to identify factors transmitting signals from the GVB to the epithelial cell barrier, we analyzed the secretome of IFN-γ-treated human intestinal endothelial cells (HIEC). To this goal, HIEC were isolated in high purity from normal colon tissues. HIEC were either untreated or stimulated with IFN-γ (10 U/mL). After 48 h, conditioned media (CM) were harvested and subjected to comparative hyper reaction monitoring mass spectrometry (HRM™ MS). In total, 1,084 human proteins were detected in the HIEC-CM. Among these, 43 proteins were present in significantly different concentrations between the CM of IFN-γ- and control-stimulated HIEC. Several of these proteins were also differentially expressed in various murine colitis models as compared to healthy animals supporting the relevance of these proteins secreted by inflammatory activated HIEC in the inter-barrier communication in IBD. The angiocrine pathogenic impact of these differentially secreted HIEC proteins on the epithelial cell barrier and their perspectives as targets to treat IBD by modulation of trans-barrier communication is discussed in detail.

Hypokalemia, despite its potential seriousness, is frequently encountered in clinical practice; with the majority of cases occurring in adulthood being rationalized by examining the triad losses: diuretics, vomiting and diarrhea, as inherited causes of hypokalemia with later onset are uncommon. Below we report a case of chronic and recurrent mild hypokalemia, in an adult patient with idiopathic congenital deafness. Early clinical and analytical findings pointed to a hereditary syndrome with augmented potassium renal excretion. Suspicion of a likely molecular basis motivated the analysis of the barttin’s gene, revealing a G47R mutation in heterozygosity as well as a second mutation within an usually unaltered area. G47R mutation when in homozygosity is associated with an attenuated BSND (Bartter syndrome accompanied by sensorineural deafness) phenotype, questioning the clinical significance of the second mutation discovered.

Immunotherapies for patients with food allergy have shown some success in limiting allergic responses. However, these approaches require lengthy protocols with repeated allergen dosing and patients can relapse following discontinuation of treatment. The purpose of this study was to test if a single dose of an adeno-associated virus (AAV) vector can safely prevent and treat egg allergy in a mouse model. AAV vectors expressing ovalbumin (OVA) under an ubiquitous or liver-specific promoter were injected prior to or after epicutaneous sensitization with OVA. Mice treated with either AAV8-OVA vector were completely protected from allergy sensitization. These animals had a significant reduction in anaphylaxis mediated by a reduction in OVA-specific IgE titers. In mice with established OVA allergy, allergic responses were mitigated only in mice treated with an AAV8-OVA vector expressing OVA from an ubiquitous promoter. In conclusion, an AAV vector with a liver-specific promoter was more effective for allergy prevention, but higher OVA levels were necessary for reducing symptoms in preexisting allergy. Overall, our AAV gene immunotherapy resulted in an expansion of OVA-specific FoxP3+ CD4+ T cells, an increase in the regulatory cytokine IL-10, and a reduction in the IgE promoting cytokine IL-13.

Craniosynostosis is a condition with neurologic and aesthetic sequelae requiring invasive surgery. Understanding its pathobiology requires familiarity with the processes underlying physiologic suture closure. Animal studies have shown that cyclical strain from chewing and suckling influences the closure of cranial vault sutures, especially the metopic, an important locus of craniosynostosis. However, there are no human data correlating strain patterns during chewing and suckling with the physiologically early closure pattern of the metopic suture. Furthermore, differences in craniofacial morphology make it challenging to directly extrapolate animal findings to humans. Eight finite-element analysis (FEA) models were built from craniofacial computer tomography (CT) scans at varying stages of metopic suture closure, including two with isolated non-syndromic metopic craniosynostosis. Muscle forces acting on the cranium during chewing and suckling were simulated using subject-specific jaw muscle cross-sectional areas. Chewing and suckling induced tension at the metopic and sagittal sutures, and compressed the coronal, lambdoid, and squamous sutures. Relative to other cranial vault sutures, the metopic suture experienced larger magnitudes of axial strain across the suture and a lower magnitude of shear strain. Strain across the metopic suture decreased during suture closure, but other sutures were unaffected. Strain patterns along the metopic suture mirrored the anterior to posterior sequence of closure: strain magnitudes were highest at the glabella and decreased posteriorly, with minima at the nasion and the anterior fontanelle. In models of physiologic suture closure, increased degree of metopic suture closure correlated with higher maximum principal strains across the frontal bone and mid-face, a strain regime not observed in models of severe metopic craniosynostosis. In summary, our work provides human evidence that bone strain patterns from chewing and suckling correlate with the physiologically early closure pattern of the metopic suture, and that deviations from physiologic strain regimes may contribute to clinically observed craniofacial dysmorphism.

A delicate balance between programmed cell death and proliferation of intestinal epithelial cells (IEC) exists in the gut to maintain homeostasis. Homeostatic cell death programs such as anoikis and apoptosis ensure the replacement of dead epithelia without overt immune activation. In infectious and chronic inflammatory diseases of the gut, this balance is invariably disturbed by increased levels of pathologic cell death. Pathological forms of cell death such as necroptosis trigger immune activation barrier dysfunction, and perpetuation of inflammation. A leaky and inflamed gut can thus become a cause of persistent low-grade inflammation and cell death in other organs of the gastrointestinal (GI) tract, such as the liver and the pancreas. In this review, we focus on the advances in the molecular and cellular understanding of programmed necrosis (necroptosis) in tissues of the GI tract. In this review, we will first introduce the reader to the basic molecular aspects of the necroptosis machinery and discuss the pathways leading to necroptosis in the GI system. We then highlight the clinical significance of the preclinical findings and finally evaluate the different therapeutic approaches that attempt to target necroptosis against various GI diseases. Finally, we review the recent advances in understanding the biological functions of the molecules involved in necroptosis and the potential side effects that may occur due to their systemic inhibition. This review is intended to introduce the reader to the core concepts of pathological necroptotic cell death, the signaling pathways involved, its immuno-pathological implications, and its relevance to GI diseases. Further advances in our ability to control the extent of pathological necroptosis will provide better therapeutic opportunities against currently intractable GI and other diseases.

Abstract Corneal mechanical changes are believed to occur before any visible structural alterations observed during routine clinical evaluation. This study proposed developing an elastography technique based on torsional waves (TWE) adapted to the specificities of the cornea. By measuring the displacements in the propagation plane perpendicular to the axis of the emitter, the effect of guided waves in plate-like media was proven negligible. Ex vivo experiments were carried out on porcine corneal samples considering a group of control and one group of alkali burn treatment ( $$\hbox {NH}_\text {4}$$ NH 4 OH) that modified the mechanical properties. Phase speed was recovered as a function of intraocular pressure (IOP), and a Kelvin-Voigt rheological model was fitted to the dispersion curves to estimate viscoelastic parameters. A comparison with uniaxial tensile testing with thin-walled assumptions was also performed. Both shear elasticity and viscosity correlated positively with IOP, being the elasticity lower and the viscosity higher for the treated group. The viscoelastic parameters ranged from 21.33 to 63.17 kPa, and from 2.82 to 5.30 Pa s, for shear elasticity and viscosity, respectively. As far as the authors know, no other investigations have studied this mechanical plane under low strain ratios, typical of dynamic elastography in corneal tissue. TWE reflected mechanical properties changes after treatment, showing a high potential for clinical diagnosis due to its rapid performance time and paving the way for future in vivo studies.

A gas sensor based on light-induced thermo-elastic spectroscopy (LITES) capable to detect methane (C1) and ethane (C2) in a wide concentration range, from percent down to part-per-billion (ppb), is here reported. A novel approach has been implemented, exploiting a compact sensor design that accommodates both a custom 9.8 kHz quartz tuning fork (QTF) used as photodetector and the gas sample in the same housing. The resulting optical pathlength was only 2.5 cm. An interband cascade laser (ICL) with emission wavelength of 3.345 µm was used to target absorption features of C1 and C2. The effects of high concentration analytes on sensor response were firstly investigated. C1 concentration varied from 1% to 10%, while C2 concentration varied from 0.1% to 1%. These ranges were selected to retrace the typical natural gas composition in a 1:10 nitrogen dilution. The LITES sensor was calibrated for both the gas species independently and returned nonlinear but monotonic responses for the two analytes. These univariate calibrations were used to retrieve the composition of C1-C2 binary mixtures with accuracy higher than 98%, without the need for further data analysis. Minimum detection limits of ∼650 ppb and ∼90 ppb were achieved at 10 s of integration time for C1 and C2, respectively, demonstrating the capability of the developed LITES sensor to operate with concentration ranges spanning over 6 orders of magnitude.

Teachers in workshops of vocational education training (VET) schools are at risk of exposure to occupational hazards, as are the rest of the teaching staff. However, due to the characteristics of these workshops, these teachers are exposed to a greater extent to other types of risks, such as noise or vibrations. Exposure to these risks for vocational training teachers has been little studied compared to other risks, such as voice disorders. In this study, exposure to noise and vibration was evaluated for teachers in a vocational training center in Cordoba (Spain), working in body shops. The values obtained from the measurements taken for different tasks and machine tools showed that the exposure limit values specified in the corresponding regulations were reached and even exceeded. This implies that these types of risks must be taken into consideration for these types of teachers, and that measures must be taken to mitigate their effects.

Research in EMG-based control of prostheses has mainly utilized adult subjects who have fully developed neuromuscular control. Little is known about children’s ability to generate consistent EMG signals necessary to control artificial limbs with multiple degrees of freedom. As a first step to address this gap, experiments were designed to validate and benchmark two experimental protocols that quantify the ability to coordinate forearm muscle contractions in typically developing children. Non-disabled, healthy adults and children participated in our experiments that aimed to measure an individual’s ability to use myoelectric control interfaces. In the first experiment, participants performed 8 repetitions of 16 different hand/wrist movements. Using offline classification analysis based on Support Vector Machine, we quantified their ability to consistently produce distinguishable muscle contraction patterns. We demonstrated that children had a smaller number of highly independent movements (can be classified with >90% accuracy) than adults did. The second experiment measured participants’ ability to control the position of a cursor on a 1-DoF virtual slide using proportional EMG control with three different visuomotor gain levels. We found that children had higher failure rates and slower average target acquisitions than adults did, primarily due to longer correction times that did not improve over repetitive practice. We also found that the performance in both experiments was age-dependent in children. The results of this study provide novel insights into the technical and empirical basis to better understand neuromuscular development in children with upper-limb loss.

Abstract SMYD2 is a histone methyltransferase, which methylates both histone H3K4 as well as a number of non-histone proteins. Dysregulation of SMYD2 has been associated with several diseases including cancer. In the present study, we investigated whether and how SMYD2 might contribute to colorectal cancer. Increased expression levels of SMYD2 were detected in human and murine colon tumor tissues compared to tumor-free tissues. SMYD2 deficiency in colonic tumor cells strongly decreased tumor growth in two independent experimental cancer models. On a molecular level, SMYD2 deficiency sensitized colonic tumor cells to TNF-induced apoptosis and necroptosis without affecting cell proliferation. Moreover, we found that SMYD2 targeted RIPK1 and inhibited the phosphorylation of RIPK1. Finally, in a translational approach, pharmacological inhibition of SMYD2 attenuated colonic tumor growth. Collectively, our data show that SMYD2 is crucial for colon tumor growth and inhibits TNF-induced apoptosis and necroptosis.

Given the current COVID-19 pandemic, most people wear a mask to effectively prevent the spread of the contagious disease. This sanitary measure has caused a significant drop in the effectiveness of current face recognition methods when handling masked faces on practical applications such as face access control, face attendance, and face authentication-based mobile payment. Under this situation, recent efforts have been focused on boosting the performance of the existing face recognition technology on masked faces. Some solutions trying to tackle this issue fine-tune the existing deep learning face recognition models on synthetic masked images, while others use the periocular region as a naive manner to eliminate the adverse effect of COVID-19 masks. Although the accuracy of masked face recognition remains an important issue, in the last few years, the development of efficient and lightweight face recognition methods has received an increased attention in the research community. In this paper, we study the effectiveness of three state-of-the-art lightweight face recognition models for addressing accurate and efficient masked face recognition, considering both fine-tuning on masked faces and periocular images. For the experimental evaluation, we create both real and simulated masked face databases as well as periocular datasets. Extensive experiments are conducted to determine the most effective solution and state further steps for the research community. The obtained results disclose that fine-tuning existing state-of-the-art face models on masked images achieve better performance than using periocular-based models. Besides, we evaluate and analyze the effectiveness of the trained masked-based models on well-established unmasked benchmarks for face recognition and assess the efficiency of the used lightweight architectures in comparison with state-of-the-art face models.

Gelatin based adhesives have been used in the last decades in different biomedical applications due to the excellent biocompatibility, easy processability, transparency, non-toxicity, and reasonable mechanical properties to mimic the extracellular matrix (ECM). Gelatin adhesives can be easily tuned to gain different viscoelastic and mechanical properties that facilitate its ocular application. We herein grafted glycidyl methacrylate on the gelatin backbone with a simple chemical modification of the precursor, utilizing epoxide ring-opening reactions and visible light-crosslinking. This chemical modification allows the obtaining of an elastic protein-based hydrogel (GELGYM) with excellent biomimetic properties, approaching those of the native tissue. GELGYM can be modulated to be stretched up to 4 times its initial length and withstand high tensile stresses up to 1.95 MPa with compressive strains as high as 80% compared to Gelatin-methacryloyl (GeIMA), the most studied derivative of gelatin used as a bioadhesive. GELGYM is also highly biocompatible and supports cellular adhesion, proliferation, and migration in both 2 and 3-dimensional cell-cultures. These characteristics along with its super adhesion to biological tissues such as cornea, aorta, heart, muscle, kidney, liver, and spleen suggest widespread applications of this hydrogel in many biomedical areas such as transplantation, tissue adhesive, wound dressing, bioprinting, and drug and cell delivery.

Latin America is one of the regions most vulnerable to the effects of climate variability on hydropower generation. Hydropower is the backbone of the Latin-American power system and a key technology for ensuring low-carbon power generation in the region. Despite its importance, our understanding of the impact and likelihood of seasonal variability and of long-term phenomena such as the El Niño Southern Oscillation (ENSO) on hydropower is limited. There is an essential need to understand how likely these effects are and to identify measures to counterbalance them. A combination of wind, solar, and hydropower offers the potential to mitigate the impact of climate variability on renewable power generation and thus improve its reliability. Here we present a modeling framework to quantify the potential benefits of such combination. The modeling framework relies on a meteorological reanalysis dataset, large-scale renewable power generation models, and statistic models. We consider the countries with the largest hydropower capacity in the region, namely Argentina, Brazil, Colombia, Mexico, and Venezuela. We examine whether the probability of a production deficit is reduced when all renewable resources are combined compared to a scenario based solely on hydropower, especially during droughts. The approach presented allows for the first time an in-depth analysis of the benefits of a combined wind, solar, and hydropower-based power generation under different geographical conditions in altered ENSO phases.Our results suggest that—depending on the country and the percentile—the hydropower generated during drought ENSO phases could be up to 50% lower than that during neutral phases. The countries most affected are Colombia and Venezuela, while the reduction is somewhat less severe in Argentina, Brazil, and Mexico. Combining hydropower with variable renewable energy (VRE) offers the potential to reduce the risk of a power deficit during the 10th percentile of the driest months of the year, both in drought and neutral phases. Argentina is the country with the most effective combination of resources to mitigate a power deficit, as each MW of installed VRE generates 0.218 GWh of additional power. It is followed by Brazil and Mexico with 0.185 GWh per MW of VRE and by Venezuela and Colombia with 0.128–0.098 GWh/MW of VRE, respectively. These results can contribute to informing future decisions on capacity planning and regional transmission grids.

Abstract Tephra layers preserved in marine sediments are strong tools to study the frequency, magnitude and source of past major explosive eruptions. Thirty‐seven volcanoes from the Ecuadorian and Colombian arc, in the northern Andes, experienced at least one eruption during the Holocene. The volcanic hazard is therefore particularly high for the populated areas of the Andes and in particular cases for the coastal region, and it is crucial to document such events to improve hazard assessment. The age and distribution of deposits from major Holocene eruptions have been studied in the Cordillera, but no descriptions of distal fallouts have been published. In this study, we focused on 28 Holocene tephra layers recorded in marine sediment cores collected along the northern Ecuador—Southern Colombia margin. New lithological, geochemical and isotope data together with 14C datings on foraminifers allow us to determine the age and volcanic source of marine tephra, and to propose a first land‐sea correlation of distal tephra fallouts. We show that at least seven explosive eruptions from Guagua Pichincha, Atacazo‐Ninahuilca, Cotopaxi, and Cerro Machín volcanoes left tephra deposits recorded in marine cores over 250 km away from their source. Volume estimates of emitted tephra range between 1.3 and 6.0 km3 for the tenth century Guagua Pichincha, ∼5 ka Atacazo‐Ninahuilca, ∼6.7 and ∼7.9 ka Cotopaxi events, suggesting that they were eruptions of Volcanic Explosivity Index of 5. The distribution of these deposits also brings new constraints for a better evaluation of the volcanic hazard in Ecuador.

Simpson, McTiernan et al. develop fully synthetic corneal implants. The resulting CLP-PEG-MPC implants show reduced corneal swelling, haze, and neovascularization compared to CLP-PEG only implants when grafted into a mini-pig cornea alkali burn model of inflammation over 12 months. This study suggests the superiority of CLP-PEG-MPC implants over the CLP-PEG only implants.

Abstract Phase-sensitive optical time-domain reflectometry (ΦOTDR) is a well-established technique that provides spatio-temporal measurements of an environmental variable in real time. This unique capability is being leveraged in an ever-increasing number of applications, from energy transportation or civil security to seismology. To date, a wide number of different approaches have been implemented, providing a plethora of options in terms of performance (resolution, acquisition bandwidth, sensitivity or range). However, to achieve high spatial resolutions, detection bandwidths in the GHz range are typically required, substantially increasing the system cost and complexity. Here, we present a novel ΦOTDR approach that allows a customized time expansion of the received optical traces. Hence, the presented technique reaches cm-scale spatial resolutions over 1 km while requiring a remarkably low detection bandwidth in the MHz regime. This approach relies on the use of dual-comb spectrometry to interrogate the fibre and sample the backscattered light. Random phase-spectral coding is applied to the employed combs to maximize the signal-to-noise ratio of the sensing scheme. A comparison of the proposed method with alternative approaches aimed at similar operation features is provided, along with a thorough analysis of the new trade-offs. Our results demonstrate a radically novel high-resolution ΦOTDR scheme, which could promote new applications in metrology, borehole monitoring or aerospace.

The paracaspase MALT1 is a crucial regulator of immune responses in various cellular contexts. Recently, there is increasing evidence suggesting that MALT1 might represent a novel key player in mucosal inflammation. However, the molecular mechanisms underlying this process and the targeted cell population remain unclear. In this study, we investigate the role of MALT1 proteolytic activity in the context of mucosal inflammation. We demonstrate a significant enrichment of MALT1 gene and protein expression in colonic epithelial cells of UC patients, as well as in the context of experimental colitis. Mechanistically we demonstrate that MALT1 protease function inhibits ferroptosis, a form of iron-dependent cell death, upstream of NF-κB signaling, which can promote inflammation and tissue damage in IBD. We further show that MALT1 activity contributes to STAT3 signaling, which is essential for the regeneration of the intestinal epithelium after injury. In summary, our data strongly suggests that the protease function of MALT1 plays a critical role in the regulation of immune and inflammatory responses, as well as mucosal healing. Understanding the mechanisms by which MALT1 protease function regulates these processes may offer novel therapeutic targets for the treatment of IBD and other inflammatory diseases.

Artificial intelligence’s rapid advancement has enabled various applications, including intelligent video surveillance systems, assisted living, and human–computer interaction. These applications often require one core task: video-based human action recognition. Research in human video-based human action recognition is vast and ongoing, making it difficult to assess the full scope of available methods and current trends. This survey concisely explores the vision-based human action recognition field and defines core concepts, including definitions and explanations of the common challenges and most used datasets. Additionally, we provide in an easy-to-understand manner the literature approaches and their evolution over time, emphasizing intuitive notions. Finally, we explore current research directions and potential future paths. The core goal of this work is to provide future works with a shared understanding of fundamental ideas and clear intuitions about current works and find new research opportunities.

Maintaining the viscosity and density of drilling fluids within their optimal performance margins is of utmost importance in running a safe and efficient operation when drilling oil and gas wells. Safety and efficiency may be adversely affected by current measurement practices of these two key properties as they still mostly rely on onsite personnel to carry out periodic manual measurements. These laborious measurement protocols limit the quantity and quality of the produced data. Here we describe an automated system for viscosity/density measurements of drilling fluids based on a tuning fork electromechanical resonator. The resonator works as the frequency-defining element of an oscillator circuit, and a digital gain control algorithm is used to control the feedback loop and actuate the device. The self-oscillating circuit allows the measurement to be repeated several times per second, enabling higher measurement precision and real-time monitoring in changing flows. The resonator was integrated into an in-tank system, which performed continuous measurements at the suction tank of the mud circulating system during drilling operations. Measurements in three different wells are presented. The results were in very good agreement with manual measurements reported from standard mud reports and further highlighted opportunities in detecting operational problems from the real-time data streams obtained.

In the past decade, research in the face recognition area has advanced tremendously, particularly in uncontrolled scenarios (face recognition in the wild). This advancement has been achieved partly due to the massive popularity and effectiveness of deep convolutional neural networks and the availability of larger unconstrained datasets. However, several face recognition challenges remain in the context of very low resolution homogeneous (same domain) and heterogeneous (different domain) face recognition. In this survey, we study the seminal and novel methods to tackle the very low resolution face recognition problem and provide an in-depth analysis of their design, effectiveness, and efficiency for a real-time surveillance application. Furthermore, we analyze the advantage of employing deep learning convolutional neural networks, while presenting future research directions for effective deep learning network design in this context.

CD147 is a widely expressed matrix metalloproteinase inducer involved in the regulation of cell migration. The high glycosylation and ability to undergo oligomerization have been linked to CD147 function, yet there is limited understanding on the molecular mechanisms behind these processes. The current study demonstrates that the expression of Golgi α1,2-mannosidase I is key to maintaining the cell surface organization of CD147 during cell migration. Using an in vitro model of stratified human corneal epithelial wound healing, we show that CD147 is clustered within lateral plasma membranes at the leading edge of adjacent migrating cells. This localization correlates with a surge in matrix metalloproteinase activity and an increase in the expression of α1,2-mannosidase subtype IC (MAN1C1). Global inhibition of α1,2-mannosidase I activity with deoxymannojirimycin markedly attenuates the glycosylation of CD147 and disrupts its surface distribution at the leading edge, concomitantly reducing the expression of matrix metalloproteinase-9. Likewise, treatment with deoxymannojirimycin or siRNA-mediated knockdown of MAN1C1 impairs the ability of the carbohydrate-binding protein galectin-3 to stimulate CD147 clustering in unwounded cells. We conclude that the mannose-trimming activity of α1,2-mannosidase I coordinates the clustering and compartmentalization of CD147 that follows an epithelial injury.

We have demonstrated a novel scheme for distributed optical fiber sensing based on the use of a dual frequency comb, which enables the development of a high-resolution (in the cm range) distributed sensor with significantly relaxed electronic requirements compared with previous schemes. This approach offers a promising solution for real time structure monitoring in a variety of fields, including transportation, manufacturing or mechatronics. In this work, we review the principle of operation of the technique, recent advances to improve its performance and different experimental tests.

Aims: Determine the effectiveness of custom-made orthopedic footwear (OF) and total contact plantar orthoses (PO) on the quality of life (QoL) and functionality of people with type 2 diabetes with diabetic peripheral neuropathic (DPN). Methods: Randomized clinical study with 2 parallel intervention groups and pre- and post-test analysis. In the standard footwear group (SFg), PO and education on foot self-care were applied and in the orthopedic footwear group (OFg) the same intervention was applied, but with personalized OF. A total of 43 type 2 diabetic patients with DPN aged 61 – 76 years were randomized: 20 in to SFg and 23 to OFg.Michigan Neuropathy Screening Instrument (MNSI) was used to screen for DPN. QoL was assessed with Short Form–36 and functional level was evaluated by Lower Extremity Functional Scale (LEFS), 6 physical tests and center of pressure (CoP) oscillation. Results: No differences in QoL were found between groups. OFg showed a better functional reach and mediolateral displacement of CoP (p ≤ 0.05). Conclusions: The OF does not show evidence on functional and QoL improvement in low-risk type 2 diabetic patients with neuropathy but both groups improved significantly in functional tests. The PO showed clinical value in these patients, so a regular and specialized treatment with appropriate footwear and plantar orthoses can play an important role in reducing the complications of diabetic neuropathy.

The objective of this work has been to implement an orderly, accessible, fast and space-saving storage system that allows the transfer to a Relational Database Management System (RDBMS) of all the data corresponding to the monitoring of a set of photovoltaic (PV) systems whose behaviour is to be analysed. The RDBMS consists of a series of linked databases, enabling all PV system information to be stored, and it is scalable so it can be expanded depending on the number of installations to be studied. The data recorded in the plants are found in a large number of very disaggregated files, and with different measured parameters, different formats, nomenclatures, or units of measurement, so the developed system is responsible for homogenising all the information for storage. For this purpose, a procedure has been developed to carry out the automatic transfer of all the data recorded in their corresponding databases. In addition, in this work, a web application called S·lar 2 has been developed to facilitate selective access to all the data once stored in the corresponding tables. This application, which is connected to the designed databases, allows the storage and management of the information coming from the PV plants, in order to determine, among other things, the operation mode of each of the components of these facilities. Using the data already organised, it has also been possible to establish a system for comparing the production of inverters within the same plant in order to have a tool that allows the quick and visual detection of possible deviations between them and thus detect malfunctions in any of the components. The whole procedure has been carried out using free software, such as Maria DB and Python.

Background: Chronic kidney disease (CKD) is an important independent risk factor for adverse cardiovascular events in patients waitlisted for kidney transplantation (KT). Although KT reduces cardiovascular risk, these patients still have a higher all-cause and cardiovascular mortality than the general population. This concerning situation is due to a high burden of traditional and nontraditional risk factors as well as uremia-related factors and transplant-specific factors, leading to 2 differentiated processes under the framework of CKD, atherosclerosis and arteriosclerosis. These can be initiated by insults to the vascular endothelial endothelium, leading to vascular calcification (VC) of the tunica media or the tunica intima, which may coexist. Several pathogenic mechanisms such as inflammation-related endothelial dysfunction, mineral metabolism disorders, activation of the renin-angiotensin system, reduction of nitric oxide, lipid disorders, and the fibroblast growth factor 23-klotho axis are involved in the pathogenesis of atherosclerosis and arteriosclerosis, including VC. Summary: This review focuses on the current understanding of atherosclerosis and arteriosclerosis, both in patients on the waiting list as well as in kidney transplant recipients, emphasizing the cardiovascular risk factors in both populations and the inflammation-related pathogenic mechanisms. Key Message: The importance of cardiovascular risk factors and the pathogenic mechanisms related to inflammation in patients waitlisted for KT and kidney transplant recipients.

Virtual reality has been widely used in various industries, such as entertainment, communication, and healthcare, to mention a few. In the health industry, in combination with the brain–computer interfaces (BCIs), virtual reality could produce rehabilitation measures that may contribute novel strategies such as remote rehabilitation or telerehabilitation. The design and development of BCIs integrate different processes, including biosignals acquisition and processing, feature extraction and selection, classification of signals, and application of the technology to patients under rehabilitation treatments. This manuscript presents a literature review of the papers focused on the implementation of BCI and assistive technologies for remote rehabilitation based on virtual reality implementation. The purpose of this comprehensive review is to identify those studies that take advantage of virtual reality in combination with a biomedical technology to improve the performances of diverse rehabilitation processes. Various revisited studies provided a complete system for remote rehabilitation. These findings could lead to applying these models in diverse rehabilitation tasks.

The effect of a third vaccine dose (3D) of homologous mRNA vaccine on blood levels of SARS-CoV-2-receptor binding domain (RBD)-total antibodies was assessed in 40 hemodialysis patients (HD) and 21 kidney transplant recipients (KTR) at a median of 46 days after 3D. Anti-RBD antibodies were detected in 39/40 HD and 19/21 KTR. Overall, 3D boosted anti-RBD antibody levels (median: 58-fold increase). Neutralizing antibodies (NtAb) against the Wuhan-Hu-1, Delta, and Omicron variants were detected in 14, 13, and 11 out of 14 HD patients, and in 5, 5, and 4 out of 8 KTR patients, respectively. The median fold increase in NtAb titers in HD patients was 77, 28, and 5 and 56, 37, and 9 in KTR patients for each respective variant. SARS-CoV-2-S S-IFN-γ-producing CD8+ and CD4+ T-cell responses were detected in the majority of HD (35 and 36/37, respectively) and all KTR (16/16) patients at 3D. Overall, the administration of 3D boosted T-cell levels in both population groups. In conclusion, a homologous mRNA COVID-19 vaccine 3D exerts a booster effect on anti-RBD antibodies, NtAb binding to Wuhan-Hu-1, Delta, and Omicron variants, and SARS-CoV-2-S-IFN-γ-producing T cells in both HD and KTR patients. The magnitude of the effect was more marked in HD than KTR patients.

Eosinophilic granuloma is a localized, non-invasive form of Langerhans cell histiocytosis. It usually develops in the long bones and is more frequent in children under the age of 10 years. It is very rare in adults. We present the case of a young woman admitted to hospital for persistent refractory left parietal headache, later revealed to be caused by an eosinophilic granuloma.

There is a growing interest in the potential role of adipose tissues in cardiac and renal pathophysiology, and determining the mechanisms by which fat compartments around the heart and kidneys influence cardiovascular disease is of clinical importance in both general and high-risk populations. Epicardial fat and perirenal fat have been associated with adverse outcomes in chronic kidney disease (CKD) patients. Epicardial fat is a rich source of free fatty acids and is capable of secreting inflammatory and pro-atherogenic cytokines that promote atherosclerosis through a local paracrine effect. Recent evidence has demonstrated that perirenal fat has a closer correlation with kidney diseases than other visceral fat deposits in obesity or metabolic disturbances. Moreover, perirenal fat has been reported as an independent risk factor for CKD progression and even associated with cardiorenal dysfunction. Accordingly, these forms of organ-specific fat deposits may act as a connecter between vascular and cardiorenal disease. This review explores the possible links between epicardial and perirenal fat and its significant role as a modulator of cardiorenal dysfunction in CKD patients.

Inflammatory cytokines initiate and sustain the perpetuation of processes leading to chronic inflammatory conditions such as inflammatory bowel diseases (IBD). The nature of the trigger causing an inflammatory reaction decides whether type 1, type 17, or type 2 immune responses, typically characterized by the respective T- helper cell subsets, come into effect. In the intestine, Type 2 responses have been linked with mucosal healing and resolution upon an immune challenge involving parasitic infections. However, type 2 cytokines are frequently elevated in certain types of IBD in particular ulcerative colitis (UC) leading to the assumption that Th2 cells might critically support the pathogenesis of UC raising the question of whether such elevated type 2 responses in IBD are beneficial or detrimental. In line with this, previous studies showed that suppression of IL-13 and other type 2 related molecules in murine models could improve the outcomes of intestinal inflammation. However, therapeutic attempts of neutralizing IL-13 in ulcerative colitis patients have yielded no benefits. Thus, a better understanding of the role of type 2 cytokines in regulating intestinal inflammation is required. Here, we took a comparative transcriptomic approach to address how Th2 responses evolve in different mouse models of colitis and human IBD datasets. Our data show that type 2 immune-related transcripts are induced in the inflamed gut of IBD patients in both Crohn's disease and UC and across widely used mouse models of IBD. Collectively our data implicate that the presence of a type 2 signature rather defines a distinct state of intestinal inflammation than a disease-specific pathomechanism.

The aim of this research consisted in assessing the effect of various kinds of environmental enrichment (EE) on the physiological responses of weaned piglets. The mean age of the 96 piglets that participated was 27 days. The piglets were weaned and then housed under two conditions: with no disruption of the social order (SO), and with disruption of the social order (DSO). After establishing the two experimental conditions, we proceeded to evaluate four different treatments; namely, control (C), suspended ropes (SR), aromatized bottles (AB) and pet toys and balls (PTB). The protocol required drawing three blood samples: at 30 (T30), 60 (T60) and 90 min (T90) after weaning. The DSO piglets had higher pH and haematocrit levels than those weaned in the SO condition (P < 0.05). Also, pCO2, potassium (K+) and base excess (BE) concentrations were higher in the SO animals than in those in the DSO group (P < 0.05). The control piglets, which did not receive any type of EE, showed higher pCO2 levels, but lower glucose and pH (P < 0.05) values, while the ones enriched with SR had increased lactate levels, but lower values for pH and HCO3- compared to the piglets in the other EE treatment regimens (P < 0.05). The SR-enriched piglets had higher lactate and haematocrit levels, but lower values for pH and bicarbonate (HCO3-) than the animals in the other EE groups (P < 0.005). The piglets subjected to sensorial EE with AB had higher plasma glucose than the ones in the other groups (P < 0.005). Finally, the PTB-enriched subjects showed higher Na+ levels than controls (P < 0.005). The alterations that were found to be related to the factor sampling time were more pronounced at T30 (P < 0.05) than T60 and T90. These results indicate that the conditions (SO, DSO) and EE (C, SR, AB, PTB) under which the piglets were weaned influenced the blood variables measured in the study.

The aim of this review is to assess the different treatments and therapeutic protocols used for neonatal asphyxia in animal production. Perinatal asphyxia is considered to be one of the main non-infectious causes of neonatal mortality in the majority of domestic mammals. However, its incidence in intensive animal production is increasing because of a series of implemented strategies aimed at improving and increasing production. For example, through the application of genetics, an increase in size and weight in newly born animals has been achieved. Nevertheless, this has resulted in a larger incidence of dystocia associated with oxygen restriction to thefoetus, which elicits metabolic and respiratory acidosis. Furthermore, aside from immediate financial implications when it comes to production, it also has an impact on the welfare of mother and offspring. Regarding the field of animal perinatology, several therapeutic strategies using respiratory and hormonal stimulants, as well as energetic supplements have been evaluated with the aim of preventing perinatal asphyxia and treating neonates with the condition, and also to diminish the incidence of stillbirths associated with it. However, during the last decades this condition has persisted mainly in porcine, equine, ovine and bovine production; for this reason, it continues to be studied extensively.

Chile es el mayor productor de cobre en el mundo, y este metal es obtenido principalmente a partir de los sulfuros de cobre, utilizando los procesos clásicos de flotación y pirometalúrgicos. En nuestro país existen siete fundiciones de cobre, las cuales generan grandes volúmenes de escoria. Este trabajo presenta los resultados obtenidos de recuperación de cobre contenido en escorias de horno de reverbero (HR) y de convertidor Teniente (CT) de la fundición Hernán Videla Lira, de Paipote mediante flotación. A través de pruebas de flotación rougher a escala de laboratorio se determinó que la granulometría, para ambos casos, corresponde a 70% menor a 74 µm, lográndose recuperaciones de 59,2% escoria HR y 86,8% para la escoria del CT, cuyas leyes de cobre en el concentrado fueron de 3,7% y 23,6% respectivamente. Las dosis de reactivos utilizados fueron 40 g/t de F-703 como colector y 30 g/t de H-70 como espumante. Los tiempos óptimos de flotación de las etapas rougher y cleaner, de ambas escorias, se determinaron mediante cinéticas de flotación. Finalmente se realizaron pruebas a nivel industrial con los resultados de laboratorio alcanzándose una ley de 18,2% de cobre (recuperación de 56,1%) para escoria HR, y para la escoria CT se obtiene una ley de 39,1% de cobre con una recuperación de 91,4%

A diverse spectrum of immune cells populates the intestinal mucosa reflecting the continuous stimulation by luminal antigens. In lesions of patients with inflammatory bowel disease, an aberrant inflammatory process is characterized by a very prominent infiltrate of activated immune cells producing cytokines and chemokines. These mediators perpetuate intestinal inflammation or may contribute to mucosal protection depending on the cellular context. In order to further characterize this complex immune cell network in intestinal inflammation, we investigated the contribution of the chemokine receptor CCR8 to development of colitis using a mouse model of experimental inflammation. We found that CCR8−/− mice compared to wildtype controls developed strong weight loss accompanied by increased histological and endoscopic signs of mucosal damage. Further experiments revealed that this gut protective function of CCR8 seems to be selectively mediated by the chemotactic ligand CCL1, which was particularly produced by intestinal macrophages during colitis. Moreover, we newly identified CCR8 expression on a subgroup of intestinal innate lymphoid cells producing IFN-γ and linked a functional CCL1/CCR8 axis with their abundance in the gut. Our data therefore suggest that this pathway supports tissue-specific ILC functions important for intestinal homeostasis. Modulation of this regulatory circuit may represent a new strategy to treat inflammatory bowel disease in humans.

Current protocols converting human induced pluripotent stem cells (iPSCs) into induced microglia-like cells (iMGL) are either dependent on overexpression of transcription factors or require substantial experience in stem-cell technologies. Here, we developed an easy-to-use two-step protocol to convert iPSCs into functional iMGL via: (1) highly efficient differentiation of hematopoietic progenitor cells (HPCs) from iPSCs, and (2) optimized maturation of HPCs to iMGL. A sequential harvesting approach led to an increased HPC yield. The protocol implemented a freezing step, thus allowing HPC biobanking and flexible timing of differentiation into iMGL. Our iMGL responded adequately to the inflammatory stimuli LPS, and iMGL RNAseq analysis matched those of other frequently used protocols. Comparing three different coating modalities, we increased the iMGL yield by culturing on uncoated glass surfaces, thereby retaining differentiation efficiency and functional hallmarks of iMGL. In summary, we provide a high-quality, easy-to-use protocol, rendering generation and functional studies on iMGL an accessible lab resource.