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Abstract Background ADCK genes encode aarF domain‐containing mitochondrial kinases involved in coenzyme Q (CoQ) biosynthesis and regulation. Haploinsufficiency of ADCK2 in humans leads to adult‐onset physical incapacity with reduced mitochondrial CoQ levels in skeletal muscle, resulting in mitochondrial myopathy and alterations in fatty acid β‐oxidation. The sole current treatment for CoQ deficiencies is oral administration of CoQ10, which causes only partial recovery with postnatal treatment, underscoring the importance of early diagnosis for successful intervention. Methods We used Adck2 heterozygous mice to examine the influence of this gene on muscle structure, function and regeneration throughout development, growth and ageing. This investigation involved techniques including immunohistochemistry, analysis of CoQ levels, mitochondrial respiratory content, muscle transcriptome analysis and functional tests. Results We demonstrated that Adck2 heterozygous mice exhibit defects from embryonic development, particularly in skeletal muscle (1102 genes deregulated). Adck2 heterozygous embryos were 7% smaller in size and displayed signs of delayed development. Prenatal administration of CoQ10 could mitigate these embryonic defects. Heterozygous Adck2 mice also showed a decrease in myogenic cell differentiation, with more severe consequences in ‘aged’ mice (41.63% smaller) (P

Abstract The present study explores the application of X-ray scattering, using synchrotron radiation, to assess the diffusive transport of nanomedicines in tumor on a chip devices fabricated by 3D stereolithography using a resin with high optical and X-ray transmittance. Unlike conventional methods that require fluorescent labeling of nanoparticles, potentially altering their in vitro and in vivo behavior, this approach enables the investigation of the transport properties for unlabeled nanoparticles. In particular, the results presented confirm the influence of the porosity of the extracellular matrix-like microenvironment, specifically Matrigel, on the diffusive transport of oligonucleotide-functionalized gold nanoparticles. The analysis of the scattering patterns allows to create 2D maps showing the nanoparticle distribution with high spatial resolution. The proposed approach demonstrates the potential for studying other factors involved in nanoparticle diffusion processes. By implementing X-ray scattering to track unmodified nanomedicines within extracellular matrix-like microenvironments, increasingly accurate models for evaluating and predicting therapeutics transport behaviors can be developed.

Abstract Intracortical microelectrodes (IMEs) are devices designed to be implanted into the cerebral cortex for various neuroscience and neuro-engineering applications. A critical feature of IMEs is their ability to detect neural activity from individual neurons. Currently, IMEs are limited by chronic failure, largely considered to be caused by the prolonged neuroinflammatory response to the implanted devices. Over the past few years, the characterization of the neuroinflammatory response has grown in sophistication, with the most recent advances focusing on mRNA expression following IME implantation. While gene expression studies increase our broad understanding of the relationship between IMEs and cortical tissue, advanced proteomic techniques have not been reported. Proteomic evaluation is necessary to describe the diverse changes in protein expression specific to neuroinflammation, neurodegeneration, or tissue and cellular viability, which could lead to the further development of targeted intervention strategies designed to improve IME functionality. In this study, we have characterized the expression of 62 proteins within 180 μm of the IME implant site at 4-, 8-, and 16-weeks post-implantation. We identified potential targets for immunotherapies, as well as key pathways that contribute to neuronal dieback around the IME implant.

Abstract With increasing attention to climate change and biodiversity loss, conservation social science research on land management practices is burgeoning. Researchers have broadened their focus from protected areas to diverse types of land management to support conservation and climate mitigation. But, developing effective strategies for these issues requires an in‐depth understanding of both the socio‐psychological factors that guide landholders' decision‐making and global trends in land management practices and literature. To assess the trends and status of land management behavior research, we systematically reviewed research published between 2010 and 2020 in five seminal conservation journals. Of 11,607 articles reviewed, we identified 100 articles about land management behavior. We assessed theoretical groundings, measurement methodology, land‐use terminology and practices, ecosystem type, and geographic distribution. We identified strengths and significant gaps and weaknesses across land management research. For example, 52% of articles made no meaningful connection to theory, only 14% of papers used observed behavioral data, 86% of studies uses non‐experimental methods and researchers disproportionately measured land management behavior in developed nations (66%). We also find that language used to describe land management behavior is very heterogeneous, making it difficult to summarize land management research using traditional systematic review methods. Conducting a limited systematic review can help summarize research and also identify trends across disciplines that might otherwise missed. Results from our limited systematic review can guide future research and support the development of evidence‐based policies to mitigate climate change and biodiversity loss.

(1) Background: “Kidney Disease: Improving Global Outcomes” (KDIGO) provides guidelines for identifying the stages of acute kidney injury (AKI) and chronic kidney disease (CKD). A data-driven rule-based engine was developed to determine KDIGO staging compared to KD-related keywords in discharge letters. (2) Methods: To assess potential differences in outcomes, we compare the patient subgroups with exact KDIGO staging to imprecise or missing staging for all-cause mortality, in-hospital mortality, selection bias and costs by applying Kaplan–Meier analysis and the Cox proportional hazards regression model. We analysed 63,105 in-patient cases from 2016 to 2023 at a tertiary hospital with AKI, CKD and acute-on-chronic KD. (3) Results: Imprecise and missing CKD staging were associated with an 85% higher risk of all-cause and in-hospital mortality (CI: 1.7 to 2.0 and 1.66 to 2.03, respectively) compared to exact staging for any given disease status; imprecise or missing AKI staging increased in-hospital mortality risk by 56% and 57% (CI: 1.43 to 1.70 and 1.37 to 1.81, respectively) in patients with AKI. (4) Conclusions: Exact staging is associated with better outcomes in KD management. Our study provides valuable insight into potential quality and outcome improvements and lower costs, considering elderly patients, women and patients with acute-on-chronic KD as the most vulnerable.

Abstract Science has a history of excluding marginalized groups, including people who are lesbian, gay, bisexual, trans, queer, and other marginalized gender and sexual identities (LGBTQ+), and recent calls urge the wildlife sciences to address disparities. Literature on inclusion in the life sciences generally has focused on personal affirmation and has neglected comprehensive discussion of barriers rooted in historical, structural, and sociocultural context. In our literature review, we construct a narrative highlighting the intersections between historic LGBTQ+ exclusion in society and wildlife science due to current policy trends, pressures of cis‐heteronormativity, and survival barriers on LGBTQ+ people in wildlife sciences in the United States. Wildlife scientists must have competency on LGBTQ+ marginalization topics to advance inclusion in our discipline, and this should include comprehension of historic and current legislation and social perceptions. To bolster inclusion efforts, we recommend thoughtful data collection on experiences of LGBTQ+ people within the wildlife sciences. To address root causes of exclusion, institutions and organizations should address disparities in financial support, housing, and physical and mental health resources as part of LGBTQ+ advocacy, in addition to interpersonal efforts.

IntroductionStereoelectroencephalography (sEEG) is a minimally invasive procedure that uses depth electrodes stereotactically implanted into brain structures to map the origin and propagation of seizures in epileptic patients. Implantation accuracy of sEEG electrodes plays a critical role in the safety and efficacy of the procedure. This study used human cadaver heads, simulating clinical practice, to evaluate (1) neurosurgeon's ability to implant a new thin-film polyimide sEEG electrode according to the instructions for use (IFU), and (2) implantation accuracy.MethodsFour neurosurgeons (users) implanted 24 sEEG electrodes into two cadaver heads with the aid of the ROSA robotic system. Usability was evaluated using a questionnaire that assessed completion of all procedure steps per IFU and user errors. For implantation accuracy evaluation, planned electrode trajectories were compared with post-implantation trajectories after fusion of pre- and postoperative computer tomography (CT) images. Implantation accuracy was quantified using the Euclidean distance for entry point error (EPE) and target point error (TPE).ResultsAll sEEG electrodes were successfully placed following the IFU without user errors, and post-implant survey of users showed favorable handling characteristics. The EPE was 1.28 ± 0.86 mm and TPE was 1.61 ± 0.89 mm. Long trajectories (>50 mm) had significantly larger EPEs and TPEs than short trajectories (

Introducción: El cáncer infantil es una enfermedad compleja que requiere intervenciones interdisciplinarias. Este estudio busca describir la calidad de vida y el agotamiento en niños diagnosticados con cáncer, utilizando instrumentos validados que reflejan las peculiaridades de esta enfermedad. Método: Se llevó a cabo un estudio observacional analítico en niños y adolescentes de 2 a 18 años con cáncer. Se emplearon el PedsQL Cancer Module y el FACIT-F para evaluar calidad de vida y fatiga, respectivamente, analizando estadísticamente para identificar correlaciones y desarrollar un modelo explicativo. Resultados: Se identificaron síntomas físicos y psicológicos notables como náuseas, fatiga, hiporexia, irritabilidad y tristeza. Los instrumentos PedsQL Cancer Module y FACIT-F indicaron una calidad de vida disminuida. Hubo una alta concordancia entre las percepciones de niños y padres, excepto en la ansiedad por procedimientos, donde los niños reportaron mayores niveles. Estos síntomas reflejan el impacto del tratamiento oncológico, en el bienestar de los niños. La concordancia en las evaluaciones sugiere que los padres comprenden bien estas experiencias, destacando la pertinencia de intervenciones psicosociales que mejoren la calidad de vida a partir de una adecuada red de apoyo. Conclusiones: Es crucial que el tratamiento del cáncer pediátrico aborde no solo aspectos médicos, sino también el apoyo integral al bienestar emocional y psicosocial de los pacientes y sus familias.

IntroductionLong-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main pathways and long-term consequences attributed to this condition by analyzing clinical parameters and functional tests supported by machine learning and serum proteome profiling.MethodsPatients with L-TPD were classified according to the results of their computer-tomography (CT) scan and diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (DLCOc) tests at 4 and 12-months post-infection.ResultsRegarding the acute phase, our data showed that L-TPD was favored in elderly patients with hypertension or insulin resistance, supported by pathways associated with vascular inflammation and chemotaxis of phagocytes, according to computer proteomics. Then, at 4-months post-infection, clinical and functional tests revealed that L-TPD patients exhibited a restrictive lung condition, impaired aerobic capacity and reduced muscular strength. At this time point, high circulating levels of platelets and CXCL9, and an inhibited FCgamma-receptor-mediated-phagocytosis due to reduced FcγRIII (CD16) expression in CD14+ monocytes was observed in patients with L-TPD. Finally, 1-year post infection, patients with L-TPD worsened metabolic syndrome and augmented body mass index in comparison with other patient groups.DiscussionOverall, our data demonstrated that CT scan and DLCOc identified patients with L-TPD after COVID-19. This condition was associated with vascular inflammation and impair phagocytosis of virus-antibody immune complexes by reduced FcγRIII expression. In addition, we conclude that COVID-19 survivors required a personalized follow-up and adequate intervention to reduce long-term sequelae and the appearance of further metabolic diseases.

In the 2022–2023 influenza season, three autonomous communities anticipated the document approved by the Public Health Commission recommending influenza vaccination for all children aged 6 to 59 months. The primary objective of this study was to evaluate the attitude of healthcare professionals towards the first universal vaccination campaign in our region, as well as the acceptability of the vaccines used and their attitude towards pilot school vaccination. This was a cross-sectional, survey-based, descriptive study. All healthcare professionals involved in the campaign were invited to participate. Overall, 91.9% of surveyed professionals thought that influenza vaccination from 6 to 59 months was important or very important, and 89.8% had previous experience regarding the intramuscular vaccine. Healthcare professionals rated the intranasal vaccine significantly more positively, but there were no differences when asking about each vaccine without comparison. The inhaled vaccine was preferred by 97.5% for the following campaign. Pilot school vaccination had a 75% acceptance rate. The inhaled vaccine was preferred by most professionals, and pilot school vaccination was highly accepted and independently associated with the importance of vaccination as considered by physicians, being a medical doctor, and participation in the pilot programme.

Neuromuscular junctions (NMJs) are a special type of chemical synapse that transmits electrical stimuli from motor neurons (MNs) to their innervating skeletal muscle to induce a motor response. They are an ideal model for the study of synapses, given their manageable size and easy accessibility. Alterations in their morphology or function lead to neuromuscular disorders, such as the congenital myasthenic syndromes, which are caused by mutations in proteins located in the NMJ. In this review, we highlight novel potential candidate genes that may cause or modify NMJs-related pathologies in humans by exploring the phenotypes of hundreds of mouse models available in the literature. We also underscore the fact that NMJs may differ between species, muscles or even sexes. Hence the importance of choosing a good model organism for the study of NMJ-related diseases: only taking into account the specific features of the mammalian NMJ, experimental results would be efficiently translated to the clinic.

Abstract Background Factors that decrease independence and increase morbidity must be reduced to improve the nutrition, health, and other challenges confronting older adults. In the United States (US), the Older Americans Act (OAA) requires each state/territory develop multi-year aging plans for spending federal funds that foster healthy aging (including support of congregate/home delivered meals programs) and separately requires grant applications for nutrition service programs supporting older Native Americans. Malnutrition (particularly protein-energy undernutrition), sarcopenia, frailty, and obesity can all result in disability but are potentially changeable. The study goal was to collect baseline information on mentions of these malnutrition-related conditions and interventions that address them in US state/territorial OAA program multi-year aging plans. Methods OAA program multi-year aging plans available on the ADvancing States website in February 2021 (n = 52) were searched for number of mentions of defined nutrition terms including malnutrition, sarcopenia, frailty, obesity, and whether terms were included in plans’ goals/objectives, strategies/actions, or solely in the narrative. Results Malnutrition, sarcopenia, frailty, and obesity were mentioned infrequently in US state/territorial OAA program multi-year aging plans. 33% of plans mentioned malnutrition but only 8% as goals/objectives and 15% as strategies/actions. 62% mentioned frailty; 6% (goals/objectives), 15% (strategies/actions). None mentioned sarcopenia whereas in contrast, 21% mentioned obesity; 2% (goals/objectives), 2% (strategies/actions). Nutrition intervention mentions were nearly nil. There were no significant differences in frequency of term mentions by US region or by states with higher percentages of older adults or obese adults. Conclusions Clearly specifying definitions of malnutrition-related conditions and incorporating them into measurable goals/objectives, defined strategies/actions, and outcomes may help improve future state/territorial OAA program multi-year aging plans to better support healthy aging.

(1) Background: Intracortical microelectrodes (IMEs) are an important part of interfacing with the central nervous system (CNS) and recording neural signals. However, recording electrodes have shown a characteristic steady decline in recording performance owing to chronic neuroinflammation. The topography of implanted devices has been explored to mimic the nanoscale three-dimensional architecture of the extracellular matrix. Our previous work used histology to study the implant sites of non-recording probes and showed that a nanoscale topography at the probe surface mitigated the neuroinflammatory response compared to probes with smooth surfaces. Here, we hypothesized that the improvement in the neuroinflammatory response for probes with nanoscale surface topography would extend to improved recording performance. (2) Methods: A novel design modification was implemented on planar silicon-based neural probes by etching nanopatterned grooves (with a 500 nm pitch) into the probe shank. To assess the hypothesis, two groups of rats were implanted with either nanopatterned (n = 6) or smooth control (n = 6) probes, and their recording performance was evaluated over 4 weeks. Postmortem gene expression analysis was performed to compare the neuroinflammatory response from the two groups. (3) Results: Nanopatterned probes demonstrated an increased impedance and noise floor compared to controls. However, the recording performances of the nanopatterned and smooth probes were similar, with active electrode yields for control probes and nanopatterned probes being approximately 50% and 45%, respectively, by 4 weeks post-implantation. Gene expression analysis showed one gene, Sirt1, differentially expressed out of 152 in the panel. (4) Conclusions: this study provides a foundation for investigating novel nanoscale topographies on neural probes.

The genetic prehistory of central America has not been well explored. Here, the authors find evidence from ancient DNA from twenty individuals who lived in Belize 9,600 to 3,700 years ago of a migration from the south that coincided with the first evidence for forest clearing and the spread of maize horticulture.

Mechanobactericidal nanomaterials, such as low‐dimensional nanoparticles in suspension or high‐aspect‐ratio nanofabricated topographies, rely on their mechanical or physical interactions with bacteria and are promising antimicrobial strategies that overcome bacterial resistance to classical antibiotics. However, the underlying killing mechanisms are poorly understood, given the challenges associated with the real‐time characterization of the mechanical interaction in a biologically relevant environment. Indeed, different death mechanisms have been proposed depending on the magnitude of the interaction forces. Herein, the real‐time and single‐cell response of bacteria to weak mechanical interactions with nanostructured topographies and “nanodarts,” exemplified by flowing single‐walled carbon nanotubes, is investigated. To that end, an advanced reporting strategy is used to follow sublethal physiological effects on bacteria upon contact with these materials. With this method, it is estimated that the contact time at which the initial stages of bacterial death occur is in the order of a few tens of minutes. This information contributes to a full understanding of the complex mechanisms of mechanically induced bacterial death.

Este trabajo combina un análisis cuantitativo y cualitativo de cómo y porqué los políticos, en el contexto del parlamento español, usan determinadas expresiones deícticas espacio-temporales. Establecemos, en primer lugar, un contraste de cómo hoy y aquí aparecen en dos corpus de gran extensión (uno de discurso parlamentario y uno de lenguaje ordinario). A continuación, argumentamos que las circunstancias extralingüísticas de habla en el parlamento así como su poder icónico como sede de alta política son los responsables del desigual registro semántico de tales formas. Concluimos que las formas específicas (restringidas a señalar las circunstancias contextuales que envuelven el acto de habla) de tales adverbios se producen con mayor frecuencia en el discurso parlamentario. Otras formas deícticas específicas al discurso parlamentario son también estudiadas.

Flow focusing is an important hydrodynamic technique for cytometric analysis, enabling the rapid study of cellular samples to identify a variety of biological processes. To date, the majority of flow-focusing devices are fabricated using conventional photolithography or flame processing of glass capillaries. This article presents a suite of low-cost, millifluidic, flow-focusing devices that were fabricated using a desktop sterolithgraphy (SLA) 3D printer. The suite of SLA printing strategies consists of a monolithic SLA method and a hybrid molding process. In the monolithic SLA approach, 1.3 mm square millifluidic channels were printed as a single piece. The printed device does not require any post processing, such as bonding or surface polishing for optical access. The hybrid molding approach consists of printing a mold using the SLA 3D printer. The mold is treated to an extended UV exposure and oven baked before using PDMS as the molding material for the channel. To demonstrate the viability of these channels, we performed a series of experiments using several flow-rate ratios to show the range of focusing widths that can be achieved in these devices. The experiments are validated using a numerical model developed in ANSYS.

Abstract Grid background and dead‐time harmonic perturbations pose challenges in maintaining power quality and stability in the grid integration of renewable energy conversion systems. Therefore, a super‐twisting algorithm with the ability to reject harmonic perturbations on three‐phase grid‐tied inverters is proposed. The algorithm design is related to dead‐time and grid background harmonics so that robust performance is achieved under these perturbations. To highlight the advantages of the proposed algorithm, it is compared against proportional‐integral (PI) control in several dead‐time and grid background harmonic sweeps. The maximum inverter current distortion obtained with PI control in simulation is 15.53%. However, by using the proposed algorithm instead, the maximum current distortion is reduced to 1.8%. Dead‐time is experimentally swept by using a permanent magnet motor as a harmonic‐free grid. Experimental results of grid background harmonics are obtained by injecting reactive energy into a grid with 2.19% voltage distortion. When PI control is used in the experimental setup, the maximum inverter current distortion obtained is 11.4%. However, with the proposed algorithm, the maximum current distortion is reduced to 1.5%, which complies with the standard IEEE 1547‐2018.

ADCK2 haploinsufficiency-mediated mitochondrial coenzyme Q deficiency in skeletal muscle causes mitochondrial myopathy associated with defects in beta-oxidation of fatty acids, aged-matched metabolic reprogramming, and defective physical performance. Calorie restriction has proven to increase lifespan and delay the onset of chronic diseases associated to aging. To study the possible treatment by food deprivation, heterozygous Adck2 knockout mice were fed under 40% calorie restriction (CR) and the phenotype was followed for 7 months. The overall glucose and fatty acids metabolism in muscle was restored in mutant mice to WT levels after CR. CR modulated the skeletal muscle metabolic profile of mutant mice, partially rescuing the profile of WT animals. The analysis of mitochondria isolated from skeletal muscle demonstrated that CR increased both CoQ levels and oxygen consumption rate (OCR) based on both glucose and fatty acids substrates, along with mitochondrial mass. The elevated aerobic metabolism fits with an increase of type IIa fibers, and a reduction of type IIx in mutant muscles, reaching WT levels. To further explore the effect of CR over muscle stem cells, satellite cells were isolated and induced to differentiate in culture media containing serum from animals in either ad libitum or CR diets for 72 h. Mutant cells showed slower differentiation alongside with decreased oxygen consumption. In vitro differentiation of mutant cells was increased under CR serum reaching levels of WT isolated cells, recovering respiration measured by OCR and partially beta-oxidation of fatty acids. The overall increase of skeletal muscle bioenergetics following CR intervention is paralleled with a physical activity improvement, with some increases in two and four limbs strength tests, and weights strength test. Running wheel activity was also partially improved in mutant mice under CR. These results demonstrate that CR intervention, which has been shown to improve age-associated physical and metabolic decline in WT mice, also recovers the defective aerobic metabolism and differentiation of skeletal muscle in mice caused by ADCK2 haploinsufficiency.

Abstract This work describes the fabrication process of moth eye antireflective poly (methyl methacrylate) transparent films via roll to roll thermal nanoimprint lithography. The process parameters are investigated and adjusted in order to obtain from a single moth-eye structured mold, a range of antireflective topographies that gradually vary their geometry from protruding to intruding nanocones. A correlation between the process parameters with the optical and mechanical properties of the films is established to illustrate the influence of the processing parameters and serve as guideline to produce antireflective flexible films with balanced properties and optimized performance adequate to the application environment. A finite element model is described predicting the mechanical behavior of the moth-eye PMMA imprinted nanostructures.

Abstract Background One of the most unusual sources of phylogenetically restricted genes is the molecular domestication of transposable elements into a host genome as functional genes. Although these kinds of events are sometimes at the core of key macroevolutionary changes, their origin and organismal function are generally poorly understood. Results Here, we identify several previously unreported transposable element domestication events in the human and mouse genomes. Among them, we find a remarkable molecular domestication that gave rise to a multigenic family in placental mammals, the Bex/Tceal gene cluster. These genes, which act as hub proteins within diverse signaling pathways, have been associated with neurological features of human patients carrying genomic microdeletions in chromosome X. The Bex/Tceal genes display neural-enriched patterns and are differentially expressed in human neurological disorders, such as autism and schizophrenia. Two different murine alleles of the cluster member Bex3 display morphological and physiopathological brain modifications, such as reduced interneuron number and hippocampal electrophysiological imbalance, alterations that translate into distinct behavioral phenotypes. Conclusions We provide an in-depth understanding of the emergence of a gene cluster that originated by transposon domestication and gene duplication at the origin of placental mammals, an evolutionary process that transformed a non-functional transposon sequence into novel components of the eutherian genome. These genes were integrated into existing signaling pathways involved in the development, maintenance, and function of the CNS in eutherians. At least one of its members, Bex3, is relevant for higher brain functions in placental mammals and may be involved in human neurological disorders.

Since its inception in 1988, the Belize Valley Archaeological Reconnaissance (BVAR) Project has had two major foci, that of cultural heritage management and archaeological research. While research has concentrated on excavation and survey, the heritage management focus of the project has included the preservation of ancient monuments, the integration of archaeology and tourism development, and cultural heritage education. In this paper, we provide a brief overview on the history of scientific investigations by the BVAR Project, highlighting the project’s dual heritage management and research goals. This background offers the basis in which to discuss the successes and challenges of the project’s efforts in cultural heritage management and public engagement, particularly in early conservation efforts, in its training and educational efforts, and its ongoing outreach activity. We emphasize the need to train Belizeans as professional archaeologists and conservators, to serve as the next generation of advocates for Belize’s heritage management. We offer some ideas on how research projects can make significant contributions to heritage education and preservation in the developing world.

Archaeology and heritage management in the Maya area have developed differently in the various modern-day countries that make up ancient Mesoamerica. In the country of Belize, heritage management has been conjoined with archaeology since at least the late 1970s. Long-term projects, such as the 1985-to-present archaeological investigations at the ancient ruins that comprise the immense city of Caracol, Belize, demonstrate the evolution of heritage management. This abandoned metropolis has also been the location of concerted stabilization and conservation efforts. Research and heritage management efforts at this urban center have been coordinated and intertwined since the project’s inception. This article contextualizes the long-standing relationships between archaeology and cultural heritage as it has been practiced at Caracol, Belize within the broader field of Maya Studies.

Swedish architects Erik and Tore Ahlsén (1901- 1988) (1906-1991) research the architectural significance of the façade, the understanding of its rules, and the ability to express aesthetic emotion. Their constant obsession is the abstract and geometric character of the façade cladding. The abstraction in the decoration, the role of the ornamentation, the figuration and its geometric movement in the murals is exemplified in the urban center of Årsta (1947-1953) and is abstractly developed in the stratified façade of the Civic Centre in Örebro (1957-1965). The façades must respond to their public dimension and brothers Erik and Tore Ahlsén will apply mural art to the urban center of Årsta to give character to the architecture it represents. In Årsta, turning to colored abstraction is the antidote to the linguistic harshness of the environment. In Örebro, the intention of these brothers was not to create a beautiful façade, but rather their architecture responded to the expressive need of its content. From the documentary materials belonging to the Swedish architects, the research analyses the systematic exploration for the façade cladding of the architectural object, from the abstract figuration that serves as a back drop for the dynamic civic life of the urban center of Årsta to the stratigraphic treatment of the Civic Centre in Örebro.DOI: https://doi.org/10.20365/disegnarecon.24.2020.9

Abstract CBS deficient individuals undergoing betaine supplementation without sufficient dietary methionine restriction can develop severe hypermethioninemia and brain edema. Brain edema has also been observed in individuals with severe hypermethioninemia without concomitant betaine supplementation. We systematically evaluated reports from 11 published and 4 unpublished patients with CBS deficiency and from additional four cases of encephalopathy in association with elevated methionine. We conclude that, while betaine supplementation does greatly exacerbate methionine accumulation, the primary agent causing brain edema is methionine rather than betaine. Clinical signs of increased intracranial pressure have not been seen in patients with plasma methionine levels below 559 μmol/L but occurred in one patient whose levels did not knowingly exceed 972 μmol/L at the time of manifestation. While levels below 500 μmol/L can be deemed safe it appears that brain edema can develop with plasma methionine levels close to 1000 μmol/L. Patients with CBS deficiency on betaine supplementation need to be regularly monitored for concordance with their dietary plan and for plasma methionine concentrations. Recurrent methionine levels above 500 μmol/L should alert clinicians to check for clinical signs and symptoms of brain edema and review dietary methionine intake. Levels approaching 1000 μmol/L do increase the risk of complications and levels exceeding 1000 μmol/L, despite best dietetic efforts, should be acutely addressed by reducing the prescribed betaine dose.

The aim of this work is to present a reproducible methodology for the evaluation of total equivalent doses in organs during proton therapy facilities. The methodology is based on measuring the dose equivalent in representative locations inside an anthropomorphic phantom where photon and neutron dosimeters were inserted. The Monte Carlo simulation was needed for obtaining neutron energy distribution inside the phantom. The methodology was implemented for a head irradiation case in the passive proton beam of iThemba Labs (South Africa). Thermoluminescent dosimeter (TLD)-600 and TLD-700 pairs were used as dosimeters inside the phantom and GEANT code for simulations. In addition, Bonner sphere spectrometry was performed inside the treatment room to obtain the neutron spectra, some relevant neutron dosimetric quantities per treatment Gy, and a percentual distribution of neutron fluence and ambient dose equivalent in four energy groups, at two locations. The neutron spectrum at one of those locations was also simulated so that a reasonable agreement between simulation and measurement allowed a validation of the simulation. Results showed that the total out-of-field dose equivalent inside the phantom ranged from 1.4 to 0.28 mSv/Gy, mainly due to the neutron contribution and with a small contribution from photons, 10% on average. The order of magnitude of the equivalent dose in organs was similar, displaying a slow reduction in values as the organ is farther from the target volume. These values were in agreement with those found by other authors in other passive beam facilities under similar irradiation and measurement conditions.

Many humans live in large, complex political centers, composed of multi-scalar communities including neighborhoods and districts. Both today and in the past, neighborhoods form a fundamental part of cities and are defined by their spatial, architectural, and material elements. Neighborhoods existed in ancient centers of various scales, and multiple methods have been employed to identify ancient neighborhoods in archaeological contexts. However, the use of different methods for neighborhood identification within the same spatiotemporal setting results in challenges for comparisons within and between ancient societies. Here, we focus on using a single method—combining Average Nearest Neighbor (ANN) and Kernel Density (KD) analyses of household groups—to identify potential neighborhoods based on clusters of households at 23 ancient centers across the Maya Lowlands. While a one-size-fits all model does not work for neighborhood identification everywhere, the ANN/KD method provides quantifiable data on the clustering of ancient households, which can be linked to environmental zones and urban scale. We found that centers in river valleys exhibited greater household clustering compared to centers in upland and escarpment environments. Settlement patterns on flat plains were more dispersed, with little discrete spatial clustering of households. Furthermore, we categorized the ancient Maya centers into discrete urban scales, finding that larger centers had greater variation in household spacing compared to medium-sized and smaller centers. Many larger political centers possess heterogeneity in household clustering between their civic-ceremonial cores, immediate hinterlands, and far peripheries. Smaller centers exhibit greater household clustering compared to larger ones. This paper quantitatively assesses household clustering among nearly two dozen centers across the Maya Lowlands, linking environment and urban scale to settlement patterns. The findings are applicable to ancient societies and modern cities alike; understanding how humans form multi-scalar social groupings, such as neighborhoods, is fundamental to human experience and social organization.

Land use practices have had important implications for structuring household inequalities and broader political systems in the past. Our contribution examines settlement patterns in relation to political structure, household wealth, ecological productivity and agricultural techniques. Combining settlement pattern data with high–precision soils data, we examine the extent to which different trajectories of polity formation impact the settlement location and land use practices of intermediate elites and commoners. The Classic Maya (CE 250/300–900) polities of Baking Pot and Lower Dover in the Upper Belize River Valley serve as enlightening case studies because despite being situated near one another, the two centers emerged along very different trajectories. Whereas the polity of Baking Pot arose slowly, in tandem with surrounding demography, the neighboring polity of Lower Dover arose rapidly in the Late Classic period (CE 600–900) in an area which was already home to established local populations. Our analysis shows that while Baking Pot had substantial settlement clustering around its epicenter, populations at Lower Dover aggregated around secondary and tertiary centers farther away from the polity core. Analyses also demonstrate that most commoner and intermediate elite residences were situated on the most productive agricultural lands in the region, though some intermediate elite households were situated on hilltops or in border zones with marginal soil productivity for political and tactical reasons. Commoner households were situated on a range of productivity zones reflecting diverse land–use practices which had implications for household wealth. Our case study illustrates the importance of integrating land use practices into our reconstructions of ancient political hierarchies, especially in terms of understanding political strategies and household wealth.

La utilidad de asegurar el riego de sus terrenos hizo que los agricultores encargaran a los ingenieros redactar proyectos de grandes presas en la isla de Gran Canaria, llegándose a diseñar más de 300 muros entre 1862 y 1980, cifra ésta más que suficiente para calibrar la importancia de lo construido durante la batalla del agua (79 grandes presas en 1.558 km²). Del racionalismo de las primeras décadas, con algunos proyectos muy atrevidos en los años 30, se impuso luego el pragmatismo funcional en los 50. Vigilancia de Presas constató en los 60 cierto retraso técnico con las presas de la España peninsular. No sólo en criterios de diseño, sino también en lo que se refiere a los materiales, medios y técnicas constructivas, lo que derivó en nuevos diseños de grandes presas y materiales en los 70. De este modo, en estas líneas pretendemos dibujar someramente, pues, la evolución temporal de lo diseñado, con especial atención a la potencia expresiva de los proyectos innovadores.

Abstract The process by which the value of delayed rewards is discounted varies from person to person. It has been suggested that these individual differences in subjective valuation of delayed rewards are supported by mesolimbic dopamine D2-like receptors (D2Rs) in the ventral striatum. However, no study to date has documented an association between direct measures of dopamine receptors and neural representations of subjective value in humans. Here, we examined whether individual differences in D2R availability were related to neural subjective value signals during decision making. Human participants completed a monetary delay discounting task during an fMRI scan and on a separate visit completed a PET scan with the high affinity D2R tracer [18 F]fallypride. Region-of-interest analyses revealed that D2R availability in the ventral striatum was positively correlated with subjective value-related activity in the ventromedial prefrontal cortex and midbrain but not with choice behavior. Whole-brain analyses revealed a positive correlation between ventral striatum D2R availability and subjective value-related activity in the left inferior frontal gyrus and superior insula. These findings identify a link between a direct measure of mesolimbic dopamine function and subjective value representation in humans and suggest a mechanism by which individuals vary in neural representation of discounted subjective value.

Multi-colored polymer lasers Highly luminescent polymers can work as lasers when incorporated with suitable cavities and now the nano-imprinting makes the fabrication much cheaper and more scalable. An international team led by Prof Juan Cabanillas-Gonzalez from Madrid Institute for Advanced Studies in Nanoscience, Spain demonstrates transparent all-polymer distributed feedback (DFB) lasers in blue, green, yellow and red. The most important step is to make sub-wavelength periodic gratings on the flexible and highly transparent cellulose diacetate substrates by thermal nano-imprinting with high fidelity to maximize the constructive interference effect. As a result, these lasers show narrow linewidths below 1 nm at low power thresholds of several μJ cm^−2, which is comparable to conventional approaches. This large area nano-imprinting method is scalable and adaptable and it enables stackable multi-colored laser emission.

This practice report examines the results of inserting program-specific, contextualised modules and instructors into an online student success course in a two-year college environment. The results of multiple semesters of pre-contextualised instruction (Northern Hemisphere Spring and Fall 2015) and post-contextualisation instruction (Northern Hemisphere Fall 2016 and Spring 2017), showed an increase in next semester retention. Additionally, ten student success course instructors were interviewed to determine critical elements of the course. Instructors revealed that time management, stress management, and program-specific assignments were the most beneficial components of the course.

Objectives:. Triaging patients at admission to determine subsequent deterioration risk can be difficult. This is especially true of coronavirus disease 2019 patients, some of whom experience significant physiologic deterioration due to dysregulated immune response following admission. A well-established acuity measure, the Rothman Index, is evaluated for stratification of patients at admission into high or low risk of subsequent deterioration. Design:. Multicenter retrospective study. Setting:. One academic medical center in Connecticut, and three community hospitals in Connecticut and Maryland. Patients:. Three thousand four hundred ninety-nine coronavirus disease 2019 and 14,658 noncoronavirus disease 2019 adult patients admitted to a medical service between January 1, 2020, and September 15, 2020. Interventions:. None. Measurements and Main Results:. Performance of the Rothman Index at admission to predict in-hospital mortality or ICU utilization for both general medical and coronavirus disease 2019 populations was evaluated using the area under the curve. Precision and recall for mortality prediction were calculated, high- and low-risk thresholds were determined, and patients meeting threshold criteria were characterized. The Rothman Index at admission has good to excellent discriminatory performance for in-hospital mortality in the coronavirus disease 2019 (area under the curve, 0.81–0.84) and noncoronavirus disease 2019 (area under the curve, 0.90–0.92) populations. We show that for a given admission acuity, the risk of deterioration for coronavirus disease 2019 patients is significantly higher than for noncoronavirus disease 2019 patients. At admission, Rothman Index–based thresholds segregate the majority of patients into either high- or low-risk groups; high-risk groups have mortality rates of 34–45% (coronavirus disease 2019) and 17–25% (noncoronavirus disease 2019), whereas low-risk groups have mortality rates of 2–5% (coronavirus disease 2019) and 0.2–0.4% (noncoronavirus disease 2019). Similarly large differences in ICU utilization are also found. Conclusions:. Acuity level at admission may support rapid and effective risk triage. Notably, in-hospital mortality risk associated with a given acuity at admission is significantly higher for coronavirus disease 2019 patients than for noncoronavirus disease 2019 patients. This insight may help physicians more effectively triage coronavirus disease 2019 patients, guiding level of care decisions and resource allocation.

Maya archaeologists have long been interested in understanding ancient diets because they provide information about broad-scale economic and societal transformations. Though paleodietary studies have primarily relied on stable carbon (δ13C) and nitrogen (δ15N) isotopic analyses of human bone collagen to document the types of food people consumed, stable sulfur (δ34S) isotope analysis can potentially provide valuable data to identify terrestrial, freshwater, or marine/coastal food sources, as well as determine human mobility and migration patterns. Here we assess applications of δ34S for investigating Maya diet and migration through stable isotope analyses of human bone collagen (δ13C, δ15N, and δ34S) from 114 individuals from 12 sites in the Eastern Maya lowlands, temporally spanning from the Late Preclassic (300 BCE-300 CE) through Colonial periods (1520-1800 CE). Results document a diet dominated by maize and other terrestrial resources, consistent with expectations for this inland region. Because δ34S values reflect local geology, our analyses also identified recent migrants to the Eastern lowlands who had non-local δ34S signatures. When combined with other indicators of mobility (e.g., strontium isotopes), sulfur isotopic data provide a powerful tool to investigate movement across a person's lifespan. This study represents the largest examination of archaeological human δ34S isotope values for the Maya lowlands and provides a foundation for novel insights into both subsistence practices and migration.

The present article analyses migratory trends between Chile and Spain in the early 19th century, based on the figure of Miguel Riesco and the Instrucciones given by his father Manuel in 1805. These trends are examined in terms of family and commercial strategies and long-range networks, as well as in terms of the transmission of social and ethical values associated to professional practice. From this perspective, the study of the Instrucciones is organised around four main axes: the first two are related to more concrete and tangible aspects, such as routes, goods, commercial profiles, the agents and their links; the final two deal with more intangible aspects, such as moral and social recommendations, private religious practice, ethical values and the transmission of professional knowledge. In short, the analysis ranges from the most intimate and private realm to the sphere of public and social characterisation; this has allowed, not only for the general outline of the commercial company of the Riesco to be revealed, but for the main tenets of Atlantic commerce during the final years of the colonial period to be defined.

FXR1P is a RNA binding protein involved in muscle development. Here, the authors show that mutations in FXR1 exon 15, which is alternatively spliced in muscle, cause multi-minicore myopathy in humans and in mouse models.

In this protocol, we demonstrate the use of a vibrating plate to drive the assembly of micro- and nanoparticles as an approach to high-throughput, large-scale directed assembly in a viscous liquid. Vibration drives the assembly of glass bead microparticles and iron oxide nanoparticles in contact with water over an area of 6400 mm2. We use a scaling analysis to show that there is a competition between acoustic radiation force and vibration-generated fluid flow in a viscous medium, which determines particle transport characteristics. For assembly in a viscous liquid, we find close agreement between the observed experimental results when compared to a numerical solution of the 2D wave equation that describes plate displacement. This model indicates that microparticles migrate along displacement gradients towards displacement anti-nodes where the magnitude of displacement is maximum. We also observe that nanoparticles migrate toward displacement nodes where the magnitude of displacement is zero. • Cost-effective directed assembly technique without the need for microfabrication facilities • Large-scale assembly produces heterogeneously ordered structures on a vibrating substrate Method name: Protocol for assembling micro- and nanoparticles in a viscous liquid above a vibrating plate, Keywords: Directed assembly, Acoustophoresis, Colloids

A combination of in situ nanocalorimetry with simultaneous nanofocus 2D Wide-Angle X-ray Scattering (WAXS) was used to study polymorphic behaviour and structure formation in a single micro-drop of isotactic polypropylene (iPP) with defined thermal history. We were able to generate, detect, and characterize a number of different iPP morphologies using our custom-built ultrafast chip-based nanocalorimetry instrument designed for use with the European Synchrotron Radiation Facility (ESRF) high intensity nanofocus X-ray beamline facility. The detected iPP morphologies included monoclinic alpha-phase crystals, mesophase, and mixed morphologies with different mesophase/crystalline compositional ratios. Monoclinic crystals formed from the mesophase became unstable at heating rates above 40 K s−1 and showed melting temperatures as low as ~30 K below those measured for iPP crystals formed by slow cooling. We also studied the real-time melt crystallization of nanogram-sized iPP samples. Our analysis revealed a mesophase nucleation time of around 1 s and the co-existence of mesophase and growing disordered crystals at high supercooling ≤328 K. The further increase of the iPP crystallization temperature to 338 K changed nucleation from homogeneous to heterogeneous. No mesophase was detected above 348 K. Low supercooling (≥378 K) led to the continuous growth of the alpha-phase crystals. In conclusion, we have, for the first time, measured the mesophase nucleation time of supercooled iPP melted under isothermal crystallization conditions using a dedicated experimental setup designed to allow simultaneous ultrafast chip-based nanocalorimetry and nanofocus X-ray diffraction analyses. We also provided experimental evidence that upon heating, the mesophase converts directly into thermodynamically stable monoclinic alpha-phase crystals via perfection and reorganization and not via partial melting. The complex phase behaviour of iPP and its dependence on both crystallization temperature and time is presented here using a time–temperature–transformation (TTT) diagram.

Resumen: En este trabajo se presenta la implementación digital del algoritmo de modulación de Sünter-Clare, para un convertidor matricial de tres hilos de 7.5 kVA. Este algoritmo es usado para calcular los ciclos de trabajo en un convertidor matricial 3x3, con lo que se generan tensiones de salida con amplitud y frecuencia constantes. El algoritmo de modulación de Sünter-Clare recalcula los tiempos y trayectorias de conmutación cada período de muestreo, con el objetivo de compensar las variaciones de amplitud y de frecuencia de las tensiones de entrada. Este algoritmo se ejecuta en cada muestreo y está en función de la tensión trifásica de entrada y de la tensión de referencia de salida, resultando adecuado para controles en lazo cerrado, cuando las señales de amplitud y de frecuencia de las tensiones de entrada son variables en el tiempo, como ocurre en los sistemas de generación de energía eléctrica a velocidad variable, que utilizan la energía del viento como fuente primaria de energía. El sistema de control para el trabajo experimental, además de la tarjeta del convertidor matricial, está compuesto por una tarjeta de arreglos de compuertas programable (FPGA) y por un procesador digital de señales (DSP) con una tarjeta de interfaz gráfica. Abstract: This paper presents the direct and easy way to implement digitally a Sünter-Clare modulation algorithm for a 7.5 KVA, three-wires, matrix converter. This modulation algorithm is used to calculate 3x3 matrix converter duty cycles to produce constant output voltage and frequency signals. The Sünter-Clare modulation algorithm recalculates switching patterns and switching times every sampling period in order to compensate the input voltage and frequency variations. This algorithm is defined in terms of the three-phase input and the output reference voltages at each sampling instant and is convenient for closed loop operations when the input voltage and frequency are variable in time as in the variable speed wind generation system. The experimental control setup is comprised of a field programmable gate array board, a digital signal processor and a graphics interface board. Palabras clave: Convertidor matricial, algoritmo de modulación Sünter-Clare, distorsión total armónica, Keywords: Matrix converter, Sünter-Clare modulation algorithm, Total Harmonic Distortion

Este artículo analiza el proyecto del arquitecto danés Jørn Utzon (1918-2008) para la construcción de la Escuela de la Unión de trabajadores daneses en Højstrup, Helsingør (1958-1962), desde las dos propuestas presentadas al concurso, que obtienen el primer y segundo premio, a las versiones del proyecto que desarrolla simultáneamente al proyecto de la Ópera de Sídney (1956-1973). El análisis de la evolucióndel proyecto de Højstrup permite aproximarse al talento plástico y al universo de extraordinario lirismo del arquitecto, a través de la exploración formal que desarrolla en torno a las plataformas y los recintos, a la relación entre los dos elementos de la escala tipológica, la torre y el cuerpo bajo, al estudio de los mecanismos de acceso mediante la porte-cochère, al sistema de agregación de las casas patio o el papel que desempeña la estructura en el proyecto, en un ejercicio de exploración arquitectónica que fluye desde los concursos, entendidos como laboratorios de experiencias formales, al desarrollo lento y gradual de los proyectos sucesivos atendiendo a la vez el sitio y la pieza tipológica, en una cuidada innovación plástica que reivindica la experimentación constructiva y la integración en el paisaje.

Abstract Background The organisation of vertebrate genomes into topologically associating domains (TADs) is believed to facilitate the regulation of the genes located within them. A remaining question is whether TAD organisation is achieved through the interactions of the regulatory elements within them or if these interactions are favoured by the pre-existence of TADs. If the latter is true, the fusion of two independent TADs should result in the rewiring of the transcriptional landscape and the generation of ectopic contacts. Results We show that interactions within the PAX3 and FOXO1 domains are restricted to their respective TADs in normal conditions, while in a patient-derived alveolar rhabdomyosarcoma cell line, harbouring the diagnostic t(2;13)(q35;q14) translocation that brings together the PAX3 and FOXO1 genes, the PAX3 promoter interacts ectopically with FOXO1 sequences. Using a combination of 4C-seq datasets, we have modelled the three-dimensional organisation of the fused landscape in alveolar rhabdomyosarcoma. Conclusions The chromosomal translocation that leads to alveolar rhabdomyosarcoma development generates a novel TAD that is likely to favour ectopic PAX3:FOXO1 oncogene activation in non-PAX3 territories. Rhabdomyosarcomas may therefore arise from cells which do not normally express PAX3. The borders of this novel TAD correspond to the original 5'- and 3'- borders of the PAX3 and FOXO1 TADs, respectively, suggesting that TAD organisation precedes the formation of regulatory long-range interactions. Our results demonstrate that, upon translocation, novel regulatory landscapes are formed allowing new intra-TAD interactions between the original loci involved.

Invitado a participar en la reunión del Team 10 en Royaumont (1962), Francisco Javier Sáenz de Oíza (Cáseda 1918 - Madrid 2000) construye en Mallorca Ciudad Blanca (1961-1963) que ilustra la asimilación de las ideas del Team 10 y la revisión crítica del Movimiento Moderno. El proyecto de Ciudad Blanca indaga en los planteamientos tratados en la reunión del Team 10 en Royaumont: Urban infrastructure and building-group concept. Redactado en colaboración con Juan Daniel Fullaondo, el proyecto de ordenación concibe un extenso desarrollo turístico frente a la bahía de Alcudia del que se construye únicamente un bloque escalonado de 100 apartamentos y una torre. La misma respuesta formal basada en la modulación y el escalonamiento se asocia a las diversas escalas, el bloque, la torre y el conjunto de la urbanización. Como revisión crítica del sistema racional de la Carta de Atenas, el bloque aislado moderno se escalona y se modela. Esta evolución formal muestra, en la trayectoria de Oíza, el tránsito de las formas compactas de los bloques aislados de vivienda colectiva a las formas articuladas y escalonadas de Ciudad Blanca; desde el orden espacial y la diversidad de la composición de los bloques autónomos de las viviendas sociales de Fuencarral A (1953) o Entrevías (1956), a una estructura arquitectónica dinámica y continua en Alcudia.

Particle-polymer dispersions are ubiquitous in additive manufacturing (AM), where they are used as inks to create composite materials with applications to wearable sensors, energy storage materials, and actuation elements. It has been observed that directional alignment of the particle phase in the polymer dispersion can imbue the resulting composite material with enhanced mechanical, electrical, thermal or optical properties. Thus, external field-driven particle alignment during the AM process is one approach to tailoring the properties of composites for end-use applications. This review article provides an overview of externally directed field mechanisms (e.g., electric, magnetic, and acoustic) that are used for particle alignment. Illustrative examples from the AM literature show how these mechanisms are used to create structured composites with unique properties that can only be achieved through alignment. This article closes with a discussion of how particle distribution (i.e., microstructure) affects mechanical properties. A fundamental description of particle phase transport in polymers could lead to the development of AM process control for particle-polymer composite fabrication. This would ultimately create opportunities to explore the fundamental impact that alignment has on particle-polymer composite properties, which opens up the possibility of tailoring these materials for specific applications.

The dermal Panniculus carnosus (PC) muscle is important for wound contraction in lower mammals and represents an interesting model of muscle regeneration due to its high cell turnover. The resident satellite cells (the bona fide muscle stem cells) remain poorly characterized. Here we analyzed PC satellite cells with regard to developmental origin and purported function. Lineage tracing shows that they originate in Myf5+, Pax3/Pax7+ cell populations. Skin and muscle wounding increased PC myofiber turnover, with the satellite cell progeny being involved in muscle regeneration but with no detectable contribution to the wound-bed myofibroblasts. Since hematopoietic stem cells fuse to PC myofibers in the absence of injury, we also studied the contribution of bone marrow-derived cells to the PC satellite cell compartment, demonstrating that cells of donor origin are capable of repopulating the PC muscle stem cell niche after irradiation and bone marrow transplantation but may not fully acquire the relevant myogenic commitment.