bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrent somatic mutations as predictors of immunotherapy response
Authors: Gajic Zoran Z. , Deshpande Aditya , Legut Mateusz , Imieliński Marcin , Sanjana Neville E.
Published: July 2022

Immune checkpoint blockade (ICB) has transformed the treatment of metastatic cancer but is hindered by variable response rates. A key unmet need is the identification of biomarkers that predict treatment response. To address this, we analyzed six whole exome sequencing cohorts with matched disease outcomes to identify genes and pathways predictive of ICB response. To increase detection power, we focus on genes and pathways that are significantly mutated following correction for epigenetic, replication timing, and sequence-based covariates. Using this technique, we identify several genes (BCLAF1, KRAS, BRAF, andTP53)and pathways (MAPK signaling, p53 associated, and immunomodulatory) as predictors of ICB response and develop the Cancer Immunotherapy Response CLassifiEr (CIRCLE). Compared to tumor mutational burden alone, CIRCLE led to superior prediction of ICB response with a 10.5% increase in sensitivity and a 11% increase in specificity. We envision that CIRCLE and more broadly the analysis of recurrently mutated cancer genes will pave the way for better prognostic tools for cancer immunotherapy.
Early life inflammation is associated with spinal cord excitability and nociceptive sensitivity in human infants
Authors: Cobo Maria M. , Green Gabrielle , Andritsou Foteini , Baxter Luke , Evans Fry Ria , Grabbe Annika , Gursul Deniz , Hoskin Amy , Mellado Gabriela Schmidt , van der Vaart Marianne , Adams Eleri , Bhatt Aomesh , Denk Franziska , Hartley Caroline , Slater Rebeccah
Published: July 2022

Immune function and sensitivity to pain are closely related, but the association between early life inflammation and sensory nervous system development is poorly understood—especially in humans. Here, in term-born infants, we measure brain activity and reflex withdrawal activity (using EEG and EMG) and behavioural and physiological activity (using the PIPP-R score) to assess the impact of suspected early-onset neonatal infection on tactile- and noxious-evoked responses. We present evidence that neonatal inflammation (assessed by measuring C-reactive protein levels) is associated with increased spinal cord excitability and evoked brain activity following both tactile and noxious stimulation. There are early indications that this hyperalgesia could be maintained post-inflammation, supporting pre-clinical reports of early-life immune dysfunction influencing pain sensitivity in adults.
Lipolysis regulates major transcriptional programs in brown adipocytes
Authors: Markussen Lasse K. , Rondini Elizabeth A. , Johansen Olivia Sveidahl , Madsen Jesper G. S. , Sustarsic Elahu G. , Marcher Ann-Britt , Hansen Jacob B. , Gerhart-Hines Zachary , Granneman James G. , Mandrup Susanne
Published: July 2022

β-Adrenergic signaling is a core regulator of brown adipocyte function stimulating both lipolysis and transcription of thermogenic genes, thereby expanding the capacity for oxidative metabolism. We have used pharmacological inhibitors and a direct activator of lipolysis to acutely modulate the activity of lipases, thereby enabling us to uncover lipolysis-dependent signaling pathways downstream of β-adrenergic signaling in cultured brown adipocytes. Here we show that induction of lipolysis leads to acute induction of several gene programs and is required for transcriptional regulation by β-adrenergic signals. Using machine-learning algorithms to infer causal transcription factors, we show that PPARs are key mediators of lipolysis-induced activation of genes involved in lipid metabolism and thermogenesis. Importantly, however, lipolysis also activates the unfolded protein response and regulates the core circadian transcriptional machinery independently of PPARs. Our results demonstrate that lipolysis generates important metabolic signals that exert profound pleiotropic effects on transcription and function of cultured brown adipocytes.
A charge transfer framework that describes supramolecular interactions governing structure and properties of 2D perovskites
Authors: Zhao Xiaoming , Ball Melissa L. , Kakekhani Arvin , Liu Tianran , Rappe Andrew M. , Loo Yueh-Lin
Published: July 2022

The elucidation of structure-to-function relationships for two-dimensional (2D) hybrid perovskites remains a primary challenge for engineering efficient perovskite-based devices. By combining insights from theory and experiment, we describe the introduction of bifunctional ligands that are capable of making strong hydrogen bonds within the organic bilayer. We find that stronger intermolecular interactions draw charge away from the perovskite layers, and we have formulated a simple and intuitive computational descriptor, the charge separation descriptor (CSD), that accurately describes the relationship between the Pb-I-Pb angle, band gap, and in-plane charge transport with the strength of these interactions. A higher CSD value correlates to less distortion of the Pb-I-Pb angle, a reduced band gap, and higher in-plane mobility of the perovskite. These improved material properties result in improved device characteristics of the resulting solar cells.
Late Miocene Tarim desert wetting linked with eccentricity minimum and East Asian monsoon weakening
Authors: Nie Junsheng , Wang Weihang , Heermance Richard , Gao Peng , Xing Li , Zhang Xiaojian , Zhang Ran , Garzione Carmala , Xiao Wenjiao
Published: July 2022

Periodic wetting is an inherent feature of many monsoon marginal region deserts. Previous studies consistently demonstrate desert wetting during times of Earth’s high orbital eccentricity and strong summer monsoon. Here we report the first evidence demonstrating desert wetting during Earth’s low orbital eccentricity from the late Miocene strata of the northwestern Tarim Basin of northern China, which is commonly thought to be beyond the range of Asian monsoon precipitation. Using mechanisms for modern Tarim wetting as analogs, we propose that East Asian summer monsoon weakening enhanced westward moisture transport and caused opposite desert wetting pattern to that observed in monsoon marginal region deserts. This inference is supported by our model simulations. This result has far-reaching implications for understanding environmental variations in non-monsoonal deserts in the next few thousands of years under high atmospheric CO2 content and low eccentricity.
Electrochemical aromatic C–H hydroxylation in continuous flow
Authors: Long Hao , Chen Tian-Sheng , Song Jinshuai , Zhu Shaobin , Xu Hai-Chao
Published: July 2022

The direct hydroxylation of arene C–H bonds is a highly sought-after transformation but remains an unsolved challenge due to the difficulty in efficient and regioselective C–H oxygenation and high reactivity of the phenolic products leading to overoxidation. Herein we report electrochemical C–H hydroxylation of arenes in continuous flow for the synthesis of phenols. The method is characterized by broad scope (compatible with arenes of diverse electronic properties), mild conditions without any catalysts or chemical oxidants, and excellent scalability as demonstrated by the continuous production of 1 mol (204 grams) of one of the phenol products.
Subnanometric Ru clusters with upshifted D band center improve performance for alkaline hydrogen evolution reaction
Authors: Hu Qi , Gao Keru , Wang Xiaodeng , Zheng Hongju , Cao Jianyong , Mi Lingren , Huo Qihua , Yang Hengpan , Liu Jianhong , He Chuanxin
Published: July 2022

Subnanometric metal clusters usually have unique electronic structures and may display electrocatalytic performance distinctive from single atoms (SAs) and larger nanoparticles (NPs). However, the electrocatalytic performance of clusters, especially the size-activity relationship at the sub-nanoscale, is largely unexplored. Here, we synthesize a series of Ru nanocrystals from single atoms, subnanometric clusters to larger nanoparticles, aiming at investigating the size-dependent activity of hydrogen evolution in alkaline media. It is found that the d band center of Ru downshifts in a nearly linear relationship with the increase of diameter, and the subnanometric Ru clusters with d band center closer to Femi level display a stronger water dissociation ability and thus superior hydrogen evolution activity than SAs and larger nanoparticles. Benefiting from the high metal utilization and strong water dissociation ability, the Ru clusters manifest an ultrahigh turnover frequency of 43.3 s−1 at the overpotential of 100 mV, 36.1-fold larger than the commercial Pt/C.
Visual timing-tuned responses in human association cortices and response dynamics in early visual cortex
Authors: Hendrikx Evi , Paul Jacob M. , van Ackooij Martijn , van der Stoep Nathan , Harvey Ben M.
Published: July 2022

Quantifying the timing (duration and frequency) of brief visual events is vital to human perception, multisensory integration and action planning. Tuned neural responses to visual event timing have been found in association cortices, in areas implicated in these processes. Here we ask how these timing-tuned responses are related to the responses of early visual cortex, which monotonically increase with event duration and frequency. Using 7-Tesla functional magnetic resonance imaging and neural model-based analyses, we find a gradual transition from monotonically increasing to timing-tuned neural responses beginning in the medial temporal area (MT/V5). Therefore, across successive stages of visual processing, timing-tuned response components gradually become dominant over inherent sensory response modulation by event timing. This additional timing-tuned response component is independent of retinotopic location. We propose that this hierarchical emergence of timing-tuned responses from sensory processing areas quantifies sensory event timing while abstracting temporal representations from spatial properties of their inputs.
Pro-inflammatory cytokines mediate the epithelial-to-mesenchymal-like transition of pediatric posterior fossa ependymoma
Authors: Aubin Rachael G. , Troisi Emma C. , Montelongo Javier , Alghalith Adam N. , Nasrallah Maclean P. , Santi Mariarita , Camara Pablo G.
Published: July 2022

Pediatric ependymoma is a devastating brain cancer marked by its relapsing pattern and lack of effective chemotherapies. This shortage of treatments is due to limited knowledge about ependymoma tumorigenic mechanisms. By means of single-nucleus chromatin accessibility and gene expression profiling of posterior fossa primary tumors and distal metastases, we reveal key transcription factors and enhancers associated with the differentiation of ependymoma tumor cells into tumor-derived cell lineages and their transition into a mesenchymal-like state. We identify NFκB, AP-1, and MYC as mediators of this transition, and show that the gene expression profiles of tumor cells and infiltrating microglia are consistent with abundant pro-inflammatory signaling between these populations. In line with these results, both TGF-β1 and TNF-α induce the expression of mesenchymal genes on a patient-derived cell model, and TGF-β1 leads to an invasive phenotype. Altogether, these data suggest that tumor gliosis induced by inflammatory cytokines and oxidative stress underlies the mesenchymal phenotype of posterior fossa ependymoma.
A calibratable sensory neuron based on epitaxial VO2 for spike-based neuromorphic multisensory system
Authors: Yuan Rui , Duan Qingxi , Tiw Pek Jun , Li Ge , Xiao Zhuojian , Jing Zhaokun , Yang Ke , Liu Chang , Ge Chen , Huang Ru , Yang Yuchao
Published: July 2022

Neuromorphic perception systems inspired by biology have tremendous potential in efficiently processing multi-sensory signals from the physical world, but a highly efficient hardware element capable of sensing and encoding multiple physical signals is still lacking. Here, we report a spike-based neuromorphic perception system consisting of calibratable artificial sensory neurons based on epitaxial VO2, where the high crystalline quality of VO2 leads to significantly improved cycle-to-cycle uniformity. A calibration resistor is introduced to optimize device-to-device consistency, and to adapt the VO2 neuron to different sensors with varied resistance level, a scaling resistor is further incorporated, demonstrating cross-sensory neuromorphic perception component that can encode illuminance, temperature, pressure and curvature signals into spikes. These components are utilized to monitor the curvatures of fingers, thereby achieving hand gesture classification. This study addresses the fundamental cycle-to-cycle and device-to-device variation issues of sensory neurons, therefore promoting the construction of neuromorphic perception systems for e-skin and neurorobotics.
Analysis on curve negotiating ability of rail grinder in grinding state
Authors: Zeng Luqing , Cui Dabin , Fu Yaodong , Li Li , Liu Zhanghong
Published: July 2022

Rail grinding becomes an important maintenance means of railway. Dynamic behavior of rail grinder is due to vehicle-track coupling relationship based on mechanical-electric-hydraulic coupling. Curve negotiating ability of rail grinder through modeling and simulation based on one-side grinding is studied in this paper. Simulation result is shown below. In typical case, rail grinding will increase transverse displacement of wheelsets, derailment coefficient of wheels in front wheelset, and unloading rate of wheelsets. In other case, increase of rail irregularity amplitude and decrease of its wavelength, which aggravates fluctuation of grinding power, has little influence on curve negotiating ability. When line radius curvature decreases, compared to state without grinding, decline to curve negotiating ability of state with grinding is more significantly. When number of grinding wheels at work increases, lateral displacement of wheelset, derailment coefficient of wheels in front wheelset, and unloading ratio of wheelsets increase. In short, rail grinding will significantly deteriorate curve negotiating ability of rail grinder.
Clinical utility of simple subjective gait speed for the risk stratification of heart failure in a primary prevention setting
Authors: Ueno Kensuke , Kaneko Hidehiro , Kamiya Kentaro , Itoh Hidetaka , Okada Akira , Suzuki Yuta , Matsuoka Satoshi , Fujiu Katsuhito , Michihata Nobuaki , Jo Taisuke , Takeda Norifumi , Morita Hiroyuki , Ako Junya , Yasunaga Hideo , Komuro Issei
Published: July 2022

Little is known regarding the relationship between self-reported gait speed and the subsequent risk of heart failure (HF) and cardiovascular disease (CVD). We sought to clarify the clinical utility of self-reported gait speed in primary CVD prevention settings. This is an observational cohort study using the JMDC Claims Database, which is an administrative health claims database. Data were collected between January 2005 and April 2020. Medical records of 2,655,359 participants without a prior history of CVD were extracted from the JMDC Claims Database. Gait speed was assessed using information from questionnaires provided at health check-ups, and study participants were categorized into fast or slow gait speed groups. The primary outcome was HF. The secondary outcomes included myocardial infarction (MI), angina pectoris (AP), and stroke. The median age was 45.0 years, and 55.3% of participants were men. 46.1% reported a fast gait speed. The mean follow-up period was 1180 ± 906 days. HF, MI, AP, and stroke occurred in 1.9%, 0.2%, 1.9%, and 1.0% of participants, respectively. Multivariable Cox regression analyses showed that, compared with slow gait speed, fast gait speed was associated with a lower incidence of HF, MI, AP, and stroke. The discriminative predictive ability for HF significantly improved by adding self-reported gait speeds to traditional risk factors (net reclassification improvement 0.0347, p < 0.001). In conclusion, our analysis demonstrated that subjective gait speed could be a simple method to stratify the risk of HF and other CVD events in the general population. Further investigations are required to clarify the underlying mechanism of our results and to develop a novel approach for primary CVD prevention.
Preventive health behaviors among people with suicide ideation using nationwide cross-sectional data in South Korea
Authors: Ki Myung , Shim Hye-Young , Lim Jiseun , Hwang Minji , Kang Jiwon , Na Kyoung-Sae
Published: July 2022

This study aimed to investigate the association between suicide ideation and health-related behaviors and preventive health service use behaviors. We used data from the 2017 Korea National Health and Nutrition Examination Survey (KNHANES), a nationally representative survey. The final sample included 4486 participants aged 40 years or older. Preventive health behaviors were assessed for smoking, high-risk drinking, physical activities, regular meal intake, influenza vaccination, general health examination, and cancer screening. Logistic regression was used to examine the association between suicide ideation and preventive health behaviors with a series of adjustments for covariates. In general, suicide ideation was associated with unfavorable outcomes of preventive health behaviors, except for flu vaccination. For example, the crude prevalence of suicide ideation and non-suicide ideation groups were 54.3% vs. 43.7% for flu vaccination, 23.1% vs. 41.6% for physical activity, and 24.8% vs. 18.6% for high-risk alcohol drinking. After adjustment for covariates, the associations of suicide ideation with behaviors remained significant for physical activity (OR 0.52, 95% CI 0.34–0.81) and high-risk alcohol drinking (OR 2.22, 95% CI 1.34–3.69). Suicide ideation leads to the disruption of self-management of health behaviours, especially for physical activity and high-risk alcohol drinking, independently of depressive feelings.
Antenna movements as a function of odorants’ biological value in honeybees (Apis mellifera L.)
Authors: Cholé Hanna , Merlin Alice , Henderson Nicholas , Paupy Estelle , Mahé Prisca , Arnold Gérard , Sandoz Jean-Christophe
Published: July 2022

In honeybees, the antennae are highly mobile sensory organs that express scanning movements in various behavioral contexts and toward many stimuli, especially odorants. The rules underlying these movements are still unclear. Using a motion-capture system, we analyzed bees’ antennal responses to a panel of pheromonal and other biologically relevant odorants. We observed clear differences in bees’ antennal responses, with opposite movements to stimuli related to opposite contexts: slow backward movements were expressed in response to alarm pheromones, while fast forward movements were elicited by food related cues as well as brood and queen related pheromones. These responses are reproducible, as a similar pattern of odor-specific responses was observed in bees from different colonies, on different years. We then tested whether odorants’ attractiveness for bees, measured using an original olfactory orientation setup, may predict antenna movements. This simple measure of odorants’ valence did however not correlate with either antennal position or velocity measures, showing that more complex rules than simple hedonics underlie bees’ antennal responses to odorants. Lastly, we show that newly-emerged bees express only limited antennal responses compared to older bees, suggesting that a significant part of the observed responses are acquired during bees’ behavioral development.
The rise of electrochromics through dynamic QR codes and grayscale images in screen printed passive matrix addressed displays
Authors: Andersson Ersman Peter , Freitag Kathrin , Kawahara Jun , Åhlin Jessica
Published: July 2022

Electronic matrix addressed displays capable of presenting arbitrary grayscale images typically require complex device architectures including switching components to provide unique pixel addressability. Here, we demonstrate high-yield manufacturing of passive matrix addressed electrochromic displays on flexible substrates by solely using screen printing. The simple pixel architecture, obtained by printing only three active layers on top of each other, concurrently provides both the electrochromic functionality and the critical non-linear pixel switching response that enables presentation of arbitrary grayscale images in the resulting passive matrix addressed displays. The all-printed display technology exhibits unprecedented performance and is further verified by dynamic QR codes, to exemplify utilization within authentication, packaging, or other emerging Internet of Things applications requiring a low-cost display for data visualization.
Quantum annealing with special drivers for circuit fault diagnostics
Authors: Leipold Hannes , Spedalieri Federico M.
Published: July 2022

We present a very general construction for quantum annealing protocols to solve Combinational Circuit Fault Diagnosis problems that restricts the evolution to the space of valid diagnoses. This is accomplished by using special local drivers that induce a transition graph on the space of feasible configurations that is regular and instance independent for each given circuit topology. Analysis of small instances shows that the energy gap has a generic form, and that the minimum gap occurs in the last third of the evolution. We used these features to construct an improved annealing schedule and benchmarked its performance through closed system simulations. We found that degeneracy can help the performance of quantum annealing, especially for instances with a higher number of faults in their minimum fault diagnosis. This contrasts with the performance of classical approaches based on brute force search that are used in industry for large scale circuits.
Using historical tropical cyclone climate datasets to examine wind speed recurrence for coastal Australia
Authors: Bell S. S. , Dowdy A. J. , Ramsay H. A. , Chand S. S. , Su C-H , Ye H.
Published: July 2022

Likelihood estimates of extreme winds, including those from tropical cyclones (TCs) at certain locations are used to inform wind load standards for structural design. Here, wind speed average recurrence intervals (ARIs) determined from TC climate data dating back to the 1970s in two quantile–quantile adjusted reanalysis datasets (ERA5 and BARRA [1990]), and best-track observations for context, were compared with Standardized ARIs (AS/NZS) across seven tropical and two subtropical Australian inland coastal regions. The novelty of this work lies in determining TC-wind speed ARIs from a range of datasets that are not typically used to evaluate this metric. Inherent differences between the data used to determine the Standard ARIs (large sample size allow for larger extrapolations; GEV function) and TC data ARIs (smaller sample size and less certain data; the more asymptotic Lognormal/Weibull functions are used) led to the use of different extreme value functions. Results indicated that although these are two distinct ways of determining design wind speeds, when they are considered equivalent, there was a moderate reproduction of the ARI curves with respect to the Standard in both reanalysis datasets, suggesting that similar analyses using climate model products can provide useful information on these types of metrics with some caveats. Trends in TC wind strength affecting coastal Australia were also analyzed, indicating a potential slight downtrend in tropical West coast TC wind strength and slight uptrend for tropical East coast TC wind strength, noting considerable uncertainty given the short time period and limitations of data quality including over longer time periods. Such trends are not only limited to the relationship between TC intensity and anthropogenic warming, but also to regional changes in TC frequency and track direction. This could lead to significant trends emerging in regional Australian TC wind gust strength before several decades of warming have occurred. It is hoped that climate models can provide both longer-term and a more homogenous base for these types of evaluations and subsequent projections with respect to climate change simulations.
Electron beam surface remelting enhanced corrosion resistance of additively manufactured Ti-6Al-4V as a potential in-situ re-finishing technique
Authors: Shahsavari Mohammadali , Imani Amin , Setavoraphan Andaman , Schaller Rebecca Filardo , Asselin Edouard
Published: July 2022

This study explores the effect of surface re-finishing on the corrosion behavior of electron beam manufactured (EBM) Ti-G5 (Ti-6Al-4V), including the novel application of an electron beam surface remelting (EBSR) technique. Specifically, the relationship between material surface roughness and corrosion resistance was examined. Surface roughness was tested in the as-printed (AP), mechanically polished (MP), and EBSR states and compared to wrought (WR) counterparts. Electrochemical measurements were performed in chloride-containing media. It was observed that surface roughness, rather than differences in the underlying microstructure, played a more significant role in the general corrosion resistance in the environment explored here. While both MP and EBSR methods reduced surface roughness and enhanced corrosion resistance, mechanical polishing has many known limitations. The EBSR process explored herein demonstrated positive preliminary results. The surface roughness (Ra) of the EBM-AP material was considerably reduced by 82%. Additionally, the measured corrosion current density in 0.6 M NaCl for the EBSR sample is 0.05 µA cm−2, five times less than the value obtained for the EBM-AP specimen (0.26 µA cm−2).
Inhibitor induced conformational changes in SARS-COV-2 papain-like protease
Authors: Ferreira Glaucio Monteiro , Pillaiyar Thanigaimalai , Hirata Mario Hiroyuki , Poso Antti , Kronenberger Thales
Published: July 2022

SARS-CoV-2’s papain-like protease (PLpro) interaction with ligands has recently been explored with a myriad of crystal structures. We used molecular dynamics (MD) simulations to study different PLpro-ligand complexes, their ligand-induced conformational changes, and interactions. We focused on inhibitors reported with known IC50 against PLpro, namely GRL-0617, XR8-89, PLP_Snyder530, and Sander’s recently published compound 7 (CPD7), and compared these trajectories against the apostructure (Apo), with a total of around 60 µs worth simulation data. We aimed to study the conformational changes using molecular dynamics simulations for the inhibitors in the PLpro. PCA analyses and the MSM models revealed distinct conformations of PLpro in the absence/presence of ligands and proposed that BL2-loop contributes to the accessibility of these inhibitors. Further, bulkier substituents closer to Tyr268 and Gln269 could improve inhibition of SARS-CoV-2 PLpro by occupying the region between BL2-groove and BL2-loop, but we also expand on the relevance of exploring multiple PLpro sub-pockets to improve inhibition.
Effects of cavity orientation on nesting success inferred from long-term monitoring of the endangered red-cockaded woodpecker
Authors: Landler Lukas , Skelton James , Jusino Michelle A. , Van Lanen Andy , Walters Jeffrey R.
Published: July 2022

Animals that create structures often display non-random patterns in the direction of their constructions. This tendency of oriented construction is widely presumed to be an adaptive trait of the constructor’s extended phenotype, but there is little empirical support for this hypothesis. Particularly, for cavity nesting-birds there is a lack of studies examining this issue. In this study of a primary cavity excavator, the endangered red-cockaded woodpecker (Dryobates borealis), we show that cavity entrances exhibited a strong westward bias in all 11 of the populations examined throughout the geographic range of the species in the southeastern United States. This species requires cavities in living pine trees for roosting and nesting that often take many years to complete, resulting in many incomplete excavations on the landscape. We used population monitoring data to show that orientation was stronger among completed cavities than incomplete cavities. There was a significant correlation between latitude and average cavity direction among populations, turning northward with increasing latitude, suggesting adaptation to local conditions. Long-term monitoring data showed that cavity orientation and breeding group size are correlated with egg hatching rates, fledging rates, and the total number of fledglings produced per nest. Our results provide empirical evidence from extensive long-term data that directional orientation in animal constructions is an important feature of the extended animal phenotype and have immediate implications for animal ecology and the conservation of endangered species.
Leveraging physical intelligence for the self-design of high performance engineering structures
Authors: Paixão Jessé , Sadoulet-Reboul Emeline , Foltête Emmanuel , Chevallier Gaël , Cogan Scott
Published: July 2022

The design of complex engineering structures largely relies on computational intelligence in the form of science-based predictive models to support design decisions. This approach requires modeling and manufacturing uncertainties to be accounted for explicitly and leads to an inescapable trade-off of performance for robustness. To remedy this situation, a novel self-design paradigm is proposed that closes the loop between the design and manufacturing processes by leveraging physical intelligence in the form of real-time experimental observations. This allows the real-time product behavior to participate in its own design. The main benefit of the proposed paradigm is that both manufacturing variability and difficult-to-model physics are accounted for implicitly via in situ measurements thus circumventing the performance-robustness trade-off and guaranteeing enhanced performance with respect to standardized designs. This paradigm shift leads to tailored design realizations which could benefit a wide range of high performance engineering applications. The proposed paradigm is applied to the design of a simply-supported plate with a beam-like absorber introduced to reduce vibrations based on an equal peaks performance criteria. The experimental setup includes a low-cost 3D printer driven by a simple decision algorithm and equipped with an online vibration testing system. The performances of a small population of self-designed plates are compared to their standardized counterparts in order to highlight the advantages and limitations of the new self-design manufacturing paradigm.
Integrated socio-environmental vulnerability assessment of coastal hazards using data-driven and multi-criteria analysis approaches
Authors: Tanim Ahad Hasan , Goharian Erfan , Moradkhani Hamid
Published: July 2022

Coastal hazard vulnerability assessment has been centered around the multi-variate analysis of geo-physical and hydroclimate data. The representation of coupled socio-environmental factors has often been ignored in vulnerability assessment. This study develops an integrated socio-environmental Coastal Vulnerability Index (CVI), which simultaneously combines information from five vulnerability groups: biophysical, hydroclimate, socio-economic, ecological, and shoreline. Using the Multi-Criteria Decision Making (MCDM) approach, two CVI (CVI-50 and CVI-90) have been developed based on average and extreme conditions of the factors. Each CVI is then compared to a data-driven CVI, which is formed based on Probabilistic Principal Component Analysis (PPCA). Both MCDM and PPCA have been tied into geospatial analysis to assess the natural hazard vulnerability of six coastal counties in South Carolina. Despite traditional MCDM-based vulnerability assessments, where the final index is estimated based on subjective weighting methods or equal weights, this study employs an entropy weighting technique to reduce the individuals’ biases in weight assignment. Considering the multivariate nature of the coastal vulnerability, the validation results show both CVI-90 and PPCA preserve the vulnerability results from biophysical and socio-economic factors reasonably, while the CVI-50 methods underestimate the biophysical vulnerability of coastal hazards. Sensitivity analysis of CVIs shows that Charleston County is more sensitive to socio-economic factors, whereas in Horry County the physical factors contribute to a higher degree of vulnerability. Findings from this study suggest that the PPCA technique facilitates the high-dimensional vulnerability assessment, while the MCDM approach accounts more for decision-makers' opinions.
Gene function prediction in five model eukaryotes exclusively based on gene relative location through machine learning
Authors: Pazos Obregón Flavio , Silvera Diego , Soto Pablo , Yankilevich Patricio , Guerberoff Gustavo , Cantera Rafael
Published: July 2022

The function of most genes is unknown. The best results in automated function prediction are obtained with machine learning-based methods that combine multiple data sources, typically sequence derived features, protein structure and interaction data. Even though there is ample evidence showing that a gene’s function is not independent of its location, the few available examples of gene function prediction based on gene location rely on sequence identity between genes of different organisms and are thus subjected to the limitations of the relationship between sequence and function. Here we predict thousands of gene functions in five model eukaryotes (Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Homo sapiens) using machine learning models exclusively trained with features derived from the location of genes in the genomes to which they belong. Our aim was not to obtain the best performing method to automated function prediction but to explore the extent to which a gene's location can predict its function in eukaryotes. We found that our models outperform BLAST when predicting terms from Biological Process and Cellular Component Ontologies, showing that, at least in some cases, gene location alone can be more useful than sequence to infer gene function.
Nutrient intakes and telomere length of cell-free circulating DNA from amniotic fluid: findings from the Mamma & Bambino cohort
Authors: Magnano San Lio Roberta , Maugeri Andrea , La Rosa Maria Clara , Giunta Giuliana , Panella Marco , Cianci Antonio , Caruso Maria Anna Teresa , Agodi Antonella , Barchitta Martina
Published: July 2022

Pregnancy represents a crucial period in which several exposures—and especially maternal diet—might shape children’s health. Thus, identifying how maternal dietary intakes early affect biological aging in children represents a public health mission. We aimed to assess the relationship between maternal intake of nutrients in early pregnancy and telomere length of cell-free circulating DNA (cfDNA) from amniotic fluid. We used data and samples from the ongoing prospective “Mamma & Bambino” study, which recruits mother–child pairs from Catania at the first prenatal visit. Maternal nutrient intakes were assessed using a Food Frequency Questionnaire, while relative telomere length of cfDNA was assessed by real-time polymerase chain reaction. Our analysis included 174 mother–child pairs. The intakes of iron, vitamin B1, and magnesium were positively correlated with relative telomere length (p-values < 0.05). However, only the intake of magnesium was positively associated with relative telomere length, after applying a linear regression model (β = 0.002; SE = 0.001; p = 0.024). Magnesium deficiency was negatively associated with relative telomere length after adjusting for the same covariates (β = −0.467; SE = 0.176; p = 0.009). To our knowledge, this is the first evidence of a positive relationship between maternal nutrient intake and telomere length of cfDNA. Further efforts are needed for deeply investigating the effect of maternal dietary intakes on telomere length, in order to develop effective public health strategies.
Performance and reproducibility of 13C and 15N hyperpolarization using a cryogen-free DNP polarizer
Authors: Ferrari Arianna , Peters Josh , Anikeeva Mariia , Pravdivtsev Andrey , Ellermann Frowin , Them Kolja , Will Olga , Peschke Eva , Yoshihara Hikari , Jansen Olav , Hövener Jan-Bernd
Published: July 2022

The setup, operational procedures and performance of a cryogen-free device for producing hyperpolarized contrast agents using dissolution dynamic nuclear polarization (dDNP) in a preclinical imaging center is described. The polarization was optimized using the solid-state, DNP-enhanced NMR signal to calibrate the sample position, microwave and NMR frequency and power and flip angle. The polarization of a standard formulation to yield ~ 4 mL, 60 mM 1-13C-pyruvic acid in an aqueous solution was quantified in five experiments to P(13C) = (38 ± 6) % (19 ± 1) s after dissolution. The mono-exponential time constant of the build-up of the solid-state polarization was quantified to (1032 ± 22) s. We achieved a duty cycle of 1.5 h that includes sample loading, monitoring the polarization build-up, dissolution and preparation for the next run. After injection of the contrast agent in vivo, pyruvate, pyruvate hydrate, lactate, and alanine were observed, by measuring metabolite maps. Based on this work sequence, hyperpolarized 15N urea was obtained (P(15N) = (5.6 ± 0.8) % (30 ± 3) s after dissolution).
Phylogeography of Nasutitermes ephratae (Termitidae: Nasutitermitinae) in neotropical region
Authors: de Faria Santos Amanda , Cancello Eliana Marques , Morales Adriana Coletto
Published: July 2022

The neotropical region ranks third in the number of termites and includes five different families. Of these, Termitidae is the most diverse and includes the speciesNasutitermes ephratae, which is widespread in the neotropics. To date, only one study has been published about phylogeography in neotropical termites (N. corniger). Here, we explored the population genetic patterns ofN. ephrataeand also evaluated the phylogeographical processes involved in the evolutionary history of the species. We used the mitochondrial genes 16S rRNA and COII as molecular markers: these were sequenced for 128 samples ofN. ephratae. We estimated the genetic diversity and divergence time as well as the demography and genetic structure. We also performed an ancestral area reconstruction and a haplotype network. The results showed high genetic variability, recent demographic expansion, and strong genetic structure. A dispersal route for the species, that occurred in both directions between South and Central America, was inferred. The results emphasize a temporary separation between the South and Central America populations that affected the origin of the current Central America populations. These populations were formed from different phylogeographic histories.
Counteracting forces of introgressive hybridization and interspecific competition shape the morphological traits of cryptic Iberian Eptesicus bats
Authors: Horta Pedro , Raposeira Helena , Baños Adrián , Ibáñez Carlos , Razgour Orly , Rebelo Hugo , Juste Javier
Published: July 2022

Cryptic species that coexist in sympatry are likely to simultaneously experience strong competition and hybridization. The first phenomenon would lead to character displacement, whereas the second can potentially promote morphological similarity through adaptive introgression. The main goal of this work was to investigate the effect of introgressive hybridization on the morphology of cryptic Iberian Eptesicus bats when facing counteracting evolutionary forces from interspecific competition. We found substantial overlap both in dentition and in wing morphology traits, though mainly in individuals in sympatry. The presence of hybrids contributes to a fifth of this overlap, with hybrids showing traits with intermediate morphometry. Thus, introgressive hybridization may contribute to species adaptation to trophic and ecological space responding directly to the macro-habitats characteristics of the sympatric zone and to local prey availability. On the other hand, fur shade tended to be browner and brighter in hybrids than parental species. Colour differences could result from partitioning of resources as an adaptation to environmental factors such as roost and microhabitats. We argue that a balance between adaptive introgression and niche partitioning shapes species interactions with the environment through affecting morphological traits under selection.
A novel inactivated virus system (InViS) for a fast and inexpensive assessment of viral disintegration
Authors: Furer Lea A. , Clement Pietro , Herwig Gordon , Rossi René M. , Bhoelan Farien , Amacker Mario , Stegmann Toon , Buerki-Thurnherr Tina , Wick Peter
Published: July 2022

The COVID–19 pandemic has caused considerable interest worldwide in antiviral surfaces, and there has been a dramatic increase in the research and development of innovative material systems to reduce virus transmission in the past few years. The International Organization for Standardization (ISO) norms 18,184 and 21,702 are two standard methods to characterize the antiviral properties of porous and non-porous surfaces. However, during the last years of the pandemic, a need for faster and inexpensive characterization of antiviral material was identified. Therefore, a complementary method based on an Inactivated Virus System (InViS) was developed to facilitate the early-stage development of antiviral technologies and quality surveillance of the production of antiviral materials safely and efficiently. The InViS is loaded with a self-quenched fluorescent dye that produces a measurable increase in fluorescence when the viral envelope disintegrates. In the present work, the sensitivity of InViS to viral disintegration by known antiviral agents is demonstrated and its potential to characterize novel materials and surfaces is explored. Finally, the InViS is used to determine the fate of viral particles within facemasks layers, rendering it an interesting tool to support the development of antiviral surface systems for technical and medical applications.
Exploring the molecular interaction of mebendazole with bovine serum albumin using multi-spectroscopic approaches and molecular docking
Authors: El Gammal Reem N. , Elmansi Heba , El-Emam Ali A. , Belal Fathalla , Hammouda Mohammed E. A.
Published: July 2022

This article presents the binding interaction between mebendazole (MBZ) and bovine serum albumin. The interaction has been studied using different techniques, such as fluorescence quenching spectroscopy, UV–visible spectroscopy, synchronous fluorescence spectroscopy, fourier transform infrared, and fluorescence resonance energy transfer in addition to molecular docking. Results from Stern Volmer equation stated that the quenching for MBZ-BSA binding was static. The fluorescence quenching spectroscopic study was performed at three temperature settings. The binding constant (kq), the number of binding sites (n), thermodynamic parameters (ΔHο, ΔSοand ΔGο), and binding forces were determined. The results exhibited that the interaction was endothermic. It was revealed that intermolecular hydrophobic forces led to the stabilization of the drug-protein system. Using the site marker technique, the binding between MBZ and BSA was found to be located at subdomain IIA (site I). This was furtherly approved using the molecular docking technique with the most stable MBZ configuration. This research may aid in understanding the pharmacokinetics and toxicity of MBZ and give fundamental data for its safe usage to avoid its toxicity.
Impact of joint interactions with humans and social interactions with conspecifics on the risk of zooanthroponotic outbreaks among wildlife populations
Authors: Balasubramaniam Krishna N. , Aiempichitkijkarn Nalina , Kaburu Stefano S. K. , Marty Pascal R. , Beisner Brianne A. , Bliss-Moreau Eliza , Arlet Malgorzata E. , Atwill Edward , McCowan Brenda
Published: July 2022

Pandemics caused by pathogens that originate in wildlife highlight the importance of understanding the behavioral ecology of disease outbreaks at human–wildlife interfaces. Specifically, the relative effects of human–wildlife and wildlife-wildlife interactions on disease outbreaks among wildlife populations in urban and peri-urban environments remain unclear. We used social network analysis and epidemiological Susceptible-Infected-Recovered models to simulate zooanthroponotic outbreaks, through wild animals’ joint propensities to co-interact with humans, and their social grooming of conspecifics. On 10 groups of macaques (Macacaspp.) in peri-urban environments in Asia, we collected behavioral data using event sampling of human–macaque interactions within the same time and space, and focal sampling of macaques’ social interactions with conspecifics and overall anthropogenic exposure. Model-predicted outbreak sizes were related to structural features of macaques’ networks. For all three species, and for both anthropogenic (co-interactions) and social (grooming) contexts, outbreak sizes were positively correlated to the network centrality of first-infected macaques. Across host species and contexts, the above effects were stronger through macaques’ human co-interaction networks than through their grooming networks, particularly for rhesus and bonnet macaques. Long-tailed macaques appeared to show intraspecific variation in these effects. Our findings suggest that among wildlife in anthropogenically-impacted environments, the structure of their aggregations around anthropogenic factors makes them more vulnerable to zooanthroponotic outbreaks than their social structure. The global features of these networks that influence disease outbreaks, and their underlying socio-ecological covariates, need further investigation. Animals that consistently interact with both humans and their conspecifics are important targets for disease control.
Multimorbidity patterns and hospitalisation occurrence in adults and older adults aged 50 years or over
Authors: Rodrigues Luciana Pereira , Vissoci João Ricardo Nickenig , França Diego Galdino , Caruzzo Nayara Malheiros , Batista Sandro Rogério Rodrigues , de Oliveira Cesar , Nunes Bruno Pereira , Silveira Erika Aparecida
Published: July 2022

Multimorbidity is highly prevalent in older adults and can lead to hospitalisation. We investigate the prevalence, associated factors, and multimorbidity pattern associated to hospitalisation, readmission, and length of stay in the population aged 50 years and older. We analysed baseline data (2015–2016) from the ELSI-Brazil cohort, a representative sample of non-institutionalised Brazilians aged ≥ 50 years. In total, 8807 individuals aged ≥ 50 years were included. Poisson regression with robust variance adjusted for confounders was used to verify the associations with hospitalisation. Multiple linear regression was used to analyse the associations with readmission and length of stay. Network analysis was conducted using 19 morbidities and the outcome variables. In 8807 participants, the prevalence of hospitalisation was 10.0% (95% CI 9.1, 11), mean readmissions was 1.55 ± 1.191, and mean length of stay was 6.43 ± 10.46 days. Hospitalisation was positively associated with male gender, not living with a partner, not having ingested alcoholic beverages in the last month, and multimorbidity. For hospital readmission, only multimorbidity ≥ 3 chronic conditions showed a statistically significant association. Regarding the length of stay, the risk was positive for males and negative for living in rural areas. Five disease groups connected to hospitalisation, readmission and length of stay were identified. To conclude, sociodemographic variables, such as gender, age group, and living in urban areas, and multimorbidity increased the risk of hospitalisation, mean number of readmissions, and mean length of stay. Through network analysis, we identified the groups of diseases that increased the risk of hospitalisation, readmissions, and length of stay.