bluuebunny/crossref_metadata_2025 huggingface dataset:
Data‐Driven Inference of the Mechanics of Slip Along Glacier Beds Using Physics‐Informed Neural Networks: Case Study on Rutford Ice Stream, Antarctica
Authors: Riel B. , Minchew B. , Bischoff T.
Published: September 2021

Reliable projections of sea‐level rise depend on accurate representations of how fast‐flowing glaciers slip along their beds. The mechanics of slip are often parameterized as a constitutive relation (or “sliding law”) whose proper form remains uncertain. Here, we present a novel deep learning‐based framework for learning the time evolution of drag at glacier beds from time‐dependent ice velocity and elevation observations. We use a feedforward neural network, informed by the governing equations of ice flow, to infer spatially and temporally varying basal drag and associated uncertainties from data. We test the framework on 1D and 2D ice flow simulation outputs and demonstrate the recovery of the underlying basal mechanics under various levels of observational and modeling uncertainties. We apply this framework to time‐dependent velocity data for Rutford Ice Stream, Antarctica, and present evidence that ocean‐tide‐driven changes in subglacial water pressure drive changes in ice flow over the tidal cycle.
Discovery and characterization of UipA, a uranium- and iron-binding PepSY protein involved in uranium tolerance by soil bacteria
Authors: Gallois Nicolas , Alpha-Bazin Béatrice , Bremond Nicolas , Ortet Philippe , Barakat Mohamed , Piette Laurie , Mohamad Ali Abbas , Lemaire David , Legrand Pierre , Theodorakopoulos Nicolas , Floriani Magali , Février Laureline , Den Auwer Christophe , Arnoux Pascal , Berthomieu Catherine , Armengaud Jean , Chapon Virginie
Published: September 2021

Uranium is a naturally occurring radionuclide. Its redistribution, primarily due to human activities, can have adverse effects on human and non-human biota, which poses environmental concerns. The molecular mechanisms of uranium tolerance and the cellular response induced by uranium exposure in bacteria are not yet fully understood. Here, we carried out a comparative analysis of four actinobacterial strains isolated from metal and radionuclide-rich soils that display contrasted uranium tolerance phenotypes. Comparative proteogenomics showed that uranyl exposure affects 39–47% of the total proteins, with an impact on phosphate and iron metabolisms and membrane proteins. This approach highlighted a protein of unknown function, named UipA, that is specific to the uranium-tolerant strains and that had the highest positive fold-change upon uranium exposure. UipA is a single-pass transmembrane protein and its large C-terminal soluble domain displayed a specific, nanomolar binding affinity for UO22+ and Fe3+. ATR-FTIR and XAS-spectroscopy showed that mono and bidentate carboxylate groups of the protein coordinated both metals. The crystal structure of UipA, solved in its apo state and bound to uranium, revealed a tandem of PepSY domains in a swapped dimer, with a negatively charged face where uranium is bound through a set of conserved residues. This work reveals the importance of UipA and its PepSY domains in metal binding and radionuclide tolerance.
Morphological studies of rose prickles provide new insights
Authors: Zhou Ningning , Simonneau Fabienne , Thouroude Tatiana , Oyant Laurence Hibrand-Saint , Foucher Fabrice
Published: September 2021

Prickles are common structures in plants that play a key role in defense against herbivores. In theRosagenus, prickles are widely present with great diversity in terms of form and density. For cut rose production, prickles represent an important issue, as they can damage the flower and injure workers. Our objectives were to precisely describe the types of prickles that exist in roses, their tissues of origin and their development. We performed a detailed histological analysis of prickle initiation and development in a rose F1 population. Based on the prickle investigation of 110 roses, we proposed the first categorization of prickles in theRosagenus. They are mainly divided into two categories, nonglandular prickles (NGPs) and glandular prickles (GPs), and subcategories were defined based on the presence/absence of hairs and branches. We demonstrated that NGPs and GPs both originate from multiple cells of the ground meristem beneath the protoderm. For GPs, the gland cells originate from the protoderm of the GP at the early developmental stage. Our findings clearly demonstrate that prickles are not modified trichomes (which originate from the protoderm). These conclusions are different from the current mainstream hypothesis. These results provide a foundation for further studies on prickle initiation and development in plants.
Application of full-genome analysis to diagnose rare monogenic disorders
Authors: Shieh Joseph T. , Penon-Portmann Monica , Wong Karen H. Y. , Levy-Sakin Michal , Verghese Michelle , Slavotinek Anne , Gallagher Renata C. , Mendelsohn Bryce A. , Tenney Jessica , Beleford Daniah , Perry Hazel , Chow Stephen K. , Sharo Andrew G. , Brenner Steven E. , Qi Zhongxia , Yu Jingwei , Klein Ophir D. , Martin David , Kwok Pui-Yan , Boffelli Dario
Published: September 2021

Current genetic tests for rare diseases provide a diagnosis in only a modest proportion of cases. The Full-Genome Analysis method, FGA, combines long-range assembly and whole-genome sequencing to detect small variants, structural variants with breakpoint resolution, and phasing. We built a variant prioritization pipeline and tested FGA’s utility for diagnosis of rare diseases in a clinical setting. FGA identified structural variants and small variants with an overall diagnostic yield of 40% (20 of 50 cases) and 35% in exome-negative cases (8 of 23 cases), 4 of these were structural variants. FGA detected and mapped structural variants that are missed by short reads, including non-coding duplication, and phased variants across long distances of more than 180 kb. With the prioritization algorithm, longer DNA technologies could replace multiple tests for monogenic disorders and expand the range of variants detected. Our study suggests that genomes produced from technologies like FGA can improve variant detection and provide higher resolution genome maps for future application.
Longevity leap: mind the healthspan gap
Authors: Garmany Armin , Yamada Satsuki , Terzic Andre
Published: September 2021

Life expectancy has increased by three decades since the mid-twentieth century. Parallel healthspan expansion has however not followed, largely impeded by the pandemic of chronic diseases afflicting a growing older population. The lag in quality of life is a recognized challenge that calls for prioritization of disease-free longevity. Contemporary communal, clinical and research trends aspiring to extend the health horizon are here outlined in the context of an evolving epidemiology. A shared action integrating public and societal endeavors with emerging interventions that target age-related multimorbidity and frailty is needed. A multidimensional buildout of a curative perspective, boosted by modern anti-senescent and regenerative technology with augmented decision making, would require dedicated resources and cost-effective validation to responsibly bridge the healthspan-lifespan gap for a future of equitable global wellbeing.
Japanese encephalitis virus live attenuated vaccine strains display altered immunogenicity, virulence and genetic diversity
Authors: Davis Emily H. , Beck Andrew S. , Li Li , White Mellodee M. , Greenberg Marianne Banks , Thompson Jill K. , Widen Steven G. , Barrett Alan D. T. , Bourne Nigel
Published: September 2021

Japanese encephalitis virus (JEV) is the etiological agent of Japanese encephalitis (JE). The most commonly used vaccine used to prevent JE is the live-attenuated strain SA14-14-2, which was generated by serial passage of the wild-type (WT) JEV strain SA14. Two other vaccine candidates, SA14-5-3 and SA14-2-8 were derived from SA14. Both were shown to be attenuated but lacked sufficient immunogenicity to be considered effective vaccines. To better contrast the SA14-14-2 vaccine with its less-immunogenic counterparts, genetic diversity, ribavirin sensitivity, mouse virulence and mouse immunogenicity of the three vaccines were investigated. Next generation sequencing demonstrated that SA14-14-2 was significantly more diverse than both SA14-5-3 and SA14-2-8, and was slightly less diverse than WT SA14. Notably, WT SA14 had unpredictable levels of diversity across its genome whereas SA14-14-2 is highly diverse, but genetic diversity is not random, rather the virus only tolerates variability at certain residues. Using Ribavirin sensitivity in vitro, it was found that SA14-14-2 has a lower fidelity replication complex compared to SA14-5-3 and SA14-2-8. Mouse virulence studies showed that SA14-2-8 was the most virulent of the three vaccine strains while SA14-14-2 had the most favorable combination of safety (virulence) and immunogenicity for all vaccines tested. SA14-14-2 contains genetic diversity and sensitivity to the antiviral Ribavirin similar to WT parent SA14, and this genetic diversity likely explains the (1) differences in genomic sequences reported for SA14-14-2 and (2) the encoding of major attenuation determinants by the viral E protein.
Paracetamol use during pregnancy — a call for precautionary action
Authors: Bauer Ann Z. , Swan Shanna H. , Kriebel David , Liew Zeyan , Taylor Hugh S. , Bornehag Carl-Gustaf , Andrade Anderson M. , Olsen Jørn , Jensen Rigmor H. , Mitchell Rod T. , Skakkebaek Niels E. , Jégou Bernard , Kristensen David M.
Published: September 2021

Paracetamol (N-acetyl-p-aminophenol (APAP), otherwise known as acetaminophen) is the active ingredient in more than 600 medications used to relieve mild to moderate pain and reduce fever. APAP is widely used by pregnant women as governmental agencies, including the FDA and EMA, have long considered APAP appropriate for use during pregnancy when used as directed. However, increasing experimental and epidemiological research suggests that prenatal exposure to APAP might alter fetal development, which could increase the risks of some neurodevelopmental, reproductive and urogenital disorders. Here we summarize this evidence and call for precautionary action through a focused research effort and by increasing awareness among health professionals and pregnant women. APAP is an important medication and alternatives for treatment of high fever and severe pain are limited. We recommend that pregnant women should be cautioned at the beginning of pregnancy to: forego APAP unless its use is medically indicated; consult with a physician or pharmacist if they are uncertain whether use is indicated and before using on a long-term basis; and minimize exposure by using the lowest effective dose for the shortest possible time. We suggest specific actions to implement these recommendations. This Consensus Statement reflects our concerns and is currently supported by 91 scientists, clinicians and public health professionals from across the globe.
Probabilistic risk assessment of solar particle events considering the cost of countermeasures to reduce the aviation radiation dose
Authors: Fujita Moe , Sato Tatsuhiko , Saito Susumu , Yamashiki Yosuke
Published: September 2021

Cosmic-ray exposure to flight crews and passengers, which is called aviation radiation exposure, is an important topic in radiological protection, particularly for solar energetic particles (SEP). We therefore assessed the risks associated with the countermeasure costs to reduce SEP doses and dose rates for eight flight routes during five ground level enhancements (GLE). A four-dimensional dose-rate database developed by the Warning System for Aviation Exposure to Solar Energetic Particles, WASAVIES, was employed in the SEP dose evaluation. As for the cost estimation, we considered two countermeasures; one is the cancellation of the flight, and the other is the reduction of flight altitudes. Then, we estimated the annual occurrence frequency of significant GLE events that would bring the maximum flight route dose and dose rate over 1.0 mSv and 80 μSv/h, respectively, based on past records of GLE as well as historically large events observed by the cosmogenic nuclide concentrations in tree rings and ice cores. Our calculations suggest that GLE events of a magnitude sufficient to exceed the above dose and dose rate thresholds, requiring a change in flight conditions, occur once every 47 and 17 years, respectively, and their conservatively-estimated annual risks associated with the countermeasure costs are up to around 1.5 thousand USD in the cases of daily-operated long-distance flights.
Simulation study on the effects of cancellous bone structure in the skull on ultrasonic wave propagation
Authors: Michimoto Itsuki , Miyashita Kazuki , Suzuyama Hidehisa , Yano Keita , Kobayashi Yasuyo , Saito Kozue , Matsukawa Mami
Published: September 2021

The transcranial Doppler method (TCD) enables the measurement of cerebral blood flow velocity and detection of emboli by applying an ultrasound probe to the temporal bone window, or the orbital or greater occipital foramina. TCD is widely used for evaluation of cerebral vasospasm after subarachnoid hemorrhage, early detection of patients with arterial stenosis, and the assessment of brain death. However, measurements often become difficult in older women. Among various factors contributing to this problem, we focused on the effect of the diploe in the skull bone on the penetration of ultrasound into the brain. In particular, the effect of the cancellous bone structure in the diploe was investigated. Using a 2D digital bone model, wave propagation through the skull bone was investigated using the finite-difference time-domain (FDTD) method. We fabricated digital bone models with similar structure but different BV/TV (bone volume/total volume) values in the diploe. At a BV/TV of approximately 50–60% (similar to that of older women), the minimum ultrasound amplitude was observed as a result of scattering and multiple reflections in the cancellous diploe. These results suggest that structural changes such as osteoporosis may be one factor hampering TCD measurements.
Effective and rugged analysis of glyphosate, glufosinate, and metabolites in Tenebrio molitor larva (mealworms) using liquid chromatography tandem mass spectrometry
Authors: Kim Leesun , Baek Sujn , Son Kyungae , Lee Hee-Dong , Choi Dal-Soon , Kim Chang Jo , Noh Hyun Ho
Published: September 2021

Tenebrio molitor larva (mealworms) has recently attracted attention as a protein source for food and feed. The larva is generally fed with wheat bran, which can be possibly contaminated with glyphosate. To establish food safe standards, a rugged and effective analytical method for glyphosate, aminomethylphosphonic acid, glufosinate, and their metabolites including 3-methylphosphinico-propionic acid, and N-acetyl glufosinate, in mealworms was optimized using liquid chromatography tandem mass spectrometry. An anionic polar pesticide column was used due to its high suitability for glyphosate. Acidified water and acetonitrile were used to extract the target compounds without contribution from various fatty and pigment interferences derived from brownish insects. Seven different clean-up procedures ((1) 50 mg C18 (2) 20 mg C18/Z-sep (3) PRiME hydrophilic-lipophilic balance (HLB) cartridge (4) 75 mg Z-sep, (5) 75 mg Z-sep+, (6) EMR-lipid cartridge, and (7) 50 mg ENVI-Carb) were compared. Due to its simplicity and cost-effectiveness, PRiME HLB was selected for clean-up. The recoveries of the target compounds were ranged from 86 to 96% with < 20% relative standard deviations. Therefore, this simple and effective method can be applied for the two pesticides and their metabolites in other edible insects or high-fat matrices.
Differences in the dynamics of community disaster resilience across the globe
Authors: Hochrainer-Stigler Stefan , Velev Stefan , Laurien Finn , Campbell Karen , Czajkowski Jeffrey , Keating Adriana , Mechler Reinhard
Published: September 2021

The consideration of disaster resilience as a multidimensional concept provides a viable and promising way forward for reducing risk and minimizing impacts today and in the future. What is missing is the understanding of the actual dynamics of resilience over time based on empirical evidence. This empirical understanding requires a consistent measure of resilience. To that end, a Technical Resilience Grading Standard for community flood resilience, was applied in a longitudinal study from 2016 to 2018 in 68 communities across the globe. We analyse the dynamics of disaster resilience using an advanced boosted regression tree modelling framework. The main outcome of our analysis is twofold: first, we found empirical evidence that the dynamics of resilience build on a typology of communities and that different community clusters experience different dynamics; and second, the dynamics of resilience follows transitional behaviour rather than a linear or continuous process. These are empirical insights that can provide ways forward, theoretically as well as practically, in the understanding of resilience as well as in regard to effective policy guidance to enhance disaster resilience.
A multilevel scenario based predictive analytics framework to model the community mental health and built environment nexus
Authors: Mukherjee Sayanti , Frimpong Boamah Emmanuel , Ganguly Prasangsha , Botchwey Nisha
Published: September 2021

The built environment affects mental health outcomes, but this relationship is less studied and understood. This article proposes a novel multi-level scenario-based predictive analytics framework (MSPAF) to explore the complex relationships between community mental health outcomes and the built environment conditions. The MSPAF combines rigorously validated interpretable machine learning algorithms and scenario-based sensitivity analysis to test various hypotheses on how the built environment impacts community mental health outcomes across the largest metropolitan areas in the US. Among other findings, our results suggest that declining socio-economic conditions of the built environment (e.g., poverty, low income, unemployment, decreased access to public health insurance) are significantly associated with increased reported mental health disorders. Similarly, physical conditions of the built environment (e.g., increased housing vacancies and increased travel costs) are significantly associated with increased reported mental health disorders. However, this positive relationship between the physical conditions of the built environment and mental health outcomes does not hold across all the metropolitan areas, suggesting a mixed effect of the built environment’s physical conditions on community mental health. We conclude by highlighting future opportunities of incorporating other variables and datasets into the MSPAF framework to test additional hypotheses on how the built environment impacts community mental health.
Prevalence and related factors of dyslipidemia among urban adults aged 35 to 79 years in Southwestern China
Authors: Huang Chuan , Zhang Wen-Qiang , Tang Wei-Wei , Liu Ya , Liu Jian-Xiong , Xu Rong-Hua , Zhao Shui-Ping , Wang Tzung-Dau , Huang Xiao-Bo
Published: September 2021

This study aimed to investigate the prevalence of dyslipidemia and its related factors among urban adults aged 35 to 79 years in Southwestern China. From September 2013 to March 2014, a multi-stage sampling was conducted, and a total of 10,221 people aged 35–79 years living in Chengdu and Chongqing were included. More than 30 investigators were trained in data collection, including questionnaire, anthropometric measurements and blood biomarkers testing. The prevalence of high triglycerides (≥ 2.3 mmol/L), high total cholesterol (≥ 6.2 mmol/L), high low-density lipoprotein cholesterol (≥ 4.1 mmol/L), low high-density lipoprotein cholesterol (< 1.0 mmol/L), and dyslipidemia were 15.7% (95% confidence interval, 15.0–16.4%), 5.4% (4.9–5.8%), 2.5% (2.2–2.8%), 5.7% (5.3–6.2%), and 27.4% (26.5–28.2%), respectively. The prevalence of dyslipidemia was positively correlated with higher education level, monthly income over 2000 CNY, smoking, hypertension, diabetes, overweight and obesity, and central obesity, and negatively correlated with daily physical exercise. The prevalence of dyslipidemia in Southwestern China is lower than the national average level, with high triglycerides being the most common form of dyslipidemia.
The quantum-mechanical Coulomb propagator in an L2 function representation
Authors: Gersbacher Rolf , Broad John T.
Published: September 2021

The quantum-mechanical Coulomb propagator is represented in a square-integrable basis of Sturmian functions. Herein, the Stieltjes integral containing the Coulomb spectral function as a weight is evaluated. The Coulomb propagator generally consists of two parts. The sum of the discrete part of the spectrum is extrapolated numerically, while three integration procedures are applied to the continuum part of the oscillating integral: the Gauss–Pollaczek quadrature, the Gauss–Legendre quadrature along the real axis, and a transformation into a contour integral in the complex plane with the subsequent Gauss–Legendre quadrature. Using the contour integral, the Coulomb propagator can be calculated very accurately from an L$$^2$$

2

basis. Using the three-term recursion relation of the Pollaczek polynomials, an effective algorithm is herein presented to reduce the number of integrations. Numerical results are presented and discussed for all procedures.
Testing covariance models for MEG source reconstruction of hippocampal activity
Authors: O’Neill George C. , Barry Daniel N. , Tierney Tim M. , Mellor Stephanie , Maguire Eleanor A. , Barnes Gareth R.
Published: September 2021

Beamforming is one of the most commonly used source reconstruction methods for magneto- and electroencephalography (M/EEG). One underlying assumption, however, is that distant sources are uncorrelated and here we tested whether this is an appropriate model for the human hippocampal data. We revised the Empirical Bayesian Beamfomer (EBB) to accommodate specific a-priori correlated source models. We showed in simulation that we could use model evidence (as approximated by Free Energy) to distinguish between different correlated and uncorrelated source scenarios. Using group MEG data in which the participants performed a hippocampal-dependent task, we explored the possibility that the hippocampus or the cortex or both were correlated in their activity across hemispheres. We found that incorporating a correlated hippocampal source model significantly improved model evidence. Our findings help to explain why, up until now, the majority of MEG-reported hippocampal activity (typically making use of beamformers) has been estimated as unilateral.
Selective T3–T4 sympathicotomy versus gray ramicotomy on outcome and quality of life in hyperhidrosis patients: a randomized clinical trial
Authors: Vanaclocha Vicente , Guijarro-Jorge Ricardo , Saiz-Sapena Nieves , Granell-Gil Manuel , Ortiz-Criado José María , Mascarós Juan Manuel , Vanaclocha Leyre
Published: September 2021

Compensatory hyperhidrosis is the leading cause of patients' dissatisfaction after thoracic sympathicotomy. The study aimed to reduce compensatory hyperhidrosis to increase patients’ satisfaction. A prospective randomized study on palmar hyperhidrosis, May 2016–September 2019. Twenty-one patients T3–T4sympathicotomy and 21 T3–T4gray ramicotomy. Data prospectively collected. Analysis at study's end. Focus on the sweating, temperature, quality of life baseline and postoperatively, compensatory hyperhidrosis, hand dryness, patients' satisfaction, and if they would undergo the procedure again and recommend it. No baseline differences between groups. Hyperhidrosis was controlled postoperatively in all patients. No mortality, serious complications, or recurrences. Sympathicotomy worse postoperative quality of life (49.05 (SD: 15.66, IR: 35.50–63.00) versus ramicotomy 24.30 (SD: 6.02, IR: 19.75–27.25). After ramicotomy, some residual sweating on the face, hands, and axillae. Compensatory sweating worse with sympathicotomy. Satisfaction higher with ramicotomy. Better results with ramicotomy than sympathicotomy regarding hand dryness, how many times a day the patients had to shower or change clothes, intention to undergo the procedure again or recommend it to somebody else, and how bothersome compensatory hyperhidrosis was. T3–T4gray ramicotomy had better results than T3–T4sympathicotomy, with less compensatory sweating and higher patients' satisfaction.
Distribution of Pb, Zn and Cd in stream and alluvial sediments in the area with past Zn smelting operations
Authors: Žibret Gorazd , Čeplak Barbara
Published: September 2021

The sources of Zn, Pb and Cd in alluvial and stream sediments have been studied in the area of historical Zn smelting tradition. 30 samples of stream sediments and samples from 4 alluvial sediment profiles were collected. Fractions 0.125–0.063 and < 0.063 mm were analysed by the means of ICP-MS prior 4-acid digestion. The highest levels of Zn, Cd and Pb were detected in the alluvial sediments in the closest vicinity to the abandoned slag and ore roasting residue waste dumps, reaching 96 and 4520 mg/kg, 522 and 26,800 mg/kg and 3.7 and 31 mg/kg for Pb, Zn and Cd in stream and alluvial sediments, respectively. The Voglajna River then transports contamination particles into the Savinja River, which afterwards flows into the Sava River. Consequently, the anomaly can even be detected in the Sava River, more than 30 km downstream. Higher levels of Pb, Zn and Cd have been found in fraction < 0.063 mm compared to 0.125–0.063 mm fraction. Impacts of historically contaminated soil erosion and in particular the wash-out of Zn-smelting waste from the improperly managed waste dump were recognised as the dominant sources of Zn, Cd and Pb in the stream and alluvial sediments.
On the role of hypocrisy in escaping the tragedy of the commons
Authors: Korman Amos , Vacus Robin
Published: September 2021

We study the emergence of cooperation in large spatial public goods games. Without employing severe social-pressure against “defectors”, or alternatively, significantly rewarding “cooperators”, theoretical models typically predict a system collapse in a way that is reminiscent of the “tragedy-of-the-commons” metaphor. Drawing on a dynamic network model, this paper demonstrates how cooperation can emerge when the social-pressure is mild. This is achieved with the aid of an additional behavior called “hypocrisy”, which appears to be cooperative from the external observer’s perspective but in fact hardly contributes to the social-welfare. Our model assumes that social-pressure is induced over both defectors and hypocritical players, though the extent of which may differ. Our main result indicates that the emergence of cooperation highly depends on the extent of social-pressure applied against hypocritical players. Setting it to be at some intermediate range below the one employed against defectors allows a system composed almost exclusively of defectors to transform into a fully cooperative one quickly. Conversely, when the social-pressure against hypocritical players is either too low or too high, the system remains locked in a degenerate configuration.
Evaluation of connectivity map shows limited reproducibility in drug repositioning
Authors: Lim Nathaniel , Pavlidis Paul
Published: September 2021

The Connectivity Map (CMap) is a popular resource designed for data-driven drug repositioning using a large transcriptomic compendium. However, evaluations of its performance are limited. We used two iterations of CMap (CMap 1 and 2) to assess their comparability and reliability. We queried CMap 2 with CMap 1-derived signatures, expecting CMap 2 would highly prioritize the queried compounds; the success rate was 17%. Analysis of previously published prioritizations yielded similar results. Low recall is caused by low differential expression (DE) reproducibility both between CMaps and within each CMap. DE strength was predictive of reproducibility, and is influenced by compound concentration and cell-line responsiveness. Reproducibility of CMap 2 sample expression levels was also lower than expected. We attempted to identify the “better” CMap by comparison with a third dataset, but they were mutually discordant. Our findings have implications for CMap usage and we suggest steps for investigators to limit false positives.
Essential role for paxillin tyrosine phosphorylation in LPS-induced mitochondrial fission, ROS generation and lung endothelial barrier loss
Authors: Fu Panfeng , Epshtein Yulia , Ramchandran Ramaswamy , Mascarenhas Joseph B. , Cress Anne E. , Jacobson Jeffrey , Garcia Joe G. N. , Natarajan Viswanathan
Published: September 2021

We have shown that both reactive oxygen species (ROS) and paxillin tyrosine phosphorylation regulate LPS-induced human lung endothelial permeability. Mitochondrial ROS (mtROS) is known to increase endothelial cell (EC) permeability which requires dynamic change in mitochondrial morphology, events that are likely to be regulated by paxillin. Here, we investigated the role of paxillin and its tyrosine phosphorylation in regulating LPS-induced mitochondrial dynamics, mtROS production and human lung microvascular EC (HLMVEC) dysfunction. LPS, in a time-dependent manner, induced higher levels of ROS generation in the mitochondria compared to cytoplasm or nucleus. Down-regulation of paxillin expression with siRNA or ecto-expression of paxillin Y31F or Y118F mutant plasmids attenuated LPS-induced mtROS in HLMVECs. Pre-treatment with MitoTEMPO, a scavenger of mtROS, attenuated LPS-induced mtROS, endothelial permeability and VE-cadherin phosphorylation. Further, LPS-induced mitochondrial fission in HLMVECs was attenuated by both a paxillin siRNA, and paxillin Y31F/Y118F mutant. LPS stimulated phosphorylation of dynamin-related protein (DRP1) at S616, which was also attenuated by paxillin siRNA, and paxillinY31/Y118 mutants. Inhibition of DRP1 phosphorylation by P110 attenuated LPS-induced mtROS and endothelial permeability. LPS challenge of HLMVECs enhanced interaction between paxillin, ERK, and DRP1, and inhibition of ERK1/2 activation with PD98059 blocked mitochondrial fission. Taken together, these results suggest a key role for paxillin tyrosine phosphorylation in LPS-induced mitochondrial fission, mtROS generation and EC barrier dysfunction.
MPT64 antigen detection test improves diagnosis of pediatric extrapulmonary tuberculosis in Mbeya, Tanzania
Authors: Grønningen Erlend , Nanyaro Marywinnie , Sviland Lisbet , Ngadaya Esther , Muller William , Torres Lisete , Mfinanga Sayoki , Mustafa Tehmina
Published: September 2021

Pediatric extrapulmonary tuberculosis (EPTB) is a diagnostic challenge. A new immunochemistry based MPT64 antigen detection test has shown improved sensitivity compared to current laboratory tests. The aim of this study was to implement and validate the test performance in a resource limited African setting. Presumptive pediatric (0–18 y) EPTB patients were prospectively enrolled at Mbeya Zonal Referral Hospital, and followed to the end of treatment or until a final diagnosis was reached. Specimens from suspected sites of infection were subject to routine diagnostics, GeneXpert MTB/RIF assay and the MPT64 test. The performance of the tests was assessed using mycobacterial culture as well as a composite reference standard. 30 patients were categorized as TB cases, 31 as non-TB cases and 2 were uncategorized. In the TB group, the three most common infections were adenitis (30%), peritonitis (30%) and meningitis (20%). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the MPT64 test was 92%, 88%, 87%, 92% and 90%, respectively. Mortality was equally high among TB/non-TB cases (23% vs 21%), and malnutrition was the main comorbidity among TB cases. The MPT64 test was implementable in the routine diagnostics in a low-resource setting and improved the diagnosis of pediatric EPTB.
Photoacoustic tomography of fingerprint and underlying vasculature for improved biometric identification
Authors: Zheng Wenhan , Lee Diana , Xia Jun
Published: September 2021

Capitalizing on the photoacoustic effect, we developed a new fingerprint sensing system that can reveal both fingerprints and underlying vascular structures at a high spatial resolution. Our system is built on a 15 MHz linear transducer array, a research ultrasound system, and a 532-nm pulsed laser. A 3D image was obtained by scanning the linear array over the fingertip. The acquired fingerprint images strongly agreed with the images acquired from ultrasound. Additional experiments were also conducted to investigate the effect of acoustic coupling. We discovered that high-quality fingerprint and vessel images can be acquired from both wet and dry fingers using our photoacoustic system. The reduced subdermal features in dry coupling can be enhanced through post-processing. Compared to existing fingerprint scanners, the photoacoustic approach provides a higher quality 3D image of the fingerprint, as well as unique subdermal vasculature structures, making the system almost impossible to counterfeit.
Modeling and verifying clustering properties in a vehicular ad hoc network protocol with Event-B
Authors: Sondi Patrick , Abbassi Imed , Ramat Eric , Chebbi Emna , Graiet Mohamed
Published: September 2021

Vehicular ad hoc network (VANET) routing protocols resort to clustering in order to optimize broadcast traffic flooding. Clustering schemes usually rely on rules which apply to each vehicle in order to reach a targeted organization in a VANET. Most of the literature works which evaluate clustering for VANET focus on performance analysis. However, with autonomous vehicles coming to roadways, more rigorous relationships will be required between clustering rules and the resulting organization, so as to anticipate road safety in a better way. We propose a formal description of the properties which are expected in a VANET, while considering the rules of a given clustering scheme. Using Event-B, we first present a description of the VANET, the vehicles movement and the traffic generated by both routing and application messages. Then, based on an Event-B model of a basic routing protocol of the literature, we describe how the specific rules of a clustering scheme can be modeled along with the properties expected in the resulting organization. Finally, we propose a validation process of the model. This paper aims at showing how our proposals have been applied to the Chain-Branch-Leaf scheme, although they can be adapted to any rule-based clustering scheme for VANET.
Integrative analysis of the gut microbiome and metabolome in a rat model with stress induced irritable bowel syndrome
Authors: Hu Yue , Chen Fang , Ye Haiyong , Lu Bin
Published: September 2021

Stress is one of the major causes of irritable bowel syndrome (IBS), which is well-known for perturbing the microbiome and exacerbating IBS-associated symptoms. However, changes in the gut microbiome and metabolome in response to colorectal distention (CRD), combined with restraint stress (RS) administration, remains unclear. In this study, CRD and RS stress were used to construct an IBS rat model. The 16S rRNA gene sequencing was used to characterize the microbiota in ileocecal contents. UHPLC-QTOF-MS/MS assay was used to characterize the metabolome of gut microbiota. As a result, significant gut microbial dysbiosis was observed in stress-induced IBS rats, with the obvious enrichment of three and depletion of 11 bacterial taxa in IBS rats, when compared with those in the control group (q < 0.05). Meanwhile, distinct changes in the fecal metabolic phenotype of stress-induced IBS rats were also found, including five increased and 19 decreased metabolites. Furthermore, phenylalanine, tyrosine and tryptophan biosynthesis were the main metabolic pathways induced by IBS stress. Moreover, the altered gut microbiota had a strong correlation with the changes in metabolism of stress-induced IBS rats. Prevotella bacteria are correlated with the metabolism of 1-Naphthol and Arg.Thr. In conclusion, the gut microbiome, metabolome and their interaction were altered. This may be critical for the development of stress-induced IBS.
Evaluating the influence of land use and land cover change on fine particulate matter
Authors: Yang Wei , Jiang Xiaoli
Published: September 2021

Fine particulate matter (i.e. particles with diameters smaller than 2.5 microns, PM2.5) has become a critical environmental issue in China. Land use and land cover (LULC) is recognized as one of the most important influence factors, however very fewer investigations have focused on the impact of LULC on PM2.5. The influences of different LULC types and different land use and land cover change (LULCC) types on PM2.5 are discussed. A geographically weighted regression model is used for the general analysis, and a spatial analysis method based on the geographic information system is used for a detailed analysis. The results show that LULCC has a stable influence on PM2.5 concentration. For different LULC types, construction lands have the highest PM2.5 concentration and woodlands have the lowest. The order of PM2.5 concentration for the different LULC types is: construction lands > unused lands > water > farmlands >grasslands > woodlands. For different LULCC types, when high-grade land types are converted to low-grade types, the PM2.5 concentration decreases; otherwise, the PM2.5 concentration increases. The result of this study can provide a decision basis for regional environmental protection and regional ecological security agencies.
Association of visual impairment with cognitive decline among older adults in Taiwan
Authors: Fang I.-Mo , Fang Yi-Jen , Hu Hsiao-Yun , Weng Shih-Han
Published: September 2021

This study investigated the association between visual impairment and cognitive decline among the elderly in Taiwan. The data were obtained from a government-sponsored, annual physical examination program for elderly citizens ≥ 65 years in Taipei City during 2005–2012. Distance presenting visual acuity was measured using the Snellen chart. Visual impairment was classified into low vision and blindness. The Short Portable Mental Status Questionnaire (SPMSQ) was selected to measure cognitive decline. The confounding factors including age, sex, sociodemographic factors: living status, marital status, education level, health behaviors: smoking, alcohol consumption, betel nut chewing, and physical comorbidities: BMI, hypertension, diabetes, cholesterol and triglyceride were collected for analysis. We recruited 105,208 participants and 4542 (4.3%) have abnormal SPMSQ. The abnormal SPMSQ had significantly higher prevalence of low vision (44.52% vs 18.79%) and blindness (8.89% vs 0.93%) compared with normal SPMSQ. The hazard ratios of abnormal SPMSQ in low vision and blindness were 2.34 (95% CI 2.17–2.52), and 5.13 (95% CI 4.50–5.85), after adjustment for confounders. In conclusion, visual impairment was independently and significantly associated with greater incident cognitive decline among elderly Asian people. Prevention of visual impairment may help to reduce the incidence of cognitive decline in the aged Asian population.
Model guided extremum seeking control of electromagnetic micromirrors
Authors: Sun Wanyan , Tan Yonghong
Published: September 2021

In this paper, a simplified dynamic model is constructed to describe the main characteristic of electromagnetic micro-mirror. Then, based on the information provided by the derived simplified model, a model-guided extremum seeking control (MGESC) scheme with backtracking line search is developed, which can automatically estimate the best value of step-size at each search iteration to improve the performance of the control system for target tracking. Then, the convergence of the proposed MGES algorithm is proved. Finally, the experimental results and the simulations are presented to verify the proposed method.
Mendelian randomization study of interleukin (IL)-1 family and lung cancer
Authors: Yang Zhao , Schooling C. Mary , Kwok Man Ki
Published: September 2021

The role of interleukin (IL)-1 family members/receptors in lung cancer remains uncertain due to the susceptibility of observed associations to confounding. We appraised the association of IL-1 family members/receptors with lung cancer and its subtypes [lung adenocarcinoma (LUAD) and squamous cell lung cancer (LUSC)] using two-sample Mendelian randomization. This study found that no IL-1 family members/receptors were significantly associated with lung cancer and its subtypes risk after correction for multiple testing. However, suggestive total effects of increased risk were noted for genetically predicted IL-1Racp with lung cancer (P = 0.006), IL-1α with LUAD (P = 0.027), and IL-1Racp with LUSC (P = 0.008). Suggestive direct effects were also noted for IL-1β, IL-1Ra, IL-36γ with lung cancer, IL-1α/β, IL-1Ra with LUAD, and IL-1β, IL-18BP with LUSC, after adjusting for genetically predicted effects of other IL-1 family members/receptors. Taken together, our findings suggest that interventions decreasing IL-1Racp might protect against lung cancer, perhaps via IL-1α/β or IL-1Ra.
Magneto-hydrodynamics of multi-phase flows in heterogeneous systems with large property gradients
Authors: Flint T. F. , Smith M. C. , Shanthraj P.
Published: September 2021

The complex interplay between thermal, hydrodynamic, and electromagnetic, forces governs the evolution of multi-phase systems in high technology applications, such as advanced manufacturing and fusion power plant operation. In this work, a new formulation of the time dependent magnetic induction equation is fully coupled to a set of conservation laws for multi-phase fluid flow, energy transport and chemical species transport that describes melting and solidification state transitions. A finite-volume discretisation of the resulting system of equations is performed, where a novel projection method is formulated to ensure that the magnetic field remains divergence free. The proposed framework is validated by accurately replicating a Hartmann flow profile. Further validation is performed through correctly predicting the experimentally observed trajectory of Argon bubbles rising in a liquid metal under varying applied magnetic fields. Finally, the applicability of the framework to technologically relevant processes is illustrated through the simulation of an electrical arc welding process between dissimilar metals. The proposed framework addresses an urgent need for numerical methods to understand the evolution of multi-phase systems with large electromagnetic property contrast.
A machine learning framework for predicting drug–drug interactions
Authors: Mei Suyu , Zhang Kun
Published: September 2021

Understanding drug–drug interactions is an essential step to reduce the risk of adverse drug events before clinical drug co-prescription. Existing methods, commonly integrating heterogeneous data to increase model performance, often suffer from a high model complexity, As such, how to elucidate the molecular mechanisms underlying drug–drug interactions while preserving rational biological interpretability is a challenging task in computational modeling for drug discovery. In this study, we attempt to investigate drug–drug interactions via the associations between genes that two drugs target. For this purpose, we propose a simple f drug target profile representation to depict drugs and drug pairs, from which an l2-regularized logistic regression model is built to predict drug–drug interactions. Furthermore, we define several statistical metrics in the context of human protein–protein interaction networks and signaling pathways to measure the interaction intensity, interaction efficacy and action range between two drugs. Large-scale empirical studies including both cross validation and independent test show that the proposed drug target profiles-based machine learning framework outperforms existing data integration-based methods. The proposed statistical metrics show that two drugs easily interact in the cases that they target common genes; or their target genes connect via short paths in protein–protein interaction networks; or their target genes are located at signaling pathways that have cross-talks. The unravelled mechanisms could provide biological insights into potential adverse drug reactions of co-prescribed drugs.
Risk prediction of clinical adverse outcomes with machine learning in a cohort of critically ill patients with atrial fibrillation
Authors: Falsetti Lorenzo , Rucco Matteo , Proietti Marco , Viticchi Giovanna , Zaccone Vincenzo , Scarponi Mattia , Giovenali Laura , Moroncini Gianluca , Nitti Cinzia , Salvi Aldo
Published: September 2021

Critically ill patients affected by atrial fibrillation are at high risk of adverse events: however, the actual risk stratification models for haemorrhagic and thrombotic events are not validated in a critical care setting. With this paper we aimed to identify, adopting topological data analysis, the risk factors for therapeutic failure (in-hospital death or intensive care unit transfer), the in-hospital occurrence of stroke/TIA and major bleeding in a cohort of critically ill patients with pre-existing atrial fibrillation admitted to a stepdown unit; to engineer newer prediction models based on machine learning in the same cohort. We selected all medical patients admitted for critical illness and a history of pre-existing atrial fibrillation in the timeframe 01/01/2002–03/08/2007. All data regarding patients’ medical history, comorbidities, drugs adopted, vital parameters and outcomes (therapeutic failure, stroke/TIA and major bleeding) were acquired from electronic medical records. Risk factors for each outcome were analyzed adopting topological data analysis. Machine learning was used to generate three different predictive models. We were able to identify specific risk factors and to engineer dedicated clinical prediction models for therapeutic failure (AUC: 0.974, 95%CI: 0.934–0.975), stroke/TIA (AUC: 0.931, 95%CI: 0.896–0.940; Brier score: 0.13) and major bleeding (AUC: 0.930:0.911–0.939; Brier score: 0.09) in critically-ill patients, which were able to predict accurately their respective clinical outcomes. Topological data analysis and machine learning techniques represent a concrete viewpoint for the physician to predict the risk at the patients’ level, aiding the selection of the best therapeutic strategy in critically ill patients affected by pre-existing atrial fibrillation.
Reconstructing and counting genomic fragments through tagmentation-based haploid phasing
Authors: Leong Patrick P. T. , Mihajlović Aleksandar , Bogdanović Nadežda , Breberina Luka , Xi Larry
Published: September 2021

Single-cell sequencing provides a new level of granularity in studying the heterogeneous nature of cancer cells. For some cancers, this heterogeneity is the result of copy number changes of genes within the cellular genomes. The ability to accurately determine such copy number changes is critical in tracing and understanding tumorigenesis. Current single-cell genome sequencing methodologies infer copy numbers based on statistical approaches followed by rounding decimal numbers to integer values. Such methodologies are sample dependent, have varying calling sensitivities which heavily depend on the sample’s ploidy and are sensitive to noise in sequencing data. In this paper we have demonstrated the concept of integer-counting by using a novel bioinformatic algorithm built on our library construction chemistry in order to detect the discrete nature of the genome.