bluuebunny/crossref_metadata_2025 huggingface dataset:
Conceptual design and virtual prototyping of a wearable upper limb exoskeleton for assisted operations
Authors: Bilancia Pietro , Berselli Giovanni
Published: October 2021

This paper introduces a novel upper limb robotic exoskeleton designed to assist industrial operators in a wide range of manual repetitive tasks, such as tool handling and lifting/moving of heavy items. Due to its reduced size and high maneuverability, the proposed portable device may also be employed for rehabilitation purposes (e.g. as an aid for people with permanent neuromuscular diseases or post-stroke patients). Its primary function is to compensate the gravity loads acting on the human shoulder by means of a hybrid system consisting of four electric motors and three passive springs. The paper focuses on the exoskeleton mechanical design and virtual prototyping. After a preliminary review of the existent architectures and procedures aimed at defining the exoskeleton functional requirements, a detailed behavioral analysis is conducted using analytical and numerical approaches. The developed interactive model allows to simulate both kinematics and statics of the exoskeleton for every possible movement within the design workspace. To validate the model, the results have been compared with the ones achieved with a commercial multibody software for three different operator’s movements.
A Path Towards a Possible Future – Adult Students’ Choice of Vocational Education
Authors: Karlsson Tobias , Muhrman Karolina , Nyström Sofia
Published: October 2021

Today’s society is characterized by high unemployment, a prevailing trust in and demands for an academic degree, and an emphasis on the individual’s own responsibility for their educational choices. This study aims to examine adults’ vocational education choices, their intentions in connection with municipal adult education (MAE) studies, and how this relates to identity formation. The study is based on 18 interviews and compares students from two vocational MAE training programmes in assistant nursing and floor laying. The analysis has identified different pathways concerning adult students’ decisions to enrol in municipal adult education and a specific vocational education and training (VET) programme. We see educational choices and paths in terms of underlying causes or as forward-looking rationalities. The results show that the process of identity formation is larger than simply one of vocational becoming within a vocational community of practice, since MAE studies involve a student’s whole being, including both their personal identity trajectories and their vocational identity formation. With this article we hope to provide a foundation for a pedagogical discussion about student intentions, focusing on how different subjectivities affect students with regard to their future vocational becoming.
Montmorillonite-Hydrochar Nanocomposites as Examples of Clay–Organic Interactions Delivering Ecosystem Services
Authors: Yuan Guodong , Wei Jing , Theng Benny K. G.
Published: October 2021

Clay–organic interaction is an important natural process that underpins soil ecosystem services. This process can also be tailored to produce clay–organic nanocomposites for industrial and environmental applications. The organic moiety of the nanocomposites, typically represented by a toxic surfactant, could be replaced by hydrochar formed from biomolecules (e.g. glucose) via hydrothermal carbonization. The effect of montmorillonite (Mnt) and glucose dosage on hydrochar formation, however, has not been clarified. In addition, the mechanisms by which Mnt-hydrochar nanocomposites (CMnt) can detoxify and remove carcinogenic Cr(VI) from aqueous solution are not well understood. In the current study, research milestones in terms of clay–organic interactions are summarized, following which the synthesis and characterization of CMnt for Cr(VI) adsorption are outlined. Briefly, 1 g of Mnt was reacted with 75 mL of glucose solution (0.1, 0.2, 0.3, 0.4, 0.5, and 0.6 mol L−1) by hydrothermal carbonization at 200°C for 16 h. The resultant CMnt samples were analyzed for chemical composition, functional groups, morphological features, and Cr(VI) adsorptive properties. Mnt promoted the conversion of glucose to hydrochars, the particle size of which (~80 nm) was appreciably smaller than that formed in the absence of Mnt (control). Furthermore, the hydrochars in CMnt had an aromatic structure with low hydrogen substitution and high stability (C/H atomic ratio 0.34–0.99). The weakened OH (from hydrochar) and Si–O–Si stretching peaks in the Fourier-transform infrared (FTIR) spectra of CMnt are indicative of chemical bonding between Mnt and hydrochar. The CMnt samples were effective at removing toxic Cr(VI) from acidic aqueous solutions. Several processes were involved, including direct reduction of Cr(VI) to Cr(III), complexation of Cr(III) with carboxyl and phenolic groups of hydrochar, electrostatic attraction between Cr(VI) and positively charged CMnt at pH 2 followed by indirect reduction of Cr(VI) to Cr(III), and Cr(III) precipitation.
Development of a DDH Care Pathway for India: A Study Methodology to Guide Similar Efforts in Other Countries and for Other Conditions
Authors: Li Jacqueline , Aroojis Alaric , Mulpuri Kishore , Shea Kevin G. , Schaeffer Emily K.
Published: October 2021

Purpose

In India and other Global South countries, developmental dysplasia of the hip (DDH) is often diagnosed after walking age, leading to more invasive surgeries and long-term disability. DDH care pathways aim to enhance early detection and must be tailored to meet a country’s needs and diverse practice settings. We describe a multi-phase methodology for context-specific DDH care pathway development, demonstrating its use in India.

Methods

In Phase I, Orthopaedic surgeons, Pediatricians/Neonatologists, and Radiologists in India were surveyed regarding DDH screening. Seven relevant Indian organizations partnered together and assembled a multidisciplinary working group, which then met fortnightly to establish an evidence base and prepare for the subsequent consensus-building phase. During Phase II, panelists participated in a modified Delphi process to reach consensus on a list of DDH screening statements. Phase III applied the statements to develop the care pathway.

Results

The Delphi process concluded after a preliminary survey and two Delphi rounds, reaching consensus on 47 statements, which were condensed into 35. The developed care pathway for India features periodic clinical hip examinations integrated with the country’s immunization schedule and selective imaging screening, providing flexibility in the timing and modality of imaging.

Discussion/Conclusion

In Global South countries, there is a need for DDH care pathways specific to local contexts. Successful care pathway development requires accounting for cultural differences in healthcare and strategies to facilitate engagement and to address country-specific barriers. This methodology was feasible in India and can be applied to other conditions and/or countries wishing to establish care pathways.

Level of Evidence

Level III.
Risk of hospital insolvency and its relationship with income and borrowings from banks: a case–control study with large-scale financial data in Japan
Authors: Tsuboi Satoshi , Mine Tomosa , Fukushima Tetsuhito
Published: October 2021

Considering the variety of stakeholders surrounding hospitals, hospital financial distress should be understood as a social issue, rather than just a matter involving the hospital owners. The present study aimed to assess Japanese hospital insolvency and related factors based on a nationwide financial dataset, and to identify indicators of the risk of insolvency. The legal financial reports used included a balance sheet and a profit-and-loss statement of hospitals owned by healthcare corporations, representing about 70% of all Japanese hospitals. This case–control study with descriptive analyses was conducted to clarify the financial status of healthcare corporations and to assess associations between specific factors and insolvency. Insolvency was found in 5.9% of healthcare corporations in 2016. Insolvency was significantly associated with operational income per sales (odds ratio, 0.16), and both short- and long-term borrowings per sales (odds ratios: 1.46 and 1.22 in this order). The present study found that 5.9% of Japanese healthcare corporations were insolvent, and hospital profitability and borrowing (both short- and long-term) could be key factors related to preventing hospital insolvency in Japan. To maintain sustainable healthcare services by hospitals, decision makers should consider the risk of insolvency, and balance the amount of borrowings against sales.
Foraminifera Iodine to Calcium Ratios: Approach and Cleaning
Authors: Winkelbauer Helge , Cordova‐Rodriguez Kathy , Reyes‐Macaya Dharma , Scott Jennifer , Glock Nicolaas , Lu Zunli , Hamilton Elliott , Chenery Simon , Holdship Phil , Dormon Charlotte , Hoogakker Babette
Published: October 2021

Planktic and benthic foraminiferal iodine (I) to calcium (Ca) molar ratios have been proposed as an exciting new proxy to assess subsurface and bottom water oxygenation in the past. Compared to trace metals, the analysis of iodine in foraminiferal calcite is more challenging, as iodine is volatile in acid solution. Here, we compare previous analyses that use tertiary amine with alternative analyses using tetramethylammonium hydroxide (TMAH) and ammonium hydroxide (NH4OH) to stabilize iodine in solution. In addition, we assess the effect of sample size and cleaning on planktic and benthic foraminiferal I/Ca. Our stabilization experiments with TMAH and NH4OH show similar trends as those using tertiary amine, giving relatively low I/Ca ratios for planktic and benthic foraminifera samples from poorly oxygenated waters, and high ratios for well‐oxygenated waters. This suggests that both alternative methods are suitable to stabilize iodine initially dissolved in acid. Samples that contain 5–10 specimens show a wide spread in I/Ca. Samples containing 20 specimens or more show more centered I/Ca values, indicating that a larger sample size is more representative of the average planktic foraminifera community. The impact of cleaning on planktic and benthic foraminifera I/Ca ratios is very similar to Mg/Ca, with the largest effect occurring during the clay removal step. The largest iodine contaminations were recorded at locations characterized by moderate to high organic carbon contents. In those circumstances, we recommend doubling the oxidative cleaning steps (4 instead of 2 repetitions) to ensure that all organic material is removed.
Estimating Intra‐Urban Inequities in PM2.5‐Attributable Health Impacts: A Case Study for Washington, DC
Authors: Castillo Maria D. , Kinney Patrick L. , Southerland Veronica , Arno C. Anneta , Crawford Kelly , van Donkelaar Aaron , Hammer Melanie , Martin Randall V. , Anenberg Susan C.
Published: October 2021

Air pollution levels are uneven within cities, contributing to persistent health disparities between neighborhoods and population sub‐groups. Highly spatially resolved information on pollution levels and disease rates is necessary to characterize inequities in air pollution exposure and related health risks. We leverage recent advances in deriving surface pollution levels from satellite remote sensing and granular data in disease rates for one city, Washington, DC, to assess intra‐urban heterogeneity in fine particulate matter (PM2.5)‐ attributable mortality and morbidity. We estimate PM2.5‐attributable cases of all‐cause mortality, chronic obstructive pulmonary disease, ischemic heart disease, lung cancer, stroke, and asthma emergency department (ED) visits using epidemiologically derived health impact functions. Data inputs include satellite‐derived annual mean surface PM2.5 concentrations; age‐resolved population estimates; and statistical neighborhood‐, zip code‐ and ward‐scale disease counts. We find that PM2.5 concentrations and associated health burdens have decreased in DC between 2000 and 2018, from approximately 240 to 120 cause‐specific deaths and from 40 to 30 asthma ED visits per year (between 2014 and 2018). However, remaining PM2.5‐attributable health risks are unevenly and inequitably distributed across the District. Higher PM2.5‐attributable disease burdens were found in neighborhoods with larger proportions of people of color, lower household income, and lower educational attainment. Our study adds to the growing body of literature documenting the inequity in air pollution exposure levels and pollution health risks between population sub‐groups, and highlights the need for both high‐resolution disease rates and concentration estimates for understanding intra‐urban disparities in air pollution‐related health risks.
Assessment of Turbulence Intensity in Different Spots of Lightning Flash Propagation
Authors: Souza Jessica C. S. , Bruning Eric C.
Published: October 2021

The updraft speed is correlated to the total lightning flashes a storm produces. Shear along updraft gradients is one of the mechanisms responsible for the production of turbulence kinetic energy (TKE). Thus, the radar‐estimated eddy dissipation rate (EDR) overlapped with Lightning Mapping Array (LMA) data is used to evaluate the storm's kinematic and electrical relationship. The majority of the sampled flashes shows higher turbulence intensities close to lightning initiation regions. As the distance from initiation increases along the lightning propagation path, there is a gradient to less turbulent regions. We identified small‐sized and medium‐sized flashes initiated at lower altitudes in regions of smaller EDR values consistent with the unmixed flow within inner part of updrafts. Furthermore, there were a concentration of small flashes initiated in the upper portion of the cloud in high EDR values due to their associated small‐scale variability.
Characterizing the Seasonal Variability of Hypolimnetic Mixing in a Large, Deep Lake
Authors: Cannon David James , Troy Cary , Bootsma Harvey , Liao Qian , MacLellan‐Hurd Rae‐Ann
Published: October 2021

In this study, we report on turbulent mixing observed during the annual stratification cycle in the hypolimnetic waters of Lake Michigan (USA), highlighting stratified, convective, and transitional mixing periods. Measurements were collected using a combination of moored instruments and microstructure profiles. Observations during the stratified summer showed a shallow, wind‐driven surface mixed layer (SML) with locally elevated dissipation rates in the thermocline () potentially associated with internal wave shear. Below the thermocline, turbulence was weak () and buoyancy‐suppressed ( < 8.5), with low hypolimnetic mixing rates () limiting benthic particle delivery. During the convective winter period, a diurnal cycle of radiative convection was observed over each day of measurement, where temperature overturns were directly correlated with elevated turbulence levels throughout the water column (; ). A transitional mixing period was observed for spring conditions when surface temperatures were near the temperature of maximum density (TMD3.98) and the water column began to stably stratify. While small temperature gradients allowed strong mixing over the transitional period (), hypolimnetic velocity shear was overwhelmed by weakly stable stratification (; ), limiting the development of the SML. These results highlight the importance of radiative convection for breaking down weak hypolimnetic stratification and driving energetic, full water column mixing during a substantial portion of the year (>100 days at our sample site). Ongoing surface water warming in the Laurentian Great Lakes is significantly reducing the annual impact of convective mixing, with important consequences for nutrient cycling, primary production, and benthic‐pelagic coupling.
Regional and Seasonal Trends in Tropical Ozone From SHADOZ Profiles: Reference for Models and Satellite Products
Authors: Thompson Anne M. , Stauffer Ryan M. , Wargan Krzysztof , Witte Jacquelyn C. , Kollonige Debra E. , Ziemke Jerald R.
Published: October 2021

Understanding lowermost stratosphere (LMS) ozone variability is an important topic in the trends and climate assessment communities because of feedbacks among changing temperature, dynamics, and ozone. LMS evaluations are usually based on satellite observations. Free tropospheric (FT) ozone assessments typically rely on profiles from commercial aircraft. Ozonesonde measurements constitute an independent data set encompassing both LMS and FT. We used Southern Hemisphere Additional Ozonesondes (SHADOZ) data (5.8°N–14°S) from 1998 to 2019 in the Goddard Multiple Linear Regression model to analyze monthly mean FT and LMS ozone changes across five well‐distributed tropical sites. Our findings: (a) both FT (5–15 km) and LMS (15–20 km) ozone trends show marked seasonal variability. (b) All stations exhibit FT ozone increases in February‐May (up to 15%/decade) when the frequency of convectively driven waves have changed. (c) After May, monthly ozone changes are both positive and negative, leading to mean trends of +(1–4)%/decade, depending on station. (d) LMS ozone losses reach (4–9)%/decade midyear, correlating with an increase in TH as derived from SHADOZ radiosonde data. (e) When the upper FT and LMS are defined by tropopause‐relative coordinates, the LMS ozone trends all become insignificant. Thus, the 20‐year decline in tropical LMS ozone reported in recent satellite‐based studies likely signifies a perturbed tropopause rather than chemical depletion. The SHADOZ‐derived ozone changes highlight regional and seasonal variability across the tropics and define a new reference for evaluating changes derived from models and satellite products over the 1998–2019 period.
Smooth muscle 22 alpha protein inhibits VSMC foam cell formation by supporting normal LXRα signaling, ameliorating atherosclerosis
Authors: Zhang Dan-Dan , Song Yu , Kong Peng , Xu Xin , Gao Ya-Kun , Dou Yong-Qing , Weng Lin , Wang Xiao-Wei , Lin Yan-Ling , Zhang Fan , Zhang Hailin , Han Mei
Published: October 2021

Vascular smooth muscle cells (VSMCs) are indispensable components in foam cell formation in atherosclerosis. However, the mechanism behind foam cell formation of VSMCs has not been addressed. We found a potential association between deletion of smooth muscle (SM) 22α and deregulated nuclear receptors liver X receptors (LXRs)/retinoid X receptor (RXR) signaling in mice. Here, we investigated the roles of SM22α in LXRα-modulated cholesterol homeostasis, and explore possible mechanisms underlying this process. We identified that the depletion of SM22α was a primary event driving VSMC cholesterol accumulation and the development of atherosclerosis in mice. Proteomic and lipidomic analysis validated that downregulation of SM22α was correlated with reduced expression of LXRα and ATP-binding cassette transporter (ABCA) 1 and increased cholesteryl ester in phenotypically modulated VSMCs induced by platelets-derived growth factor (PDGF)-BB. Notably, LXRα was mainly distributed in the cytoplasm rather than the nucleus in the neointimal andSm22α−/−VSMCs. Loss of SM22α inhibited the nuclear import of LXRα and reduced ABCA1-mediated cholesterol efflux via promoting depolymerization of actin stress fibers. Affinity purification and mass spectrometry (AP-MS) analysis, co-immunoprecipitation and GST pull-down assays, confocal microscopy, and stochastic optical reconstruction microscopy (STORM) revealed that globular-actin (G-actin), monomeric actin, interacted with and retained LXRα in the cytoplasm in PDGF-BB-treated andSm22α−/−VSMCs. This interaction blocked LXRα binding to Importin α, a karyopherin that mediates the trafficking of macromolecules across the nuclear envelope, and the resulting reduction of LXRα transcriptional activity. Increasing SM22α expression restored nuclear localization of LXRα and removed cholesterol accumulation via inducing actin polymerization, ameliorating atherosclerosis. Our findings highlight that LXRα is a mechanosensitive nuclear receptor and that the nuclear import of LXRα maintained by the SM22α-actin axis is a potential target for blockade of VSMC foam cell formation and development of anti-atherosclerosis.
Harmonizing corporate carbon footprints
Authors: Klaaßen Lena , Stoll Christian
Published: October 2021

Global greenhouse gas emissions need to reach net-zero around mid-century to limit global warming to 1.5 °C. This decarbonization challenge has, inter alia, increased the political and societal pressure on companies to disclose their carbon footprints. As a response, numerous companies announced roadmaps to become carbon neutral or even negative. The first step on the journey towards carbon neutrality, however, is to quantify corporate emissions accurately. Current carbon accounting and reporting practices remain unsystematic and not comparable, particularly for emissions along the value chain (so-called scope 3). Here we present a framework to harmonize scope 3 emissions by accounting for reporting inconsistency, boundary incompleteness, and activity exclusion. In a case study of the tech sector, we find that corporate reports omit half of the total emissions. The framework we present may help companies, investors, and policy makers to identify and close the gaps in corporate carbon footprints.
Globally consistent assessment of coastal eutrophication
Authors: Maúre Elígio de Raús , Terauchi Genki , Ishizaka Joji , Clinton Nicholas , DeWitt Michael
Published: October 2021

Eutrophication is an emerging global issue associated with increasing anthropogenic nutrient loading. The impacts and extent of eutrophication are often limited to regions with dedicated monitoring programmes. Here we introduce the first global and Google Earth Engine-based interactive assessment tool of coastal eutrophication potential (CEP). The tool evaluates trends in satellite-derived chlorophyll-a (CHL) to devise a global map of CEP. Our analyses suggest that, globally, coastal waters (depth ≤200 m) covering ∼1.15 million km2 are eutrophic potential. Also, waters associated with CHL increasing trends—eutrophication potential—are twofold higher than those showing signs of recovery. The tool effectively identified areas of known eutrophication with severe symptoms, like dead zones, as well as those with limited to no information of the eutrophication. Our tool introduces the prospect for a consistent global assessment of eutrophication trends with major implications for monitoring Sustainable Development Goals (SDGs) and the application of Earth Observations in support of SDGs.
RIPK1 regulates starvation resistance by modulating aspartate catabolism
Authors: Mei Xinyu , Guo Yuan , Xie Zhangdan , Zhong Yedan , Wu Xiaofen , Xu Daichao , Li Ying , Liu Nan , Zhu Zheng-Jiang
Published: October 2021

RIPK1 is a crucial regulator of cell death and survival. Ripk1 deficiency promotes mouse survival in the prenatal period while inhibits survival in the early postnatal period without a clear mechanism. Metabolism regulation and autophagy are critical to neonatal survival from severe starvation at birth. However, the mechanism by which RIPK1 regulates starvation resistance and survival remains unclear. Here, we address this question by discovering the metabolic regulatory role of RIPK1. First, metabolomics analysis reveals that Ripk1 deficiency specifically increases aspartate levels in both mouse neonates and mammalian cells under starvation conditions. Increased aspartate in Ripk1−/− cells enhances the TCA  flux and ATP production. The energy imbalance causes defective autophagy induction by inhibiting the AMPK/ULK1 pathway. Transcriptional analyses demonstrate that Ripk1−/− deficiency downregulates gene expression in aspartate catabolism by inactivating SP1. To summarize, this study reveals that RIPK1 serves as a metabolic regulator responsible for starvation resistance.
Little evidence for sex or ovarian hormone influences on affective variability
Authors: Weigard Alexander , Loviska Amy M. , Beltz Adriene M.
Published: October 2021

Women were historically excluded from research participation partly due to the assumption that ovarian hormone fluctuations lead to variation, especially in emotion, that could not be experimentally controlled. Although challenged in principle and practice, relevant empirical data are limited by single measurement occasions. The current paper fills this knowledge gap using data from a 75-day intensive longitudinal study. Three indices of daily affective variability—volatility, emotional inertia, and cyclicity—were evaluated using Bayesian inferential methods in 142 men, naturally cycling women, and women using three different oral contraceptive formulations (that “stabilize” hormone fluctuations). Results provided more evidence for similarities between men and women—and between naturally cycling women and oral contraceptive users—than for differences. Even if differences exist, effects are likely small. Thus, there is little indication that ovarian hormones influence affective variability in women to a greater extent than the biopsychosocial factors that influence daily emotion in men.
Anti-cancer efficacy including Rb-deficient tumors and VHL-independent HIF1α proteasomal destabilization by dual targeting of CDK1 or CDK4/6 and HSP90
Authors: Zhao Shuai , Zhou Lanlan , Dicker David T. , Lev Avital , Zhang Shengliang , Ross Eric , El-Deiry Wafik S.
Published: October 2021

A prevalent characteristic of solid tumors is intra-tumoral hypoxia. Hypoxia-inducible factor 1α (HIF1α) predominantly mediates the adaptive response to O2 oscillation and is linked to multiple malignant hallmarks. Here we describe a strategy to robustly target HIF1α by dual inhibition of CDK(s) and heat shock protein 90 (HSP90). We show that CDK1 may contribute to HSP90-mediated HIF1α stabilization. CDK1 knockdown enhances the decrease of HIF1α by HSP90 inhibition. Dual inhibition of CDK1 and HSP90 significantly increases apoptosis and synergistically inhibits cancer cell viability. Similarly, targeting CDK4/6 using FDA-approved inhibitors in combination with HSP90 inhibition shows a class effect on HIF1α inhibition and cancer cell viability suppression not only in colorectal but also in various other cancer types, including Rb-deficient cancer cells. Dual inhibition of CDK4/6 and HSP90 suppresses tumor growth in vivo. In summary, combined targeting of CDK(s) (CDK1 or CDK4/6) and HSP90 remarkably inhibits the expression level of HIF1α and shows promising anti-cancer efficacy with therapeutic potential.
Interrelationships between the structural, spectroscopic, and antibacterial properties of nanoscale (< 50 nm) cerium oxides
Authors: Iqbal Neelam , Anastasiou Antonios , Aslam Zabeada , Raif El Mostafa , Do Thuy , Giannoudis Peter V. , Jha Animesh
Published: October 2021

Bone healing is a complex process, and if not managed successfully, it can lead to non-union, metal-work failure, bacterial infections, physical and psychological patient impairment. Due to the growing urgency to minimise antibiotic dependency, alternative treatment strategies, including the use of nanoparticles, have attracted significant attention. In the present study, cerium oxide nanoparticles (Ce4+, Ce3+) have been selected due to their unique antibacterial redox capability. We found the processing routes affected the agglomeration tendency, particle size distribution, antibacterial potential, and ratio of Ce3+:Ce4+ valence states of the cerium oxide nanoparticles. The antibacterial efficacy of the nanoparticles in the concentration range of 50–200 µg/ml is demonstrated against Escherichia coli, Staphylococcus epidermis, and Pseudomonas aeruginosa by determining the half-maximal inhibitory concentration (IC50). Cerium oxide nanoparticles containing a more significant amount of Ce3+ ions, i.e., FRNP, exhibited 8.5 ± 1.2%, 10.5 ± 4.4%, and 13.8 ± 5.8% increased antibacterial efficacy compared with nanoparticles consisting mainly of Ce4+ ions, i.e., nanoparticles calcined at 815 °C.
NPF activates a specific NPF receptor and regulates food intake in Pacific abalone Haliotis discus hannai
Authors: Kim Kyeong Seop , Kim Mi Ae , Park Keunwan , Sohn Young Chang
Published: October 2021

Neuropeptides function through G protein-coupled receptors (GPCRs) with high specificity, implying a significant degree of neuropeptide-GPCR coevolution. However, potential neuropeptide signaling systems in non-chordates are relatively elusive. We determined the specificity of the neuropeptide F (Hdh-NPF) signaling system with a cognate receptor (Hdh-NPFR) in the Pacific abalone, Haliotis discus hannai. Phylogenetic and exon–intron arrangement analyses of bilaterian NPF and the chordate ortholog NPY with their receptor sequences revealed a likely common ancestor, and Hdh-NPFR was similar to the NPYR2 subtype among the NPYR1, NPYR2, and NPYR5 subtypes. Among four Hdh-NPFR-related receptors, Hdh-NPFR specifically responded to Hdh-NPF peptide, supported by the dose–response luciferase reporter curve, intracellular Ca2+ mobilization, and phosphorylation of ERK1/2 and its inhibition with a protein kinase C inhibitor. Peptide fragmentations and shuffling of Hdh-NPF with human NPY could not activate the cellular response of Hdh-NPFR. Three-dimensional in silico modeling suggested that interaction of Hdh-NPF C-terminal amino acids with the extracellular loops of Hdh-NPFR is critical for Hdh-NPFR activation. In vivo injection of Hdh-NPF peptide increased food consumption, and knockdown of Hdh-NPF expression decreased food consumption in Pacific abalone. These findings provide evidence for co-evolution of the NPF/Y ligand-receptor system, enabling further research on mollusk orexigenic neuropeptides.
Quantification of the spatial distribution of primary tumors in the lung to develop new prognostic biomarkers for locally advanced NSCLC
Authors: Vuong Diem , Bogowicz Marta , Wee Leonard , Riesterer Oliver , Vlaskou Badra Eugenia , D’Cruz Louisa Abigail , Balermpas Panagiotis , van Timmeren Janita E. , Burgermeister Simon , Dekker André , De Ruysscher Dirk , Unkelbach Jan , Thierstein Sandra , Eboulet Eric I. , Peters Solange , Pless Miklos , Guckenberger Matthias , Tanadini-Lang Stephanie
Published: October 2021

The anatomical location and extent of primary lung tumors have shown prognostic value for overall survival (OS). However, its manual assessment is prone to interobserver variability. This study aims to use data driven identification of image characteristics for OS in locally advanced non-small cell lung cancer (NSCLC) patients. Five stage IIIA/IIIB NSCLC patient cohorts were retrospectively collected. Patients were treated either with radiochemotherapy (RCT): RCT1* (n = 107), RCT2 (n = 95), RCT3 (n = 37) or with surgery combined with radiotherapy or chemotherapy: S1* (n = 135), S2 (n = 55). Based on a deformable image registration (MIM Vista, 6.9.2.), an in-house developed software transferred each primary tumor to the CT scan of a reference patient while maintaining the original tumor shape. A frequency-weighted cumulative status map was created for both exploratory cohorts (indicated with an asterisk), where the spatial extent of the tumor was uni-labeled with 2 years OS. For the exploratory cohorts, a permutation test with random assignment of patient status was performed to identify regions with statistically significant worse OS, referred to as decreased survival areas (DSA). The minimal Euclidean distance between primary tumor to DSA was extracted from the independent cohorts (negative distance in case of overlap). To account for the tumor volume, the distance was scaled with the radius of the volume-equivalent sphere. For the S1 cohort, DSA were located at the right main bronchus whereas for the RCT1 cohort they further extended in cranio-caudal direction. In the independent cohorts, the model based on distance to DSA achieved performance: AUCRCT2 [95% CI] = 0.67 [0.55–0.78] and AUCRCT3 = 0.59 [0.39–0.79] for RCT patients, but showed bad performance for surgery cohort (AUCS2 = 0.52 [0.30–0.74]). Shorter distance to DSA was associated with worse outcome (p = 0.0074). In conclusion, this explanatory analysis quantifies the value of primary tumor location for OS prediction based on cumulative status maps. Shorter distance of primary tumor to a high-risk region was associated with worse prognosis in the RCT cohort.
Interspecific variation of antennal lobe composition among four hornet species
Authors: Couto Antoine , Arnold Gérard , Ai Hiroyuki , Sandoz Jean-Christophe
Published: October 2021

Olfaction is a crucial sensory modality underlying foraging, social and mating behaviors in many insects. Since the olfactory system is at the interface between the animal and its environment, it receives strong evolutionary pressures that promote neuronal adaptations and phenotypic variations across species. Hornets are large eusocial predatory wasps with a highly developed olfactory system, critical for foraging and intra-specific communication. In their natural range, hornet species display contrasting ecologies and olfactory-based behaviors, which might match to adaptive shifts in their olfactory system. The first olfactory processing center of the insect brain, the antennal lobe, is made of morphological and functional units called glomeruli. Using fluorescent staining, confocal microscopy and 3D reconstructions, we compared antennal lobe structure, glomerular numbers and volumes in four hornet species (Vespa crabro, Vespa velutina, Vespa mandarinia and Vespa orientalis) with marked differences in nesting site preferences and predatory behaviors. Despite a conserved organization of their antennal lobe compartments, glomeruli numbers varied strongly between species, including in a subsystem thought to process intraspecific cuticular signals. Moreover, specific adaptations involving enlarged glomeruli appeared in two species, V. crabro and V. mandarinia, but not in the others. We discuss the possible function of these adaptations based on species-specific behavioral differences.
Modeling and analysis of transient lubrication characteristic of the helicopter main transmission spiral bevel gears in point contacts
Authors: Wang Yanzhong , Yang Kai , Chu Xiaomeng , Tang Wen , Huang Changyong
Published: October 2021

An engineering calculation model is introduced for point-contact elastohydrodynamic lubrication analysis of spiral bevel gears. This model can analyze transient lubrication characteristics of spiral bevel gears. The influence of the angle between the lubricant entrainment and the minor axis of the contact ellipse is included in this model. The contact parameters of the spiral bevel gear are calculated, which will change with time during the meshing process. The variation of lubricant film thickness during the meshing process of spiral bevel gears is unraveled. Due to the influence of entrainment velocity, the oil film thickness at the out mesh side is smaller than that at the enter mesh side under the same contact force. It is evident that the higher the pressure is, the larger the contact area will be. Meanwhile, the thickness of the oil film is reduced, and the oil film distribution in the contact area is relatively uniform. Taking helicopter main transmission spiral bevel gears as an example, this study finally calculates the distribution characteristics of the oil film thickness of the spiral bevel gear, and solves the lubrication performance of the spiral bevel gear under different working conditions.
ZSWIM8 is a myogenic protein that partly prevents C2C12 differentiation
Authors: Okumura Fumihiko , Oki Nodoka , Fujiki Yuha , Ikuta Rio , Osaki Kana , Hamada Shun , Nakatsukasa Kunio , Hisamoto Naoki , Hara Taichi , Kamura Takumi
Published: October 2021

Cell adhesion molecule-related/downregulated by oncogenes (Cdon) is a cell-surface receptor that mediates cell–cell interactions and positively regulates myogenesis. The cytoplasmic region of Cdon interacts with other proteins to form a Cdon/JLP/Bnip-2/CDC42 complex that activates p38 mitogen-activated protein kinase (MAPK) and induces myogenesis. However, Cdon complex may include other proteins during myogenesis. In this study, we found that Cullin 2-interacting protein zinc finger SWIM type containing 8 (ZSWIM8) ubiquitin ligase is induced during C2C12 differentiation and is included in the Cdon complex. We knocked-down Zswim8 in C2C12 cells to determine the effect of ZSWIM8 on differentiation. However, we detected neither ZSWIM8-dependent ubiquitination nor the degradation of Bnip2, Cdon, or JLP. In contrast, ZSWIM8 knockdown accelerated C2C12 differentiation. These results suggest that ZSWIM8 is a Cdon complex-included myogenic protein that prevents C2C12 differentiation without affecting the stability of Bnip2, Cdon, and JLP.
Crizotinib efficacy in advanced non-squamous NSCLC patients with ALK or ROS1 rearrangement
Authors: Krawczyk Paweł , Grenda Anna , Terlecka Paulina , Błach Justyna , Wojas-Krawczyk Kamila , Kucharczyk Tomasz , Chmielewska Izabela , Kieszko Robert , Jarosz Bożena , Gil Michał , Reszka Katarzyna , Milanowski Janusz
Published: October 2021

In patients with advanced non-small cell lung cancer (NSCLC), comprehensive genetic diagnostics is currently carried out in order to qualify for molecularly targeted therapies and immunotherapy. The aim of the study was to assess the usefulness of the reverse transcriptase (RT-PCR) method in the diagnosis of gene rearrangements, the effectiveness of EGFR, ALK, ROS1, and PD-L1 inhibitors in first-line treatment in NSCLC patients. We enrolled 95 non-squamous NSCLC patients with known status of EGFR, ALK, ROS1, MET and RET genes and PD-L1 protein expression. We used the real time PCR, fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and RT-PCR techniques for determination of predictive factors. In patients with ALK and ROS1 genes alteration, the median overall survival was 34 months in crizotinib treated patients and 6 months in patients who received chemotherapy (HR = 0.266, p = 0.0056). The risk of death was lower in patients treated with molecularly targeted therapies or immunotherapy compared to patients with predictive factors without personalized treatment (HR = 0.265, 95% CI 0.116–0.606) and to patient without predictive factors who received chemotherapy (HR = 0.42, 95% CI 0.162–1.09). Diagnosis of predictive factors and implementation of personalized treatment are key to prolonging the survival in advanced NSCLC patients.
Swim training affects Akt signaling and ameliorates loss of skeletal muscle mass in a mouse model of amyotrophic lateral sclerosis
Authors: Cieminski Karol , Flis Damian Jozef , Dzik Katarzyna , Kaczor Jan Jacek , Czyrko Emilia , Halon-Golabek Malgorzata , Wieckowski Mariusz Roman , Antosiewicz Jedrzej , Ziolkowski Wieslaw
Published: October 2021

We tested the hypothesis that swim training reverses the impairment of Akt/FOXO3a signaling, ameliorating muscle atrophy in ALS mice. Transgenic male mice B6SJL-Tg (SOD1G93A) 1Gur/J were used as the ALS model (n = 35), with wild-type B6SJL (WT) mice as controls (n = 7). ALS mice were analyzed before ALS onset, at ALS onset, and at terminal ALS. Levels of insulin/Akt signaling pathway proteins were determined, and the body and tibialis anterior muscle mass and plasma creatine kinase. Significantly increased levels of FOXO3a in ALS groups (from about 13 to 21-fold) compared to WT mice were observed. MuRF1 levels in the ONSET untrained group (12.0 ± 1.7 AU) were significantly higher than in WT mice (1.12 ± 0.2 AU) and in the BEFORE ALS group (3.7 ± 0.9 AU). This was associated with body mass and skeletal muscle mass reduction. Swim training significantly ameliorated the reduction of skeletal muscle mass in both TERMINAL groups (p < 0.001) and partially reversed changes in the levels of Akt signaling pathway proteins. These findings shed light on the swimming-induced attenuation of skeletal muscle atrophy in ALS with possible practical implications for anti-cachexia approaches.
Manganese toxicity disrupts indole acetic acid homeostasis and suppresses the CO2 assimilation reaction in rice leaves
Authors: Takagi Daisuke , Ishiyama Keiki , Suganami Mao , Ushijima Tomokazu , Fujii Takeshi , Tazoe Youshi , Kawasaki Michio , Noguchi Ko , Makino Amane
Published: October 2021

Despite the essentiality of Mn in terrestrial plants, its excessive accumulation in plant tissues can cause growth defects, known as Mn toxicity. Mn toxicity can be classified into apoplastic and symplastic types depending on its onset. Symplastic Mn toxicity is hypothesised to be more critical for growth defects. However, details of the relationship between growth defects and symplastic Mn toxicity remain elusive. In this study, we aimed to elucidate the molecular mechanisms underlying symplastic Mn toxicity in rice plants. We found that under excess Mn conditions, CO2 assimilation was inhibited by stomatal closure, and both carbon anabolic and catabolic activities were decreased. In addition to stomatal dysfunction, stomatal and leaf anatomical development were also altered by excess Mn accumulation. Furthermore, indole acetic acid (IAA) concentration was decreased, and auxin-responsive gene expression analyses showed IAA-deficient symptoms in leaves due to excess Mn accumulation. These results suggest that excessive Mn accumulation causes IAA deficiency, and low IAA concentrations suppress plant growth by suppressing stomatal opening and leaf anatomical development for efficient CO2 assimilation in leaves.
Temperature dependence of intrinsic and extrinsic contributions to anisotropic magnetoresistance
Authors: Park Ji-Ho , Ko Hye-Won , Kim Jeong-Mok , Park Jungmin , Park Seung-Young , Jo Younghun , Park Byong-Guk , Kim Se Kwon , Lee Kyung-Jin , Kim Kab-Jin
Published: October 2021

Electrical conduction in magnetic materials depends on their magnetization configuration, resulting in various magnetoresistances (MRs). The microscopic mechanisms of MR have so far been attributed to either an intrinsic or extrinsic origin, yet the contribution and temperature dependence of either origin has remained elusive due to experimental limitations. In this study, we independently probed the intrinsic and extrinsic contributions to the anisotropic MR (AMR) of a permalloy film at varying temperatures using temperature-variable terahertz time-domain spectroscopy. The AMR induced by the scattering-independent intrinsic origin was observed to be approximately 1.5% at T = 16 K and is virtually independent of temperature. In contrast, the AMR induced by the scattering-dependent extrinsic contribution was approximately 3% at T = 16 K but decreased to 1.5% at T = 155 K, which is the maximum temperature at which the AMR can be resolved using THz measurements. Our results experimentally quantify the temperature-dependent intrinsic and extrinsic contributions to AMR, which can stimulate further theoretical research to aid the fundamental understanding of AMR.
Robust autofocusing for scanning electron microscopy based on a dual deep learning network
Authors: Lee Woojin , Nam Hyeong Soo , Kim Young Gon , Kim Yong Ju , Lee Jun Hee , Yoo Hongki
Published: October 2021

Scanning electron microscopy (SEM) is a high-resolution imaging technique with subnanometer spatial resolution that is widely used in materials science, basic science, and nanofabrication. However, conducting SEM is rather complex due to the nature of using an electron beam and the many parameters that must be adjusted to acquire high-quality images. Only trained operators can use SEM equipment properly, meaning that the use of SEM is restricted. To broaden the usability of SEM, we propose an autofocus method for a SEM system based on a dual deep learning network, which consists of an autofocusing-evaluation network (AENet) and an autofocusing-control network (ACNet). The AENet was designed to evaluate the quality of given images, with scores ranging from 0 to 9 regardless of the magnification. The ACNet can delicately control the focus of SEM online based on the AENet’s outputs for any lateral sample position and magnification. The results of these dual networks showed successful autofocus performance on three trained samples. Moreover, the robustness of the proposed method was demonstrated by autofocusing on unseen samples. We expect that our autofocusing system will not only contribute to expanding the versatility of SEM but will also be applicable to various microscopes.
Clinically silent LINE 1 insertion in the PNPLA3 gene may impede genotyping of the p.I148M variant
Authors: Leníček Martin , Šmíd Václav , Pajer Petr , Nazarova Anna , Dvořák Karel , Subhanová Iva , Brůha Radan , Vítek Libor
Published: October 2021

The patatin-like phospholipase domain containing 3 (PNPLA3) gene (viz. its I148M variant) is one of the key players in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We have identified a novel insertion/deletion variant of 1114 bp, localized in the second intron of the PNPLA3 gene, which corresponds to the 3′ terminal sequence of the long-interspersed element (LINE-1). DNA analysis of 122 NAFLD patients and 167 control subjects as well as RNA analysis of 19 liver biopsies revealed that the novel variant is very common (frequency = 0.41), fully linked to the clinically important I148M variant, and clinically silent. Although the LINE-1 insertion does not seem to have any biological effect, it can impede genotyping of the I148M variant. If insertion prevents the attachment of the diagnostic primer, then the non-insertion allele will be selectively amplified; and thus the frequency of the 148M "risk" allele will be significantly overestimated due to the complete linkage of the LINE-1 insertion and the 148I allele of the PNPLA3 gene. Therefore, our findings underline the importance of careful design and consistent documentation of the methodology, including primer sequences. Critical revisions of the results of some studies that have already been reported may therefore be needed.
Numerous chondritic impactors and oxidized magma ocean set Earth’s volatile depletion
Authors: Sakuraba Haruka , Kurokawa Hiroyuki , Genda Hidenori , Ohta Kenji
Published: October 2021

Earth’s surface environment is largely influenced by its budget of major volatile elements: carbon (C), nitrogen (N), and hydrogen (H). Although the volatiles on Earth are thought to have been delivered by chondritic materials, the elemental composition of the bulk silicate Earth (BSE) shows depletion in the order of N, C, and H. Previous studies have concluded that non-chondritic materials are needed for this depletion pattern. Here, we model the evolution of the volatile abundances in the atmosphere, oceans, crust, mantle, and core through the accretion history by considering elemental partitioning and impact erosion. We show that the BSE depletion pattern can be reproduced from continuous accretion of chondritic bodies by the partitioning of C into the core and H storage in the magma ocean in the main accretion stage and atmospheric erosion of N in the late accretion stage. This scenario requires a relatively oxidized magma ocean ($$\log _{10} f_{{\mathrm{O}}_2}$$

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$$\gtrsim$$
≳
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$$-2$$

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, where $$f_{{\mathrm{O}}_2}$$

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is the oxygen fugacity, $$\mathrm{IW}$$
IW
is $$\log _{10} f_{{\mathrm{O}}_2}^{\mathrm{IW}}$$

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10

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at the iron-wüstite buffer), the dominance of small impactors in the late accretion, and the storage of H and C in oceanic water and carbonate rocks in the late accretion stage, all of which are naturally expected from the formation of an Earth-sized planet in the habitable zone.