bluuebunny/crossref_metadata_2025 huggingface dataset:
Copper-Containing Alloy as Immunoregulatory Material in Bone Regeneration via Mitochondrial Oxidative Stress
Authors: Xu Daorong , Qian Jikun , Guan Xin , Ren Ling , Yang Kaifan , Huang Xuan , Zhang Shuyuan , Chai Yu , Wu Xiaohu , Wu Hangtian , Zhang Xianrong , Yang Ke , Yu Bin
Published: January 2021

In the mammalian skeletal system, osteogenesis and angiogenesis are closely linked by type H vessels during bone regeneration and repair. Our previous studies confirmed the promotion of these processes by copper-containing metal (CCM) in vitro and in vivo. However, whether and how the coupling of angiogenesis and osteogenesis participates in the promotion of bone regeneration by CCM in vivo is unknown. In this study, M2a macrophages but not M2c macrophages were shown to be immunoregulated by CCM. A CCM, 316L−5Cu, was applied to drilling hole injuries of the tibia of C57/6 mice for comparison. We observed advanced formation of cortical bone and type H vessels beneath the new bone in the 316L−5Cu group 14 and 21 days postinjury. Moreover, the recruitment of CD206-positive M2a macrophages, which are regarded as the primary source of platelet-derived growth factor type BB (PDGF-BB), was significantly promoted at the injury site at days 14 and 21. Under the stimulation of CCM, mitochondria-derived reactive oxygen species were also found to be upregulated in CD206hi M2a macrophages in vitro, and this upregulation was correlated with the expression of PDGF-BB. In conclusion, our results indicate that CCM promotes the evolution of callus through the generation of type H vessels during the process of bone repair by upregulating the expression of PDGF-BB derived from M2a macrophages.
Microbiota-Derived Metabolite Trimethylamine N-Oxide Protects Mitochondrial Energy Metabolism and Cardiac Functionality in a Rat Model of Right Ventricle Heart Failure
Authors: Videja Melita , Vilskersts Reinis , Korzh Stanislava , Cirule Helena , Sevostjanovs Eduards , Dambrova Maija , Makrecka-Kuka Marina
Published: January 2021

Aim: Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite synthesized in host organisms from specific food constituents, such as choline, carnitine and betaine. During the last decade, elevated TMAO levels have been proposed as biomarkers to estimate the risk of cardiometabolic diseases. However, there is still no consensus about the role of TMAO in the pathogenesis of cardiovascular disease since regular consumption of TMAO-rich seafood (i.e., a Mediterranean diet) is considered to be beneficial for the primary prevention of cardiovascular events. Therefore, the aim of this study was to investigate the effects of long-term TMAO administration on mitochondrial energy metabolism in an experimental model of right ventricle heart failure.

Methods: TMAO was administered to rats at a dose of 120 mg/kg in their drinking water for 10 weeks. Then, a single subcutaneous injection of monocrotaline (MCT) (60 mg/kg) was administered to induce right ventricular dysfunction, and treatment with TMAO was continued (experimental groups: Control; TMAO; MCT; TMAO+MCT). After 4 weeks, right ventricle functionality was assessed by echocardiography, mitochondrial function and heart failure-related gene and protein expression was determined.

Results: Compared to the control treatment, the administration of TMAO (120 mg/kg) for 14 weeks increased the TMAO concentration in cardiac tissues up to 14 times. MCT treatment led to impaired mitochondrial function and decreased right ventricular functional parameters. Although TMAO treatment itself decreased mitochondrial fatty acid oxidation-dependent respiration, no effect on cardiac functionality was observed. Long-term TMAO administration prevented MCT-impaired mitochondrial energy metabolism by preserving fatty acid oxidation and subsequently decreasing pyruvate metabolism. In the experimental model of right ventricle heart failure, the impact of TMAO on energy metabolism resulted in a tendency to restore right ventricular function, as indicated by echocardiographic parameters and normalized organ-to-body weight indexes. Similarly, the expression of a marker of heart failure severity, brain natriuretic peptide, was substantially increased in the MCT group but tended to be restored to control levels in the TMAO+MCT group.

Conclusion: Elevated TMAO levels preserve mitochondrial energy metabolism and cardiac functionality in an experimental model of right ventricular heart failure, suggesting that under specific conditions TMAO promotes metabolic preconditioning-like effects.
Study of the Segmental Dynamics and Ion Transport of Solid Polymer Electrolytes in the Semi-crystalline State
Authors: Chen Xi Chelsea , Sacci Robert L. , Osti Naresh C. , Tyagi Madhusudan , Wang Yangyang , Keum Jong K. , Dudney Nancy J.
Published: January 2021

Solid polymer electrolytes are promising in fulfilling the requirements for a stable lithium metal anode toward higher energy and power densities. In this work, we investigate the segmental dynamics, ionic conductivity, and crystallinity of a polymer electrolyte consisting of poly(ethylene oxide) (PEO) and lithium triflate salt, in the semi-crystalline state. Using quasi-elastic neutron scattering, the segmental dynamics of PEO chains confined between the crystalline lamellae is quantified, using Cole–Cole analysis. We show that the structural relaxation time, τ0, of PEO equilibrated near room temperature is six-fold longer than the same sample that had just cooled down to room temperature. This corresponds to a three-fold smaller ionic conductivity in the equilibrated condition. This work reveals that the segmental dynamics of semi-crystalline polymer electrolytes is very sensitive to thermal history. We demonstrate that quasi-elastic neutron scattering can be used to characterize the ion transport and segmental dynamics in the semi-crystalline state.
Reproducibility Problems of Amyloid-β Self-Assembly and How to Deal With Them
Authors: Faller Peter , Hureau Christelle
Published: January 2021

The self-assembly of peptides and proteins into amyloid fibrils and other aggregates are linked to several diseases. One of the most studied cases is the peptide amyloid-β (Aβ), found self-assembled in Alzheimer's disease patients' brains. In test tubes, assays with chemically synthesized or recombinant Aβ are widely investigated to understand the aggregation process and to find modulators, which could be of therapeutic interest. Experience over more than a decade in our laboratory through discussions with colleagues, expertly studying the literature, and as reviewers revealed to us the widely encountered difficulty to control the aggregation and obtain reproducible results in the test tube. However, this issue is scarcely reported and discussed in the publications, which we think hampers strongly the progress in this field and can deceive newcomers. Here, we describe the difficulty and potential reasons to obtain reproducible aggregation data and propose some guidelines for working with it.
A Cooperative Photoactive Class-I Hybrid Polyoxometalate With Benzothiadiazole–Imidazolium Cations
Authors: Kibler Alexander J. , Souza Virginia S. , Fernandes Jesum Alves , Lewis William , Argent Stephen P. , Dupont Jairton , Newton Graham N.
Published: January 2021

An organic–inorganic hybrid species based on the Wells–Dawson polyoxotungstate [P2W18O62]6− and novel fluorescent benzothiadiazole–imidazolium cations, [BTD-4,7-ImH]2+, has been synthesized. X-ray crystallographic analysis shows that the inorganic and organic components form a hydrogen-bonded superstructure and that the cations are revealed to be non-equivalent with varying degrees of rotation between the BTD and imidazolium rings due to competition between weak intra- and intermolecular interactions. The UV–vis diffuse reflectance spectra indicate that the hybrid has a band gap of 3.13 eV, while the solid-state fluorescence properties of the cation are quenched in the hybrid material, suggesting the existence of electron transfer between the inorganic and organic components. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies of the polyoxometalate (POM) and BTD-4,7-ImH precursors, estimated through UV–vis absorption spectroscopy and cyclic voltammetry, indicate that electron transfer from the BTD cations to the POM may occur in the excited state.
Susceptibility Analysis in Several Mouse Strains Reveals Robust T-Cell Responses After Mycoplasma pneumoniae Infection in DBA/2 Mice
Authors: Tamiya Shigeyuki , Yoshikawa Eisuke , Suzuki Koichiro , Yoshioka Yasuo
Published: January 2021

Mycoplasma pneumoniae (Mp) is a highly contagious respiratory pathogen responsible for human community-acquired pneumonia. The number of antibiotic-resistant Mp strains is increasing; therefore, to develop novel therapeutics, it is crucial to precisely understand the pathogenesis of mycoplasma pneumonia. Herein, we examined the susceptibility and response to Mp among eight inbred mouse strains. Following infection, the bacterial load in the bronchoalveolar lavage fluid (BALF) from DBA/2 mice was higher than that in the other tested strains such as BALB/c mice, which are frequently used in Mp research. In contrast, the numbers of CD45+ immune cells and neutrophils in BALF were comparable between BALB/c and DBA/2 mice, with lower numbers observed in C57BL/6J and CBA/N mice than in BALB/c mice. Among the tested strains, the BALF level of interleukin 12 subunit p40 was highest in DBA/2 mice; however, significant differences in other cytokines levels were not observed between BALB/c and DBA/2 mice. After Mp infection, Mp-specific Th1 and Th17 responses were significantly enhanced in DBA/2 mice when compared with BALB/c mice. Furthermore, prior infection with Mp increased the number of neutrophils in BALF after the reinfection of DBA/2 mice through an Mp-specific CD4+ T cell-dependent mechanism. Thus, DBA/2 may be an appropriate strain for evaluating Mp infection. Moreover, a comparison of responses revealed by various inbred mouse strains could be useful for elucidating the pathogenesis of Mycoplasma pneumonia.
Mycobacterium avium Modulates the Protective Immune Response in Canine Peripheral Blood Mononuclear Cells
Authors: Kim Suji , Park Hyun-Eui , Park Woo Bin , Kim Seo Yihl , Park Hong-Tae , Yoo Han Sang
Published: January 2021

Mycobacterium avium, an opportunistic intracellular pathogen, is a member of the non-tuberculous mycobacteria species. M. avium causes respiratory disease in immunosuppressed individuals and a wide range of animals, including companion dogs and cats. In particular, the number of infected companion dogs has increased, although the underlying mechanism of M. avium pathogenesis in dogs has not been studied. Therefore, in the present study, the host immune response against M. avium in dogs was investigated by transcriptome analysis of canine peripheral blood mononuclear cells. M. avium was shown to induce different immune responses in canine peripheral blood mononuclear cells at different time points after infection. The expression of Th1-associated genes occurred early during M. avium infection, while that of Th17-associated genes increased after 12 h. In addition, the expression of apoptosis-related genes decreased and the abundance of intracellular M. avium increased in monocyte-derived macrophages after infection for 24 h. These results reveal the M. avium induces Th17 immune response and avoids apoptosis in infected canine cells. As the number of M. avium infection cases increases, the results of the present study will contribute to a better understanding of host immune responses to M. avium infection in companion dogs.
Establishment and Application of a Dual-Labeling Time-Resolved Fluorescence Immunoassay Method for Simultaneous Detection of the Troponin I-C Complex and Full-Size-Troponin I
Authors: Huang Biao , Wu Jian , Chen Hao , Zhang Li , Zhou Xiumei , Wu Qingqing , Li Ting , Wang Yigang , Xia Penguo , Dai Yaping , Kai Guoyin , Liu Pengfei , Pei Hao
Published: January 2021

Background: The measurement of cardiac troponin I (cTnI) is widely used in the diagnosis of acute myocardial infarction (AMI). Although existing cTnI detection methods measure total cTnI, the significance of undegraded full-size-cTnI levels is still not well-understood. In this study, we have established a novel dual-labeling time-resolved fluorescence immunoassay (TRFIA) technique that simultaneously detects the cTnI-C complex and full-size-cTnI, allowing us to explore the clinical value of full-size-cTnI determination.

Methods: An antibody against the 23–43 amino acid region of cTnI protected by endogenous cTnC is coupled to magnetic beads to provide a solid-phase antibody for capturing all cTnI. An antibody against cTnC in the cTnI-C complex labeled with Eu3+ was used to detect the cTnI-C complex, and an antibody labeled with Sm3+ near the C-terminal 190–203 amino acids of cTnI was used to detect full-size-cTnI. Through dual-labeling TRFIA, cTnI-C complex, full-size-cTnI, and the full-size-cTnI/cTnI-C ratio can be detected simultaneously. The dual-labeling TRFIA technique was used to analyze serum samples collected at different times during treatment and compare their full-size-cTnI/cTnI-C ratios.

Results: The sensitivity for the cTnI-C-TRFIA complex was 0.02 ng/mL, the measurement range was 0.02–40 ng/mL, the average intra-batch coefficient of variation (CV) was 4.35%, and the inter-average CV was 6.23%. The correlation coefficient between cTnI-C-TRFIA and commercial cTnI-CLIA methods was R2 = 0.8887. The sensitivity for full-size-cTnI-TRFIA was 0.04 ng/mL, the measurement range was 0.04–40 ng/mL, the average intra-batch CV was 4.95%, and the average inter-batch CV was 7.79%. The correlation coefficient between full-size-cTnI-TRFIA and commercial cTnI-CLIA methods was R2 = 0.7247.

Conclusions: Dual-labeling full-size-cTnI/cTnI-C-TRFIA analysis is helpful for determining the length of time of chest pain before admission and the degree of continuous release of cTnI in the myocardium. Thus, it is more for early prognosis than just detecting cTnI.
Characteristics of the Electrocardiogram in Japanese Fabry Patients Under Long-Term Enzyme Replacement Therapy
Authors: Morimoto Satoshi , Nojiri Ayumi , Fukuro Eiko , Anan Ikuko , Kawai Makoto , Sakurai Ken , Kobayashi Masahisa , Kobayashi Hiroshi , Ida Hiroyuki , Ohashi Toya , Shibata Takahiro , Yoshimura Michihiro , Eto Yoshikatsu , Hongo Kenichi
Published: January 2021

Objective: An electrocardiogram (ECG) is an important tool for demonstrating cardiac manifestations in various heart diseases. The present study clarified the characteristics of ECG parameters in Japanese Fabry patients under long-term enzyme replacement therapy (ERT).

Methods: We analyzed the ECGs of 40 Fabry patients (male, n = 17; female, n = 23) before and after treatment with ERT. To evaluate the atrio-ventricular conduction, the PQ interval, corrected PQ and PQ minus P-wave in lead II (Pend-Q) were calculated. The QRS duration, QTc, Sokolow-Lyon index, and strain pattern were also examined.

Results: At the baseline, the shortening of the PQ interval, corrected PQ and Pend-Q was identified in 7.5, 25.0, and 47.5% of cases, respectively. The prolongation of QRS duration and QTc was found in 7.5 and 40.0% of cases, respectively. The strain pattern was mainly identified in female patients, irrespective of left ventricular hypertrophy (LVH). During long-term ERT, the PQ interval, corrected PQ and Pend-Q did not change significantly. The QRS duration was significantly prolonged in both genders, whereas the QTc was significantly prolonged only in male patients. A subgroup analysis revealed that the prolongation of the QRS duration and QTc only occurred in male patients with LVH and only occurred in female patients with the classical type mutation. The prevalence of the strain was significantly increased only in male patients with LVH.

Conclusions: These results suggest that the shortening of the Pend-Q is a specific finding in Japanese Fabry patients, and the strain pattern without LVH in female patients can be considered Fabry disease. During long-term ERT, prolongation of the QRS duration and QTc can indicate the progression of myocardial damage in male patients with LVH and in female patients with the classical type mutation.
The Triglyceride-Glucose Index, an Insulin Resistance Marker, Was Non-linear Associated With All-Cause and Cardiovascular Mortality in the General Population
Authors: Liu Xiao-cong , He Guo-dong , Lo Kenneth , Huang Yu-qing , Feng Ying-qing
Published: January 2021

Background: The triglyceride-glucose (TyG) index could serve as a convenient substitute of insulin resistance (IR), but epidemiological evidence on its relationship with the long-term risk of mortality is limited.

Methods: Participants from the National Health and Nutrition Examination Survey during 1999–2014 were grouped according to TyG index (<8, 8–9, 9–10, >10). Cox regression was conducted to compute the hazard ratios (HRs) and 95% confidence interval (CI). Restricted cubic spline and piecewise linear regression were performed to detect the shape of the relationship between TyG index and mortality.

Results: A total of 19,420 participants (48.9% men) were included. On average, participants were followed-up for 98.2 months, and 2,238 (11.5%) and 445 (2.3%) cases of mortality due to all-cause or cardiovascular disease were observed. After adjusting for confounders, TyG index was independently associated with an elevated risk of all-cause (HR, 1.10; 95% CI, 1.00–1.20) and cardiovascular death (HR, 1.29; 95% CI, 1.05–1.57). Spline analyses showed that the relationship of TyG index with mortality was non-linear (All non-linear P < 0.001), and the threshold value were 9.36 for all-cause and 9.52 for cardiovascular death, respectively. The HRs above the threshold point were 1.50 (95% CI, 1.29–1.75) and 2.35 (95% CI, 1.73–3.19) for all-cause and cardiovascular death. No significant difference was found below the threshold points (All P > 0.05).

Conclusion: Elevated TyG index reflected a more severe IR and was associated with mortality due to all-cause and cardiovascular disease in a non-linear manner.
Identifying Clinical and Genomic Features Associated With Chronic Kidney Disease
Authors: Moreno M. Megan , Bain Travaughn C. , Moreno Melissa S. , Carroll Katherine C. , Cunningham Emily R. , Ashton Zoe , Poteau Roby , Subasi Ersoy , Lipkowitz Michael , Subasi Munevver Mine
Published: January 2021

We apply a pattern-based classification method to identify clinical and genomic features associated with the progression of Chronic Kidney disease (CKD). We analyze the African-American Study of Chronic Kidney disease with Hypertension dataset and construct a decision-tree classification model, consisting 15 combinatorial patterns of clinical features and single nucleotide polymorphisms (SNPs), seven of which are associated with slow progression and eight with rapid progression of renal disease among African-American Study of Chronic Kidney patients. We identify four clinical features and two SNPs that can accurately predict CKD progression. Clinical and genomic features identified in our experiments may be used in a future study to develop new therapeutic interventions for CKD patients.
Seasonal and Spatial Differences in Metal and Metalloid Concentrations in the Snow Cover of Hansbreen, Svalbard
Authors: Koziol Krystyna , Uszczyk Aleksander , Pawlak Filip , Frankowski Marcin , Polkowska Żaneta
Published: January 2021

Metals and metalloids in snow on glaciers, depending on the season of deposition, may come from various sources: local rock dust (erosion of the geological substratum), marine aerosol, local human activity (e.g., impurities in combusted fuel and waste incineration), and long-range atmospheric transport. Hansbreen, a glacier located close to the Polish Polar Station in southern Svalbard, is a perfect site to study metals and metalloids: it has a complex geological substratum, has a year-round presence of a small group of people, and is near the coast. We analyzed a snapshot of metal and metalloid concentrations in snow samples from shallow cores corresponding to autumn, winter, and spring deposition on Hansbreen. Eighteen cores of snow were collected across the glacier, revealing the influence of potential local sources of metals and metalloids. In these samples, we predominantly found Na, Mg, and K, followed by Zn, Ca, Al, and Fe. Heavy metals, such as Bi or Hg, were also detected. Cluster analysis of the determined elemental concentrations divided them into three distinct groups: Group 1: Ag, As, Bi, Cd, Hg, Mo, Sb, Se, and Zn—the most diverse cluster, representing mostly long-range transported volatile elements, with possible extra local geological sources; Group 2: Al, Fe, Cu, and Mn—elements with crustal sources; and Group 3: Na, Ca, Mg, K, and Sr—with the main source in sea spray aerosol. The latter interpretation was confirmed by the calculation of sea salt contribution based on the composition of mean seawater and the positive significant correlation between their concentrations and the electrical conductivity of snow samples. In the study site, snow was up to six times more efficient in bringing metal pollution into terrestrial environment, when compared to rain.
High-Resolution Environmental Magnetism Using the Quantum Diamond Microscope (QDM): Application to a Tropical Speleothem
Authors: Fu Roger R. , Hess Kimberly , Jaqueto Plinio , Novello Valdir F. , Kukla Tyler , Trindade Ricardo I. F. , Stríkis Nicolás M. , Cruz Francisco W. , Ben Dor Oren
Published: January 2021

Quantum diamond microscope (QDM) magnetic field imaging is a recently developed technique capable of mapping magnetic field sources in geologic samples at 1 micrometer resolution. Applying QDM imaging to speleothems can provide high‐resolution time series of detrital input into the cave environment, which, in turn, can yield useful paleoenvironmental information. Here we map the magnetic field over a speleothem from midwest Brazil over a 174 year timespan with annual to sub-annual resolution and perform backfield remanence acquisition experiments to quantify changes in the magnetic grain population through time. We find that magnetic particles occur in highly enriched layers of 10–100 µm thickness that sample the same detrital source population. Combined with petrographic observations and electron microprobe mapping of Mg and Ca, we conclude that detrital enrichment in our sample is caused by drier conditions leading to slow or halted speleothem growth. This interpretation is compatible with oxygen isotopic data and implies that speleothem magnetism can be used to infer the past occurrence of drought and potentially quantify their duration. Future high-resolution magnetic imaging of speleothems may provide additional insight into the mechanism of detrital enrichment and establish their role as a proxy for local moisture and infiltration.
“Hello, My Name Is Melinda” – Students' Views on a Digital Assistant for Navigation in Digital Learning Environments; A Qualitative Interview Study
Authors: Herrmann-Werner Anne , Loda Teresa , Junne Florian , Zipfel Stephan , Madany Mamlouk Amir
Published: January 2021

Background: The goal of the current investigation was to find out about students attitudes and needs toward the development of a new personal digital assistant (PDA) to help them navigate through an increasingly digital learning environment (DLE). As students have repeatedly been shown to be an especially stress-prone user-group, a PDA serving as a digital secretary might additionally significantly reduce study-related stress.

Methods:N = 12 STEM (science, technology, engineering, and math) students in various years of study at the University of Luebeck, Germany, participated in the study. A qualitative research design of semi-structured interviews was used with the interviews evaluated according to Mayring's qualitative content analysis using MAXQDA Version 2018.

Results: Students being educated in a DLE in many cases report positive as well as negative impacts on communication through progressing digitalisation. In line with previous findings, students indicated several study-related and personal stressors during their academic life, but they also reported a variety of preventive factors such as motivation and interest in their studies as well as social support. When asked specifically about desired functions of a future PDA, students wished for a kind of digital secretary with functions such as recording, calendarisation and automated exam registration.

Conclusions: Valuable insights were obtained regarding all areas of interest – DLE, stressors and preventive factors of students being educated within DLE, and ideas regarding the development of a new, student-user-friendly PDA. Previous results from stress research in student samples combined with the insights from the present study support the thought that a PDA combining administrative and counseling functions might be a new idea for students and could potentially complement a simple administrative PDA, additionally helping to provide students with therapeutic or counseling needs.
Risk Factors and Resilience Strategies: Voices From Chinese Novice Foreign Language Teachers
Authors: Fan Lin , Ma Fang , Liu Yan-mei , Liu Tao , Guo Lin , Wang Lu-nan
Published: January 2021

In recent years, due to the concern of the high rate of burnout and attrition of teachers in their early career years, teacher resilience has become a vital theme in the study of their professional development. However, little has been done in China. This study contextualized teacher resilience development in Chinese universities and interviewed seven resilient novice foreign language (FL) teachers to explore risk factors confronting them in Chinese contexts and resilience strategies they have employed to cope with these challenges. In-depth interview data and informants' reflective journals were analyzed inductively by using thematic analysis. The results of the study unfolded risk factors peculiar to Chinese context, and novices' adoption of resilience strategies was found to involve teachers' highly selective and dynamic interaction with risk and protective factors, and individual agency manifested itself as an important factor in novice FL teacher resilience development.
Multibody Dynamic Analysis of a Wind Turbine Drivetrain in Consideration of the Shaft Bending Effect and a Variable Gear Mesh Including Eccentricity and Nacelle Movement
Authors: Park Yonghui , Park Hyunchul , Ma Zhe , You Jikun , Shi Wei
Published: January 2021

Due to the energy crisis and global warming issues, the wind energy is becoming one of the most attractive renewable energy resources in the world. The drivetrains in the wind turbine tend to fail more prematurely than those in any other applications. Gearbox is the subsystem that causes the most downtime for the wind turbines. In the previous research, only the torsional flexibility of the shaft was considered in the drivetrain model. However, because the shaft is longer than other parts, and components connected by the shaft affect each other via shaft bending, the flexibility of the shaft cannot be ignored. In this study, a spherical joint that consists of three rotational springs was used to define the shaft bending. This shaft bending will affect the drivetrain rotation, the translational motion and the gear mesh contact force. Additionally, the eccentricity and the nacelle movement are analyzed due to the coupled motion. In this paper, a mathematical model of the drivetrain is proposed, which is a three-dimensional dynamic model that includes flexible bearings, a gear mesh model, shaft flexibility, eccentricity, and nacelle movement. The equation of motion of the drivetrain is derived using Lagrange's equation. The governing equation is solved numerically via direct numerical integration. The dynamic responses of the system and contact forces between the gear tooth in the time and frequency domains are calculated numerically. The study shows that this dynamic model of the drivetrain will be highly useful for subsequent studies on the wind turbine condition monitoring.
The Role of Pathogen Dynamics and Immune Gene Expression in the Survival of Feral Honey Bees
Authors: Hinshaw Chauncy , Evans Kathleen C. , Rosa Cristina , López-Uribe Margarita M.
Published: January 2021

Studies of the ecoimmunology of feral organisms can provide valuable insight into how host–pathogen dynamics change as organisms transition from human-managed conditions back into the wild. Honey bees (Apis mellifera Linnaeus) offer an ideal system to investigate these questions as colonies of these social insects often escape management and establish in the wild. While managed honey bee colonies have low probability of survival in the absence of disease treatments, feral colonies commonly survive in the wild, where pathogen pressures are expected to be higher due to the absence of disease treatments. Here, we investigate the role of pathogen infections [Deformed wing virus (DWV), Black queen cell virus (BQCV), and Nosema ceranae] and immune gene expression (defensin-1, hymenoptaecin, pgrp-lc, pgrp-s2, argonaute-2, vago) in the survival of feral and managed honey bee colonies. We surveyed a total of 25 pairs of feral and managed colonies over a 2-year period (2017–2018), recorded overwintering survival, and measured pathogen levels and immune gene expression using quantitative polymerase chain reaction (qPCR). Our results showed that feral colonies had higher levels of DWV but it was variable over time compared to managed colonies. Higher pathogen levels were associated with increased immune gene expression, with feral colonies showing higher expression in five out of the six examined immune genes for at least one sampling period. Further analysis revealed that differential expression of the genes hymenoptaecin and vago increased the odds of overwintering survival in managed and feral colonies. Our results revealed that feral colonies express immune genes at higher levels in response to high pathogen burdens, providing evidence for the role of feralization in altering pathogen landscapes and host immune responses.
Blockade of LAG-3 in PD-L1-Deficient Mice Enhances Clearance of Blood Stage Malaria Independent of Humoral Responses
Authors: Furtado Raquel , Chorro Laurent , Zimmerman Natalie , Guillen Erik , Spaulding Emily , Chin Shu Shien , Daily Johanna P. , Lauvau Grégoire
Published: January 2021

T cells expressing high levels of inhibitory receptors such as PD-1 and LAG-3 are a hallmark of chronic infections and cancer. Checkpoint blockade therapies targeting these receptors have been largely validated as promising strategies to restore exhausted T cell functions and clearance of chronic infections and tumors. The inability to develop long-term natural immunity in malaria-infected patients has been proposed to be at least partially accounted for by sustained expression of high levels of inhibitory receptors on T and B lymphocytes. While blockade or lack of PD-1/PD-L1 and/or LAG-3 was reported to promote better clearance ofPlasmodiumparasites in various mouse models, how exactly blockade of these pathways contributes to enhanced protection is not known. Herein, using the mouse model of non-lethalP. yoelii (Py)infection, we reveal that the kinetics of blood parasitemia as well as CD4+T follicular helper (TFH) and germinal center (GC) B cell responses are indistinguishable between PD-1-/-, PD-L1-/-and WT mice. Yet, we also report that monoclonal antibody (mAb) blockade of LAG-3 in PD-L1-/-mice promotes accelerated control of blood parasite growth and clearance, consistent with prior therapeutic blockade experiments. However, neither CD4+TFHand GC B cell responses, nor parasite-specific Ab serum titers and capacity to transfer protection differed. We also found that i) the majority of LAG-3+cells are T cells, ii) selective depletion of CD4+but not CD8+T cells prevents anti-LAG-3-mediated protection, and iii) production of effector cytokines by CD4+T cells is increased in anti-LAG-3-treated versus control mice. Thus, taken together, these results are consistent with a model in which blockade and/or deficiency of PD-L1 and LAG-3 on parasite-specific CD4+T cells unleashes their ability to effectively clear blood parasites, independently from humoral responses.
Macrophage Plasticity in Reproduction and Environmental Influences on Their Function
Authors: Chambers Megan , Rees April , Cronin James G. , Nair Manju , Jones Nicholas , Thornton Catherine A.
Published: January 2021

Macrophages are key components of the innate immune system and exhibit extensive plasticity and heterogeneity. They play a significant role in the non-pregnant cycling uterus and throughout gestation they contribute to various processes underpinning reproductive success including implantation, placentation and parturition. Macrophages are also present in breast milk and impart immunomodulatory benefits to the infant. For a healthy pregnancy, the maternal immune system must adapt to prevent fetal rejection and support development of the semi-allogenic fetus without compromising host defense. These functions are dependent on macrophage polarization which is governed by the local tissue microenvironmental milieu. Disruption of this microenvironment, possibly by environmental factors of infectious and non-infectious origin, can affect macrophage phenotype and function and is linked to adverse obstetric outcomes, e.g. spontaneous miscarriage and preterm birth. Determining environmental influences on cellular and molecular mechanisms that control macrophage polarization at the maternal-fetal interface and the role of this in pregnancy complications could support approaches to alleviating adverse pregnancy outcomes.
Marine Heatwave of Sea Surface Temperature of the Oyashio Region in Summer in 2010–2016
Authors: Miyama Toru , Minobe Shoshiro , Goto Hanako
Published: January 2021

The sea surface temperature (SST) of the Oyashio region in boreal summer abruptly increased in 2010 and high summertime SST repeated every year until 2016. Observations and an ocean reanalysis show that this marine heatwave occurred not only at the surface but also at deeper depths down to 200 m. Furthermore, salinity in summer also increased in parallel with the temperature. The rises in temperature and salinity indicate the strengthening of the Kuroshio water influence. The sea surface height and velocity show that the southward intrusion of the Oyashio near the coast in summer weakened from 2010 accompanied by an increase in anticyclonic eddies from the Kuroshio Extension. The much more frequent existence of anticyclonic eddies to the east of the first intrusion of the Oyashio in summer is closely associated with the weakening of the first intrusion and the strengthening of the second intrusion. It is suggested that the rise in the water temperature could increase a catch of yellowtail (Seriola quinqueradiata) in northern Japan.
Lessons From the Trenches: Students’ Perspectives of Their Own Marine Transdisciplinary Education
Authors: Wilson Megan N. , Laufer Adrian E. , Howard Erin M. , Wong-Ala Jennifer A. T. K.
Published: January 2021

Recent environmental changes have demonstrated that the Earth has entered the Anthropocene. In this new age, complex interactions between human and natural systems exacerbate “wicked problems” that challenge researchers to engage both deep disciplinary expertise and broad integrative knowledge to address these societally relevant problems. Researchers and practitioners are making an increased effort to bridge the divide between human and natural systems research by facilitating multi-, inter-, and transdisciplinary collaborations. Despite 21st century changes to the research environment, the structure of a typical graduate education remains largely unchanged over the past several decades. Wicked problems necessitate communication and collaboration expertise; innovative transdisciplinary training and research opportunities can equip graduate students with these necessary skills. Oregon State University has offered such an opportunity through an NSF-funded Research Traineeship Program (NRT) for students focusing on Risk and Uncertainty Quantification and Communication in Marine Science. Herein, we reflect on the experience of graduate students who successfully completed the NRT and assert that support for transdisciplinary training and research at the graduate stage is urgently needed. We present five lessons learned from our year-long transdisciplinary project focused on the development of an approach for integrating diverse data sets within a social-ecological systems framework to reach a broader understanding of the interconnections between a marine reserve system, people, and the environment. Finally, we present current challenges and paths forward to enhance the success of early career transdisciplinary research.
Quantifying Coral Reef Resilience to Climate Change and Human Development: An Evaluation of Multiple Empirical Frameworks
Authors: Bang Ashley H. Y. , Kuo Chao-Yang , Wen Colin Kuo-Chang , Cherh Kah-Leng , Ho Ming-Jay , Cheng Nien-Yun , Chen Yen-Chia , Chen Chaolun Allen
Published: January 2021

The integrity of coral reefs has increasingly been threatened by human development and climate change. As a result, the concept of ecological resilience – an ecosystem's capability to resist and recover from environmental stressors – has become an important aspect of coral reef conservation. In this study, coral reef resilience was quantitatively scored in Kenting National Park (KNP), Taiwan, using four different assessment frameworks: the first uses the opinions of local reef experts, the second includes metrics specific to the local reef context, the third combines the previous two approaches, and the fourth relies solely on ecological metrics from biodiversity surveys. To evaluate the accuracy of each assessment, the resulting resilience scores were compared with historical coral recovery rates, which served as a proxy for resilience. While each approach to measuring resilience has its merits and drawbacks, the picture of resilience became clearest when a few key indicators were included to reflect core ecosystem processes. Trends in resilience scores varied depending on the makeup of the assessment's indicators, and there was little correlation between the baseline metrics measured using different data collection methods. However, all resilience assessment trends indicated that KNP's Nanwan area is high in resilience. This is likely due to the effects of local tidally-induced upwelling, which significantly relieve the growing thermal stress placed on surrounding coral communities. Ultimately, the most successful assessments were those that empirically quantified ecological processes and local factors with only a few indicators, rather than broader approaches that measured many indicators. These findings are particularly relevant for reef managers to consider as they develop and employ resilience-based management strategies.
Future Risk for Southern Ocean Ecosystem Services Under Climate Change
Authors: Cavanagh Rachel D. , Melbourne-Thomas Jess , Grant Susie M. , Barnes David K. A. , Hughes Kevin A. , Halfter Svenja , Meredith Michael P. , Murphy Eugene J. , Trebilco Rowan , Hill Simeon L.
Published: January 2021

The Southern Ocean supports ecosystem services that are important on a global scale. Climate change and human activities (tourism, fishing, and research) will affect both the demand for, and the provision of, these services into the future. Here we synthesize recent assessments of the current status and expected future climate-driven changes in Southern Ocean ecosystems and evaluate the potential consequences of these changes for the provision of ecosystem services. We explore in detail three key services (the ‘blue carbon’ pathway, the Antarctic krill fishery, and Antarctic tourism), tracing the consequences of climate change from physical drivers through biological impacts to the benefits to humans. We consider potential non-climatic drivers of change, current and future demands for the services, and the main global and regional policy frameworks that could be used to manage risks to the provision of these services in a changing climate. We also develop a formal representation of the network of interactions between the suite of potential drivers and the suite of services, providing a framework to capture the complexity of this network and its embedded feedback loops. Increased consideration of the linkages and feedbacks between drivers and ecosystem services will be required to underpin robust management responses into the future.
An Experimental Investigation on the Repairing Performance and Fatigue Life of Asphalt Pavement Potholes With an Inclined Interface Joint
Authors: Li Linyu , Huang Yangquan , Shao Zhutao , Ren Dongya
Published: January 2021

A pothole is a typical structural damage of asphalt pavements that significantly influence the life of asphalt pavements and driving safety. The durability of the existing pit repair methods is generally low. The existing studies in the context of pothole repair mainly focus on the selection and the amount of tack coat materials, nonetheless, very limited studies emphasize the effect of the joint interface shape. This study aims to investigate the influence of the interface joint shape on the service life of pothole repair by experimental testing. The strength and fatigue behavior of the joints were studied and the effectiveness of pothole repairs was evaluated under various conditions, including four temperature levels (5, 10, 15 and 25°C), four strain levels (750 με, 1,000 με, 1,250 με, and 1,500 με) and three loading frequencies (2, 5, and 10 Hz). The optimal interface joint shape was obtained by orthogonal tests. The results indicated that the bond strength and fatigue life of the high viscoelastic emulsified asphalt with an area density of 0.6 kg/m2 in the form of a 30° inclination joint was 473 and 80 times higher than those of traditional pothole repair (i.e., vertical joint form and no tack coat), respectively. Finally, a prediction model was proposed for the interface joint fatigue life considering external parameters through multiple regression analyses. This prediction model can provide a reference for the further study of asphalt pavement pothole repair.
ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Infection in COVID-19 Patients
Authors: Fan Caibin , Lu Wei , Li Kai , Ding Yanhong , Wang Jianqing
Published: January 2021

In December 2019, a new type of pneumonia caused by SARS-Cov-2 (COVID-19) occurred in Wuhan and has been discovered in many countries around the world. ACE2 (angiotensin-converting enzyme 2) has been shown to be one of the major receptors that mediate the entry of SARS-Cov-2 into human cells. Here in this study, we used the online datasets to analyze ACE2 expression in different human organs. The results indicated that ACE2 highly expresses in renal tubular cells, Sertoli cells, Leydig cells, and cells in seminiferous ducts in testis. Recombinant SARS-CoV-2 spike protein (RBD) domain and ACE2 of RPTEC/SerC cell-binding assays confirmed that SARS-Cov-2 can bind to ACE2 on the surface of these cells. Our results suggest that ACE2 expression could contribute to kidney and testis infection after COVID-19 infection. Renal function evaluation and special care should be performed during clinical work. Clinicians should also pay attention to the risk of testicular lesions in patients during hospitalization and later clinical follow-up, especially the assessment and appropriate intervention in young patients' fertility.
Frailty, MRI, and FDG-PET Measures in an Australian Memory Clinic Cohort
Authors: Jordan Nan , Gvalda Matthew , Cody Ross , Galante Olivia , Haywood Cilla , Yates Paul
Published: January 2021

Given that the global population is aging, the number of age-related syndromes, such as frailty, is expected to rise in conjunction. Frailty is characterized by the loss of homeostatic reserve, rendering the individual vulnerable to poor health outcomes. Many biological mechanisms have been proposed to contribute to frailty. However, few studies have assessed the associations between frailty and brain diseases or neuroimaging biomarkers.

Aims: The aims of this study were to measure the prevalence of frailty in a memory clinic and to examine associations between frailty and brain changes found on magnetic resonance imaging (MRI) and 18-F deoxyglucose (FDG) positron emission tomography (PET) in memory clinic attendees.

Methods: A 54-items Frailty Index was retrospectively assessed for all clinic attendees from 2014. Frailty was defined as FI > 0.25. MR images were analyzed for stroke, cerebral small vessel disease [CSVD, including cerebral microbleeds (CMBs), cortical superficial siderosis (CSS), and white matter hyperintensity (WMH)], and neurodegenerative changes [MRI: mesial temporal atrophy (MTA), FDG-PET: regional hypometabolism], blind to clinical findings.

Results: There were 209 clinic attendees in 2014, of whom 121 had MRI performed. The prevalence of frailty (using FI) in the memory clinic in 2014 was 38.3% overall (patients without MRI: 43.2%, patients with MRI 34.7%, p = 0.25). Frailty was associated with presence of deep WMH, increased severity of periventricular WMH, and presence of CSS, but not neurodegeneration markers (MTA atrophy/FDG-PET hypometabolism).

Conclusion: The findings support the idea that previously reported associations between frailty and imaging evidence of CSVD in other cohorts are also relevant to the Australian clinic setting. Given that a large proportion of memory clinic attendees are frail, there may be opportunities for interventions to reduce preventable adverse health outcomes, such as falls and fractures, and reduce the prevalence and impact of frailty in this cohort.
The Potential Roles of Exosomes in Chronic Obstructive Pulmonary Disease
Authors: Wang Nan , Wang Qin , Du Tiantian , Gabriel Abakundana Nsenga Ariston , Wang Xue , Sun Li , Li Xiaomeng , Xu Kanghong , Jiang Xinquan , Zhang Yi
Published: January 2021

Currently, chronic obstructive pulmonary disease (COPD) is one of the most common chronic lung diseases. Chronic obstructive pulmonary disease is characterized by progressive loss of lung function due to chronic inflammatory responses in the lungs caused by repeated exposure to harmful environmental stimuli. Chronic obstructive pulmonary disease is a persistent disease, with an estimated 384 million people worldwide living with COPD. It is listed as the third leading cause of death. Exosomes contain various components, such as lipids, microRNAs (miRNAs), long non-coding RNAs(lncRNAs), and proteins. They are essential mediators of intercellular communication and can regulate the biological properties of target cells. With the deepening of exosome research, it is found that exosomes are strictly related to the occurrence and development of COPD. Therefore, this review aims to highlight the unique role of immune-cell-derived exosomes in disease through complex interactions and their potentials as potential biomarkers new types of COPD.