bluuebunny/crossref_metadata_2025 huggingface dataset:
Quintus in Britannia: visiting Roman Britain with the Cambridge Latin Course
Authors: Watson James
Published: September 2020

This article records its author's travels to sites in Britain that either provide settings for or are relevant to the stories of the Cambridge Latin Course. A version of this article was delivered as an oral presentation, entitled ‘In the footsteps of Quintus Caecilius: visiting Roman Britain with the Cambridge Latin Course’, at the American Classical League Centennial Institute in New York in June 2019. The article provides an overview of the sites, attempts to situate them in the geography and history of Roman Britain, and considers how such knowledge might be of benefit to teachers and learners.
Classics at Lionheart Trust
Authors: Reynard Anna
Published: September 2020

We are now in our second year of Latin teaching at Lionheart Trust and it's fair to say that it has grown substantially as an initiative. The idea to teach Latin as an extra-curricular subject grew from our very positive experience of running Classics Clubs after school for Year 7s. These clubs were based on Greek and Roman mythology, local archaeology (plentiful given we are based in Leicester, a Roman city) and a little bit of Latin. The children loved all of these experiences and we realised quite quickly that there was an appetite for greater Latin teaching.
Impact of Droughts on Water Supply in U.S. Watersheds: The Role of Renewable Surface and Groundwater Resources
Authors: Apurv Tushar , Cai Ximing
Published: September 2020

We use a simplified water supply system model based on the water availability assessment via the Variable Infiltration Capacity (VIC) hydrologic model to analyze water supply droughts (WSDs), which are periods with deficient water supply. The model is applied to 27 representative watersheds of the contiguous U.S. to explore how different management strategies can be more effective in mitigating WSDs in watersheds with different drought propagation mechanisms. We find that water supply deficits during droughts (WSDDs) are generally the highest in the Great Plains watersheds, followed by the western U.S. watersheds, and lowest in the eastern U.S. watersheds. We show that different measures can be adopted to mitigate WSDs in different regions. Specifically, in the western U.S. watersheds, the conjunctive use of surface and groundwater can reduce WSDD, that is, increasing surface water utilization and using groundwater recharged through winter precipitation to supplement surface water supply during droughts. In the Great Plains region, water demands need to be brought down to sustainable levels; meanwhile switching from groundwater to surface water supply can significantly reduce WSDD as the alluvial aquifers in this region provide a stable baseflow, which can act as a steady source of water supply during droughts. In the eastern U.S. watersheds, the depletion of limited storage capacity during droughts can lead to WSDD for short periods of time, which highlights the need for expansion of storage capacity in this region.
Chicago Wetlands Shrank by 40% During the 20th Century
Authors: Cartier Kimberly
Published: September 2020

A team of graduate students measured wetland and biodiversity changes during the 100 years following the reversal of the Chicago River.
Model Forecast Error Correction Based on the Local Dynamical Analog Method: An Example Application to the ENSO Forecast by an Intermediate Coupled Model
Authors: Hou Zhaolu , Zuo Bin , Zhang Shaoqing , Huang Fei , Ding Ruiqiang , Duan Wansuo , Li Jianping
Published: September 2020

Numerical forecasts always have associated errors. Analog correction methods combine numerical simulations with statistical analyses to reduce model forecast errors. However, identifying appropriate analogs remains a challenging task. Here, we use the Local Dynamical Analog (LDA) method to locate analogs and correct model forecast errors. As an example, an El Niño–Southern Oscillation (ENSO) intermediate coupled model forecast error correction experiment confirms that the LDA method locates high quality analogs of states of interest and improves the model forecast performance, which is due to the initial and evolution information included in the LDA method. In addition, the LDA method can be applied using a scalar time series, which reduces the complexity of the dynamical system. The LDA method is a promising method to locate dynamic analogs and can be applied to existing numerical models and forecast results.
Impact of Martian Crustal Magnetic Field on the Ion Escape
Authors: Dubinin E. , Fraenz M. , Pätzold M. , Woch J. , McFadden J. , Fan K. , Wei Y. , Tsareva O. , Zelenyi L.
Published: September 2020

Based on the Mars Atmosphere and Volatile EvolutioN (MAVEN) observations, we have analyzed the role of the crustal magnetic field on ion loss driven by the direct interaction of the solar wind with the Mars ionosphere. Crustal magnetic fields significantly attenuate the ion ionospheric motions and raise the flux of returning ions. On the other hand, since the ion densities in the ionosphere with strong crustal field are significantly higher than in the ionosphere with a weak crustal magnetic field, the net escape fluxes from the ionosphere with the crustal sources remain vital. The crustal magnetic field also leads to the expansion of the ionosphere and increase of the area exposed to solar wind. As a result, fluxes from higher altitudes essentially contribute to the flow pattern in Martian tail producing an excess of ion loss rate (∼15%) through the southern part of the tail. Thus, effects of inhibition and enhancement of the escape rate by the crustal magnetic field at Mars operate in competition producing a minor influence on the total ion loss.
Warm Handoff, or Cold Shoulder? An Analysis of Handoffs for Primary Care Behavioral Health Consultation on Patient Engagement and Systems Utilization
Authors: Young Nicholas D. , Mathews Brittany L. , Pan Amy Y. , Herndon Jason L. , Bleck Amanda A. , Takala Christopher R.
Published: September 2020

Objective: Referrals initiated via the “warm handoff” (HO) common to consultation-based models of integrated primary care are theorized to add value for patient outcomes relative to referral as usual (RAU) processes often used in colocated service models. The current evaluation tested this assumption in terms of impact on patient engagement, medical system utilization, and behavioral health system utilization. Method: Short-term longitudinal data were extracted for 175 integrated behavioral health referrals across urban pediatric primary care patients. A retrospective cohort design was used to assess differences between patients exposed to an HO immediately following referral versus RAU (control). Results: Analyses revealed significant differences for patients referred via HO at different time points, including fewer primary care provider appointment no-show/same-day cancellations, greater total behavioral health encounters, and fewer days from referral to any scheduled or completed follow-up behavioral health encounter. Conclusions: Consultation via HOs was associated with some short-term benefits on patient engagement and systems utilization for urban pediatric primary care patients compared to RAU. Preliminary findings may help stakeholders leverage the need for integrated (vs. colocated) models of pediatric integrated primary care to help inform economic- or value-based decisions on program development and promote care approaches that increase the likelihood of families staying engaged in care.

Implications for Impact Statement

“Warm handoffs” for immediate behavioral health consultation were associated with better pediatric patient engagement compared to referral as usual. Findings can help guide improvement with integrated primary care services, although future investigations are needed to further support or refute these preliminary results.
Reflections on Changing Times for Pediatric Integrated Primary Care During COVID-19 Pandemic
Authors: Stancin Terry
Published: September 2020

Objective: The COVID-19 pandemic has had a monumental impact on health care delivery. The pediatric integrated primary care (IPC) program at MetroHealth Medical Center, 1 of the oldest such programs in the United States, has been profoundly changed by the COVID-19 pandemic of 2020. Method: This commentary provides a reflection on the early response of 1 established IPC program to the COVID-19 pandemic. Results: Initial markers of successful adaptation to care delivery and training models include efforts that incorporate virtual consultation and telehealth practices. Conclusions: The impact of the COVID-19 pandemic on pediatric psychology in IPC settings will largely depend on the flexibility and adaptability of workflows and training methods to meet the needs of the changing landscape.

Implications for Impact Statement

Pediatric integrated primary care (IPC) has been profoundly impacted by the COVID19 pandemic of 2020. The future success of IPC will depend on adapting models and training efforts that incorporate virtual and telehealth formats.
Clinical relevance of blood-based ctDNA analysis: mutation detection and beyond
Authors: Keller Laura , Belloum Yassine , Wikman Harriet , Pantel Klaus
Published: September 2020

Cell-free DNA (cfDNA) derived from tumours is present in the plasma of cancer patients. The majority of currently available studies on the use of this circulating tumour DNA (ctDNA) deal with the detection of mutations. The analysis of cfDNA is often discussed in the context of the noninvasive detection of mutations that lead to resistance mechanisms and therapeutic and disease monitoring in cancer patients. Indeed, substantial advances have been made in this area, with the development of methods that reach high sensitivity and can interrogate a large number of genes. Interestingly, however, cfDNA can also be used to analyse different features of DNA, such as methylation status, size fragment patterns, transcriptomics and viral load, which open new avenues for the analysis of liquid biopsy samples from cancer patients. This review will focus on the new perspectives and challenges of cfDNA analysis from mutation detection in patients with solid malignancies.
PIK3R3 inhibits cell senescence through p53/p21 signaling
Authors: Chen Qianzhi , Sun Xuling , Luo Xuelai , Wang Jing , Hu Junbo , Feng Yongdong
Published: September 2020

Cellular senescence is a stress response of human cells that removes potentially harmful cells by initiating cell cycle arrest. Inducing senescence of tumor cells may be an effective tumor-inhibiting strategy. In this study we found that PIK3R3 could inhibit the cell senescence of colorectal cancer cells and promote cell proliferation through the p53/p21 signal pathway. PIK3R3 could bind to p53 and inhibit the binding of p53 to the p21 gene promoter region, and thus affecting the transcriptional activity of p21 gene. Our study has provided new evidence of the role of PIK3R3 in p53 regulation and inhibition of PIK3R3 may be one of the potential targets of tumor therapy.
A genome-wide association study uncovers a critical role of the RsPAP2 gene in red-skinned Raphanus sativus L.
Authors: Fan Lianxue , Wang Yan , Xu Liang , Tang Mingjia , Zhang Xiaoli , Ying Jiali , Li Cui , Dong Junhui , Liu Liwang
Published: September 2020

Radish (Raphanus sativus L.) taproot contains high concentrations of flavonoids, including anthocyanins (ATCs), in red-skinned genotypes. However, little information on the genetic regulation of ATC biosynthesis in radish is available. A genome-wide association study of radish red skin color was conducted using whole-genome sequencing data derived from 179 radish genotypes. The R2R3-MYB transcription factor production of anthocyanin pigment 2 (PAP2) gene was found in the region associated with a leading SNP located on chromosome 2. The amino acid sequence encoded by the RsPAP2 gene was different from those of the other published RsMYB genes responsible for the red skin color of radish. The overexpression of the RsPAP2 gene resulted in ATC accumulation in Arabidopsis and radish, which was accompanied by the upregulation of several ATC-related structural genes. RsPAP2 was found to bind the RsUFGT and RsTT8 promoters, as shown by a dual-luciferase reporter system and a yeast one-hybrid assay. The promoter activities of the RsANS, RsCHI, RsPAL, and RsUFGT genes could be strongly activated by coinfiltration with RsPAP2 and RsTT8. These findings showed the effectiveness of GWAS in identifying candidate genes in radish and demonstrated that RsPAP2 could (either directly or together with its cofactor RsTT8) regulate the transcript levels of ATC-related genes to promote ATC biosynthesis, facilitating the genetic enhancement of ATC contents and other related traits in radish.
Anomalous supply shortages from dynamic pricing in on-demand mobility
Authors: Schröder Malte , Storch David-Maximilian , Marszal Philip , Timme Marc
Published: September 2020

Dynamic pricing schemes are increasingly employed across industries to maintain a self-organized balance of demand and supply. However, throughout complex dynamical systems, unintended collective states exist that may compromise their function. Here we reveal how dynamic pricing may induce demand-supply imbalances instead of preventing them. Combining game theory and time series analysis of dynamic pricing data from on-demand ride-hailing services, we explain this apparent contradiction. We derive a phase diagram demonstrating how and under which conditions dynamic pricing incentivizes collective action of ride-hailing drivers to induce anomalous supply shortages. We identify characteristic patterns in the price dynamics reflecting these supply anomalies by disentangling different timescales in price time series of ride-hailing services at 137 locations across the globe. Our results provide systemic insights for the regulation of dynamic pricing, in particular in publicly accessible mobility systems, by unraveling under which conditions dynamic pricing schemes promote anomalous supply shortages.
Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells
Authors: Du Jiajun , Su Yapeng , Qian Chenxi , Yuan Dan , Miao Kun , Lee Dongkwan , Ng Alphonsus H. C. , Wijker Reto S. , Ribas Antoni , Levine Raphael D. , Heath James R. , Wei Lu
Published: September 2020

Non-invasively probing metabolites within single live cells is highly desired but challenging. Here we utilize Raman spectro-microscopy for spatial mapping of metabolites within single cells, with the specific goal of identifying druggable metabolic susceptibilities from a series of patient-derived melanoma cell lines. Each cell line represents a different characteristic level of cancer cell de-differentiation. First, with Raman spectroscopy, followed by stimulated Raman scattering (SRS) microscopy and transcriptomics analysis, we identify the fatty acid synthesis pathway as a druggable susceptibility for differentiated melanocytic cells. We then utilize hyperspectral-SRS imaging of intracellular lipid droplets to identify a previously unknown susceptibility of lipid mono-unsaturation within de-differentiated mesenchymal cells with innate resistance to BRAF inhibition. Drugging this target leads to cellular apoptosis accompanied by the formation of phase-separated intracellular membrane domains. The integration of subcellular Raman spectro-microscopy with lipidomics and transcriptomics suggests possible lipid regulatory mechanisms underlying this pharmacological treatment. Our method should provide a general approach in spatially-resolved single cell metabolomics studies.
Persistent and reversible solid iodine electrodeposition in nanoporous carbons
Authors: Prehal Christian , Fitzek Harald , Kothleitner Gerald , Presser Volker , Gollas Bernhard , Freunberger Stefan A. , Abbas Qamar
Published: September 2020

Aqueous iodine based electrochemical energy storage is considered a potential candidate to improve sustainability and performance of current battery and supercapacitor technology. It harnesses the redox activity of iodide, iodine, and polyiodide species in the confined geometry of nanoporous carbon electrodes. However, current descriptions of the electrochemical reaction mechanism to interconvert these species are elusive. Here we show that electrochemical oxidation of iodide in nanoporous carbons forms persistent solid iodine deposits. Confinement slows down dissolution into triiodide and pentaiodide, responsible for otherwise significant self-discharge via shuttling. The main tools for these insights are in situ Raman spectroscopy and in situ small and wide-angle X-ray scattering (in situ SAXS/WAXS). In situ Raman confirms the reversible formation of triiodide and pentaiodide. In situ SAXS/WAXS indicates remarkable amounts of solid iodine deposited in the carbon nanopores. Combined with stochastic modeling, in situ SAXS allows quantifying the solid iodine volume fraction and visualizing the iodine structure on 3D lattice models at the sub-nanometer scale. Based on the derived mechanism, we demonstrate strategies for improved iodine pore filling capacity and prevention of self-discharge, applicable to hybrid supercapacitors and batteries.
Stability of heterogeneous single-atom catalysts: a scaling law mapping thermodynamics to kinetics
Authors: Su Ya-Qiong , Zhang Long , Wang Yifan , Liu Jin-Xun , Muravev Valery , Alexopoulos Konstantinos , Filot Ivo A. W. , Vlachos Dionisios G. , Hensen Emiel J. M.
Published: September 2020

Heterogeneous single-atom catalysts (SACs) hold the promise of combining high catalytic performance with maximum utilization of often precious metals. We extend the current thermodynamic view of SAC stability in terms of the binding energy (Ebind) of single-metal atoms on a support to a kinetic (transport) one by considering the activation barrier for metal atom diffusion. A rapid computational screening approach allows predicting diffusion barriers for metal–support pairs based on Ebindof a metal atom to the support and the cohesive energy of the bulk metal (Ec). Metal–support combinations relevant to contemporary catalysis are explored by density functional theory. Assisted by machine-learning methods, we find that the diffusion activation barrier correlates with (Ebind)2/Ecin the physical descriptor space. This diffusion scaling-law provides a simple model for screening thermodynamics to kinetics of metal adatom on a support.
Global terrestrial carbon fluxes of 1999–2019 estimated by upscaling eddy covariance data with a random forest
Authors: Zeng Jiye , Matsunaga Tsuneo , Tan Zheng-Hong , Saigusa Nobuko , Shirai Tomoko , Tang Yanhong , Peng Shushi , Fukuda Yoko
Published: September 2020

The terrestrial biosphere is a key player in slowing the accumulation of carbon dioxide in the atmosphere. While quantification of carbon fluxes at global land scale is important for mitigation policy related to climate and carbon, measurements are only available at sites scarcely distributed in the world. This leads to using various methods to upscale site measurements to the whole terrestrial biosphere. This article reports a product obtained by using a Random Forest to upscale terrestrial net ecosystem exchange, gross primary production, and ecosystem respiration from FLUXNET 2015. Our product covers land from −60°S to 80°N with a spatial resolution of 0.1° × 0.1° every 10 days during the period 1999–2019. It was compared with four existing products. A distinguishable feature of our method is using three derived variables of leaf area index to represent plant functional type (PFT) so that measurements from different PFTs can be mixed better by the model. This product can be valuable for the carbon-cycle community to validate terrestrial biosphere models and cross check datasets.
How Alfvén waves induce compressive flows in the neighborhood of a 2.5D magnetic null-point
Authors: Sabri S. , Farahani S. Vasheghani , Ebadi H. , Poedts S.
Published: September 2020

The aim of the present study is to provide insight on the induced compressive perturbations together with the modifications of the environmental parameters in the course of Alfvén wave interaction with a solar magnetic null-point. The shock-capturing Godunov-type code PLUTO is used to solve the set of ideal magnetohydrodynamic equations. The nonlinear effects connected with an initial Alfvén pulse nearing a magnetic null point induces fast and slow magnetoacoustic waves with anti phase conduct. The induced current density and flows are independent of the local plasma-$$\beta$$
β
at the reconnection site. The induced inflows and outflows highly depend on the polarization. The inflows have a stronger effect compared to the outflows in both the x and y directions showing its peak in the x-direction. The dominant wave that couples to flows is the fast wave due to the in-phase harmony between perturbations of the compressive parameters and the fast wave. The induced current density possesses a steady orientation at the reconnection site which governs the diffusion or propagation of the waves. Induced perturbations by the nonlinear forces together with their back reaction on the Alfvén wave have a significant role in the current density excitation being responsible for the creation of inflows and outflows that are possible candidates for the creation of solar jets which has a significant contribution towards coronal seismology.
SET/TAF1 forms a distance-dependent feedback loop with Aurora B and Bub1 as a tension sensor at centromeres
Authors: Asai Yuichiro , Matsumura Rieko , Hasumi Yurina , Susumu Hiroaki , Nagata Kyosuke , Watanabe Yoshinori , Terada Yasuhiko
Published: September 2020

During mitosis, spatiotemporal regulation of phosphorylation at the kinetochore is essential for accurate chromosome alignment and proper chromosome segregation. Aurora B kinase phosphorylates kinetochore substrates to correct improper kinetochore-microtubule (KT-MT) attachments, whereas tension across the centromeres inactivates Aurora B kinase, and PP2A phosphatase dephosphorylates the kinetochore proteins to stabilize the attachments. However, the molecular entity of the tension sensing mechanism remains elusive. In a previous report, we showed that centromeric SET/TAF1 on Sgo2 up-regulates Aurora B kinase activity via PP2A inhibition in prometaphase. Here we show that Aurora B and Bub1 at the centromere/kinetochore regulate both kinase activities one another in an inter-kinetochore distance-dependent manner, indicating a positive feedback loop. We further show that the centromeric pool of SET on Sgo2 depends on Bub1 kinase activity, and the centromeric localization of SET decreases in a distance-dependent manner, thereby inactivating Aurora B in metaphase. Consistently, ectopic targeting of SET to the kinetochores during metaphase hyperactivates Aurora B via PP2A inhibition, and thereby rescues the feedback loop. Thus, we propose that SET, Aurora B and Bub1 form a distance-dependent positive feedback loop, which spatiotemporally may act as a tension sensor at centromeres.
Sodium nitrate co-supplementation does not exacerbate low dose metronomic doxorubicin-induced cachexia in healthy mice
Authors: Campelj Dean G. , Debruin Danielle A. , Timpani Cara A. , Hayes Alan , Goodman Craig A. , Rybalka Emma
Published: September 2020

The purpose of this study was to determine whether (1) sodium nitrate (SN) treatment progressed or alleviated doxorubicin (DOX)-induced cachexia and muscle wasting; and (2) if a more-clinically relevant low-dose metronomic (LDM) DOX treatment regimen compared to the high dosage bolus commonly used in animal research, was sufficient to induce cachexia in mice. Six-week old male Balb/C mice (n = 16) were treated with three intraperitoneal injections of either vehicle (0.9% NaCl; VEH) or DOX (4 mg/kg) over one week. To test the hypothesis that sodium nitrate treatment could protect against DOX-induced symptomology, a group of mice (n = 8) were treated with 1 mM NaNO3 in drinking water during DOX (4 mg/kg) treatment (DOX + SN). Body composition indices were assessed using echoMRI scanning, whilst physical and metabolic activity were assessed via indirect calorimetry, before and after the treatment regimen. Skeletal and cardiac muscles were excised to investigate histological and molecular parameters. LDM DOX treatment induced cachexia with significant impacts on both body and lean mass, and fatigue/malaise (i.e. it reduced voluntary wheel running and energy expenditure) that was associated with oxidative/nitrostative stress sufficient to induce the molecular cytotoxic stress regulator, nuclear factor erythroid-2-related factor 2 (NRF-2). SN co-treatment afforded no therapeutic potential, nor did it promote the wasting of lean tissue. Our data re-affirm a cardioprotective effect for SN against DOX-induced collagen deposition. In our mouse model, SN protected against LDM DOX-induced cardiac fibrosis but had no effect on cachexia at the conclusion of the regimen.
Network Hamiltonian models reveal pathways to amyloid fibril formation
Authors: Yu Yue , Grazioli Gianmarc , Unhelkar Megha H. , Martin Rachel W. , Butts Carter T.
Published: September 2020

Amyloid fibril formation is central to the etiology of a wide range of serious human diseases, such as Alzheimer’s disease and prion diseases. Despite an ever growing collection of amyloid fibril structures found in the Protein Data Bank (PDB) and numerous clinical trials, therapeutic strategies remain elusive. One contributing factor to the lack of progress on this challenging problem is incomplete understanding of the mechanisms by which these locally ordered protein aggregates self-assemble in solution. Many current models of amyloid deposition diseases posit that the most toxic species are oligomers that form either along the pathway to forming fibrils or in competition with their formation, making it even more critical to understand the kinetics of fibrillization. A recently introduced topological model for aggregation based on network Hamiltonians is capable of recapitulating the entire process of amyloid fibril formation, beginning with thousands of free monomers and ending with kinetically accessible and thermodynamically stable amyloid fibril structures. The model can be parameterized to match the five topological classes encompassing all amyloid fibril structures so far discovered in the PDB. This paper introduces a set of network statistical and topological metrics for quantitative analysis and characterization of the fibrillization mechanisms predicted by the network Hamiltonian model. The results not only provide insight into different mechanisms leading to similar fibril structures, but also offer targets for future experimental exploration into the mechanisms by which fibrils form.
Optimization for maximum specific energy density of a lithium-ion battery using progressive quadratic response surface method and design of experiments
Authors: Kim Ji-San , Lee Dong-Chan , Lee Jeong-Joo , Kim Chang-Wan
Published: September 2020

The demand for high-capacity lithium-ion batteries (LIB) in electric vehicles has increased. In this study, optimization to maximize the specific energy density of a cell is conducted using the LIB electrochemical model and sequential approximate optimization (SAO). First, the design of experiments is performed to analyze the sensitivity of design factors important to the specific energy density, such as electrode and separator thicknesses, porosity, and particle size. Then, the design variables of the cell are optimized for maximum specific energy density using the progressive quadratic response surface method (PQRSM), which is one of the SAO techniques. As a result of optimization, the thickness ratio of the electrode was optimized and the porosity was reduced to keep the specific energy density high, while still maintaining the specific power density performance. This led to an increase in the specific energy density of 56.8% and a reduction in the polarization phenomenon of 11.5%. The specific energy density effectively improved through minimum computation despite the nonlinearity of the electrochemical model in PQRSM optimization.
Helicobacter pylori infection induces STAT3 phosphorylation on Ser727 and autophagy in human gastric epithelial cells and mouse stomach
Authors: Piao Juan-Yu , Kim Su-Jung , Kim Do-Hee , Park Ji Hyun , Park Sin-Aye , Han Hyeong-jun , Na Hye-Kyung , Yoon Kichul , Lee Ha-Na , Kim Nayoung , Hahm Ki Baik , Surh Young-Joon
Published: September 2020

Helicobacter pylori (H. pylori) infection is considered as one of the principal risk factors of gastric cancer. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) plays an important role in inflammation-associated gastric carcinogenesis. In the canonical STAT3 pathway, phosphorylation of STAT3 on Tyr705 is a major event of STAT3 activation. However, recent studies have demonstrated that STAT3 phosphorylated on Ser727 has an independent function in mitochondria. In the present study, we found that human gastric epithelial AGS cells infected with H. pylori resulted in localization of STAT3 phosphorylated on Ser727 (P-STAT3Ser727), predominantly in the mitochondria. Notably, H. pylori-infected AGS cells exhibited the loss of mitochondrial integrity and increased expression of the microtubule-associated protein light chain 3 (LC3), the autophagosomal membrane-associated protein. Treatment of AGS cells with a mitophagy inducer, carbonyl cyanide 3-chlorophenylhydrazone (CCCP), resulted in accumulation of P-STAT3Ser727 in mitochondria. In addition, the elevated expression and mitochondrial localization of LC3 induced by H. pylori infection were attenuated in AGS cells harboring STAT3 mutation defective in Ser727 phosphorylation (S727A). We also observed that both P-STAT3Ser727 expression and LC3 accumulation were increased in the mitochondria of H. pylori-inoculated mouse stomach.
Ontogeny of different subsets of yellow fever virus-specific circulatory CXCR5+ CD4+ T cells after yellow fever vaccination
Authors: DeGottardi Quinn , Gates Theresa J. , Yang Junbao , James Eddie A. , Malhotra Uma , Chow I-Ting , Simoni Yannick , Fehlings Michael , Newell Evan W. , DeBerg Hannah A. , Kwok William W.
Published: September 2020

Monitoring the frequency of circulatory CXCR5+ (cCXCR5+) CD4+ T cells in periphery blood provides a potential biomarker to draw inferences about T follicular helper (TFH) activity within germinal center. However, cCXCR5+ T cells are highly heterogeneous in their expression of ICOS, PD1 and CD38 and the relationship between different cCXCR5 subsets as delineated by these markers remains unclear. We applied class II tetramer reagents and mass cytometry to investigate the ontogeny of different subsets of cCXCR5+ T cell following yellow fever immunization. Through unsupervised analyses of mass cytometry data, we show yellow fever virus-specific cCXCR5 T cells elicited by vaccination were initially CD38+ICOS+PD1+, but then transitioned to become CD38+ICOS−PD1+ and CD38−ICOS−PD1+ before coming to rest as a CD38−ICOS−PD1− subset. These results imply that most antigen-specific cCXCR5+ T cells, including the CD38−ICOS−PD1− CXCR5+ T cells are derived from the CXCR5+CD38+ICOS+PD1+ subset, the subset that most resembles preTFH/TFH in the germinal center.
Serum proteins may facilitate the identification of Kawasaki disease and promote in vitro neutrophil infiltration
Authors: Li Sung-Chou , Tsai Kuo-Wang , Huang Lien-Hung , Weng Ken-Pen , Chien Kuang-Jen , Lin Yuyu , Tu Chi-Ying , Lin Pei-Hsien
Published: September 2020

Kawasaki disease (KD) usually affects the children younger than 5 years of age and subsequently causes coronary artery lesions (CALs) without timely identification and treatment. Developing a robust and fast prediction method may facilitate the timely diagnosis of KD, significantly reducing the risk of CALs in KD patients. The levels of inflammatory serum proteins dramatically vary during the onsets of many immune diseases, including in KD. However, our understanding of their pathogenic roles in KD is behind satisfaction. The purpose of this study was to evaluate candidate diagnostic serum proteins and the potential mechanism in KD using iTRAQ gel-free proteomics. We enrolled subjects and conducted iTRAQ gel-free proteomics to globally screen serum proteins followed by specific validation with ELISA. Further in vitro leukocyte trans-endothelial model was also applied to investigate the pathogenesis roles of inflammatory serum proteins. We identified six KD protein biomarkers, including Protein S100-A8 (S100A8), Protein S100-A9 (S100A9), Protein S100-A12 (S100A12), Peroxiredoxin-2 (PRDX2), Neutrophil defensin 1 (DEFA1) and Alpha-1-acid glycoprotein 1 (ORM1). They enabled us to develop a high-performance KD prediction model with an auROC value of 0.94, facilitating the timely identification of KD. Further assays concluded that recombinant S100A12 protein treatment activated neutrophil surface adhesion molecules responsible for adhesion to endothelial cells. Therefore, S100A12 promoted both freshly clinically isolated neutrophils and neutrophil-like cells to infiltrate through the endothelial layer in vitro. Finally, the antibody against S100A12 may attenuate the infiltration promoted by S100A12. Our result demonstrated that evaluating S100A8, S100A9, S100A12, PRDX2, DEFA1 and ORM1 levels may be a good diagnostic tool of KD. Further in vitro study implied that S100A12 could be a potential therapeutic target for KD.
Rapid fabrication of sieved microwells and cross-flow microparticle trapping
Authors: Romita Lauren , Thompson Shyan , Hwang Dae Kun
Published: September 2020

The use of microwells is popular for a wide range of applications due to its’ simplicity. However, the seeding of conventional microwells, which are closed at the bottom, is restricted to gravitational sedimentation for cell or particle deposition and therefore require lengthy settling times to maximize well occupancy. The addition of microfluidics to the capture process has accelerated cell or particle dispersion and improved capture ability but is mostly limited to gravitationally-driven settling for capture into the wells. An alternative approach to conventional closed-microwells, sieved microwells supersedes reliance on gravity by using hydrodynamic forces through the open pores at the bottom of the microwells to draw targets into the wells. We have developed a rapid fabrication method, based on flow lithography techniques, which allows us to easily customize the mesh pore sizes in a simple two-step process. Finally, by combining this microwell design with cross-flow trapping in a microfluidic two-layered channel, we achieve an 88 ± 6% well occupancy in under 10 s.
A retrospective study on the incidence of acute kidney injury and its early prediction using troponin-I in cooled asphyxiated neonates
Authors: Mok Tze Yee Diane , Tseng Min-Hua , Lee Jin-Chiao , Chou Yu-Ching , Lien Reyin , Lai Mei-Yin , Lee Chien-Chung , Lin Jainn-Jim , Chou I-Jun , Lin Kuang-Lin , Chiang Ming-Chou
Published: September 2020

Acute kidney injury (AKI) is a common complication of perinatal asphyxia and is associated with poorer short-term and long-term outcomes. This retrospective study describes the incidence of AKI in asphyxiated neonates who have received therapeutic hypothermia using the proposed modified Kidney Diseases: Improving Global Outcomes (KDIGO) definition and investigates clinical markers that would allow earlier recognition of at-risk neonates. We included asphyxiated  neonates who underwent therapeutic hypothermia between the period of January 2011 and May 2018 in our study. The serum creatinine levels within a week of birth were used in establishing AKI according to the modified KDIGO definition. Demographic data, resuscitation details, laboratory results and use of medications were collected and compared between the AKI and non-AKI groups to identify variables that differed significantly. A total of 66 neonates were included and 23 out of them (35%) were found to have AKI. The neonates with AKI had a lower gestational age (p = 0.006), lower hemoglobin level (p = 0.012), higher lactate level before and after therapeutic hypothermia (p = 0.013 and 0.03 respectively) and higher troponin-I level after therapeutic hypothermia (p < 0.001). After logistic regression analysis, elevated troponin-I after therapeutic hypothermia was independently associated with risk of AKI (OR 1.69, 95% CI 1.067–2.699,p = 0.025). The receiver operating curve showed that troponin-I after therapeutic hypothermia had an area under curve of 0.858 at the level 0.288 ng/ml. Our study concludes that the incidence of AKI among asphyxiated newborns who received therapeutic hypothermia is 35% and an elevated troponin-I level after therapeutic hypothermia is independently associated with an increased risk of AKI in asphyxiated newborns.
Thyroid redox imbalance in adult Wistar rats that were exposed to nicotine during breastfeeding
Authors: Miranda Rosiane Aparecida , de Moura Egberto Gaspar , Soares Patrícia Novaes , Peixoto Thamara Cherem , Lopes Bruna Pereira , de Andrade Cherley Borba Vieira , de Oliveira Elaine , Manhães Alex C. , de Faria Caroline Coelho , Fortunato Rodrigo Soares , Lisboa Patricia Cristina
Published: September 2020

Maternal nicotine exposure causes several consequences in offspring phenotype, such as obesity and thyroid dysfunctions. Nicotine exposure can increase oxidative stress levels, which could lead to thyroid dysfunction. However, the mechanism by which nicotine exposure during breastfeeding leads to thyroid gland dysfunction remains elusive. We aimed to investigate the long-term effects of maternal nicotine exposure on redox homeostasis in thyroid gland, besides other essential steps for thyroid hormone synthesis in rats from both sexes. Lactating Wistar rats were implanted with osmotic minipumps releasing nicotine (NIC, 6 mg/kg/day) or saline (control) from postnatal day 2 to 16. Offspring were analyzed at 180-day-old. NIC males showed lower plasma TSH, T3 and T4 while NIC females had higher T3 and T4. In thyroid, NIC males had higher sodium-iodide symporter protein expression, whereas NIC females had higher thyroid-stimulating hormone receptor (TSHr) and thyroperoxidase (TPO) protein expression. TPO activity was lower in NIC males. Hydrogen peroxide generation was decreased in NIC males. Activities of superoxide dismutase, catalase and glutathione peroxidase were compromised in NIC animals from both sexes. 4-Hydroxynonenal was higher only in NIC females, while thiol was not affected in NIC animals from both sexes. NIC offspring also had altered expression of sex steroid receptors in thyroid gland. Both sexes showed similar thyroid morphology, with lower follicle and colloid size. Thyroid from female offspring exposed to nicotine during breastfeeding developed oxidative stress, while the male gland seemed to be protected from redox damage. Thyroid dysfunctions seem to be associated with redox imbalance in a sex-dependent manner.
Prevalence and associated factors of hyperuricemia among urban adults aged 35–79 years in southwestern China: a community-based cross-sectional study
Authors: Huang Xiao-Bo , Zhang Wen-Qiang , Tang Wei-Wei , Liu Ya , Ning Yuan , Huang Chuan , Liu Jian-Xiong , Yi Yan-Jing , Xu Rong-Hua , Wang Tzung-Dau
Published: September 2020

Hyperuricemia is prevalent throughout the world. However, a well-designed large-scale epidemiological investigation of hyperuricemia in southwestern China is lacking. A regional representative sample of 10,141 participants were included using multistage, stratified sampling in Chengdu and Chongqing from September 2013 to March 2014. Hyperuricemia was defined as the self-reported of the doctor's diagnosis of hyperuricemia, or serum uric acid > 420 μmol/L in men or serum uric acid > 360 μmol/L in women. The overall age- and sex-standardized prevalence of hyperuricemia among adults aged 35–79 years was 13.5%. Compared with women, the prevalence of hyperuricemia in men was higher (17.3% versus 10.0%). Hypertension, hyperlipidemia, overweight or obesity, central obesity were associated with an increased risk for hyperuricemia both in men and in women. Married men and women were not susceptible to hyperuricemia. Current cigarette smoking was an associated risk factor of hyperuricemia only in women. Hyperuricemia has become a major health problem among urban adults aged 35–79 years in southwestern China, and special attention should be paid to men. Comorbidities associated with hyperuricemia and causality worth further investigation.
Enhanced ion–cavity coupling through cavity cooling in the strong coupling regime
Authors: Christoforou Costas , Pignot Corentin , Kassa Ezra , Takahashi Hiroki , Keller Matthias
Published: September 2020

Incorporating optical cavities in ion traps is becoming increasingly important in the development of photonic quantum networks. However, the presence of the cavity can hamper efficient laser cooling of ions because of geometric constraints that the cavity imposes and an unfavourable Purcell effect that can modify the cooling dynamics substantially. On the other hand the coupling of the ion to the cavity can also be exploited to provide a mechanism to efficiently cool the ion. In this paper we demonstrate experimentally how cavity cooling can be implemented to improve the localisation of the ion and thus its coupling to the cavity. By using cavity cooling we obtain an enhanced ion–cavity coupling of $$2\pi \times (16.7\pm 0.1)$$

2
π
×
(
16.7
±
0.1
)

MHz, compared with $$2\pi \times (15.2\pm 0.1)$$

2
π
×
(
15.2
±
0.1
)

MHz when using only Doppler cooling.
Immune cell composition in normal human kidneys
Authors: Park Jun-Gyu , Na Myeongsu , Kim Min-Gang , Park Su Hwan , Lee Hack June , Kim Dong Ki , Kwak Cheol , Kim Yon Su , Chang Sunghoe , Moon Kyung Chul , Lee Dong-Sup , Han Seung Seok
Published: September 2020

An understanding of immunological mechanisms in kidney diseases has advanced using mouse kidneys. However, the profiling of immune cell subsets in human kidneys remains undetermined, particularly compared with mouse kidneys. Normal human kidneys were obtained from radically nephrectomised patients with urogenital malignancy (n = 15). Subsequently, human kidney immune cell subsets were analysed using multicolor flow cytometry and compared with subsets from C57BL/6 or BALB/c mice under specific pathogen-free conditions. Twenty kidney sections from healthy kidney donors or subjects without specific renal lesions were additionally analysed by immunohistochemistry. In human kidneys, 47% ± 12% (maximum 63%) of immune cells were CD3+ T cells. Kidney CD4+ and CD8+ T cells comprised 44% and 56% of total T cells. Of these, 47% ± 15% of T cells displayed an effector memory phenotype (CCR7− CD45RA− CD69−), and 48% ± 19% were kidney-resident cells (CCR7− CD45RA− CD69+). However, the proportions of human CD14+ and CD16+ myeloid cells were approximately 10% of total immune cells. A predominance of CD3+ T cells and a low proportion of CD14+ or CD68+ myeloid cells were also identified in healthy human kidney sections. In mouse kidneys, kidney-resident macrophages (CD11blow F4/80high) were the most predominant subset (up to 50%) but the proportion of CD3+ T cells was less than 20%. These results will be of use in studies in which mouse results are translated into human cases under homeostatic conditions or with disease.
Influence of temperature on the electrochemical window of boron doped diamond: a comparison of commercially available electrodes
Authors: McLaughlin Maeve H. S. , Corcoran Emma , Pakpour-Tabrizi Alexander C. , de Faria Débora Campos , Jackman Richard B.
Published: September 2020

This work compares the electrochemical windows of polished and unpolished boron doped diamond (BDD) electrodes with hydrogen and oxygen terminations at a series of temperatures up to 125 °C. The experiment was run at 5 bar pressure to avoid complications due to bubble formation. An alternative method for determining the electrochemical window is compared to the most commonly used method, which defines the window at an arbitrary current density cut-off (Jcut-off) value. This arbitrary method is heavily influenced by the mass transport of the electrolyte and cannot be used to compare electrodes across literature where different Jcut-off values have been used. A linear fit method is described which is less affected by the experimental conditions in a given measurement system. This enables a more accurate comparison of the relative electrochemical window from various diamond electrode types from reported results. Through comparison of polished and unpolished BDD electrodes, with hydrogen and oxygen surface terminations, it is determined that the electrochemical window of BDD electrodes narrows as temperature increases; activation energies are reported.
Author Correction: Plantaricin NC8 αβ exerts potent antimicrobial activity against Staphylococcus spp. and enhances the effects of antibiotics
Authors: Bengtsson Torbjörn , Selegård Robert , Musa Amani , Hultenby Kjell , Utterström Johanna , Sivlér Petter , Skog Mårten , Nayeri Fariba , Hellmark Bengt , Söderquist Bo , Aili Daniel , Khalaf Hazem
Published: September 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The effect of different anaesthetics on echocardiographic evaluation of diastolic dysfunction in a heart failure with preserved ejection fraction model
Authors: Cuijpers Ilona , Carai Paolo , Mendes-Ferreira Pedro , Simmonds Steven J. , Mulder Paul , Miranda-Silva Daniela , De Giorgio Daria , Pokreisz Peter , Heymans Stephane , Jones Elizabeth A. V.
Published: September 2020

Heart failure with preserved ejection fraction (HFpEF) is currently untreated. Therapeutics development demands effective diagnosis of diastolic dysfunction in animal models mimicking human pathology, which requires appropriate anaesthetics. Here, we investigated which anaesthetic, ketamine/xylazine or isoflurane, could be used to reveal diastolic dysfunction in HFpEF-diseased obese ZSF1 rats by echocardiography. First, diastolic dysfunction was confirmed by pressure-volume loops in obese compared to lean control ZSF1 rats. In echocardiography, ketamine/xylazine, unlike isoflurane, was able to demonstrate impaired relaxation in obese ZSF1 rats, as reflected by impaired early (E) and late (A) filling peak velocities, decreased E/A ratio, and a prolonged deceleration and isovolumic relaxation time. Interestingly, ketamine/xylazine induced a wider separation of both tissue and pulsed wave Doppler-derived echocardiographic waves required for diastolic dysfunction diagnosis, potentially by reducing the heart rate (HR), while isoflurane resulted in merged waves. To assess whether HR-lowering alone explained the differences between the anaesthetics, echocardiography measurements under isoflurane with and without the HR-lowering drug ivabradine were compared. However, diastolic dysfunction could not be diagnosed in ivabradine-treated obese ZSF1 rats. In summary, ketamine/xylazine compared to isoflurane is the anaesthetic of choice to detect diastolic dysfunction by echocardiography in rodent HFpEF, which was only partly mediated by HR-lowering.
Optimization of electromagnetic hot spots in surface-enhanced Raman scattering substrates for an ultrasensitive drug assay of emergency department patients’ plasma
Authors: Liyanage Thakshila , Masterson Adrianna N. , Hati Sumon , Ren Greta , Manicke Nicholas E. , Rusyniak Daniel E. , Sardar Rajesh
Published: September 2020

Nanoplasmonic superlattice surface-enhanced Raman scattering substrates have been developed for an ultrasensitive detection of fentanyl and cocaine from patients’ plasma.
A gas pressure and colorimetric signal dual-mode strategy for sensitive detection of spermine using ssDNA-coated Au@Pt nanoparticles as the probe
Authors: Jiang Huan , Rao Xinyue , Li Ling , Liu Zhongde
Published: September 2020

Based on target-responsive aggregation occurrence of Au@PtNPs, a dual-mode strategyviagas pressure and colorimetric signal readout was established for the detection of spermine, not only in laboratory but also in point-of-care setting.