bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of dynamic flow interaction methods between pipe system and overland in urban flood analysis
Authors: Hao Xiaoli , Li Yanmin , Liu Shu
Published: June 2021

Urban flooding can be predicted by using different modeling approaches. This study considered different methods of modeling the dynamic flow interactions between pipe systems and surface flooding in urban areas. These approaches can be divided into two categories based on surface runoff collection units. This paper introduces a new hydrodynamic model that couples the storm water management model and the 2D overland model. The model’s efficiency was validated based on the aforementioned experimental dataset; agreement was verified by correlation values above 0.6. Additionally, this study used different approaches and compared their accuracy in predicting flooding patterns. The results show that the use of sub-catchments to model the collection of surface runoff was not predictive of the inundation process, indicating a lower goodness of fit with the recorded values than that of adopting cells. Moreover, to determine which method of adopting cells to collect runoff could better predict rainstorm-induced inundation, an error and correlation analysis was conducted. The analysis found low error and high correlation, suggesting that inundation can be effectively predicted by the new approaches. Ultimately, this study contributes to existing work on numerical analysis of the interaction methods of urban flooding.
Surface wave reflection from a metasurface termination
Authors: Berry S. J. , Hibbins A. P. , Sambles J. R.
Published: June 2021

The reflection coefficient of a microwave surface wave incident at the termination of a metasurface is explored. Two different surface types are examined. One is a square array of square metallic patches on a dielectric-coated metallic ground plane, the other a Sievenpiper ‘mushroom’ array. In the latter the surface wave fields are more confined within the structure. Comparison of the measured surface-wave reflection spectra is made with that obtained from analytic theory and numerical modelling. The reflection coefficient is shown to be dependent on both the momentum mismatch between the surface wave and the freely propagating modes as well as the different field distributions of the two modes.
Strain-tunable triple point Fermions in diamagnetic rare-earth half-Heusler alloys
Authors: Bhattacharya Anupam , Bhardwaj Vishal , Mani Brajesh K , Dutt Jayanta K , Chatterjee Ratnamala
Published: June 2021

Topologically non-trivial electronic structure is a feature of many rare-earth half-Heusler alloys, which host atoms with high spin-orbit coupling bringing in the non-triviality. In this article, using the first-principles simulations, rare-earth half-Heusler YPdBi, ScPdBi, LaPdBi, LuPdBi, YPtBi and LuPtBi alloys are studied under strain to reveal multiple band inversions associated with topological phase transitions. From our simulations we find that, as a result of first band-inversion, the Brillouin zone of the diamagnetic half-Heusler alloys hosts eight triple points whereas, the second band inversion causes the emergence of sixteen more triple points. These band-inversions are observed to be independent of the spin-orbit coupling and are the reason behind increasing occupation of bismuth 7s orbitals as volume of the unit cell increases. The surface electronic transport in different triple point semi-metallic phases is found to evolve under strain, as the number of Fermi arcs change due to multiple band inversions. Once the second band inversion occurs, further application of tensile strain does not increase the number of triple points and Fermi arcs. However, increasing tensile strain (or decreasing compressive strain) pushes the triple point crossing to higher momenta, making them more effective as source of highly mobile electrons. These observations make a pathway to tune the bulk as well as surface transport through these semi-metals by application of tensile or compressive strain depending on the unstrained relative band-inversion strength of the material.
Regulatory properties of vitronectin and its glycosylation in collagen fibril formation and collagen-degrading enzyme cathepsin K activity
Authors: Date Kimie , Sakagami Hiromi , Yura Kei
Published: June 2021

Vitronectin (VN) is a glycoprotein found in extracellular matrix and blood. Collagen, a major extracellular matrix component in mammals, is degraded by cathepsin K (CatK), which is essential for bone resorption under acidic conditions. The relationship between VN and cathepsins has been unclear. We discovered that VN promoted collagen fibril formation and inhibited CatK activity, and observed its activation in vitro. VN accelerated collagen fibril formation at neutral pH. Collagen fibers formed with VN were in close contact with each other and appeared as scattered flat masses in scanning electron microscopy images. VN formed collagen fibers with high acid solubility and significantly inhibited CatK; the IC50 was 8.1–16.6 nM and competitive, almost the same as those of human and porcine VNs. VN inhibited the autoprocessing of inactive pro-CatK from active CatK. DeN-glycosylation of VN attenuated the inhibitory effects of CatK and its autoprocessing by VN, but had little effect on acid solubilization of collagen and VN degradation via CatK. CatK inhibition is an attractive treatment approach for osteoporosis and osteoarthritis. These findings suggest that glycosylated VN is a potential biological candidate for CatK inhibition and may help to understand the molecular mechanisms of tissue re-modeling.
Author Correction: The therapeutic effects of adipose-derived mesenchymal stem cells on obesity and its associated diseases in diet-induced obese mice
Authors: jaber Hala , Issa Khodr , Eid Ali , Saleh Fatima A.
Published: June 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Borane catalysed cyclopropenation of arylacetylenes
Authors: Stefkova Katarina , Heard Matthew J. , Dasgupta Ayan , Melen Rebecca L.
Published: June 2021

Triarylborane catalysed cyclopropenation of a arylacetylenes using donor–acceptor diazoesters.
Bioresponsive nanomedicines based on dynamic covalent bonds
Authors: Xin Xiaoqian , Zhang Zhongxia , Zhang Xican , Chen Jian , Lin Xi , Sun Pinghua , Liu Xiaowen
Published: June 2021

Efficient drug delivery to target tissues is essential for improved outcomes. Bioresponsive nanomedicine with dynamic covalent bonds (DCBs) is promising.
Early B-cell factors involve in the tumorigenesis and predict the overall survival of gastric cancer
Authors: Wang Qing , Liang Jiahong , Hu Xianyu , Gu Songgang , Xu Qiaodong , Yan Jiang
Published: June 2021

Gastric cancer (GC) is a heavy health burden around the world, which is the fifth most frequent tumor and leads to the third most common cancer-related deaths. It is urgent to identify prognostic markers as the guideline for personalized treatment and follow-up. We accessed the prognostic value of Early B-cell factors (EBFs) in GC. A total of 415 GC tissues and 34 normal tissues from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort, 616 external patients from GSE15459, GSE22377, GSE51105, GSE62245 were enrolled for analysis. Univariate and multivariate Cox regression analyses were employed to evaluate the sole and integrative prognostic value of EBFs, respectively. Genetic alterations, DNA methylation of EBFs were also evaluated, as well as the involved signaling pathways. We revealed that increased EBFs associated with the poor prognosis of GC patients, the prognostic model was established in TCGA-STAD cohort, and validated in Gene Expression Omnibus (GEO) cohorts, with effectiveness in both HER2 positive and negative patients. DNA methylation was involved in the impact on prognosis. Cell cycle, immune-associated, and MAPK pathways were influenced by EBFs. Anti-CTLA4 immunotherapy is more suitable for EBFs determining high-risk groups, but not anti-PD-1/PD-L1 therapy. 5-Fluorouracil, methotrexate, vorinostat are suitable to inhibit the function of EBFs. Our new findings provide novel insight into the prediction of prognosis and clinical treatment of GC patients based on EBFs.
Incaspitolide A extracted fromCarpesium cernuuminduces apoptosisin vitrovia the PI3K/AKT pathway in benign prostatic hyperplasia
Authors: Chen Xiaoyue , Song Jingrui , Yuan Dongbo , Rao Qing , Jiang Kehua , Feng Shuhui , Zhu Guohua , Yan Chen , Li Yanmei , Zhu Jianguo
Published: June 2021

Benign prostatic hyperplasia (BPH) is a common disease that occurs mainly in older men. The pathogenesis of BPH is complex and patients face a prolonged treatment course, and novel drugs with better selectivity and lower toxicity are required. Incaspitolide A (compound TMJ-12) is a germacrane-type sesquiterpenoid compound extracted from the plant Carpesium carnuum. Extracts of C. carnuum are known to exert suppressive effects on BPH-1 cells. In the present study, we investigated the molecular mechanisms underlying the suppressive effect of TMJ-12 specifically on BPH-1 cells. A cytotoxicity assay indicated that TMJ-12 inhibited BPH-1 cell proliferation, while flow cytometry assays showed that TMJ-12 induced G2/M phase cell cycle arrest and the apoptosis of BPH-1 cells. TMJ-12 was also shown to regulate the expression of several apoptosis- and cell cycle-related proteins, namely Bcl-2, Bax, Bad, Caspase-9, Caspase-3, cyclin-dependent kinase 1 (CDK1), Cyclin B1, CDC25C, and c-Myc, among others. Collapse of the mitochondrial membrane potential (ΔΨm) following exposure to TMJ-12 was detected with the JC-1 staining assay. Further investigation revealed that treatment with TMJ-12 inhibited the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway by increasing the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Taken together, the results suggest that TMJ-12 prevents BPH-1 cell proliferation via the PI3K/AKT pathway by inducing apoptosis and cell cycle arrest.
The Dutch Main Concept Analysis: Translation and Establishment of Normative Data
Authors: Criel Yana , Deleu Marie , De Groote Evelien , Bockstael Annelies , Kong Anthony Pak-Hin , De Letter Miet
Published: June 2021

Purpose

The main concept analysis (MCA; Kong, 2009) quantifies the effectiveness and efficiency of information transfer during verbal discourse by means of four sets of sequential pictorial stimuli. This test was originally developed for a Cantonese-speaking population. The main goals of this study were (a) to translate and adapt the MCA to Dutch; (b) to establish normative data for healthy native Dutch-speaking adults; (c) to assess the effect of age, education level, and gender on MCA outcome; and (d) to establish inter- and intrarater reliability of the Dutch MCA.

Method

Language samples were collected from 60 healthy native Dutch speakers, equally recruited in different age (20–39 years, 40–59 years, 60–79 years) and education (middle and highly educated) categories through administration of the MCA. Utterances produced by at least 75% of the participants were included as a main concept in the Dutch MCA. Subsequently, age-specific normative data were established for each of the MCA parameters. Finally, an ICC was calculated in order to verify inter- and intrarater reliability of the Dutch MCA.

Results

The translated MCA consisted of 19 main concepts. Age-specific normative data were obtained. Both age and education level had a significant effect on MCA outcome. Information transfer in elderly was both less effectively and efficiently compared to young- and middle-aged adults. In addition, highly educated participants transferred information less efficiently compared to middle educated participants. Based on inter- and intrarater reliability measures, the Dutch MCA proved to be a reliable measuring instrument.

Conclusions

The MCA was translated to Dutch, and age-specific normative data were established for a healthy, Dutch-speaking population. The Dutch MCA is a reliable tool for eliciting and quantifying discourse production. Validation of the test for people with aphasia is necessary in order for the test to be useful in a clinical practice.
Describing Vocalizations in Young Children: A Big Data Approach Through Citizen Science Annotation
Authors: Semenzin Chiara , Hamrick Lisa , Seidl Amanda , Kelleher Bridgette L. , Cristia Alejandrina
Published: June 2021

Purpose

Recording young children's vocalizations through wearables is a promising method to assess language development. However, accurately and rapidly annotating these files remains challenging. Online crowdsourcing with the collaboration of citizen scientists could be a feasible solution. In this article, we assess the extent to which citizen scientists' annotations align with those gathered in the lab for recordings collected from young children.

Method

Segments identified by Language ENvironment Analysis as produced by the key child were extracted from one daylong recording for each of 20 participants: 10 low-risk control children and 10 children diagnosed with Angelman syndrome, a neurogenetic syndrome characterized by severe language impairments. Speech samples were annotated by trained annotators in the laboratory as well as by citizen scientists on Zooniverse. All annotators assigned one of five labels to each sample: Canonical, Noncanonical, Crying, Laughing, and Junk. This allowed the derivation of two child-level vocalization metrics: the Linguistic Proportion and the Canonical Proportion.

Results

At the segment level, Zooniverse classifications had moderate precision and recall. More importantly, the Linguistic Proportion and the Canonical Proportion derived from Zooniverse annotations were highly correlated with those derived from laboratory annotations.

Conclusions

Annotations obtained through a citizen science platform can help us overcome challenges posed by the process of annotating daylong speech recordings. Particularly when used in composites or derived metrics, such annotations can be used to investigate early markers of language delays.
Study on the erosion characteristics of copper‐carbon electrode pairs by DC air arc
Authors: Xie Wenhan , Wu Guangning , Yang Zefeng , She Pengpeng , Wang Hong , Zuo Haozi , Wei Wenfu , Gao Guoqiang , Tu Chuanjun
Published: June 2021

As common electric contact materials, copper‐carbon electrode pairs are widely used in the field of electric contact such as in high‐speed railways, motor collector rings and grounding brushes. They play a key role in energy transmission in the above‐mentioned systems. Arc erosion has become a key issue threatening system safety. In this work, a dedicated arc erosion platform was built to study the polarity effect of copper‐carbon electrode pairs. It was found that arc dynamics and electrodes erosion behaviours were significantly different under different polarities, which could be understood from the mechanism of heat transfer, cooling and electron emission of the electrode. Then, when the carbon material was used as an anode, the arc caused carbon transfer: the carbon material sublimated quickly due to electron condensation and thermal conduction and quickly condensed on the low‐temperature metal electrode, while the carbon material transfer could partly inhibit the oxidation of the cathode metal electrode. In addition, the rapid sublimation of the carbon material produced high‐temperature airflow, which would make the arc impedance fluctuate and cause the arc voltage to jump. Finally, the anode heat transfer and cathode cooling mechanism directly affected the material state, and the erosion of the anode material was more serious.
Deformation of binary and boron-doped Ni3Al alloys at high pressures studied with synchrotron x-ray diffraction
Authors: Raju S. V. , Vasin R. N. , Godwal B. K. , Jeanloz R. , Wenk H.-R. , Saxena S. K.
Published: June 2021

In situ x-ray synchrotron diffraction experiments were carried out on nickel-based high-strength superalloys under pressure to understand their deformation mechanism using a diamond anvil cell (DAC). Radial x-ray diffraction determines the room-temperature equations of state and yield strengths of binary Ni3Al alloy and 500 ppm boron-doped Ni3Al to pressures of 20 and 46 GPa, respectively. Crystallographic preferred orientations observed in these superalloys due to anisotropic stress field in DAC indicate the onset of plastic deformation. Inverse pole figure analysis reveals that the underlying deformation mechanisms change from an octahedral slip to a simultaneous activation of octahedral and cube slips upon doping with boron. The yield-strength values were found to increase with pressure and are comparable to those determined from axial diffraction experiments. The results indicate that the yield strength of Ni3Al:B is about 0.5 GPa higher (at pressures below 20 GPa) due to grain boundary strengthening by boron. It is shown that due to high elastic anisotropy of Ni3Al alloy, the yield-strength estimations from diffraction experiments strongly depend on the micromechanical model used to convert the measured elastic strains into stresses.
Diversity of CAM plant photosynthesis (crassulacean acid metabolism): a tribute to Barry Osmond
Authors: Winter Klaus
Published: June 2021

This special issue is a tribute to the Australian plant biologist Professor Charles Barry Osmond – Fellow of the Australian Academy of Sciences, the Royal Society of London, and Leopoldina, the German National Academy of Sciences – and his many contributions to our understanding of the biochemistry and physiological ecology of CAM (crassulacean acid metabolism) photosynthesis. This water-conserving photosynthetic pathway is characterised by nocturnal uptake of atmospheric CO2 and typically enables succulent plants to perform and survive in warm semiarid terrestrial and epiphytic habitats. The idea for this issue is to mark the occasion of Barry’s 80th birthday in 2019. The foreword highlights some of his outstanding contributions and introduces the research papers of the special issue.
Tomato leaf curl New Delhi virus (tomato New Delhi virus).
Authors: Gómez Pedro , Juárez Miguel
Published: June 2021

Tomato leaf curl New Delhi virus (ToLCNDV) is a bipartite, single-stranded DNA virus transmitted by the whitefly, Bemisia tabaci. The virus was first identified in India in 1995 affecting solanaceous crops (Padidam et al., 1995) and thereafter, causing major damage to cucurbit crops on the Indian subcontinent (Zaidi et al., 2017). ToLCNDV was first detected in Europe in 2012, affecting zucchini squash crops in Spain (Juárez et al., 2014), with subsequent detections in Tunisia (Mnari-Hattab et al., 2015), Italy (Panno et al., 2016) and Morocco (Sifres et al., 2018). ToLCNDV is responsible for severe outbreaks of disease in cucurbit crops in the Mediterranean basin (Juárez et al., 2019; Panno et al., 2019) and represents a serious threat to economically imp1ortant solanaceous crops in the region (Moriones et al., 2017). ToLCNDV appears to be spreading rapidly and is listed as a quarantine pest by EPPO (EPPO, 2019a). There are quarantine measures to control its whitefly vector (Bertin et al., 2018).
Puccinia buxi.
Authors:   USA, USDA-ARS
Published: June 2021

P. buxi is an autoecious microcyclic rust, completing its life cycle with two spore forms on one host. It is native to parts of Europe and Asia. An introduction to the USA, is evidence that it can be invasive with respect to other temperate countries, particularly because its hosts in the genus Buxus are often propagated vegetatively and may carry latent infections. Boxwoods have long been popular as ornamentals, therefore the rust's current absence from North America and temperate regions of the southern hemisphere is puzzling; in the earliest introductions of the host, the pathogen would probably have been ignored or overlooked. Conditions of boxwood cultivation may discourage the rust's growth and survival.
Eigenmodes of a disordered FeCo magnonic crystal at finite temperatures
Authors: Paischer S , Buczek P A , Buczek N , Eilmsteiner D , Ernst A
Published: June 2021

In this report we present a systematic study of the magnonic modes in the disordered Fe0.5Co0.5 alloy based on the Heisenberg Hamiltonian using two complementary approaches. In order to account for substitutional disorder, on the one hand we directly average the transverse magnetic susceptibility in real space over different disorder configurations and on the other hand we use the coherent potential approximation (CPA). While the method of direct averaging is numerically exact, it is computationally expensive and limited by the maximal size of the supercell which can be simulated on a computer. On the contrary the CPA does not suffer from this drawback and yields a cheap numerical scheme. Therefore, we additionally compare the results of these two approaches and show that the CPA gives very good results for most of the magnetic properties considered in this report, including the magnon energies and the spatial shape of the eigenmodes. However, it turns out that while reproducing the general trend, the CPA systematically underestimates the disorder induced damping of the magnons. This provides evidence that the physics of impurity scattering in this system is governed by non-local effects missing in the CPA. Finally, we study the real space eigenmodes of the system, including their spatial shapes, and analyze their temperature dependence within the random phase approximation.
A methodology for the analysis of the three-dimensional mechanical behavior of a Nb3Sn superconducting accelerator magnet during a quench
Authors: Ferradas Troitino J , Bajas H , Bianchi L , Castaldo B , Ferracin P , Guinchard M , Izquierdo S , Lorenzo J V , Mangiarotti F , Perez J C , Takala E , Vallone G , Senatore C
Published: June 2021

The fast thermal and electromagnetic transients that occur in a superconducting magnet in case of a quench have the potential of generating large mechanical stresses both in the superconducting coils and in the magnet structure. While the investigation of such quench loads should generally be conducted to ensure a safe operation of the system, its importance is greatly enlarged in the case of high-field magnets based on strain sensitive superconductors. For these, a rigorous analysis of the magnet mechanics during a quench becomes critical. The scope of this work is hence to bring, for the first time, a detailed understanding of the three-dimensional mechanical behavior of a Nb3Sn accelerator magnet during a quench discharge. The study relies on the use of finite element models, where various multi-domain simulations are employed together to solve the coupled physics of the problem. Our analysis elaborates on the case study of the new MQXF quadrupole magnet, currently being developed for the high-luminosity upgrade of the LHC. Notably, we could find a very good agreement between the results of the simulation and experimental data from full-scale magnet tests. The validated model confirms the appearance of new peak stresses in the superconducting coils. An increase in the most relevant transverse coil stresses of 20–40 MPa with respect to the values after magnet cool-down has been found for the examined case.
Evaluating the contribution of osmotic and oxidative stress components on barley growth under salt stress
Authors: Nefissi Ouertani Rim , Abid Ghassen , Karmous Chahine , Ben Chikha Mariem , Boudaya Oumaima , Mahmoudi Henda , Mejri Samiha , Jansen Robert K , Ghorbel Abdelwahed
Published: June 2021

Salt stress is considered one of the most devastating environmental stresses, affecting barley growth and leading to significant yield loss. Hence, there is considerable interest in investigating the most effective traits that determine barley growth under salt stress. The objective of this study was to elucidate the contribution of osmotic and oxidative stress components in leaves and roots growth under salt stress. Two distinct barley (Hordeum vulgare) salt-stress tolerant genotypes, Barrage Malleg (BM, tolerant) and Saouef (Sf, sensitive), were subjected to 200 mM NaCl at early vegetative stages. Stressed and control leaves and roots tissue were assessed for several growth traits, including fresh and dry weight and plant length, as well as the content of osmoprotectants proline and soluble sugars. In addition, malondialdehyde content and activities of superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX), as well as their corresponding gene expression patterns, were investigated. The results showed better performance of BM over Sf for leaf dry weight (LDW), root dry weight (RDW) and root length (RL). The salt-tolerant genotype (BM) had better osmoprotection against salt stress compared with the salt-sensitive genotype (Sf), with a higher accumulation of proline and soluble sugars in leaves and roots and a stronger antioxidant system as evidenced by higher activities of SOD, CAT and APX and more abundant Cu/Zn-SOD transcripts, especially in roots. Stepwise regression analysis indicated that under salt stress the most predominant trait of barley growth was Cu/Zn-SOD gene expression level, suggesting that alleviating oxidative stress and providing cell homeostasis is the first priority.
AQUARIUM: accurate quantification of circular isoforms using model-based strategy
Authors: Wen Guoxia , Li Musheng , Li Fuyu , Yang Zengyan , Zhou Tong , Gu Wanjun
Published: June 2021

Currently, most computational methods estimate the expression of circular RNAs (circRNAs) using the number of sequencing reads that support back–splicing junctions (BSJ) in RNA-seq data, which may introduce biased estimation of circRNA expression due to the uneven distribution of sequencing reads. To overcome this, we previously developed a model-based strategy for circRNA quantification, enabling consideration of sequencing reads from the entire transcript. Yet, the lack of exact transcript structure of circRNAs may limit its accuracy. Here, we proposed a substantially improved circRNA quantification tool, AQUARIUM, by introducing the full-length RNA structure of circular isoforms. We assessed its performance in circRNA quantification using both biological and simulated rRNA-depleted RNA-seq datasets, and demonstrated its superior performance at both BSJ and isoform level.

Availability and implementation

AQUARIUM is freely available at https://github.com/wanjun-group-seu/AQUARIUM.

Supplementary information

Supplementary data are available at Bioinformatics online.
Application of ICH Guidelines for Studying the Degradation Behavior of Rocuronium Bromide Coupled with Stability-Indicating RP-LC Method
Authors: El Houssini Ola M , Abd El-Rahman Mohamed K , Fahem Diana K , Zaazaa Hala E
Published: June 2021

Non-depolarizing neuromuscular blocking agent Rocuronium bromide was quantified in drug substance and drug product using reversed-phase liquid chromatographic method. Forced degradation studies were conducted for Rocuronium bromide in drug substance under acidic (2MHCl), basic (2MNaOH), oxidative (3% H2O2), thermal (135°C) and photolytic (254 nm) stress conditions. An Agilent H12 C18 column was used for separation using diammonium hydrogen phosphate buffer (pH 8; 0.04M)- acetonitrile (50:50; v/v) as mobile phase at flow rate of 1 mL/min. The quantification was done using UV detection at 210 nm. The limit of quantification and detection was 11.1 and 3.66 μg/mL, respectively, and the recovery percentage was 99% in drug substance and drug product. ICH guidelines were adopted for method validation. The proposed LC method monitored the degradation profile for Rocuronium bromide under various stress conditions and provided a specific LC method for its routine analysis. Besides, the MS data were used to identify all Rocuronium bromide degradation products and the possible degradation pathway was designated.
Using fiction to engage audiences with infectious disease: the effect of the coronavirus pandemic on participation in the Bad Bugs Bookclub
Authors: Verran Joanna
Published: June 2021

During Bad Bugs Bookclub meetings, scientists and non-scientists discuss novels in which infectious disease forms part of the plot in order to encourage public understanding of, and engagement with, microbiology. The website presents meeting reports and reading guides for over 70 novels. The aim of this work was to raise awareness of the bookclub and increase website engagement. In 2019, events designed to reach new audiences maintained an increase in page views from the end of 2018 (around 200 per month). In 2020, the coronavirus pandemic forced bookclub meetings online (Zoom). These, with podcasts and some Twitter discussion, increased page views with a peak of 400 per month. Membership increased, and global ‘attendance’ was facilitated. Feelings and observations related to each book and the pandemic were noted in meeting reports. A survey of current and previous bookclub members carried out early in lockdown with the aim of determining the future direction of the bookclub revealed the continuing value of both literary and scientific experiences to members. The bookclub has engaged scientists and non-scientists in meaningful discussion about infectious disease. Reach is modest, but the resource is significant, with potential impact in education and engagement.
Spectral element modeling of elastic wave propagation in an anisotropic background with discrete anisotropic fractures
Authors: Xu Jiaqi , Hu Hengshan , Liu Qing Huo , Zhan Qiwei , Zhuang Mingwei
Published: June 2021

We formulate and implement a spectral element method to simulate elastic wave propagation in an arbitrary anisotropic background with discrete anisotropic fractures. The approach uses a general linear-slip condition to incorporate the anisotropic fractures into SEM, which allows for discontinuities of displacement fields across the surfaces of fractures. We treat the extremely thin fractures as geometry interfaces instead of meshing them, thus reducing computational cost. The results obtained by the proposed method agree well with the reference solutions for both a single horizontal anisotropic planar fracture and a tilted fracture. Based on the numerical simulation, we analyse the effects of anisotropic fracture on the wavefields. We find that due to the presence of off-diagonal element in the anisotropic fracture stiffness matrix, the wavefields generated by the anisotropic fracture are different from the isotropic fracture. The method can also simulate the wavefields in the anisotropic background including the multiple fractures or the intersecting fractures.
Impact of gestational age on risk of cerebral palsy: unravelling the role of neonatal morbidity
Authors: Chen Ruoqing , Sjölander Arvid , Johansson Stefan , Lu Donghao , Razaz Neda , Tedroff Kristina , Villamor Eduardo , Cnattingius Sven
Published: June 2021

Background

The contribution of adverse consequences of preterm birth to gestational-age-related risk of cerebral palsy (CP) has rarely been studied. We aimed to assess the potential mediating roles of neonatal morbidity on the association between gestational age and risk of CP.

Methods

In this Swedish population-based study, 1 402 240 singletons born at 22–40 gestational weeks during 1998–2016 were followed from day 28 after birth for a CP diagnosis until 2017. Potential mediators included asphyxia, respiratory-related, infection-/inflammatory-related and neurological-related diseases within 0–27 days of life. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Causal mediation analysis was performed to estimate the proportion of the association mediated through pathways involving the four sequential mediators.

Results

We found an inverse dose–response relationship between gestational age and risk of CP, where the strongest association was observed for 22–24 weeks (HR 47.26, 95% CI 34.09–65.53) vs 39–40 weeks. Compared with non-diseased peers, children with neonatal morbidity, particularly those with neurological-related diseases (HR 31.34, 95% CI 26.39–37.21), had a higher risk of CP. The increased risk of CP was, at 24 weeks, almost entirely explained by neonatal morbidity (91.7%); this proportion decreased to 46.1% and 16.4% at 32 and 36 weeks, respectively. Asphyxia was the main mediating pathway from 22 to 34 weeks, and neurological-related neonatal diseases led the mediating pathways from 34 weeks onwards.

Conclusion

Neonatal morbidity mediates a large proportion of the effect of preterm birth on CP, but the magnitude declines as gestational age increases.
Time-Varying Association Between Severe Respiratory Syncytial Virus Infections and Subsequent Severe Asthma and Wheeze and Influences of Age at the Infection
Authors: Wang Xin , Li You , Nair Harish , Campbell Harry ,   RESCEU Investigators, Wang Xin , Reeves Rachel M , Li You , Campbell Harry , Nair Harish , van Wijhe Maarten , Kølsen Fischer Thea , Simonsen Lone , Trebbien Ramona , Tong Sabine , Bangert Mathieu , Demont Clarisse , Lehtonen Toni , University Hospital Turku , Heikkinen Terho , Teirlinck Anne , van Boven Michiel , van der Hoek Wim , van der Maas Nicoline , Meijer Adam , Vazquez Fernandez Liliana , Bøas Håkon , Bekkevold Terese , Flem Elmira , Stona Luca , Speltra Irene , Giaquinto Carlo , Cheret Arnaud , Leach Amanda , Stoszek Sonia , Beutels Philippe , Bont Louis , Pollard Andrew , Openshaw Peter , Abram Michael , Swanson Kena , Rosen Brian , Molero Eva
Published: June 2021

Background

Early-life severe respiratory syncytial virus (RSV) infection has been associated with subsequent risk of asthma and recurrent wheeze. However, changes in the association over time and the interaction effect of the age at first RSV infection are less well understood. We aimed to assess the time-varying association between RSV and subsequent asthma and wheeze admission and explore how the association was affected by the age at RSV infection.

Methods

We retrospectively followed up a cohort of 23 365 children for a median of 6.9 years using Scottish health databases. Children who were born between 2001 and 2013 and had RSV-associated respiratory tract infection (RTI) admissions under 2 years were in the exposed group; those with unintentional accident admissions under 2 years comprised the control group. The Cox proportional-hazards model was used to report adjusted hazard ratios (HRs) of RSV admissions on subsequent asthma and wheeze admissions. We did subgroup analyses by follow-up years. We also explored how this association was affected by the age at first RSV admission.

Results

The association was strongest in the first 2 years of follow-up and decreased over time. The association persisted for 6 years in children whose first RSV-RTI admission occurred at 6–23 months of age, with an adjusted HR of 3.9 (95% confidence interval [CI], 3.1–4.9) for the first 2 years, 2.3 (95% CI, 1.6–3.2) for 2 to <4 years, and 1.9 (95% CI, 1.2–2.9) for 4 to <6 years of follow-up. In contrast, the association was only significant for the first 2 years after first RSV-RTI admissions occurring at 0–5 months.

Conclusions

We found a more persistent association for subsequent asthma and wheeze in children whose first severe RSV infection occurred at 6–23 months compared to those whose first severe RSV infection occurred at 0–6 months. This provides new evidence for further assessment of the association and RSV intervention programs.
Molecular mechanism of MdWUS2–MdTCP12 interaction in mediating cytokinin signaling to control axillary bud outgrowth
Authors: Li Guofang , Tan Ming , Ma Juanjuan , Cheng Fang , Li Ke , Liu Xiaojie , Zhao Caiping , Zhang Dong , Xing Libo , Ren Xiaolin , Han Mingyu , An Na
Published: June 2021

Shoot branching is an important factor that influences the architecture of apple trees and cytokinin is known to promote axillary bud outgrowth. The cultivar ‘Fuji’, which is grown on ~75% of the apple-producing area in China, exhibits poor natural branching. The TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) family genes BRANCHED1/2 (BRC1/2) are involved in integrating diverse factors that function locally to inhibit shoot branching; however, the molecular mechanism underlying the cytokinin-mediated promotion of branching that involves the repression of BRC1/2 remains unclear. In this study, we found that apple WUSCHEL2 (MdWUS2), which interacts with the co-repressor TOPLESS-RELATED9 (MdTPR9), is activated by cytokinin and regulates branching by inhibiting the activity of MdTCP12 (a BRC2 homolog). Overexpressing MdWUS2 in Arabidopsis or Nicotiana benthamiana resulted in enhanced branching. Overexpression of MdTCP12 inhibited axillary bud outgrowth in Arabidopsis, indicating that it contributes to the regulation of branching. In addition, we found that MdWUS2 interacted with MdTCP12 in vivo and in vitro and suppressed the ability of MdTCP12 to activate the transcription of its target gene, HOMEOBOX PROTEIN 53b (MdHB53b). Our results therefore suggest that MdWUS2 is involved in the cytokinin-mediated inhibition of MdTCP12 that controls bud outgrowth, and hence provide new insights into the regulation of shoot branching by cytokinin.
Quasi-essentiality of RNase Y inBacillus subtilisis caused by its critical role in the control of mRNA homeostasis
Authors: Benda Martin , Woelfel Simon , Faßhauer Patrick , Gunka Katrin , Klumpp Stefan , Poehlein Anja , Kálalová Debora , Šanderová Hana , Daniel Rolf , Krásný Libor , Stülke Jörg
Published: June 2021

RNA turnover is essential in all domains of life. The endonuclease RNase Y (rny) is one of the key components involved in RNA metabolism of the model organism Bacillus subtilis. Essentiality of RNase Y has been a matter of discussion, since deletion of the rny gene is possible, but leads to severe phenotypic effects. In this work, we demonstrate that the rny mutant strain rapidly evolves suppressor mutations to at least partially alleviate these defects. All suppressor mutants had acquired a duplication of an about 60 kb long genomic region encompassing genes for all three core subunits of the RNA polymerase—α, β, β′. When the duplication of the RNA polymerase genes was prevented by relocation of the rpoA gene in the B. subtilis genome, all suppressor mutants carried distinct single point mutations in evolutionary conserved regions of genes coding either for the β or β’ subunits of the RNA polymerase that were not tolerated by wild type bacteria. In vitro transcription assays with the mutated polymerase variants showed a severe decrease in transcription efficiency. Altogether, our results suggest a tight cooperation between RNase Y and the RNA polymerase to establish an optimal RNA homeostasis in B. subtilis cells.
Demographics and Automation
Authors: Acemoglu Daron , Restrepo Pascual
Published: June 2021

We argue theoretically and document empirically that aging leads to greater (industrial) automation, because it creates a shortage of middle-aged workers specializing in manual production tasks. We show that demographic change is associated with greater adoption of robots and other automation technologies across countries and with more robotics-related activities across U.S. commuting zones. We also document more automation innovation in countries undergoing faster aging. Our directed technological change model predicts that the response of automation technologies to aging should be more pronounced in industries that rely more on middle-aged workers and those that present greater opportunities for automation and that productivity should improve and the labor share should decline relatively in industries that are more amenable to automation. The evidence supports all four of these predictions.
Distortions and Efficiency in Production Economies with Heterogeneous Beliefs
Authors: Heyerdahl-Larsen Christian , Walden Johan
Published: June 2021

We study consumption, savings, and asset prices in economies with disagreement and production, focusing on settings with real effects of disagreement. Aggregate savings may be significantly distorted under disagreement, possibly related to the undersaving puzzle. In the production economy, mispricing mainly manifests itself in idiosyncratic risk, in contrast to the exchange economy, where the risk-free rate and expected return on the market may be distorted. Potential policy implications include the introduction of investment taxes or subsidies. Our results highlight the real effects of disagreement in financial markets, and the differences between economies with and without production.
Illuminating the Proteasome: Fluorescence Assays for Investigating the Kinetics of Proteasome Substrate Processing
Authors: Bard Jared Abraham , Jonsson Erik , Martin Andreas
Published: June 2021

Degradation of ubiquitinated substrates by the 26S proteasome is a tightly regulated multi‐step process. The 33 unique subunits of the proteasome must coordinate to bind the substrate's ubiquitin targeting signal, engage its unstructured region, translocate and unfold the polypeptide chain while concurrently removing the ubiquitin chains, and finally hydrolyze the peptide bonds. Many of the details of how the proteasome performs these tasks are still unknown. A better understanding of the timing and coordination of these events would provide critical insight into how the cell regulates the rate or extent of protein degradation by the proteasome.

In order to gain molecular understanding of these processes, we have developed a fluorescent assay for directly studying the binding, engagement, and translocation of substrates by the heterohexameric AAA+ motor that feeds these substrates into the proteasome core for degradation. This was achieved by incorporating unnatural amino acids into the proteasome, which allowed for the site‐specific attachment of fluorescent dyes. Combined with previously developed tools for the heterologous expression, purification, and in‐vitro reconstitution of proteasome subcomplexes, this assay allows for a kinetic dissection of the substrate‐processing pathway. It will also allow us to test the effects of manipulating the substrate geometry or mutating proteasome components on the rate of individual processing steps. In addition to ensemble experiments, single‐molecule studies will reveal how individual processing events are timed and coordinated.

Support or Funding Information

J.B acknowledges support from the US National Science Foundation Graduate Research Fellowship. A.M. acknowledges support from the Searle Scholars Program, the US National Institutes of Health (grant R01‐GM094497), the US National Science Foundation CAREER Program (NSF‐MCB‐1150288), and A.M. and E.J. acknowledges support from the Howard Hughes Medical Institute.
Research for All: Large Introductory Laboratory Classes Investigate the Evolutionary Conservation of Metabolic Pathways
Authors: O'Connor Clare M. , Warner Douglas M.
Published: June 2021

The explosion of genomic sequence information, particularly for microbial organisms, presents opportunities to engage large numbers of undergraduate students in authentic research within regular laboratory classes. The Pathways over Time project was designed as a semester‐long research investigation in which students investigate the phylogenetic conservation of enzymes involved in a metabolic pathway. The project was designed to teach students core concepts of molecular biology, including evolution, structure/function relationships, information transfer, energy transformation and systems biology. Other course goals include the application of the scientific process, quantitative analysis, and the use of databases and bioinformatics tools.

Each semester, 150–200 students enroll in 12 parallel sections of BIOL2040, Investigations in Molecular Cell Biology. Working in teams of three, students study the conservation of enzymes involved in methionine biosynthesis between the budding yeast, S. cerevisiae, and the fission yeast, Schizosaccharomyces pombe, species separated by close to a billion years of evolution. Methionine biosynthesis in yeast involves several multi‐enzyme pathways, which are subject to a variety of regulatory controls. Working in teams of three, students become “experts” on one particular MET gene as they learn the basic techniques of microbiology, bioinformatics, molecular cell biology and genetics. The rapid pace of the course does not allow students to repeat experiments. Instead, students post their data to a data‐sharing wiki site to determine if their results are reproducible.

Student learning is assessed with pre‐lab quizzes, lab notebooks, oral and poster presentations, database and literature assignments, and a series of “micro‐reports” that are assembled into a final research report in the format of a scientific publication. Pre‐and post‐course evaluation instruments include concept tests and self‐assessed confidence and learning gains. Assessment data indicate significant gains on all measures.

The Pathways over Time project was designed with sustainability in mind. The project can be easily adapted to other organisms and enzyme systems, depending on instructor experience and interest. The three elements required for course design are a multi‐gene system to study, a genetically‐tractable organism for complementation analyses, and a test organism with a sequenced genome. At Boston College, for example, students have successfully demonstrated the conservation of multiple MET gene functions between S. cerevisiae and S. pombe. Moving forward, Boston College will use a new test organism in which MET gene function has been predicted from DNA sequence comparisons, but function has not been tested by complementation.

Support or Funding Information

National Science Foundation grant 114028
Gamma EEG Activation During Picture‐Word Semantic Processing in 3 Year Olds Varies As A Function of Gender And Infant Diet
Authors: Pivik R T , Andres A , Cleves M A , Badger T M
Published: June 2021

Semanticrelationships between images and words essential for language comprehension andcognitive function begin to emerge in toddlers, but it is not known if theearly development of these relationships is modulated by infant diet andgender. In this study 254 healthy 3yr‐olds [breast‐fed (BF: 86, 42 boys), or fed milk formula (MF: 88, 40 boys),or soy formula (SF: 80, 44 boys) as infants] viewed images of known objects/animalswhile hearing single words that were either congruent or incongruent with theimages, or were non‐words. For each ofthese image‐word conditions we used ANOVA to compare group, gender, and groupby gender‐related changes in frontal and temporal gamma (30–50 Hz) EEG powerduring the word relative to an immediately preceding baseline. Gamma activityis considered to index activation of associative memory networks, with gammaresponse amplitude increasing with memory strength. All word types elicitedincreases in gamma amplitude, and across groups at both frontal and temporalsites increases were significantly greater to congruent and incongruent wordscompared with non‐words (p < 0.05). Significant gender influences were evident as main effects andgroup‐gender interactions (p < 0.05), reflecting greater gamma amplitudeincreases in boys than girls—most prominent in SF children and least evident inBF children—and in SF compared with MF boys. These findings are the first tolink infant diet and gender to brain activity indexing cross‐modality semanticrelationships in toddlers. The results provide evidence that early infantdiet‐gender interactions may contribute differentially to the development offunctional neural networks involved in semantic processing in children, andsuggest that semantic relationships at this time are more strongly developed inSF boys.

Support or Funding Information

Funded by USDA‐ARS Project 6026‐51000‐010‐05S