bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of front strength on the development and equilibration of symmetric instability. Part 1. Growth and saturation
Authors: Wienkers A.F. , Thomas L.N. , Taylor J.R.
Published: September 2021

Submesoscale fronts with large horizontal buoyancy gradients and

$O(1)$

Rossby numbers are common in the upper ocean. These fronts are associated with large vertical transport and are hotspots for biological activity. Submesoscale fronts are susceptible to symmetric instability (SI) – a form of stratified inertial instability which can occur when the potential vorticity is of the opposite sign to the Coriolis parameter. Here, we use a weakly nonlinear stability analysis to study SI in an idealised frontal zone with a uniform horizontal buoyancy gradient in thermal wind balance. We find that the structure and energetics of SI strongly depend on the front strength, defined as the ratio of the horizontal buoyancy gradient to the square of the Coriolis frequency. Vertically bounded non-hydrostatic SI modes can grow by extracting potential or kinetic energy from the balanced front and the relative importance of these energy reservoirs depends on the front strength and vertical stratification. We describe two limiting behaviours as ‘slantwise convection’ and ‘slantwise inertial instability’ where the largest energy source is the buoyancy flux and geostrophic shear production, respectively. The growing linear SI modes eventually break down through a secondary shear instability, and in the process transport considerable geostrophic momentum. The resulting breakdown of thermal wind balance generates vertically sheared inertial oscillations and we estimate the amplitude of these oscillations from the stability analysis. We finally discuss broader implications of these results in the context of current parameterisations of SI.
Renormalization group analysis of the magnetohydrodynamic turbulence and dynamo
Authors: Mizerski Krzysztof A.
Published: September 2021

The magnetohydrodynamic (MHD) turbulence appears in engineering laboratory flows and is a common phenomenon in natural systems, e.g. stellar and planetary interiors and atmospheres and the interstellar medium. The applications in engineering are particularly interesting due to the recent advancement of tokamak devices, reaching very high plasma temperatures, thus giving hope for the production of thermonuclear fusion power. In the case of astrophysical applications, perhaps the main feature of the MHD turbulence is its ability to generate and sustain large-scale and small-scale magnetic fields. However, a crucial effect of the MHD turbulence is also the enhancement of large-scale diffusion via interactions of small-scale pulsations, i.e. the generation of the so-called turbulent viscosity and turbulent magnetic diffusivity, which typically exceed by orders of magnitude their molecular counterparts. The enhanced resistivity plays an important role in the turbulent dynamo process. Estimates of the turbulent electromotive force (EMF), including the so-called$\alpha$-effect responsible for amplification of the magnetic energy and the turbulent magnetic diffusion are desired. Here, we apply the renormalization group technique to extract the final expression for the turbulent EMF from the fully nonlinear dynamical equations (Navier–Stokes, induction equation). The simplified renormalized set of dynamical equations, including the equations for the means and fluctuations, is derived and the effective turbulent coefficients such as the viscosity, resistivity, the$\alpha$-coefficient and the Lorentz-force coefficients are explicitly calculated. The results are also used to demonstrate the influence of magnetic fields on energy and helicity spectra of strongly turbulent flows, in particular the magnetic energy spectrum.
A FAMILY OF -SUPERCONGRUENCES MODULO THE CUBE OF A CYCLOTOMIC POLYNOMIAL
Authors: GUO VICTOR J. W. , SCHLOSSER MICHAEL J.
Published: September 2021

We establish a family of q-supercongruences modulo the cube of a cyclotomic polynomial for truncated basic hypergeometric series. This confirms a weaker form of a conjecture of the present authors. Our proof employs a very-well-poised Karlsson–Minton type summation due to Gasper, together with the ‘creative microscoping’ method introduced by the first author in recent joint work with Zudilin.
Accuracy of equations for predicting 24-h urinary potassium excretion from spot urine samples in Chinese children
Authors: Nie Xiaolu , Peng Yaguang , Cai Siyu , Wu Zehao , Zhang Ying , Li Kun , Yu Yuncui , Peng Xiaoxia
Published: September 2021

Accurate assessments of potassium intake in children are important for the early prevention of CVD. Currently, there is no simple approach for accurate estimation of potassium intake in children. We aim to evaluate the accuracy of 24-h urinary potassium excretion (24UKV) estimation in children using three common equations: the Kawasaki, Tanaka and Mage formulas, in a hospital-based setting. A total of 151 participants aged 5–18 years were initially enrolled, and spot urine samples were collected in the whole 24-h duration to measure the concentrations of potassium and creatinine. We calculated the mean difference, absolute and relative difference and misclassification rate between measured 24UKV and the predicted ones using Kawasaki, Tanaka and Mage formulas in 129 participants. The mean measured 24UKV was 1193·3 mg/d in our study. Mean differences between estimated and measured 24UKV were 1215·6, −14·9 and 230·3 mg/d by the Kawasaki, Tanaka and Mage formulas, respectively. All estimated 24UKV were significantly different from the measured values in all the time point (all P < 0·05), except for the predicted values from Tanaka formula using morning, afternoon and evening spot urine. The proportions with relative differences over 40 % were 87·2%, 32·5% and 47·3 % for Kawasaki, Tanaka and Mage formulas, respectively. Misclassification rates were 91·5 % for Kawasaki, 44·4 % for Tanaka and 58·9 % for Mage formula at the individual level. Our findings showed that misclassification could occur on the individual level when using Kawasaki, Tanaka and Mage formulas to estimate 24UKV from spot urine in the child population.
Entités institutionnelles et attitudes mentales
Authors: Ouzilou Olivier
Published: September 2021

La thèse affirmant la dépendance mentale des entités institutionnelles est particulièrement débattue en ontologie sociale. L'une de ses implications est la position infaillibiliste selon laquelle l'existence des entités institutionnelles nécessite que certaines de leurs propriétés soient connues. Quelles sont ces propriétés ? Après avoir présenté la conception searlienne des entités institutionnelles et le type de dépendance mentale qu'elles manifestent, je circonscris le contenu de la position infaillibiliste. Je montre ensuite que ces propriétés sont les pouvoirs déontiques associés à ces entités et que l'attitude mentale vis-à-vis des pouvoirs déontiques doit prendre la forme d'un savoir pratique. Je montre enfin que cette interprétation est compatible avec l'existence d'au moins certaines entités institutionnelles naturalisées.
Inheritance Institutions and Landholding Inequality in Nineteenth-Century Germany: Evidence from Hesse-Cassel Villages and Towns
Authors: Wegge Simone A.
Published: September 2021

This paper considers the German principality of Hesse-Cassel in the 1850s, comparing inheritance institutions and landholding inequality for roughly a thousand mostly agricultural villages and towns. The principality lay between impartible northern Europe and the partible southwest. Inequality in landholding size is measured, showing an average Gini of 0.615 and substantial variation across communities. Places with relatively larger populations and ones that practiced impartible inheritance had mostly higher wealth inequality. The main result is that inheritance norms played a role in causing higher landholding inequality. Higher emigration rates in the impartible communities helped to alleviate landholding inequality.
Crowding and Tail Risk in Momentum Returns
Authors: Barroso Pedro , Edelen Roger M. , Karehnke Paul
Published: September 2021

Several theoretical studies suggest that coordination problems can cause arbitrageur crowding to push asset prices beyond fundamental value as investors feedback trade on each others’ demands. Using this logic, we develop a crowding model for momentum returns that predicts tail risk when arbitrageurs ignore feedback effects. However, crowding does not generate tail risk when arbitrageurs rationally condition on feedback. Consistent with rational demands, our empirical analysis generally finds a negative relation between crowding proxies constructed from institutional holdings and expected crash risk. Thus our analysis casts both theoretical and empirical doubt on crowding as a stand-alone source of tail risk.
Die Raumfrage als Schnittstelle von Theologie, Politik und Sozialgeschichte: Kulturwissenschaftliche Raumwende und neutestamentliche Exegese
Authors: Blumenthal Christian
Published: September 2021

The following article is part of an essay trilogy dealing with space and spatial concepts in the New Testament. In this trilogy, the spatial thematic approach is profiled as an interface for political, social-historical and theological–christological questions. The article illustrates how this interface function works in the basileia theme in Matthew and Luke.
Διακρίνειν als Leseaufgabe: Petrus und Kornelius zwischen ungeschriebenem Gesetz und unzuverlässiger Erzählung
Authors: Baltes Guido
Published: September 2021

The Cornelius incident (Acts 10.1–11.18) has traditionally been read as a narrative marking the abolition or transgression of Jewish food and purity laws in early Christianity. Strong halakic statements made by Peter himself and by some of his opponents in fact seem to claim that halakic norms have been abrogated or violated. The article suggests however that these statements should not be read as accurate descriptions of facts, but instead as examples of ‘unreliable narration’: using this technique, a narrator deliberately introduces misjudgements and distorted perceptions of reality on the side of his main character in order to temporarily mislead his readers, only to unmask the deception in the later course of his narrative. It turns out that Peter's refusal of food offered in a vision as well as his halakic judgements on the ‘impurity of gentiles’ and the prohibition of table fellowship are misconceptions, based not on biblical pretexts or Jewish halakah, but purely on social convention. The narrative therefore does not describe the abolition or transgression of halakic boundaries, but invites the reader to make a proper distinction between halakic boundaries (which are to be kept) and social conventions (which in this case need to be transgressed).
Molecular typing of Strongyloides stercoralis in Latin America, the clinical connection
Authors: Repetto Silvia Analía , Quarroz Braghini Juan , Risso Marikena Guadalupe , Argüello Lisana Belén , Batalla Estela Inés , Stecher Daniel Ricardo , Sierra Mariela Fernanda , Burgos Juan Miguel , Radisic Marcelo Víctor , González Cappa Stella Maris , Ruybal Paula
Published: September 2021

This study analysed Strongyloides stercoralis genetic variability based on a 404 bp region of the cox1 gene from Latin-American samples in a clinical context including epidemiological, diagnosis and follow-up variables. A prospective, descriptive, observational study was conducted to evaluate clinical and parasitological evolution after ivermectin treatment of 41 patients infected with S. stercoralis. Reactivation of the disease was defined both by clinical symptoms appearance and/or direct larvae detection 30 days after treatment or later. We described 10 haplotypes organized in two clusters. Most frequent variants were also described in the Asian continent in human (HP24 and HP93) and canine (HP24) samples. Clinical presentation (intestinal, severe, cutaneous and asymptomatic), immunological status and eosinophil count were not associated with specific haplotypes or clusters. Nevertheless, presence of cluster 1 haplotypes during diagnosis increased the risk of reactivation with an odds ratio (OR) of 7.51 [confidence interval (CI) 95% 1.38–44.29, P = 0.026]. In contrast, reactivation probability was 83 times lower if cluster 2 (I152V mutation) was detected (OR = 0.17, CI 95% 0.02–0.80, P = 0.02). This is the first analysis of S. stercoralis cox1 diversity in the clinical context. Determination of clusters during the diagnosis could facilitate and improve the design of follow-up strategies to prevent severe reactivations of this chronic disease.
Early childhood adversity and non-affective psychosis: a study of refugees and international adoptees in Sweden
Authors: Hjern Anders , Palacios Jesús , Vinnerljung Bo
Published: September 2021

Background

Previous Scandinavian studies have shown increased levels of psychiatric morbidity in young refugees and international adoptees with an origin outside Europe. This study investigated their risk of non-affective psychotic disorders (NAPD) and whether this risk is influenced by early childhood adversity, operationalised as age at adoption/residency, and/or gender.

Methods

Register study in Swedish national cohorts born 1972–1990 including 21 615 non-European international adoptees, 42 732 non-European refugees that settled in Sweden at age 0–14 years and 1 610 233 Swedish born. The study population was followed from age 18 to year 2016 for hospitalisations with a discharge diagnosis of NAPD. Hazard ratios (HRs) were calculated in gender stratified Cox regression models, adjusted for household income at age 17.

Results

The adjusted risks of NAPD were 2.33 [95% confidence interval (CI) 2.07–2.63] for the international adoptees and 1.92 (1.76–2.09) for the former child refugees, relative to the Swedish-born population. For the international adoptees there was a stepwise gradient for NAPD by age of adoption from adjusted HR 1.66 (1.29–2.03) when adopted during the first year of life to adjusted HR 4.56 (3.22–6.46) when adopted at ages 5–14 years, with a similar risk pattern in women and men. Age at residency did not influence the risk of NAPD in the refugees, but their male to female risk ratio was higher than in Swedish-born and the adoptees.

Conclusion

The risk pattern in the international adoptees gives support to a link between early childhood adversity and NAPD. Male gender increased the risk of NAPD more among the refugees.
Rescaling the global borderlands: Transperipheral projections from ‘the heart of the Amazon’
Authors: Windle Joel , Moita-Lopes Luiz Paulo
Published: September 2021

This article examines semiotic resignifications undertaken in ‘peripheral’ cultural production through an ethnographic analysis of the trajectory of the Amazonian artist, Jaloo. Jaloo occupies multiple positions of marginality in Brazilian society and artistic scenes, which he connects to other global peripheries in his performances, aesthetics, and self-narratives. Building on anthropological and sociolinguistic scholarship, we show how ‘peripheral’ status is managed by Jaloo in the context of a growing and politicised audience for outsider and alternative cultural production. We theorise Jaloo's negotiation of his relationship with audiences and the media as rescaling. Further, we argue that this rescaling entails the ordering of semiotic resources into a social imaginary that reconfigures peripheral territories and identities, which we consider in terms of a transperipheral chronotope. (Inequality, chronotopes, indexicality, race, coloniality, scales, periphery)
Optimal motion control of three-sphere based low-Reynolds number swimming microrobot
Authors: Nejat Pishkenari Hossein , Mohebalhojeh Matin
Published: September 2021

Microrobots with their promising applications are attracting a lot of attention currently. A microrobot with a triangular mechanism was previously proposed by scientists to overcome the motion limitations in a low-Reynolds number flow; however, the control of this swimmer for performing desired manoeuvres has not been studied yet. Here, we have proposed some strategies for controlling its position. Considering the constraints on arm lengths, we proposed an optimal controller based on quadratic programming. The simulation results demonstrate that the proposed optimal controller can steer the microrobot along the desired trajectory as well as minimize fluctuations of the actuators length.
EFFECT SIZE–DRIVEN SAMPLE-SIZE PLANNING, RANDOMIZATION, AND MULTISITE USE IN L2 INSTRUCTED VOCABULARY ACQUISITION EXPERIMENTAL SAMPLES
Authors: Vitta Joseph P. , Nicklin Christopher , McLean Stuart
Published: September 2021

In this focused methodological synthesis, the sample construction procedures of 110 second language (L2) instructed vocabulary interventions were assessed in relation to effect size–driven sample-size planning, randomization, and multisite usage. These three areas were investigated because inferential testing makes better generalizations when researchers consider them during the sample construction process. Only nine reports used effect sizes to plan or justify sample sizes in any fashion, with only one engaging in an a priori power procedure referencing vocabulary-centric effect sizes from previous research. Randomized assignment was observed in 56% of the reports while no report involved randomized sampling. Approximately 15% of the samples observed were constructed from multiple sites and none of these empirically investigated the effect of site clustering. Leveraging the synthesized findings, we conclude by offering suggestions for future L2 instructed vocabulary researchers to consider a priori effect size–driven sample planning processes, randomization, and multisite usage when constructing samples.
Doubly labelled water–calibration approach attenuates the underestimation of energy intake calculated from self-reported dietary assessment data in Japanese older adults
Authors: Watanabe Daiki , Yoshida Tsukasa , Yoshimura Eiichi , Nanri Hinako , Goto Chiho , Ishikawa-Takata Kazuko , Ebine Naoyuki , Fujita Hiroyuki , Kimura Misaka , Yamada Yosuke ,   Kyoto-Kameoka Study Group
Published: September 2021

Objective:

Self-reported energy intake (EI) estimation may incur systematic errors that could be attenuated through biomarker calibration. We aimed to confirm whether calibrated EI was comparable to total energy expenditure (TEE) measured using the doubly labelled water (DLW) technique.

Design:

Cross-sectional study.

Setting:

General older population from the Kyoto–Kameoka Study, Japan.

Participants:

This study included sub- and main cohorts of 72 and 8058 participants aged≥ 65 years, respectively. EI was evaluated using a validated FFQ, and calibrated EI was obtained using a previously developed equation based on the DLW method. TEE was considered representative of true EI and also measured using the DLW method. We used a Wilcoxon signed-rank test and correlation analysis to compare the uncalibrated and calibrated EI with TEE.

Results:

In the sub-cohort, the median TEE, uncalibrated EI and calibrated EI were 8559 kJ, 7088 kJ and 9269 kJ, respectively. The uncalibrated EI was significantly lower than the TEE (median difference = –1847 kJ; interquartile range (IQR): –2785 to –1096), although the calibrated EI was not (median difference = 463 kJ; IQR: –330 to 1541). The uncalibrated (r = 0·275) and calibrated EI (r = 0·517) significantly correlated with TEE. The reproducibility was higher for calibrated EI (interclass correlation coefficient (ICC) = 0·982) than for uncalibrated EI (ICC = 0·637). Similar findings were observed when stratifying the sample by sex. For medians, uncalibrated EI was lower (about 17 %) than calibrated EI in the main cohort.

Conclusions:

Biomarker calibration may improve the accuracy of self-reported dietary intake estimation.
Higher Probability of Occurrence of Hotter and Shorter Heat Waves Followed by Heavy Rainfall
Authors: You Jiewen , Wang Shuo
Published: September 2021

The consecutive heat wave and heavy rainfall (CHWHR) events, defined as the occurrence of heat waves followed by heavy rainfall, can cause more damages than individual extremes. Nevertheless, this type of compound event has not been diagnosed systematically. Here we examine the occurrence of CHWHR events and underlying characteristics. We find 22% of land areas experienced statistically significant CHWHR events within 7 days in China during 1981–2005, with an average 26% of heat waves being followed by heavy rainfall (vs. 10% expected by chance). More importantly, the shorter and hotter heat waves are more likely to be followed by heavy rainfall than other heat waves. This phenomenon is associated with atmospheric convection and moisture convergence. In addition, climate projection shows the CHWHR events will occur more frequently and abruptly in China throughout the 21st century, which contribute to the increased compound risk of back‐to‐back heat waves and flash floods.
The Effect of Mindfulness-Based Stress Reduction Among Parents of Children With Inflammatory Bowel Disease
Authors: Oseran Ilan , Shamir Raanan , Assa Amit
Published: September 2021

Objective:

Parents of children with inflammatory bowel disease (IBD) experience greater emotional distress, depression, and lack of emotional support, compared to parents of healthy children. We aimed to investigate the feasibility and efficacy of a mindfulness-based stress reduction (MBSR) group intervention for these parents.

Method:

In this single arm trial, 4 eight-week MBSR courses were offered to parents of children with IBD treated at the Schneider Children's Medical Center. Parents completed the Perceived Stress Scale (PSS) and the Profile of Mood States (POMS) at baseline, postintervention, and at 3 months follow-up.

Results:

Of 30 parents recruited, 26 (86%) attended at least 5 out of 9 classes (Mean parent’s age 43.3 ± 5.6 years, 19, 73%, females, patients' mean age of 12.1 ± 3.8, 73% Crohn's disease). Parents reported a 20% reduction in perceived stress ( p < .01); 56% reduction in tension ( p < .001); 36% reduction in fatigue ( p < .001); and 42% reduction in anger ( p < .05), following the intervention. None of these changes remained significant at 3 months follow-up.

Conclusions:

Our study suggests that MBSR appears to be a feasible and effective intervention to reduce stress and improve emotional functioning for parents of children with IBD, as was found immediately postintervention but not at follow-up. Strategies to sustain long-term benefit should be further investigated.

Implications for Impact Statement

This study showed that a mindfulness-based stress reduction (MBSR) group intervention for parents of children with IBD significantly reduced parents’ perceived stress, tension, fatigue, and anger. The effect of the intervention was short implying that a maintenance strategy may be considered. Attendance rates were high, indicating that MBSR is a feasible and effective intervention for these parents.
KRAS-related long noncoding RNAs in human cancers
Authors: Saliani Mahsa , Mirzaiebadizi Amin , Javadmanesh Ali , Siavoshi Akram , Ahmadian Mohammad Reza
Published: September 2021

KRAS is one of the most widely prevalent proto-oncogenes in human cancers. The constitutively active KRAS oncoprotein contributes to both tumor onset and cancer development by promoting cell proliferation and anchorage-independent growth in a MAPK pathway-dependent manner. The expression of microRNAs (miRNAs) and the KRAS oncogene are known to be dysregulated in various cancers, while long noncoding RNAs (lncRNAs) can act as regulators of the miRNAs targetingKRASoncogene in different cancers and have gradually become a focus of research in recent years. In this review article, we summarize recent advances in the research on lncRNAs that have sponging effects on KRAS-targeting miRNAs as crucial mediators of KRAS expression in different cell types and organs. A deeper understanding of lncRNA function in KRAS-driven cancers is of major fundamental importance and will provide a valuable clinical tool for the diagnosis, prognosis, and eventual treatment of cancers.
A novel mouse model of PMS2 founder mutation that causes mismatch repair defect due to aberrant splicing
Authors: Biswas Kajal , Couillard Martin , Cavallone Luca , Burkett Sandra , Stauffer Stacey , Martin Betty K. , Southon Eileen , Reid Susan , Plona Teri M. , Baugher Ryan N. , Mellott Stephanie D. , Pike Kristen M. , Albaugh Mary E. , Maedler-Kron Chelsea , Hamel Nancy , Tessarollo Lino , Marcus Victoria , Foulkes William D. , Sharan Shyam K.
Published: September 2021

Hereditary non-polyposis colorectal cancer, now known as Lynch syndrome (LS) is one of the most common cancer predisposition syndromes and is caused by germline pathogenic variants (GPVs) in DNA mismatch repair (MMR) genes. A common founder GPV in PMS2 in the Canadian Inuit population, NM_000535.5: c.2002A>G, leads to a benign missense (p.I668V) but also acts as a de novo splice site that creates a 5 bp deletion resulting in a truncated protein (p.I668*). Individuals homozygous for this GPV are predisposed to atypical constitutional MMR deficiency with a delayed onset of first primary malignancy. We have generated mice with an equivalent germline mutation (Pms2c.1993A>G) and demonstrate that it results in a splicing defect similar to those observed in humans. Homozygous mutant mice are viable like the Pms2 null mice. However, unlike the Pms2 null mice, these mutant mice are fertile, like humans homozygous for this variant. Furthermore, these mice exhibit a significant increase in microsatellite instability and intestinal adenomas on an Apc mutant background. Rectification of the splicing defect in human and murine fibroblasts using antisense morpholinos suggests that this novel mouse model can be valuable in evaluating the efficacy aimed at targeting the splicing defect in PMS2 that is highly prevalent among the Canadian Inuits.
Electronic Floquet gyro-liquid crystal
Authors: Esin Iliya , Gupta Gaurav Kumar , Berg Erez , Rudner Mark S. , Lindner Netanel H.
Published: September 2021

Floquet engineering uses coherent time-periodic drives to realize designer band structures on-demand, thus yielding a versatile approach for inducing a wide range of exotic quantum many-body phenomena. Here we show how this approach can be used to induce non-equilibrium correlated states with spontaneously broken symmetry in lightly doped semiconductors. In the presence of a resonant driving field, the system spontaneously develops quantum liquid crystalline order featuring strong anisotropy whose directionality rotates as a function of time. The phase transition occurs in the steady state of the system achieved due to the interplay between the coherent external drive, electron-electron interactions, and dissipative processes arising from the coupling to phonons and the electromagnetic environment. We obtain the phase diagram of the system using numerical calculations that match predictions obtained from a phenomenological treatment and discuss the conditions on the system and the external drive under which spontaneous symmetry breaking occurs. Our results demonstrate that coherent driving can be used to induce non-equilibrium quantum phases of matter with dynamical broken symmetry.
The concurrence of DNA methylation and demethylation is associated with transcription regulation
Authors: Shi Jiejun , Xu Jianfeng , Chen Yiling Elaine , Li Jason Sheng , Cui Ya , Shen Lanlan , Li Jingyi Jessica , Li Wei
Published: September 2021

The mammalian DNA methylome is formed by two antagonizing processes, methylation by DNA methyltransferases (DNMT) and demethylation by ten-eleven translocation (TET) dioxygenases. Although the dynamics of either methylation or demethylation have been intensively studied in the past decade, the direct effects of their interaction on gene expression remain elusive. Here, we quantify the concurrence of DNA methylation and demethylation by the percentage of unmethylated CpGs within a partially methylated read from bisulfite sequencing. After verifying ‘methylation concurrence’ by its strong association with the co-localization of DNMT and TET enzymes, we observe that methylation concurrence is strongly correlated with gene expression. Notably, elevated methylation concurrence in tumors is associated with the repression of 40~60% of tumor suppressor genes, which cannot be explained by promoter hypermethylation alone. Furthermore, methylation concurrence can be used to stratify large undermethylated regions with negligible differences in average methylation into two subgroups with distinct chromatin accessibility and gene regulation patterns. Together, methylation concurrence represents a unique methylation metric important for transcription regulation and is distinct from conventional metrics, such as average methylation and methylation variation.
Atomistic processes of surface-diffusion-induced abnormal softening in nanoscale metallic crystals
Authors: Wang Xiang , Zheng Sixue , Shinzato Shuhei , Fang Zhengwu , He Yang , Zhong Li , Wang Chongmin , Ogata Shigenobu , Mao Scott X.
Published: September 2021

Ultrahigh surface-to-volume ratio in nanoscale materials, could dramatically facilitate mass transport, leading to surface-mediated diffusion similar to Coble-type creep in polycrystalline materials. Unfortunately, the Coble creep is just a conceptual model, and the associated physical mechanisms of mass transport have never been revealed at atomic scale. Akin to the ambiguities in Coble creep, atomic surface diffusion in nanoscale crystals remains largely unclear, especially when mediating yielding and plastic flow. Here, by using in situ nanomechanical testing under high-resolution transmission electron microscope, we find that the diffusion-assisted dislocation nucleation induces the transition from a normal to an inverse Hall-Petch-like relation of the strength-size dependence and the surface-creep leads to the abnormal softening in flow stress with the reduction in size of nanoscale silver, contrary to the classical “alternating dislocation starvation” behavior in nanoscale platinum. This work provides insights into the atomic-scale mechanisms of diffusion-mediated deformation in nanoscale materials, and impact on the design for ultrasmall-sized nanomechanical devices.
Quantitative modelling of amino acid transport and homeostasis in mammalian cells
Authors: Gauthier-Coles Gregory , Vennitti Jade , Zhang Zhiduo , Comb William C. , Xing Shuran , Javed Kiran , Bröer Angelika , Bröer Stefan
Published: September 2021

Homeostasis is one of the fundamental concepts in physiology. Despite remarkable progress in our molecular understanding of amino acid transport, metabolism and signaling, it remains unclear by what mechanisms cytosolic amino acid concentrations are maintained. We propose that amino acid transporters are the primary determinants of intracellular amino acid levels. We show that a cell’s endowment with amino acid transporters can be deconvoluted experimentally and used this data to computationally simulate amino acid translocation across the plasma membrane. Transport simulation generates cytosolic amino acid concentrations that are close to those observed in vitro. Perturbations of the system are replicated in silico and can be applied to systems where only transcriptomic data are available. This work explains amino acid homeostasis at the systems-level, through a combination of secondary active transporters, functionally acting as loaders, harmonizers and controller transporters to generate a stable equilibrium of all amino acid concentrations.
Hydrogen radical-shuttle (HRS)-enabled photoredox synthesis of indanones via decarboxylative annulation
Authors: Yang Bo , Li Shi-Jun , Wang Yongdong , Lan Yu , Zhu Shifa
Published: September 2021

Hydrogen atom transfer (HAT) process is a powerful and effective strategy for activating C-H bonds followed by further functionalization. Intramolecular 1,n (n = 5 or 6)-HATs are common and frequently encountered in organic synthesis. However, intramolecular 1,n (n = 2 or 3)-HAT is very challenging due to slow kinetics. Compared to proton-shuttle process, which is well established for organic synthesis, hydrogen radical-shuttle (HRS) is unexplored. In this work, a HRS-enabled decarboxylative annulation of carbonyl compounds via photoredox catalysis for the synthesis of indanones is developed. This protocol features broad substrate scope, excellent functional group tolerance, internal hydrogen radical transfer, atom- and step-economy. Critical to the success of this process is the introduction of water, acting as both HRS and hydrogen source, which was demonstrated by mechanistic experiments and density functional theory (DFT) calculations. Importantly, this mechanistically distinctive HAT provides a complement to that of typical proton-shuttle-promoted, representing a breakthrough in hydrogen radical transfer, especially in the inherently challenging 1,2- or 1,3-HAT.
β-actin dependent chromatin remodeling mediates compartment level changes in 3D genome architecture
Authors: Mahmood Syed Raza , Xie Xin , Hosny El Said Nadine , Venit Tomas , Gunsalus Kristin C. , Percipalle Piergiorgio
Published: September 2021

β-actin is a crucial component of several chromatin remodeling complexes that control chromatin structure and accessibility. The mammalian Brahma-associated factor (BAF) is one such complex that plays essential roles in development and differentiation by regulating the chromatin state of critical genes and opposing the repressive activity of polycomb repressive complexes (PRCs). While previous work has shown that β-actin loss can lead to extensive changes in gene expression and heterochromatin organization, it is not known if changes in β-actin levels can directly influence chromatin remodeling activities of BAF and polycomb proteins. Here we conduct a comprehensive genomic analysis of β-actin knockout mouse embryonic fibroblasts (MEFs) using ATAC-Seq, HiC-seq, RNA-Seq and ChIP-Seq of various epigenetic marks. We demonstrate that β-actin levels can induce changes in chromatin structure by affecting the complex interplay between chromatin remodelers such as BAF/BRG1 and EZH2. Our results show that changes in β-actin levels and associated chromatin remodeling activities can not only impact local chromatin accessibility but also induce reversible changes in 3D genome architecture. Our findings reveal that β-actin-dependent chromatin remodeling plays a role in shaping the chromatin landscape and influences the regulation of genes involved in development and differentiation.
Directed evolution of prenylated FMN-dependent Fdc supports efficient in vivo isobutene production
Authors: Saaret Annica , Villiers Benoît , Stricher François , Anissimova Macha , Cadillon Mélodie , Spiess Reynard , Hay Sam , Leys David
Published: September 2021

Isobutene is a high value gaseous alkene used as fuel additive and a chemical building block. As an alternative to fossil fuel derived isobutene, we here develop a modified mevalonate pathway for the production of isobutene from glucose in vivo. The final step in the pathway consists of the decarboxylation of 3-methylcrotonic acid, catalysed by an evolved ferulic acid decarboxylase (Fdc) enzyme. Fdc belongs to the prFMN-dependent UbiD enzyme family that catalyses reversible decarboxylation of (hetero)aromatic acids or acrylic acids with extended conjugation. Following a screen of an Fdc library for inherent 3-methylcrotonic acid decarboxylase activity, directed evolution yields variants with up to an 80-fold increase in activity. Crystal structures of the evolved variants reveal that changes in the substrate binding pocket are responsible for increased selectivity. Solution and computational studies suggest that isobutene cycloelimination is rate limiting and strictly dependent on presence of the 3-methyl group.
Spectroscopic glimpses of the transition state of ATP hydrolysis trapped in a bacterial DnaB helicase
Authors: Malär Alexander A. , Wili Nino , Völker Laura A. , Kozlova Maria I. , Cadalbert Riccardo , Däpp Alexander , Weber Marco E. , Zehnder Johannes , Jeschke Gunnar , Eckert Hellmut , Böckmann Anja , Klose Daniel , Mulkidjanian Armen Y. , Meier Beat H. , Wiegand Thomas
Published: September 2021

The ATP hydrolysis transition state of motor proteins is a weakly populated protein state that can be stabilized and investigated by replacing ATP with chemical mimics. We present atomic-level structural and dynamic insights on a state created by ADP aluminum fluoride binding to the bacterial DnaB helicase from Helicobacter pylori. We determined the positioning of the metal ion cofactor within the active site using electron paramagnetic resonance, and identified the protein protons coordinating to the phosphate groups of ADP and DNA using proton-detected 31P,1H solid-state nuclear magnetic resonance spectroscopy at fast magic-angle spinning > 100 kHz, as well as temperature-dependent proton chemical-shift values to prove their engagements in hydrogen bonds. 19F and 27Al MAS NMR spectra reveal a highly mobile, fast-rotating aluminum fluoride unit pointing to the capture of a late ATP hydrolysis transition state in which the phosphoryl unit is already detached from the arginine and lysine fingers.
Single-cell transcriptomic analysis of bloodstream Trypanosoma brucei reconstructs cell cycle progression and developmental quorum sensing
Authors: Briggs Emma M. , Rojas Federico , McCulloch Richard , Matthews Keith R. , Otto Thomas D.
Published: September 2021

Developmental steps in the trypanosome life-cycle involve transition between replicative and non-replicative forms specialised for survival in, and transmission between, mammalian and tsetse fly hosts. Here, using oligopeptide-induced differentiation in vitro, we model the progressive development of replicative ‘slender’ to transmissible ‘stumpy’ bloodstream form Trypanosoma brucei and capture the transcriptomes of 8,599 parasites using single cell transcriptomics (scRNA-seq). Using this framework, we detail the relative order of biological events during asynchronous development, profile dynamic gene expression patterns and identify putative regulators. We additionally map the cell cycle of proliferating parasites and position stumpy cell-cycle exit at early G1 before progression to a distinct G0 state. A null mutant for one transiently elevated developmental regulator, ZC3H20 is further analysed by scRNA-seq, identifying its point of failure in the developmental atlas. This approach provides a paradigm for the dissection of differentiation events in parasites, relevant to diverse transitions in pathogen biology.
Boron-doped sodium layered oxide for reversible oxygen redox reaction in Na-ion battery cathodes
Authors: Guo Yu-Jie , Wang Peng-Fei , Niu Yu-Bin , Zhang Xu-Dong , Li Qinghao , Yu Xiqian , Fan Min , Chen Wan-Ping , Yu Yang , Liu Xiangfeng , Meng Qinghai , Xin Sen , Yin Ya-Xia , Guo Yu-Guo
Published: September 2021

Na-ion cathode materials operating at high voltage with a stable cycling behavior are needed to develop future high-energy Na-ion cells. However, the irreversible oxygen redox reaction at the high-voltage region in sodium layered cathode materials generates structural instability and poor capacity retention upon cycling. Here, we report a doping strategy by incorporating light-weight boron into the cathode active material lattice to decrease the irreversible oxygen oxidation at high voltages (i.e., >4.0 V vs. Na+/Na). The presence of covalent B–O bonds and the negative charges of the oxygen atoms ensures a robust ligand framework for the NaLi1/9Ni2/9Fe2/9Mn4/9O2 cathode material while mitigating the excessive oxidation of oxygen for charge compensation and avoiding irreversible structural changes during cell operation. The B-doped cathode material promotes reversible transition metal redox reaction enabling a room-temperature capacity of 160.5 mAh g−1 at 25 mA g−1 and capacity retention of 82.8% after 200 cycles at 250 mA g−1. A 71.28 mAh single-coated lab-scale Na-ion pouch cell comprising a pre-sodiated hard carbon-based anode and B-doped cathode material is also reported as proof of concept.
Ecological memory of recurrent drought modifies soil processes via changes in soil microbial community
Authors: Canarini Alberto , Schmidt Hannes , Fuchslueger Lucia , Martin Victoria , Herbold Craig W. , Zezula David , Gündler Philipp , Hasibeder Roland , Jecmenica Marina , Bahn Michael , Richter Andreas
Published: September 2021

Climate change is altering the frequency and severity of drought events. Recent evidence indicates that drought may produce legacy effects on soil microbial communities. However, it is unclear whether precedent drought events lead to ecological memory formation, i.e., the capacity of past events to influence current ecosystem response trajectories. Here, we utilize a long-term field experiment in a mountain grassland in central Austria with an experimental layout comparing 10 years of recurrent drought events to a single drought event and ambient conditions. We show that recurrent droughts increase the dissimilarity of microbial communities compared to control and single drought events, and enhance soil multifunctionality during drought (calculated via measurements of potential enzymatic activities, soil nutrients, microbial biomass stoichiometry and belowground net primary productivity). Our results indicate that soil microbial community composition changes in concert with its functioning, with consequences for soil processes. The formation of ecological memory in soil under recurrent drought may enhance the resilience of ecosystem functioning against future drought events.
Super fine cerium hydroxide abrasives for SiO2 film chemical mechanical planarization performing scratch free
Authors: Son Young-Hye , Jeong Gi-Ppeum , Kim Pil-Su , Han Man-Hyup , Hong Seong-Wan , Bae Jae-Young , Kim Sung-In , Park Jin-Hyung , Park Jea-Gun
Published: September 2021

Face-centered-cubic crystallized super-fine (~ 2 nm in size) wet-ceria-abrasives are synthesized using a novel wet precipitation process that comprises a Ce4+ precursor, C3H4N2 catalyst, and NaOH titrant for a synthesized termination process at temperature of at temperature of 25 °C. This process overcomes the limitations of chemical–mechanical-planarization (CMP)-induced scratches from conventional dry ceria abrasives with irregular surfaces or wet ceria abrasives with crystalline facets in nanoscale semiconductor devices. The chemical composition of super-fine wet ceria abrasives depends on the synthesis termination pH, that is, Ce(OH)4 abrasives at a pH of 4.0–5.0 and a mixture of CeO2 and Ce(OH)4 abrasives at a pH of 5.5–6.5. The Ce(OH)4 abrasives demonstrate better abrasive stability in the SiO2-film CMP slurry than the CeO2 abrasives and produce a minimum abrasive zeta potential (~ 12 mV) and a minimum secondary abrasive size (~ 130 nm) at the synthesis termination pH of 5.0. Additionally, the abrasive stability of the SiO2-film CMP slurry that includes super-fine wet ceria abrasives is notably sensitive to the CMP slurry pH; the best abrasive stability (i.e., a minimum secondary abrasive size of ~ 130 nm) is observed at a specific pH (6.0). As a result, a maximum SiO2-film polishing rate (~ 524 nm/min) is achieved at pH 6.0, and the surface is free of stick-and-slip type scratches.
Discontinuous phase transitions in the q-voter model with generalized anticonformity on random graphs
Authors: Abramiuk-Szurlej Angelika , Lipiecki Arkadiusz , Pawłowski Jakub , Sznajd-Weron Katarzyna
Published: September 2021

We study the binary q-voter model with generalized anticonformity on random Erdős–Rényi graphs. In such a model, two types of social responses, conformity and anticonformity, occur with complementary probabilities and the size of the source of influence $$q_c$$

q
c

in case of conformity is independent from the size of the source of influence $$q_a$$

q
a

in case of anticonformity. For $$q_c=q_a=q$$

q
c

=

q
a

=
q

the model reduces to the original q-voter model with anticonformity. Previously, such a generalized model was studied only on the complete graph, which corresponds to the mean-field approach. It was shown that it can display discontinuous phase transitions for $$q_c \ge q_a + \Delta q$$

q
c

≥

q
a

+
Δ
q

, where $$\Delta q=4$$

Δ
q
=
4

for $$q_a \le 3$$

q
a

≤
3

and $$\Delta q=3$$

Δ
q
=
3

for $$q_a>3$$

q
a

>
3

. In this paper, we pose the question if discontinuous phase transitions survive on random graphs with an average node degree $$\langle k\rangle \le 150$$

⟨
k
⟩
≤
150

observed empirically in social networks. Using the pair approximation, as well as Monte Carlo simulations, we show that discontinuous phase transitions indeed can survive, even for relatively small values of $$\langle k\rangle$$

⟨
k
⟩

. Moreover, we show that for $$q_a < q_c - 1$$

q
a

<

q
c

-
1

pair approximation results overlap the Monte Carlo ones. On the other hand, for $$q_a \ge q_c - 1$$

q
a

≥

q
c

-
1

pair approximation gives qualitatively wrong results indicating discontinuous phase transitions neither observed in the simulations nor within the mean-field approach. Finally, we report an intriguing result showing that the difference between the spinodals obtained within the pair approximation and the mean-field approach follows a power law with respect to $$\langle k\rangle$$

⟨
k
⟩

, as long as the pair approximation indicates correctly the type of the phase transition.
Modified N-linked glycosylation status predicts trafficking defective human Piezo1 channel mutations
Authors: Li Jinyuan Vero , Ng Chai-Ann , Cheng Delfine , Zhou Zijing , Yao Mingxi , Guo Yang , Yu Ze-Yan , Ramaswamy Yogambha , Ju Lining Arnold , Kuchel Philip W. , Feneley Michael P. , Fatkin Diane , Cox Charles D.
Published: September 2021

Mechanosensitive channels are integral membrane proteins that sense mechanical stimuli. Like most plasma membrane ion channel proteins they must pass through biosynthetic quality control in the endoplasmic reticulum that results in them reaching their destination at the plasma membrane. Here we show that N-linked glycosylation of two highly conserved asparagine residues in the ‘cap’ region of mechanosensitive Piezo1 channels are necessary for the mature protein to reach the plasma membrane. Both mutation of these asparagines (N2294Q/N2331Q) and treatment with an enzyme that hydrolyses N-linked oligosaccharides (PNGaseF) eliminates the fully glycosylated mature Piezo1 protein. The N-glycans in the cap are a pre-requisite for N-glycosylation in the ‘propeller’ regions, which are present in loops that are essential for mechanotransduction. Importantly, trafficking-defective Piezo1 variants linked to generalized lymphatic dysplasia and bicuspid aortic valve display reduced fully N-glycosylated Piezo1 protein. Thus the N-linked glycosylation status in vitro correlates with efficient membrane trafficking and will aid in determining the functional impact of Piezo1 variants of unknown significance.