bluuebunny/crossref_metadata_2025 huggingface dataset:
Compressed imaging with focused light
Authors: Pathak Biswajit , Booth Martin J , Turcotte Raphaël
Published: April 2022

Compressed sensing applied to optical microscopy enables imaging with a number of measurements below the Nyquist criterion. The illumination basis selected, often unstructured for randomness considerations, influences the performance of image reconstruction algorithms. Here, we show through modelling based on multimode fiber imaging that an illumination basis composed of a series of uniformly spaced foci provides improved robustness to noise, increased volumetric imaging performance, and greater resilience to external perturbation when compared to a speckle illumination basis. These observations have broad implications for computational super-resolution imaging, endo-microscopy, and post-processing of images acquired with any point-scanning imaging system.
1. The behavioural origins of CBT
Authors: McManus Freda
Published: April 2022

‘The behavioural origins of CBT’ explains how thoughts and feelings mediate between what happens to someone and their responses and reactions. Cognitive behaviour therapy (CBT) is a commonly used model of psychological therapy in both the UK and the USA. CBT grew out of theories about how people learn, such as classical and operant conditioning, and observational learning. There have been a number of seminal studies from the work of several psychologists who studied the cognitive processes that underlie how the world is perceived. The psychodynamic psychotherapy of Sigmund Freud was the dominant model of psychotherapy prior to CBT.
2. Putting the ‘C’ into CBT
Authors: McManus Freda
Published: April 2022

‘Putting the ‘C’ into CBT’ details the observance of Wolfgang Kohler of chimpanzees finding solutions to access a banana. Insight learning is what happens when one suddenly ‘sees’ the solution to a problem even when one is not trying to solve it. Edward Tolman found evidence of latent learning in rats as they learn their way around a maze. The chapter discusses vicarious reinforcement, which is learning that is influenced by observing behaviour of being rewarded or punished, such as public executions that act as a deterrent to others. The evolution and fusion of other cognitive and behavioural approaches led to the development of modern cognitive behaviour therapy.
Brain white matter hyperintensities-predicted age reflects neurovascular health in middle-to-old aged subjects
Authors: Huang Chu-Chung , Chou Kun-Hsien , Lee Wei-Ju , Yang Albert C , Tsai Shih-Jen , Chen Liang-Kung , Chung Chih-Ping , Lin Ching-Po
Published: April 2022

Background

age-related neurovascular structural and functional impairment is a major aetiology of dementia and stroke in older people. There is no single marker representative of neurovascular biological age yet.

Objective

this study aims to develop and validate a white matter hyperintensities (WMH)-based model for characterising individuals’ neurovascular biological age.

Methods

in this prospective single-site study, the WMH-based age-prediction model was constructed based on WMH volumes of 491 healthy participants (21–89 years). In the training dataset, the constructed linear-regression model with log-transformed WMH volumes showed well-balanced complexity and accuracy (root mean squared error, RMSE = 10.20 and mean absolute error, MAE = 7.76 years). This model of neurovascular age estimation was then applied to a middle-to-old aged testing dataset (n = 726, 50–92 years) as the testing dataset for external validation.

Results

the established age estimator also had comparable generalizability with the testing dataset (RMSE = 7.76 and MAE = 6.38 years). In the testing dataset, the WMH-predicted age difference was negatively associated with visual executive function. Individuals with older predicted-age for their chronological age had greater cardiovascular burden and cardiovascular disease risks than individuals with normal or delayed predicted age. These associations were independent of chronological age.

Conclusions

our model is easy to use in clinical practice that helps to evaluate WMH severity objective to chronological age. Current findings support our WMH-based age measurement to reflect neurovascular health and have potential diagnostic and prognostic value for clinical or research purposes in age-related neurovascular disorders.
Chromosome diversity in Dasypyrum villosum, an important genetic and trait resource for hexaploid wheat engineering
Authors: Wu Nan , He Ziming , Fang Jiaxin , Liu Xin , Shen Xia , Zhang Juan , Lei Yanhong , Xia Yating , He Huagang , Liu Wenxuan , Chu Chenggen , Wang Conglei , Qi Zengjun
Published: April 2022

Background and Aims

Dasypyrum villosum (2n = 2x = 14) harbours potentially beneficial genes for hexaploid and tetraploid wheat improvement. Highly diversified chromosome variation exists among and within accessions due to its open-pollination nature. The wheat–D. villosum T6VS·6AL translocation was widely used in breeding mainly because gene Pm21 in the 6VS segment conferred high and lasting powdery mildew resistance. However, the widespread use of this translocation may narrow the genetic base of wheat. A better solution is to utilize diversified D. villosum accessions as the genetic source for wheat breeding. Analysis of cytological and genetic polymorphisms among D. villosum accessions also provides genetic evolution information on the species. Using cytogenetic and molecular tools we analysed genetic polymorphisms among D. villosum accessions and developed consensus karyotypes to assist the introgression of beneficial genes from D. villosum into wheat.

Methods

A multiplex probe of repeats for FISH, GISH and molecular markers were used to detect chromosome polymorphisms among D. villosum accessions. Polymorphic signal block types, chromosome heterogeneity and heterozygosity, and chromosome polymorphic information content were used in genetic diversity analysis.

Key Results

Consensus karyotypes of D. villosum were developed, and the homoeologous statuses of individual D. villosum chromosomes relative to wheat were determined. Tandem repeat probes of pSc119.2, (GAA)10 and the AFA family produced high-resolution signals and not only showed different signal patterns in D. villosum chromosomes but also revealed the varied distribution of tandem repeats among chromosomes and accessions. A total of 106 polymorphic chromosomes were identified from 13 D. villosum accessions and high levels of chromosomal heterozygosity and heterogeneity were observed. A subset of 56 polymorphic chromosomes was transferred into durum wheat through wide crosses, and seven polymorphic chromosomes are described in two newly developed durum–D. villosum amphidiploids.

Conclusions

Consensus karyotypes of D. villosum and oligonucleotide FISH facilitated identification of polymorphic signal blocks and a high level of chromosomal heterozygosity and heterogeneity among D. villosum accessions, seen in newly developed amphiploids. The abundant genetic diversity of D. villosum and range of alleles, exploitable through interploid crosses, backcrosses and recombination (chromosome engineering), allow introduction of biotic and abiotic stress resistances into wheat, translating into increasing yield, end-use quality and crop sustainability.
Social Inference from Middle to Older Adulthood
Authors: Martin A K , Ceslis A , Robinson G A
Published: April 2022

Objective

Inferring the emotional state or the true meaning of another person’s utterance is a key aspect of social cognition and critical for successful social interactions. In this study, we assess age-related differences in emotion recognition and sincere and sarcastic social exchanges in the context of cognitive and demographic factors.

Method

One hundred and eighty-seven adults ranging from middle to older adulthood completed the Mini-SEA Emotion Recognition test and Part B of The Awareness of Social Inference Test – Short Form (TASIT-S). Fluid intelligence and executive abilities were also assessed. Sex differences and the relationship with education level were also investigated. Regression models were used to assess age-related differences controlling for baseline cognitive and demographic factors.

Results

Age was negatively associated with accuracy for inferring sincere social exchanges. No differences were identified for accuracy for inferring sarcastic exchanges. Likewise, no age differences were identified for emotion recognition (Mini-SEA). Fluid intelligence was associated with accuracy for inferring sincere exchanges, but this was independent of age-related effects. A female advantage was identified for emotion recognition.

Conclusion

Age is associated with difficulty in inferring sincere exchanges, which is not explained by fluid intelligence, verbal abstract reasoning, or auditory verbal attention. A female advantage in emotion recognition is consistent with findings reported in younger adults. Both age and sex should be considered in clinical assessments using the Mini-SEA and the TASIT-S.
Kernel-based hierarchical structural component models for pathway analysis
Authors: Hwangbo Suhyun , Lee Sungyoung , Lee Seungyeoun , Hwang Heungsun , Kim Inyoung , Park Taesung
Published: April 2022

Motivation

Pathway analyses have led to more insight into the underlying biological functions related to the phenotype of interest in various types of omics data. Pathway-based statistical approaches have been actively developed, but most of them do not consider correlations among pathways. Because it is well known that there are quite a few biomarkers that overlap between pathways, these approaches may provide misleading results. In addition, most pathway-based approaches tend to assume that biomarkers within a pathway have linear associations with the phenotype of interest, even though the relationships are more complex.

Results

To model complex effects including non-linear effects, we propose a new approach, Hierarchical structural CoMponent analysis using Kernel (HisCoM-Kernel). The proposed method models non-linear associations between biomarkers and phenotype by extending the kernel machine regression and analyzes entire pathways simultaneously by using the biomarker-pathway hierarchical structure. HisCoM-Kernel is a flexible model that can be applied to various omics data. It was successfully applied to three omics datasets generated by different technologies. Our simulation studies showed that HisCoM-Kernel provided higher statistical power than other existing pathway-based methods in all datasets. The application of HisCoM-Kernel to three types of omics dataset showed its superior performance compared to existing methods in identifying more biologically meaningful pathways, including those reported in previous studies.

Availability and implementation

The HisCoM-Kernel software is freely available at http://statgen.snu.ac.kr/software/HisCom-Kernel/. The RNA-seq data underlying this article are available at https://xena.ucsc.edu/, and the others will be shared on reasonable request to the corresponding author.

Supplementary information

Supplementary data are available at Bioinformatics online.
CnnPOGTP: a novel CNN-based predictor for identifying the optimal growth temperatures of prokaryotes using only genomick-mers distribution
Authors: Wang Shaojing , Li Guoqiang , Liao Zitong , Cao Yunke , Yun Yuan , Su Zhaoying , Tian Xuefeng , Gui Ziyu , Ma Ting
Published: April 2022

Temperature is very important for the growth of microorganisms. Appropriate temperature conditions can improve the possibility for isolation of currently uncultured microorganisms. The development of metagenomic binning technology had dramatically increased the availability of genomic information of prokaryotes, providing convenience to infer the optimal growth temperature (OGT). Here, we proposed CnnPOGTP, a predictor for OGTs of prokaryotes based on deep learning method using only k-mers distribution derived from genomic sequence. This method was annotation free, and the predicted OGT could be obtained by simply providing the genome sequence to the CnnPOGTP website.

Availability and implementation

http://www.orgene.net/CnnPOGTP.

Supplementary information

Supplementary data are available at Bioinformatics online.
TrkB-dependent EphrinA reverse signaling regulates callosal axon fasciculate growth downstream of Neurod2/6
Authors: Yan Kuo , Bormuth Ingo , Bormuth Olga , Tutukova Svetlana , Renner Ana , Bessa Paraskevi , Schaub Theres , Rosário Marta , Tarabykin Victor
Published: April 2022

Abnormal development of corpus callosum is relatively common and causes a broad spectrum of cognitive impairments in humans. We use acallosal Neurod2/6-deficient mice to study callosal axon guidance within the ipsilateral cerebral cortex. Initial callosal tracts form but fail to traverse the ipsilateral cingulum and are not attracted towards the midline in the absence of Neurod2/6. We show that the restoration of Ephrin-A4 (EfnA4) expression in the embryonic neocortex of Neurod2/6-deficient embryos is sufficient to partially rescue targeted callosal axon growth towards the midline. EfnA4 cannot directly mediate reverse signaling within outgrowing axons, but it forms co-receptor complexes with TrkB (Ntrk2). The ability of EfnA4 to rescue the guided growth of a subset of callosal axons in Neurod2/6-deficient mice is abolished by the co-expression of dominant negative TrkBK571N (kinase-dead) or TrkBY515F (SHC-binding deficient) variants, but not by TrkBY816F (PLCγ1-binding deficient). Additionally, EphA4 is repulsive to EfnA4-positive medially projecting axons in organotypic brain slice culture. Collectively, we suggest that EfnA4-mediated reverse signaling acts via TrkB-SHC and is required for ipsilateral callosal axon growth accuracy towards the midline downstream of Neurod family factors.
Complex forelimb movements and cortical topography evoked by intracortical microstimulation in male and female mice
Authors: Brown Andrew R , Mitra Shaarang , Teskey G Campbell , Boychuk Jeffery A
Published: April 2022

The motor cortex is crucial for the voluntary control of skilled movement in mammals and is topographically organized into representations of the body (motor maps). Intracortical microstimulation of the motor cortex with long-duration pulse trains (LD-ICMS; ~500 ms) evokes complex movements, occurring in multiple joints or axial muscles, with characteristic movement postures and cortical topography across a variety of mammalian species. Although the laboratory mouse is extensively used in basic and pre-clinical research, high-resolution motor maps elicited with electrical LD-ICMS in both sexes of the adult mouse has yet to be reported. To address this knowledge gap, we performed LD-ICMS of the forelimb motor cortex in both male (n = 10) and naturally cycling female (n = 8) C57/BL6J mice under light ketamine-xylazine anesthesia. Complex and simple movements were evoked from historically defined caudal (CFA) and rostral (RFA) forelimb areas. Four complex forelimb movements were identified consisting of Elevate, Advance, Dig, and Retract postures with characteristic movement sequences and endpoints. Furthermore, evoked complex forelimb movements and cortical topography in mice were organized within the CFA in a unique manner relative to a qualitative comparison with the rat.
Inducible apelin receptor knockdown reduces differentiation efficiency and contractility of hESC-derived cardiomyocytes
Authors: Macrae Robyn G C , Colzani Maria T , Williams Thomas L , Bayraktar Semih , Kuc Rhoda E , Pullinger Anna L , Bernard William G , Robinson Emma L , Davenport Emma E , Maguire Janet J , Sinha Sanjay , Davenport Anthony P
Published: April 2022

Aims

The apelin receptor, a G protein-coupled receptor, has emerged as a key regulator of cardiovascular development, physiology, and disease. However, there is a lack of suitable human in vitro models to investigate the apelinergic system in cardiovascular cell types. For the first time we have used human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and a novel inducible knockdown system to examine the role of the apelin receptor in both cardiomyocyte development and to determine the consequences of loss of apelin receptor function as a model of disease.

Methods and results

Expression of the apelin receptor and its ligands in hESCs and hESC-CMs was determined. hESCs carrying a tetracycline-inducible short hairpin RNA targeting the apelin receptor were generated using the sOPTiKD system. Phenotypic assays characterized the consequences of either apelin receptor knockdown before hESC-CM differentiation (early knockdown) or in 3D engineered heart tissues as a disease model (late knockdown). hESC-CMs expressed the apelin signalling system at a similar level to the adult heart. Early apelin receptor knockdown decreased cardiomyocyte differentiation efficiency and prolonged voltage sensing, associated with asynchronous contraction. Late apelin receptor knockdown had detrimental consequences on 3D engineered heart tissue contractile properties, decreasing contractility and increasing stiffness.

Conclusions

We have successfully knocked down the apelin receptor, using an inducible system, to demonstrate a key role in hESC-CM differentiation. Knockdown in 3D engineered heart tissues recapitulated the phenotype of apelin receptor down-regulation in a failing heart, providing a potential platform for modelling heart failure and testing novel therapeutic strategies.
Geophysical inversion and optimal transport
Authors: Sambridge Malcolm , Jackson Andrew , Valentine Andrew P
Published: April 2022

We propose a new approach to measuring the agreement between two oscillatory time-series, such as seismic waveforms, and demonstrate that it can be used effectively in inverse problems. Our approach is based on Optimal Transport theory and the Wasserstein distance, with a novel transformation of the time-series to ensure that necessary normalization and positivity conditions are met. Our measure is differentiable, and can readily be used within an optimization framework. We demonstrate performance with a variety of synthetic examples, including seismic source inversion, and observe substantially better convergence properties than achieved with conventional L2 misfits. We also briefly discuss the relationship between Optimal Transport and Bayesian inference.
Prevalence, incidence and years lived with disability due to polycystic ovary syndrome in 204 countries and territories, 1990–2019
Authors: Safiri Saeid , Noori Maryam , Nejadghaderi Seyed Aria , Karamzad Nahid , Carson-Chahhoud Kristin , Sullman Mark J M , Collins Gary S , Kolahi Ali-Asghar , Avery Jodie
Published: April 2022

STUDY QUESTION

What is the global, regional and national burden of polycystic ovary syndrome (PCOS), by age and socio-demographic index (SDI), over the period 1990–2019?

SUMMARY ANSWER

In 2019, the global age-standardized point prevalence, incidence and years lived with disability (YLD) of PCOS were 30.4, 29.5 and 29.9 per 100 000 population, respectively.

WHAT IS KNOWN ALREADY

Data from the Global Burden of Disease (GBD) study 2017 showed that the global age-standardized PCOS incidence rate increased 1.45% over the period 1990–2017.

STUDY DESIGN, SIZE, DURATION

A systematic analysis of the PCOS prevalence, incidence and YLDs across 204 countries and territories was performed.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Data on the point prevalence, annual incidence and YLDs due to PCOS were retrieved from the GBD study 2019 for 204 countries and territories from 1990 to 2019. The counts and age-standardized rates (per 100 000) are presented, along with their corresponding 95% uncertainty intervals (UIs).

MAIN RESULTS AND THE ROLE OF CHANCE

In 2019, the global age-standardized point prevalence and annual incidence rates for PCOS were 1677.8 (95% UI: 1166.0 to 2192.4) and 59.8 (95% UI: 41.7 to 78.9) per 100 000, which represents a 30.4% and 29.5% increase since 1990, respectively. Moreover, the global age-standardized YLD rate in 2019 was 14.7 (6.3–29.5), an increase of 29.9% since 1990. In 2019, Italy (7897.0), Japan (6298.7) and New Zealand (5419.1) had the highest estimated age-standardized point prevalences of PCOS. Globally, the number of prevalent cases and the point prevalence of PCOS peaked in the 25–29 years and 40–44 years age groups, respectively. Positive associations were found between the burden of PCOS and the SDI at the regional and national levels.

LIMITATIONS, REASONS FOR CAUTION

Variations in how PCOS was defined is a major limitation that prevents valid comparisons between different regions.

WIDER IMPLICATIONS OF THE FINDINGS

Globally, the burden of PCOS has increased at an alarming rate, making it a major public health concern. Increasing public awareness about this common condition, improving management options and increasing support to reduce factors which lead to further complications, need to be public health priorities.

STUDY FUNDING/COMPETING INTEREST(S)

The Bill and Melinda Gates Foundation, who were not involved in any way in the preparation of this manuscript, funded the GBD study. The Shahid Beheshti University of Medical Sciences, Tehran, Iran (Grant No. 28709) also supported the present report. The authors declare no competing interests.

TRIAL REGISTRATION NUMBER

N/A.
Sums of Powers of Binomials, Their Apéry Limits, and Franel’s Suspicions
Authors: Straub Armin , Zudilin Wadim
Published: April 2022

We explicitly determine the Apéry limits for the sums of powers of binomial coefficients. As an application, we prove a weak version of Franel’s conjecture on the order of the recurrences for these sequences. Namely, we prove the conjectured minimal order under the assumption that such a recurrence can be obtained via creative telescoping.
CRISPR-Cas in Diagnostics and Therapy of Infectious Diseases
Authors: Gleerup Jens Lind , Mogensen Trine H
Published: April 2022

Infectious diseases are a major threat to the global health. The rise in antimicrobial-resistant organisms, incurable chronic infections, and an increasing demand for rapid accurate diagnostics have prompted researchers to experiment with new approaches. Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) is a naturally occurring adaptive immune system in bacteria that has been developed as a tool for performing genomic alterations in any genome of interest, including humans and microbes. Accordingly, several studies have been conducted to investigate how the technology can be utilized in infectious diseases to improve diagnostics, disrupt antimicrobial resistance, and cure chronic infections. This review provides an overview of the CRISPR-Cas system and how it has been applied in studies on infectious diseases. The review also investigates the current challenges of the technology and the improvements that are needed for the platform to be adopted for clinical use in patients.
HIV-1 pretreatment drug resistance in vertically infected children is associated with poor virological response to protease inhibitor (PI)-based first-line antiretroviral therapy (ART): results from a cohort study in Argentina
Authors: Rozenszajn Mijael , Arazi-Caillaud Solange , Taicz Moira , Bologna Rosa , Mangano Andrea , Aulicino Paula C
Published: April 2022

Background

Increasing evidence from adult cohorts suggests an important role of HIV-1 pretreatment drug resistance (PDR) in ART failure, in spite of treatment being fully active according to baseline genotyping tests. Whether this is also true for children is unknown.

Methods

Virological and immunological parameters were longitudinally assessed in a group of 39 HIV-1 vertically infected children starting first-line lopinavir/ritonavir-based ART at a median of 5.0 months (IQR = 3.0–9.0). Evolution of viral load (VL) over time was compared between children with and without baseline PDR, as defined by the WHO mutation list.

Results

Resistance-associated mutations (RAMs) in the HIV-1 pol gene were present in nine HIV-1-infected children (23%) before initiation of first-line ART (PDR group). Of them, six carried RAMs associated with NNRTIs (NNRTI-PDR subgroup). At 4–8 weeks after ART initiation, the proportion of children achieving ≥1 log VL reduction was 87% for the no-PDR group versus 33% and 16.7% for the PDR group and the NNRTI-PDR subgroup, respectively. During follow-up, children with no PDR reached virological suppression almost four times faster than children with PDR or NNRTI-PDR [no-PDR = 631 days and PDR = 2134 days (P = 0.1249) and NNRTI-PDR = 2134 days (P = 0.0447)]. CD4 T cells remained similar between the study groups over time.

Conclusions

HIV-1 baseline genotyping at diagnosis in vertically infected children is important for improved personalized medicine. While the mechanism is unclear, cases with PDR (particularly to NNRTIs) require closer monitoring of their first-line ART regimens in order to avoid early virological failures and prevent further accumulation of resistance.
Variations in clinical manifestations and outcomes of penetrating ocular injuries with intraocular foreign bodies: a case series
Authors: Adriono Gitalisa A , Agustiawan Referano , Fibrian Kartika C , Ardiani Lily S , Irawati Yunia
Published: April 2022

Intraocular foreign bodies (IOFBs) are the most common emergency cases in ophthalmology causing severe visual impairment to blindness. We present nine male patients with IOFBs, aged 28–64 years old, which displayed a wide spectrum of findings. Based on IOFB location, four cases were intravitreal, two were intraretinal, two were intralenticular and one was intracorneal. The most common material was metal, from hammering projectiles (six patients). The injuries mainly occurred at workplace (five patients). All IOFBs were successfully extracted. Initial visual acuity (VA) ranged from light perception to 20/32; six patients had better final VA, up to 20/20. A wide range of ocular manifestations is associated with IOFBs. Removing retained IOFB procedure is dependent on location, nature, lens opacity and vitreoretinal involvement. Meticulous ocular examination and imaging modality are vital to identify the IOFB presence. Various visual outcomes depend on zone involvement, IOFB size and level of difficulties of surgery.
High-throughput phenotyping of physiological traits for wheat resilience to high temperature and drought stress
Authors: Correia Pedro M P , Cairo Westergaard Jesper , Bernardes da Silva Anabela , Roitsch Thomas , Carmo-Silva Elizabete , Marques da Silva Jorge
Published: April 2022

Interannual and local fluctuations in wheat crop yield are mostly explained by abiotic constraints. Heatwaves and drought, which are among the top stressors, commonly co-occur, and their frequency is increasing with global climate change. High-throughput methods were optimized to phenotype wheat plants under controlled water deficit and high temperature, with the aim to identify phenotypic traits conferring adaptative stress responses. Wheat plants of 10 genotypes were grown in a fully automated plant facility under 25/18 °C day/night for 30 d, and then the temperature was increased for 7 d (38/31 °C day/night) while maintaining half of the plants well irrigated and half at 30% field capacity. Thermal and multispectral images and pot weights were registered twice daily. At the end of the experiment, key metabolites and enzyme activities from carbohydrate and antioxidant metabolism were quantified. Regression machine learning models were successfully established to predict plant biomass using image-extracted parameters. Evapotranspiration traits expressed significant genotype–environment interactions (G×E) when acclimatization to stress was continuously monitored. Consequently, transpiration efficiency was essential to maintain the balance between water-saving strategies and biomass production in wheat under water deficit and high temperature. Stress tolerance included changes in carbohydrate metabolism, particularly in the sucrolytic and glycolytic pathways, and in antioxidant metabolism. The observed genetic differences in sensitivity to high temperature and water deficit can be exploited in breeding programmes to improve wheat resilience to climate change.
An analysis of the Word Adjacency Network method—Part 1—The evidence of its unsoundness
Authors: Rizvi Pervez
Published: April 2022

A new mathematical method for authorship attribution, known as the Word Adjacency Network method, has emerged and its inventors have claimed a high success rate with it. They have announced that their method has shown that Christopher Marlowe wrote some scenes in the Henry VI trilogy of plays, an attribution which has made newspaper headlines. This first part of a two-part paper replicates the method’s success in attributing complete plays but demonstrates that it cannot be relied on to attribute individual scenes correctly, particularly where Marlowe is a candidate author. It shows by examining the method’s calculations that its unreliability is due to its mass exclusion of relevant evidence, that exclusion being necessitated by its use of a mathematical formula which can now be seen to be unsuited to the texts of early modern plays.
Fermi bubbles: the collimated outburst needed to explain forward-shock edges
Authors: Mondal Santanu , Keshet Uri , Sarkar Kartick C , Gurwich Ilya
Published: April 2022

The bipolar, non-thermal, high-latitude lobes known as the Fermi bubbles (FBs) are thought to originate from a massive energy release near the Galactic Centre (GC). We constrain the FB engine and the circumgalactic medium (CGM) by analytically and numerically modelling the FB edges as strong forward shocks, as inferred from recent observations. A non-directed energy release produces shocks too spherical to account for observations even for a maximally massive Galactic disc, critical CGM rotation, or injection effectively offset from the GC. In contrast, collimated injection nearly perpendicular to the disc can account for observations in both ballistic (free expansion) and slowdown regimes, as we show using a simple stratified evolution model verified by hydrodynamic simulations. FBs still in their ballistic regime require injection (at z ≃ 100 pc heights in our model) with a half-opening angle θ ≃ 4°, a normalized velocity β−2 ≡ v/(0.01c) ≳ 0.4, and an energy $E\gtrsim 2\beta _{-2}^2\times 10^{55}$ erg, launched $\mathbb {T}\simeq 3.3\beta _{-2}^{-1}$ Myr ago, showing a distinctive low-pressure region behind the bubble head. Slowing-down (mass accumulated) FBs require a faster injection, a thinner jet, a smaller E/(β−2θ)2, and a comparable $\mathbb {T}$, and follow a ballistic stage that must reach a height zs ≳ 5 kpc.
RSAT 2022: regulatory sequence analysis tools
Authors: Santana-Garcia Walter , Castro-Mondragon Jaime A , Padilla-Gálvez Mónica , Nguyen Nga Thi Thuy , Elizondo-Salas Ana , Ksouri Najla , Gerbes François , Thieffry Denis , Vincens Pierre , Contreras-Moreira Bruno , van Helden Jacques , Thomas-Chollier Morgane , Medina-Rivera Alejandra
Published: April 2022

RSAT (Regulatory Sequence Analysis Tools) enables the detection and the analysis of cis-regulatory elements in genomic sequences. This software suite performs (i) de novo motif discovery (including from genome-wide datasets like ChIP-seq/ATAC-seq) (ii) genomic sequences scanning with known motifs, (iii) motif analysis (quality assessment, comparisons and clustering), (iv) analysis of regulatory variations and (v) comparative genomics. RSAT comprises 50 tools. Six public Web servers (including a teaching server) are offered to meet the needs of different biological communities. RSAT philosophy and originality are: (i) a multi-modal access depending on the user needs, through web forms, command-line for local installation and programmatic web services, (ii) a support for virtually any genome (animals, bacteria, plants, totalizing over 10 000 genomes directly accessible). Since the 2018 NAR Web Software Issue, we have developed a large REST API, extended the support for additional genomes and external motif collections, enhanced some tools and Web forms, and developed a novel tool that builds or refine gene regulatory networks using motif scanning (network-interactions). The RSAT website provides extensive documentation, tutorials and published protocols. RSAT code is under open-source license and now hosted in GitHub. RSAT is available at http://www.rsat.eu/.
A programmable pAgo nuclease with RNA target preference from the psychrotolerant bacterium Mucilaginibacter paludis
Authors: Li Wenqiang , Liu Yang , He Ruyi , Wang Longyu , Wang Yaping , Zeng Wanting , Zhang Zhiwei , Wang Fei , Ma Lixin
Published: April 2022

Argonaute (Ago) proteins are programmable nucleases found in eukaryotes and prokaryotes. Prokaryotic Agos (pAgos) share a high degree of structural homology with eukaryotic Agos (eAgos), and eAgos originate from pAgos. Although eAgos exclusively cleave RNA targets, most characterized pAgos cleave DNA targets. This study characterized a novel pAgo, MbpAgo, from the psychrotolerant bacterium Mucilaginibacter paludis which prefers to cleave RNA targets rather than DNA targets. Compared to previously studied Agos, MbpAgo can utilize both 5′phosphorylated(5′P) and 5′hydroxylated(5′OH) DNA guides (gDNAs) to efficiently cleave RNA targets at the canonical cleavage site if the guide is between 15 and 17 nt long. Furthermore, MbpAgo is active at a wide range of temperatures (4–65°C) and displays no obvious preference for the 5′-nucleotide of a guide. Single-nucleotide and most dinucleotide mismatches have no or little effects on cleavage efficiency, except for dinucleotide mismatches at positions 11–13 that dramatically reduce target cleavage. MbpAgo can efficiently cleave highly structured RNA targets using both 5′P and 5′OH gDNAs in the presence of Mg2+ or Mn2+. The biochemical characterization of MbpAgo paves the way for its use in RNA manipulations such as nucleic acid detection and clearance of RNA viruses.
Kidney outcomes with finerenone: an analysis from the FIGARO-DKD study
Authors: Ruilope Luis M , Pitt Bertram , Anker Stefan D , Rossing Peter , Kovesdy Csaba P , Pecoits-Filho Roberto , Pergola Pablo , Joseph Amer , Lage Andrea , Mentenich Nicole , Scheerer Markus F , Bakris George L
Published: April 2022

Background

In FIGARO-DKD, finerenone reduced the risk of cardiovascular events in patients with type 2 diabetes (T2D) and stage 1–4 chronic kidney disease (CKD). In FIDELIO-DKD, finerenone improved kidney and cardiovascular outcomes in patients with advanced CKD. This analysis further explores kidney outcomes in FIGARO-DKD.

Methods

FIGARO-DKD (NCT02545049) included patients with urine albumin-to-creatinine ratio (UACR) 30–<300 mg/g and estimated glomerular filtration rate (eGFR) 25–90 mL/min/1.73 m2 or UACR 300–5000 mg/g and eGFR ≥60 mL/min/1.73 m2. Outcomes included two composite kidney endpoints, a composite of ≥40% decrease in eGFR from baseline sustained over ≥4 weeks, kidney failure or renal death, and a composite of ≥57% decrease in eGFR from baseline sustained over ≥4 weeks, kidney failure or renal death. Changes in albuminuria and eGFR slope were also analyzed. Kidney and CV outcomes were evaluated by baseline UACR.

Results

A lower incidence rate for the eGFR ≥40% kidney composite endpoint was observed with finerenone compared with placebo, but the between-group difference was not significant [hazard ratio (HR) = 0.87; 95% confidence interval (CI): 0.76–1.01; P = .069]. A greater treatment effect was observed on the eGFR ≥57% kidney composite endpoint (HR = 0.77; 95% CI: 0.60–0.99; P = 0.041) with a 36% relative risk reduction for end-stage kidney disease. A larger magnitude of effect on kidney outcomes was observed with finerenone versus placebo for patients with severely increased albuminuria than with moderately increased albuminuria. Improvements in UACR, eGFR slope and cardiovascular risk were evident in both subgroups with finerenone.

Conclusions

The present analyses suggest that finerenone protects against kidney disease progression and cardiovascular events in patients with T2D and early- or late-stage CKD.
Unprecedented strong and reversible atomic orbital hybridization enables a highly stable Li–S battery
Authors: Yan Min , Dong Wenda , Liu Fu , Chen Lihua , Hasan Tawfique , Li Yu , Su Bao-Lian
Published: April 2022

The shuttle effect and excessive volume change of the sulfur cathode severely impede the industrial implementation of Li–S batteries. It is still highly challenging to find an efficient way to suppress the shuttle effect and volume expansion. Here, we report, for the first time, an innovative atomic orbital hybridization concept to construct the hierarchical hollow sandwiched sulfur nanospheres with double-polyaniline layers as the cathode material for large-scale high-performance Li–S batteries. This hierarchically 3D, cross-linked and stable sulfur–polyaniline backbone with interconnected disulfide bonds provides a new type and strong intrinsic chemical confinement of sulfur owing to the atomic orbital hybridization of Li 2s, S 3p, C 2p and N 2p. Crucially, such atomic orbital hybridization of sulfur sandwiched in the double sulfur–polyaniline network is highly reversible during the discharge/charge process and can very efficiently suppress the shuttle effect and volume expansion, contributing to a very high capacity of 1142 mAh g–1 and an excellent stabilized capacity of 886 mAh g–1 at 0.2 C after 500 cycles with a suppressed volume expansion and an unprecedented electrode integrity. This innovative atomic orbital hybridization concept can be extended to the preparation of other electrode materials to eliminate the shuttle effect and volume expansion in battery technologies. The present work also provides a commercially viable and up-scalable cathode material based on this strong and highly reversible atomic orbital hybridation for large-scale high-performance Li–S batteries.
Adjacencies and Its Negations
Authors: Cimini Amy
Published: April 2022

“How can worlds of sound be joined?” While Amacher developed this question in realized and unrealized concert music during the mid-1960s, it also conjoined spectral and spatial ways of listening in her inaugural broadcast and environmental projects, City-Links WBFO, Buffalo, and In City, Buffalo 1967 on much different historical and material terrain. A close look at conceptual and notational strategies in Amacher’s electroacoustic percussion work Adjacencies illuminates her musical thought at an early stage and reveals how spectral listening could function as meeting place within which sound and ongoing life exchange intensities elsewhere. Critical comparisons with Karlheinz Stockhausen’s Mikrophonie I (1964) and Anthony Braxton’s Composition No. 9 for Amplified Shoveller Quartet (1969) elaborate how musical forms and experiences amid resonant metals, dramaturgy, and promissory grammar can work in concert or in conflict with historical spaces of biopolitics. Following Adjacencies’ archival traces across the radio broadcast City-Links and festival-like In City moves its connective ways of listening into concrete changes amid so-called redevelopment in urban history and policy debates, entwining social histories and media aesthetics that will inform Amacher’s long-distance projects in the decade to follow.
Explosion
Authors: Jin Kim Helen
Published: April 2022

Graham’s largest “crusade” was just one massive revival in a series of transpacific “explosions.” Explo ’72 and Explo ’74—or, Holy Spirit “explosions”—hosted by Campus Crusade were massive revivals respectively in Texas and Seoul. South Korean Protestants made a powerful declaration challenging US exceptionalism, imagining South Korea as the “new emerging Christian kingdom.” Indeed, in the years leading up to Reagan’s rise, South Koreans, in a race for revival, challenged US evangelical empire by prompting Americans to recenter Christian power from the West to the East. By the 1980 World Evangelization Crusade, Joon Gon Kim argued for a “Korean-modeled and Korean-led missionary movement,” making the “world and all people become our working unit.” South Koreans’ faith in individual conversions alone as a means for social change, however, led them to forge an unholy alliance with authoritarian Park Chung-hee. These networks ultimately connected South Korean authoritarianism with US political conservatism, establishing a transpacific Christian Right.
Sex-Specific Workplace Discrimination
Authors: Vodanovich Stephen J. , Rupp Deborah E.
Published: April 2022

This chapter discusses various forms of sex discrimination. As mentioned in Chapter 5, the late addition of “sex” as a protected group into Title VII led to the slow development of protections for women in the workplace. The chapter begins with coverage of the Equal Pay Act, which was passed in 1963, a year before Title VII of the Civil Rights Act. Despite efforts to guarantee that the two Acts offered the same legal safeguards, this has not succeeded as planned. Next, the authors cover the Pregnancy Discrimination Act (PDA). The PDA was introduced when Title VII was amended in 1978 to cover numerous negative employment decisions (e.g., failure to hire, termination) based on pregnancy. Following discussion of the PDA is a summary of the Family and Medical Leave Act, which guaranteed three months of unpaid leave and was passed after several years of debate and compromise. A section on dress and appearance requirements is presented, followed by an analysis of LGBTQ+ issues in employment. A focus of this last section involves a discussion of the meaning of “sex” within Title VII.
Retaliation
Authors: Vodanovich Stephen J. , Rupp Deborah E.
Published: April 2022

This chapter addresses the most common type of suit filed with the Equal Employment Opportunity Commission (EEOC): that of alleged workplace retaliation. The authors discuss the type of activities that are protected from retaliation, along with relevant court cases. The authors also review many court decisions that relate to the determination of what constitutes a “material adverse action” and the criteria for establishing a causal connection between engaging in a protected activity and the alleged retaliatory behavior taken by an organization. Another section summarizes who is protected from workplace retaliation, including so-called third-party cases. Finally, the authors provide a tabular summary of important retaliation cases, supplemental readings, recommended best practices, and representative retaliation settlements with the EEOC.
Political Centrality of ‘Capital’ Cities
Authors: Prasad Purendra
Published: April 2022

In this phase of neoliberalization, cities are witnessing large-scale transformation under the influence of expanding capital and new technologies. Despite growing inequalities and segregations, there has been renewed interest over the last decade or so in building new cities variously labelled ‘smart’, ‘green’, or ‘integrated’. This chapter attempts to explain how ‘state’ has become more prominent in shaping the conditions for capital accumulation and circulation, especially in leveraging its control over land for certain political interests. Taking ideas from Henri Lefebvre, David Harvey, and Neil Brenner, the chapter elaborates on rescaling strategies, and the way a capital city has become the critical place where one could see how physical space, political power, and the logic of accumulation play out in the neoliberal context. The purpose in analysing three cities is to explain the underlying forces that have been contributing to the current forms of capitalist urbanization.
The Remaking of the Choreographer
Authors: Meglin Joellen A.
Published: April 2022

The turn that Page took away from ballet Americana and toward European opera with her “opera-into-ballet” La Revanche (Revenge, 1951) was a pragmatic and strategic one, related to postwar politics, anti-American sentiment in French cultural circles, and indirectly the cosmopolitan climate of the Marshall Plan for European recovery. She and Fisher understood that a political as well as an artistic choreography was required for their cosmopolitan project. With her adaptation of Giuseppe Verdi’s 1853 opera, Il Trovatore, Page turned to European Romanticism and timeless themes of obsession, revenge, and compassion, appealing to a sense of enduring European legacies and traditions. Music collaborator Isaac Van Grove’s view of opera’s kinesthetic roots in popular dance forms and Page’s own lived experience of choreographing countless operas in Chicago led to a theory of “re-creation” in which the body “sang” the story. She set Revenge on Boris Kochno’s newly resurrected Ballets des Champs-Élysées—a company the very spirit of which was considered to be French. Page/Fisher, as a result of his recent legal successes, were able to play the role of “angels” and help the financially floundering company. For the ballet’s design, they employed Spanish visual artist Antoni Clavé, whose bold, avant-garde sets for Roland Petit’s Carmen had catapulted him to fame. Revenge was a triumph largely because of Page’s effective encapsulation of the narrative, her dramatic rendering of the characters, and Clavé’s striking designs. The ballet succeeded in solidifying her status as a cosmopolitan choreographer in the international ballet world.
Introduction
Authors: Schuldberg David , Richards Ruth , Guisinger Shan
Published: April 2022

This introduction charts out the topics to come in the book, describing the advantages and indeed the necessity of nonlinear dynamical systems (NDS) approaches to knowledge. It argues that a paradigm shift is occurring in the social sciences, one that is especially vital for the individual and societal dilemmas we are experiencing today. The editors provide preliminary examples and explanations of chaos, dynamics, and nonlinearity. The introduction lays out our first approach to the book’s six organizing themes and makes suggestions about how readers with varying levels of exposure to NDS can approach the rest of the book, discusses the volume’s structure and how to use the comments from the editors, and finally summarizes the chapters.
Creativity, Chaos, Complexity, and Healthy Change
Authors: Richards Ruth
Published: April 2022

This chapter uses the “four Ps of creativity” (product, process, person, and press of the environment) as a frame to explore ways chaos and complexity help illuminate creative phenomena. For many, “product” (or outcome) is the sole concern. Yet one may also “turn the camera around” to include creator and environment. Four subtopics to consider: (a) the Aha! moment of insight and sudden bifurcations; (b) ongoing creative functioning, involving different person, process, and press variables in delicate nonlinear balance (including personal traits and issues of the edge of chaos); (c) states of consciousness that may favor creativity, to which one might learn to “tune in” (along with issues of conscious and unconscious factors and “normalcy”); and (d) fractals, or “the fingerprints of chaos,” in creative product and in natural phenomena that influence us, and potentially involved as part of creative process, as in fractal organization of memory. Included are separatrices, or as-yet uncommitted boundaries between separate solution areas (or basins of attraction) in mind. Might one thereby learn yet more about origins of creative insight?