bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning-aided multidimensional phenotyping of Parkinson’s disease patient stem cell-derived midbrain dopaminergic neurons
Authors: Vuidel Aurore , Cousin Loïc , Weykopf Beatrice , Haupt Simone , Hanifehlou Zahra , Wiest-Daesslé Nicolas , Segschneider Michaela , Peitz Michael , Ogier Arnaud , Brino Laurent , Brüstle Oliver , Sommer Peter , Wilbertz Johannes H. 
Published: March 2022

SummaryCombining multiple Parkinson’s disease (PD) relevant cellular phenotypes might increase the accuracy of midbrain dopaminergic (mDA) in vitro models. We differentiated patient-derived induced pluripotent stem cells (iPSCs) with a LRRK2 G2019S mutation, isogenic control and genetically unrelated iPSCs into mDA neurons. Using automated fluorescence microscopy in 384-well plate format, we identified elevated levels of α-synuclein and Serine 129 phosphorylation (pS129), reduced dendritic complexity, and mitochondrial dysfunction. Next, we measured additional image-based phenotypes and used machine learning (ML) to accurately classify mDA neurons according to their genotype. Additionally, we show that chemical compound treatments, targeting LRRK2 kinase activity or α-synuclein levels, are detectable when using ML classification based on multiple image-based phenotypes. We validated our approach using a second isogenic patient derived SNCA gene triplication mDA neuronal model. This phenotyping and classification strategy improves the exploitability of mDA neurons for disease modelling and the identification of novel PD drug targets.
Feeding growing mushrooms
Authors: Sonnenberg Anton S.M. , Baars Johan J.P. , Straatsma Gerben , Hendrickx Patrick M. , Hendrix Ed , Blok Chris , Peer Arend van 
Published: March 2022

AbstractA number of experiments were done to further our understanding of the substrate utilization in button mushroom crops (Agaricus bisporus). An analysis of the degradation of dry matter of the substrate during a crop cycle revealed that for pin formation the upper layer is used, for the production of flush one all layers are involved and for flush two mainly the lower layer is used. A reduction in substrate depth leads to a decrease in yield/m2 but an apparent increase in yield per ton of substrate but with a lower mushroom quality. A short daily interruption of the connection between the casing soil with all the substrate results in a delay of the first flush. Repetitive interruption of the connection with all or only part of the substrate leads to a shift in yield from flush one to flush two but the total yield remains unchanged. The mycelial biomass in the substrate increases from filling up to pinning, a steeper increase during flush one, levelling off during flush two, indicating that in the period of venting and up to/including flush one, enzymes are secreted by growing hyphae generating nutrients to feed a fixed amount of mushroom biomass for two flushes. A sidewise extension of the substrate (without casing soil, thus not producing mushrooms) showed that the substrate at a distance more than 20-50 cm away from the casing soil does not contribute to feeding mushrooms in the first two flushes. The observations are discussed with respect to relevant previous research.ImportanceButton mushrooms (Agaricus bisporus) are cultivated on a substrate prepared of composted wheat straw, chicken and/or horst manure and gypsum. This manuscript describes a number of experiments indicating that in a harvesting strategy towards quality mushrooms there is a fixed amount of nutrients prepared/available to feed two flushes. The increase of mycelial biomass in the substrate after venting and especially during the development of flush one indicates that likely a branching of mycelium occurs during this period, leading to a substantial number of growing hyphal tips excreting lignocellulolytic enzymes that degrade substrate and make nutrients available during flush one which are utilised in flush one and two. The presently used substrate seems to have reached its limits and there are hardly opportunities for further improvement. Research on alternative, more energy dense, substrates are needed to improve the efficiency of the present production system.
Non-occupational physical activity and risk of 22 cardiovascular disease, cancer, and mortality outcomes: a dose-response meta-analysis of large prospective studies
Authors: Garcia Leandro , Pearce Matthew , Abbas Ali , Mok Alexander , Strain Tessa , Ali Sara , Crippa Alessio , Dempsey Paddy C , Golubic Rajna , Kelly Paul , Laird Yvonne , McNamara Eoin , Moore Samuel , de Sa Thiago Herick , Smith Andrea D , Wijndaele Katrien , Woodcock James , Brage Søren 
Published: March 2022

ABSTRACTObjectiveTo estimate dose-response associations between non-occupational physical activity and multiple chronic disease outcomes in the general adult population.Eligibility criteriaProspective cohort studies with (a) general population samples >10,000 adults, (b) ≥3 exposure categories, and (c) risk measures and confidence intervals for all-cause mortality, total cardiovascular disease, coronary heart disease, stroke, heart failure, total cancer, and site-specific cancers (head and neck, myeloid leukemia, myeloma, gastric cardia, lung, liver, endometrium, colon, breast, bladder, rectum, esophagus, prostate, kidney).Information sourcesPubMed, Scopus, Web of Science, and reference lists of published studies, searched in February 2019.Data extraction and synthesisIndependent extraction and double-checking of study characteristics, exposure, and outcome assessment by two reviewers for each paper. Primary exposure was non-occupational physical activity volume, harmonized to physical activity energy expenditure in marginal MET-hours per week (mMET-h/week). The current minimum recommendations for physical activity (150 min/week of moderate-to-vigorous physical activity) equate to 8.75 mMET-h/week. Outcomes were risks of mortality, cardiovascular diseases, and cancers. We used restricted cubic splines in random-effects meta-analyses. Potential population impact was quantified using impact fractions.Results196 articles were included, covering 94 cohorts. The evidence base was largest for all-cause mortality (50 independent results; 163,415,543 person-years; 811,616 events), and incidence of cardiovascular disease (37 independent results; 28,884,209 person-years; 74,757 events) and cancer (31 independent results; 35,500,867 person-years; 185,870 events). In general, inverse non-linear associations were observed, steeper between 0 and 8.75 mMET-h/week, with smaller marginal reductions in risk above this level to 17.5 mMET-h/week, beyond which additional reductions were small and uncertain. Associations were stronger for all-cause and cardiovascular disease mortality than for cancer mortality. If all insufficiently active individuals had met the recommended physical activity level, 15.7% (95%CI: 13.1 to 18.2%) of all premature deaths would have been averted.ConclusionsInverse non-linear dose-response associations suggest substantial protection against a range of chronic disease outcomes from small increases in non-occupational physical activity in inactive adults.Review registrationPROSPERO CRD42018095481.
Flipped Over U: Structural Basis for dsRNA Cleavage by the SARS-CoV-2 Endoribonuclease
Authors: Frazier Meredith N. , Wilson Isha M. , Krahn Juno M. , Butay Kevin John , Dillard Lucas B. , Borgnia Mario J. , Stanley Robin E. 
Published: March 2022

AbstractCoronaviruses generate double-stranded (ds) RNA intermediates during viral replication that can activate host immune sensors. To evade activation of the host pattern recognition receptor MDA5, coronaviruses employ Nsp15, which is uridine-specific endoribonuclease. Nsp15 is proposed to associate with the coronavirus replication-transcription complex within double-membrane vesicles to cleave these dsRNA intermediates. How Nsp15 recognizes and processes dsRNA is poorly understood because previous structural studies of Nsp15 have been limited to small single-stranded (ss) RNA substrates. Here we present cryo-EM structures of SARS-CoV-2 Nsp15 bound to a 52nt dsRNA. We observed that the Nsp15 hexamer forms a platform for engaging dsRNA across multiple protomers. The structures, along with site-directed mutagenesis and RNA cleavage assays revealed critical insight into dsRNA recognition and processing. To process dsRNA Nsp15 utilizes a base-flipping mechanism to properly orient the uridine within the active site for cleavage. Our findings show that Nsp15 is a distinctive endoribonuclease that can cleave both ss- and dsRNA effectively.
Nematode histone H2A variant evolution reveals diverse histories of retention and loss and evidence for conserved core-like variants
Authors: Singh Swadha , Chu Diana , Roy Scott 
Published: March 2022

ABSTRACTHistone variants are paralogs that replace canonical histones in nucleosomes, often imparting novel functions. Despite their importance, how histone variants arise and evolve is poorly understood. Reconstruction of histone protein evolution is challenging due to high amino acid conservation and large differences in evolutionary rates across gene lineages and sites. Here we combined amino acid sequences and intron position data from 108 nematode genomes to trace the evolutionary histories of the three H2A variants found in Caenorhabditis elegans: the ancient H2A.ZHTZ-1, the sperm-specific HTAS-1, and HIS-35, which differs from canonical H2A by a single glycine-to-alanine C-terminal change. We find disparate evolutionary histories. Although the H2A.ZHTZ-1 protein is highly conserved, its gene exhibits recurrent intron gain and loss. This pattern suggests that it is intron presence, rather than specific intron sequences or positions, that may be important to H2A.Z functionality. In contrast, for HTAS-1 and HIS-35, we find variant-specific intron positions that are conserved across species. HIS-35 arose in the ancestor of Caenorhabditis and its sister group, including the genus Diploscapter, while the sperm-specific variant HTAS-1 arose more recently in the ancestor of a subset of Caenorhabditis species. HIS-35 exhibits gene retention in some descendent lineages but also recurrent gene loss in others, suggesting that histone variant use or functionality is highly flexible in this case. We also find that the single amino acid differentiating HIS-35 from core H2A is ancestral and common across canonical Caenorhabditis H2A sequences and identify one nematode species that bear identical HIS-35 and canonical H2A proteins, findings that are not predicted from the hypothesis that HIS-35 has a distinct function. Instead, we speculate that HIS-35 enables H2A expression across the cell cycle or in distinct tissues; genes encoding such partially-redundant functions may be advantageous yet relatively replaceable over evolutionary times, consistent with the patchwork pattern of retention and loss of both genes. Our study shows the evolutionary trajectory for histone H2A variants with distinct functions and the utility of intron positions for reconstructing the evolutionary history of gene families, particularly those undergoing idiosyncratic sequence evolution.
Inducible CRISPR/Cas9 allows for multiplexed and rapidly segregated single target genome editing in Synechocystis sp. PCC 6803
Authors: Cengic Ivana , Cañadas Inés C. , Minton Nigel P. , Hudson Elton P. 
Published: March 2022

AbstractEstablishing various synthetic biology tools is crucial for the development of cyanobacteria for biotechnology use, especially tools that allow for precise and markerless genome editing in a time-efficient manner. Here we describe a riboswitch-inducible CRISPR/Cas9 system, contained on one single replicative vector, for the model cyanobacteria Synechocystis sp. PCC 6803. A theophylline-responsive riboswitch allowed tight control of Cas9 expression, which enabled reliable transformation of the CRISPR/Cas9 vector into Synechocystis. Induction of the CRISPR/Cas9 mediated various types of genomic edits, specifically deletions and insertions of varying size. The editing efficiency varied depending on the target and intended edit; smaller edits overall performed better, reaching e.g. 100% for insertion of a FLAG-tag onto rbcL. Importantly, the single-vector CRISPR/Cas9 system described herein was also shown to mediate multiplexed editing of up to three targets in parallel in Synechocystis. All single-target and several double-target mutants were also fully segregated after the first round of induction, adding to the usefulness of this system. Further, a vector curing system that is separately induced by nickel and contained on the CRISPR/Cas9 vector itself, improved curing efficiencies by roughly 4-fold, enabling the final mutants to become truly markerless.
Sights and sounds of dolphins, Tursiops truncatus, preying on native fish of San Diego Bay and offshore in the Pacific Ocean
Authors: Ridgway Sam H. , Dibble Dianna S. , Baird Mark 
Published: March 2022

AbstractFor the first time, dolphins wearing video cameras were observed capturing and eating live native fish. While freely swimming in San Diego Bay, one dolphin caught 69 resident fish, 64 demersal, 5 near surface, while the other caught 40, 36 demersal and 4 near the surface. Two other dolphins were observed capturing 135 live native fish in a sea water pool. Two additional dolphins were observed feeding opportunistically during open water sessions in the Pacific Ocean. Notably, one of these dolphins was observed to consume 8 yellow-bellied sea snakes (Hydrophis platurus). Searching dolphins clicked at intervals of 20 to 50 ms. On approaching prey, click intervals shorten into a terminal buzz and then a squeal. Squeals were bursts of clicks that varied in duration, peak frequency, and amplitude. Squeals continued as the dolphin seized, manipulated and swallowed the prey. If fish escaped, the dolphin continued the chase and sonar clicks were heard less often than the continuous terminal buzz and squeal. During captures, the dolphins’ lips flared to reveal nearly all of the teeth. The throat expanded outward. Fish continued escape swimming even as they entered the dolphins’ mouth, yet the dolphin appeared to suck the fish right down.
Optimal shape design of a class of permanent magnet motors in a multiple-objectives context
Authors: Di Barba Paolo , Mognaschi Maria Evelina , Petkovska Lidija , Cvetkovski Goga Vladimir 
Published: March 2022

Purpose
This paper aims to deal with the optimal shape design of a class of permanent magnet motors by minimizing multiple objectives according to an original interpretation of Pareto optimality. The proposed method solves a many-objective problems characterized by five objective functions and five design variables with evolution strategy algorithms, classically used for single- and multi-objective (two objective functions) optimization problems.

Design/methodology/approach
Two approaches are proposed in the paper: the All-Objectives (AO) and the Many-Objectives (MO) optimization approach. The former is based on a single-objective optimization of a preference function, i.e. a normalized weighted sum. In contrast, in the MO a multi-objective optimization algorithm is applied to the minimization of a weight-free preference function and simultaneously to a maximization of the distance of the current solution from the prototype. The optimizations are based on an equivalent circuit model of the Permanent Magnet (PM) motor, but the results are assessed by means of finite element analyses (FEAs).

Findings
An extensive study of the solutions obtained by means of the different optimization approaches is provided by means of post-processing analyses. Both the approaches find non-dominated solutions with respect to the prototype that are substantially improving the initial solution. The points of strength along with the weakness points of each solution with respect to the prototype are analysed in depth.

Practical implications
The paper gives a good guide to the designers of electric motors, focussed on a shape design optimization.

Originality/value
Considering simultaneously five objective functions in an automated optimal design procedure is challenging. The proposed approach, based on a well-known and established optimization algorithm, but exploiting a new concept of degree of conflict, can lead to new results in the field of automated optimal design in a many-objective context.
Neural network inverse model for multi-band unequal Wilkinson power divider
Authors: Sallam Tarek , Attiya Ahmed M. 
Published: March 2022

Purpose
The purpose of this paper is to build a neural network (NN) inverse model for the multi-band unequal-power Wilkinson power divider (WPD). Because closed-form expressions of the inverse input–output relationship do not exist, the NN becomes an appropriate choice, because it can be trained to learn from the data in inverse modeling. The design parameters of WPD are the characteristic impedances, lengths of the transmission line sections and the isolation resistors. The design equations used to train the NN inverse model are based on the even–odd mode analysis.

Design/methodology/approach
An inverse model of a multi-band unequal WPD using NNs is presented. In inverse modeling of a microwave component, the inputs to the model are the required electrical parameters such as reflection coefficients, and the outputs of the model are the geometrical or the physical parameters.

Findings
For verification purposes, a quad-band WPD and a penta-band WPD are designed. The results of the full-wave simulations verify the validity of the design procedure. The resulting NN model outperforms traditional time-consuming optimization procedures in terms of computation time with acceptable accuracy. The designed WPDs using NN are implemented by microstrip lines and verified by using full-wave analysis based on high-frequency structure simulator (HFSS). The results of the microstrip WPDs have good agreements with the corresponding results obtained by using ideal transmission line sections.

Originality/value
The associated time-consuming procedure and computational burden in realizing WPD through optimization are major disadvantages; needless to mention the substantial increase in optimization time because of the multi-band design. NNs are one of the best candidates in addressing the abovementioned challenges, owing to their ability to process the interrelation between electrical and geometrical/physical characteristics of the WPD in a superfast manner.
Employee participation in performance measurement system: focusing on job satisfaction and leadership
Authors: Jang Soojeen , Chung Yanghon , Son Hosung 
Published: March 2022

PurposeThis study examines how employee participation in the performance measurement system affects the relationship between authentic leadership and job satisfaction.Design/methodology/approachSurvey data for this study were obtained from 322 employees in South Korea. Structural equation modeling and bootstrapping method were applied to test the proposed hypotheses.FindingsThis study first confirmed that authentic leadership positively affects job satisfaction. In addition, the results showed that employees' participation in developing performance measures partially mediated the relationship between authentic leadership and job satisfaction.Practical implicationsThe findings imply that employees' participation in developing performance measures, which is promoted by authentic leadership, can be a strategy for enhancing job satisfaction. Therefore, in order to increase employees' job satisfaction, organizations need to promote employee participation in the performance measurement system and develop authenticity in leaders.Originality/valueEmployees' participation in developing performance measures has not been investigated sufficiently from the leadership perspective. This study expands the literature on the influence of employee participation in the performance measurement system on work-related outcomes by demonstrating that employees' participation in developing performance measures partially mediates the effect of authentic leadership on employee job satisfaction.
Australian consumers and environmental characteristics of wine: price premium indications
Authors: Gow Jeff , Rana Rezwanul Hasan , Moscovici Daniel , Ugaglia Adeline Alonso , Valenzuela Lionel , Mihailescu Radu , Coelli Robert 
Published: March 2022

Purpose
There has been increasing consumer interest in recent times in the environmental providence of what they eat and drink. A number of different environmental wine certifications have been created and these include biodynamic, fairtrade, organic, natural and sustainable. The purpose of this study is to survey wine consumers in Australia about their interest in these eco-certifications and their willingness to pay (WTP) a price premium for wine with one of these eco-certifications.

Design/methodology/approach
An online survey was developed to capture the knowledge and attitudes of consumers and their socio-demographic characteristics about their WTP for eco-certified wine. Data from 454 wine consumers in Australia were collected and analysed. Descriptive statistics and Pearson’s chi-squared test analysed the significant factors which determine consumers’ attitudes towards eco-certified wines. Ordinal logistic regression with marginal effects was used to examine whether the WTP a premium for different certified wines differs significantly based on wine knowledge, attitudes and socio-demographic characteristics.

Findings
The findings of this study indicate that consumers often buy pro-environmental goods. The majority have a positive (greater than 0) WTP a premium for biodynamic, fairtrade, organic, natural and sustainable-labelled wines. The main factors influencing eco-certified wine purchase decisions by Australian consumers are previously bought eco-certified goods, previously bought eco-certified wine and respondent age. Income, education or previous wine knowledge did not positively influence WTP a price premium for eco-certified wines. Gender was not significant in the ordinal logistic regression.

Research limitations/implications
Most studies in the literature use stated preference experiments to elicit WTP and these are valuable exercises, as they can provide an indication of consumer preferences for potential certifications, before they have been introduced to the market. In this study, we used an ordinal dependent variable in the logistic regression instead of a continuous variable (because of data limitations). Using ordinal dependent variables provides information on the probability or likelihood of occurring an event.

Originality/value
The study results provide the first price premium indications that Australian consumers are willing to pay for eco-certified wines (other than organic).