bluuebunny/crossref_metadata_2025 huggingface dataset:
Benchmarks in Pancreatic Surgery
Authors: Sánchez-Velázquez Patricia , Muller Xavier , Malleo Giuseppe , Park Joon-Seong , Hwang Ho-Kyoung , Napoli Niccolò , Javed Ammar A. , Inoue Yosuke , Beghdadi Nassiba , Kalisvaart Marit , Vigia Emanuel , Walsh Carrie D. , Lovasik Brendan , Busquets Juli , Scandavini Chiara , Robin Fabien , Yoshitomi Hideyuki , Mackay Tara M. , Busch Olivier R. , Hartog Hermien , Heinrich Stefan , Gleisner Ana , Perinel Julie , Passeri Michael , Lluis Nuria , Raptis Dimitri A , Tschuor Christoph , Oberkofler Christian E. , DeOliveira Michelle L. , Petrowsky Henrik , Martinie John , Asbun Horacio , Adham Mustapha , Schulick Richard , Lang Hauke , Koerkamp Bas Groot , Besselink Marc G. , Han Ho-Seong , Miyazaki Masaru , Ferrone Cristina R. , Fernández-del Castillo Carlos , Lillemoe Keith D. , Sulpice Laurent , Boudjema Karim , Del Chiaro Marco , Fabregat Joan , Kooby David A. , Allen Peter , Lavu Harish , Yeo Charles J. , Barroso Eduardo , Roberts Keith , Muiesan Paolo , Sauvanet Alain , Saiura Akio , Wolfgang Christopher L. , Cameron John L. , Boggi Ugo , Yoon Dong-Sup , Bassi Claudio , Puhan Milo A. , Clavien Pierre-Alain
Published: March 2019

Objective:

To use the concept of benchmarking to establish robust and standardized outcome references after pancreatico-duodenectomy (PD).

Background:

Best achievable results after PD are unknown. Consequently, outcome comparisons among different cohorts, centers or with novel surgical techniques remain speculative.

Methods:

This multicenter study analyzes consecutive patients (2012–2015) undergoing PD in 23 international expert centers in pancreas surgery. Outcomes in patients without significant comorbidities and major vascular resection (benchmark cases) were analyzed to establish 20 outcome benchmarks for PD. These benchmarks were tested in a cohort with a poorer preoperative physical status (ASA class ≥3) and a cohort treated by minimally invasive approaches.

Results:

Two thousand three hundred seventy-five (38%) low-risk cases out of a total of 6186 PDs were analyzed, disclosing low in-hospital mortality (≤1.6%) but high morbidity, with a 73% benchmark morbidity rate cumulated within 6 months following surgery. Benchmark cutoffs for pancreatic fistulas (B-C), severe complications (≥ grade 3), and failure-to-rescue rate were 19%, 30%, and 9%, respectively. The ASA ≥3 cohort showed comparable morbidity but a higher in hospital-mortality (3% vs 1.6%) and failure-to-rescue rate (16% vs 9%) than the benchmarks. The proportion of benchmark cases performed varied greatly across centers and continents for both open (9%–93%) and minimally invasive (11%–62%) PD. Centers operating mostly on complex PD cases disclosed better results than those with a majority of low-risk cases.

Conclusion:

The proposed outcome benchmarks for PD, established in a large-scale international patient cohort and tested in 2 different cohorts, may allow for meaningful comparisons between different patient cohorts, centers, countries, and surgical techniques.
Primary Endpoints in Current Phase II/III Trials for Alzheimer Disease
Authors: Takeshima Nozomi , Ishiwata Keita , Sozu Takashi , Furukawa Toshi A.
Published: March 2019

This study examined the primary and secondary endpoints used by recent phase II/III randomized controlled trials (RCTs) of drugs for the Alzheimer disease. We searched the Clinical Trials.gov database to identify all RCTs registered from January 1, 2011 until August 19, 2018. We identified 122 RCTs and examined primary and secondary endpoints most commonly used. The median number of primary endpoints was 1 (range: 1 to 48) and the median number of secondary endpoints was 4 (range: 1 to 19). Cognitive function was used as a primary endpoint by 59% of the RCTs identified. Although few trials included a primary outcome set that fulfilled the US Food and Drug Administration (FDA) or European Committee for Medicinal Products for Human Use (CHMP) requirements, these were met by a combination of the primary and secondary outcomes of more than half of the trials.
A core microbiota of the plant-earthworm interaction conserved across soils
Authors: Jacquiod Samuel , Puga-Freitas Ruben , Spor Aymé , Mounier Arnaud , Monard Cécile , Mougel Christophe , Philippot Laurent , Blouin Manuel
Published: March 2019

Microorganisms participate in most crucial soil functions and services benefiting human activities, such as biogeochemical cycles, bioremediation and food production. Their activity happens essentially in hotspots created by major soil macroorganisms, like rhizosphere and cast shaped by plants and earthworms respectively1. While effects of individual macroorganism on soil microbes are documented, no studies attempted to decipher how the mosaic of microhabitats built by multiple macroorganisms and their interaction determine the structure of microbial communities. Here we show a joint shaping of soil bacterial communities by these two macroorganisms, with a prevalent role of plants over earthworms. In a controlled microcosm experiment with three contrasted soils and meticulous microhabitat sampling, we found that the simultaneous presence of barley and endogeic earthworms resulted in non-additive effects on cast and rhizosphere bacterial communities. Using a source-sink approach derived from the meta-community theory2,3, we found specific cast and rhizospherecore microbiota4,5of the plant-eartworm interaction, detected in all soils only when both macroorganisms are present. We also evidenced acore networkof the plant-earthworm interaction, with cosmopolitan OTUs correlated both in cast and rhizosphere of all soils. Our study provides a new framework to explore aboveground-belowground interactions through the prism of microbial communities. This multiple-macroorganisms shaping of bacterial communities also affects fungi and archaea, while being strongly influenced by soil type. Further functional investigations are needed to understand how thesecore microbiotaandcore networkcontribute to the modulation of plant adaptive response to local abiotic and biotic conditions.
Expression of ppsD, a gene involved in synthesis of Mycobacterium tuberculosis virulence factor PDIM, reflects treatment response in pulmonary tuberculosis patients
Authors: Sriraman Kalpana , Kekane Rupali , Shah Daksha , Saranath Dhananjaya , Mistry Nerges
Published: March 2019

Drug resistant tuberculosis (TB) cases are primarily driven by transmission, however, treatment failure and acquisition of drug resistance are still significant issues in drug sensitive TB cases. Study of gene expression in Mycobacterium tuberculosis (Mtb) isolated from poor outcome patients may offer clues towards prediction of treatment response. In the current study, expression of five non-drug target genes (ppsD, embC, Rv1457c, Rv1687c and recB) previously identified to be associated with drug resistance was studied in clinical isolates from patients with different treatment outcomes to examine its correlation to treatment response and acquisition of drug resistance in Mtb. Our results show that expression of ppsD, a gene involved in synthesis of cell wall lipid PDIM, was significantly increased in patients who developed drug resistance during treatment and patients who were drug resistant at diagnosis. On the other hand in longitudinal isolates collected during treatment, ppsD expression decreased consistently in patients who responded to treatment and became culture negative, while it increased in patients who did not respond to treatment as indicated by their culture positive status towards the end of treatment. These results demonstrate that ppsD expression reflects treatment response in TB patients and hence can be potentially used as a marker for predicting treatment response. Additional longitudinal studies with a larger cohort of patients are required to establish application of ppsD expression as a marker of treatment response.
Botswana’s wildlife losing ground as Kalahari Wildlife Management Areas (WMAs) are dezoned for livestock expansion
Authors: Keeping Derek , Kashe Njoxlau , Langwane Horekwe (Karoha) , Sebati Panana , Molese Nicholas , Gielen Marie-Charlotte , Keitsile-Barungwi Amo , Xhukwe Quashe (/Uase) , Brahman !Nate (Shortie)
Published: March 2019

Botswana is rightfully lauded for maintaining 42% of its land base for conservation, and ranking top in the world for effort to conserve megafauna. Yet during the recent preservationist political climate characterized by a hunting moratorium and deterioration of CBNRM, changes to the national land use map suggest Botswana is losing grip on its lofty status. While conservation attention is turned to elephants and KAZA, discussion about the official dezoning of 8,268 km2of free-ranging wildlife estate in the Kalahari ecosystem has been notably absent. Using track-based methods we quantified wildlife populations inhabiting this relinquished wilderness now awaiting imminent conversion to fenced and private livestock holdings. We find that the affected areas contain approximately 3,900 free-ranging large herbivores and 50 large carnivores, all of which will become consumed, displaced or potential conflict animals. Erstwhile publicly-owned wildlife particularly important for local communities will effectively become de facto private property for an elite minority. The land use changes spell negative consequences for wildlife not only via mechanisms of habitat loss and edge effects but also reduced landscape connectivity between protected areas that limits seasonal movements and gene flow thus eroding long-term population resilience in a drought-prone environment. As Botswana’s agricultural lobby continues to exert pressure on the Kalahari ecosystem, we suggest that ground surveys conducted by Kalahari trackers be implemented to inform decision-making rather than relying on the inadequate coarse-grained aerial survey record only.
Land-use and related pressures have reduced biotic integrity more on islands than on mainlands
Authors: Sanchez-Ortiz Katia , Gonzalez Ricardo E. , De Palma Adriana , Newbold Tim , Hill Samantha L. L. , Tylianakis Jason M. , Börger Luca , Lysenko Igor , Purvis Andy
Published: March 2019

Tracking progress towards biodiversity targets requires indicators that are sensitive to changes at policy-relevant scales, can easily be aggregated to any spatial scale and are simple to understand. The Biodiversity Intactness Index (BII), which estimates the average abundance of a diverse set of organisms in a given area relative to their reference populations, was proposed in 2005 in response to this need. A new implementation of BII was developed as part of the PREDICTS project in 2016 and has been adopted by GEO BON, IPBES and CBD. The previous global models for BII estimation could not account for pressures having different effects in different settings. Islands are a setting of particular interest: many are home to a disproportionate number of endemic species; oceanic islands may have relatively low overall species diversity because of their isolation; and the pattern and timing of human pressures can be very different from that seen on mainlands. Here, we test whether biotic integrity – as estimated by BII – has decreased more severely on islands than mainlands. We update methods previously used to estimate BII globally (Newbold et al., 2016) to allow pressure effects to differ between islands and mainlands, while also implementing some other recent improvements in modelling. We estimate BII for islands and mainlands by combining global models of how two aspects of biodiversity – overall abundance, and compositional similarity to minimally-impacted sites – have been affected by human pressures. We use these models to project high-resolution (∼1km2) global maps of BII for the year 2005. We calculate average BII for island and mainland biomes, countries, IPBES regions and biodiversity hotspots; and repeat our analyses using a richness-based version of BII. BII on both islands and mainlands has fallen below the values proposed as safe limits across most regions, biomes and biodiversity hotspots. Our BII estimates are lower than those published in 2016, globally, within all biodiversity hotspots and within most biomes, and show greater spatial heterogeneity; detailed analysis of these differences shows that they arise mostly from a combination of improvements to the modelling framework. Average BII does not strongly differ between islands and mainlands, but richness-based BII has fallen by more on islands. It seems native species are more negatively affected by rising human population density and road development on islands than mainlands, and islands have seen more land conversion. Our results highlight the parlous state of biodiversity native to islands.
Diversification of the type IV filament super-family into machines for adhesion, secretion, DNA transformation and motility
Authors: Denise Rémi , Abby Sophie S , Rocha Eduardo PC
Published: March 2019

Processes of molecular innovation require tinkering and co-option of existing genes. How this occurs in terms of molecular evolution at long evolutionary scales remains poorly understood. Here, we analyse the natural history of a vast group of membrane-associated molecular systems in Bacteria and Archaea – type IV filament super-family (TFF-SF) – that diversified in systems involved in flagellar or twitching motility, adhesion, protein secretion, and DNA natural transformation. We identified such systems in all phyla of the two domains of life, and their phylogeny suggests that they may have been present in the last universal common ancestor. From there, two lineages, a Bacterial and an Archaeal, diversified by multiple gene duplications of the ATPases, gene fission of the integral membrane platform, and accretion of novel components. Surprisingly, we find that the Tad systems originated from the inter-kingdom transfer from Archaea to Bacteria of a system resembling the Epd pilus. The phylogeny and content of ancestral systems suggest that initial bacterial pili were engaged in cell motility and/or DNA transformation. In contrast, specialized protein secretion systems arose much later, and several independent times, in natural history. All these processes of functional diversification were accompanied by genetic rearrangements with implications for genetic regulation and horizontal gene transfer: systems encoded in fewer loci were more frequently exchanged between taxa. Overall, the evolutionary history of the TFF-SF by itself provides an impressive catalogue of the variety of molecular mechanisms involved in the origins of novel functions by tinkering and co-option of cellular machineries.
Common variants associated withOSMRexpression contribute to carotid plaque vulnerability, but not to cardiovascular disease in humans
Authors: van Keulen D. , van Koeverden I.D. , Boltjes A. , Princen H.M.G. , van Gool A.J. , de Borst G.J. , Asselbergs F.W. , Tempel D. , Pasterkamp G. , van der Laan S.W.
Published: March 2019

Background and aims

Oncostatin M (OSM) signaling is implicated in atherosclerosis, however the mechanism remains unclear. We investigated the impact of common genetic variants in OSM and its receptors,OSMRandLIFR, on overall plaque vulnerability, plaque phenotype, intraplaqueOSMRandLIFRexpression, coronary artery calcification burden and cardiovascular disease susceptibility.

Methods and results

We queried Genotype-Tissue Expression data and found that rs13168867 (C allele) was associated with decreasedOSMRexpression and that rs10491509 (A allele) was associated with increasedLIFRexpression in arterial tissues. No variant was significantly associated withOSMexpression.

We associated these two variants with plaque characteristics from 1,443 genotyped carotid endarterectomy patients in the Athero-Express Biobank Study. After correction for multiple testing, rs13168867 was significantly associated with an increased overall plaque vulnerability (β=0.118 ± s.e.=0.040,p=3.00×10-3, C allele). Looking at individual plaque characteristics, rs13168867 showed strongest associations with intraplaque fat (β=0.248 ± s.e.=0.088, p=4.66 × 10-3, C allele) and collagen content (β=-0.259 ± s.e.=0.095, p=6.22 × 10-3, C allele), but these associations were not significant after correction for multiple testing. rs13168867 was not associated with intraplaqueOSMRexpression. Neither was intraplaqueOSMRexpression associated with plaque vulnerability and no knownOSMReQTLs were associated with coronary artery calcification burden, or cardiovascular disease susceptibility. No associations were found for rs10491509 in theLIFRlocus.

Conclusions

Our study suggests that rs1316887 in the OSMR locus is associated with increased plaque vulnerability, but not with coronary calcification or cardiovascular disease risk. It remains unclear through which precise biological mechanisms OSM signaling exerts its effects on plaque morphology. However, the OSM-OSMR/LIFR pathway is unlikely to be causally involved in lifetime cardiovascular disease susceptibility.
Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression
Authors: Hafemeister Christoph , Satija Rahul
Published: March 2019

Single-cell RNA-seq (scRNA-seq) data exhibits significant cell-to-cell variation due to technical factors, including the number of molecules detected in each cell, which can confound biological heterogeneity with technical effects. To address this, we present a modeling framework for the normalization and variance stabilization of molecular count data from scRNA-seq experiments. We propose that the Pearson residuals from ’regularized negative binomial regression’, where cellular sequencing depth is utilized as a covariate in a generalized linear model, successfully remove the influence of technical characteristics from downstream analyses while preserving biological heterogeneity. Importantly, we show that an unconstrained negative binomial model may overfit scRNA-seq data, and overcome this by pooling information across genes with similar abundances to obtain stable parameter estimates. Our procedure omits the need for heuristic steps including pseudocount addition or log-transformation, and improves common downstream analytical tasks such as variable gene selection, dimensional reduction, and differential expression. Our approach can be applied to any UMI-based scRNA-seq dataset and is freely available as part of the R packagesctransform, with a direct interface to our single-cell toolkitSeurat.
Spatially modulated alpha-band activity does not mediate tactile remapping and fast overt orienting behavior
Authors: Ossandón José P. , König Peter , Heed Tobias
Published: March 2019

Posterior oscillatory alpha-band activity is commonly associated with spatial-attentional orienting and prioritization across sensory modalities. It has also been suggested to mediate the automatic transformation of tactile stimuli from a skin-based, somatotopic reference frame into an external one. Previous research has not convincingly separated these two possible roles of alpha-band activity. In particular, the use of delay paradigms, implemented to allow temporal evolution of segregable oscillatory brain responses to stimulus, motor planning, and response, have prohibited strong conclusions about a causal role of oscillatory activity in tactile-spatial transformations. Here, we assessed alpha-band modulation with massive univariate deconvolution, an analysis approach that disentangles brain signals overlapping in time and space. Thirty-one participants performed a delay-free, visual serial-search task in which saccade behavior was unrestricted. A tactile cue to uncrossed or crossed hands was either informative or uninformative about visual target location. Alpha-band suppression following tactile stimulation was lateralized relative to the stimulated hand over centro-parietal sensors, but relative to its external location over parieto-occipital sensors. Alpha-band suppression reflected external touch location only after informative cues, challenging the proposition that posterior alpha-band lateralization indexes automatic tactile transformation. Moreover, alpha-band suppression occurred ~200 ms later than externally directed saccade responses after tactile stimulation. These findings suggest that alpha-band activity does not play a causal role in tactile-spatial transformation but, instead, reflects delayed, supramodal processes of attentional re-orienting.
In silicolearning of tumor evolution through mutational time series
Authors: Auslander Noam , Wolf Yuri I. , Koonin Eugene V.
Published: March 2019

Cancer arises through the accumulation of somatic mutations over time. Understanding the sequence of mutation occurrence during cancer progression can assist early and accurate diagnosis and improve clinical decision-making. Here we employ Long Short-Term Memory networks (LSTMs), a class of recurrent neural network, to learn the evolution of a tumor through an ordered sequence of mutations. We demonstrate the capacity of LSTMs to learn complex dynamics of the mutational time series governing tumor progression, allowing accurate prediction of the mutational burden and the occurrence of mutations in the sequence. Using the probabilities learned by the LSTM, we simulate mutational data and show that the simulation results are statistically indistinguishable from the empirical data. We identify passenger mutations that are significantly associated with established cancer drivers in the sequence and demonstrate that the genes carrying these mutations are substantially enriched in interactions with the corresponding driver genes. Breaking the network into modules consisting of driver genes and their interactors, we show that these interactions are associated with poor patient prognosis, thus likely conferring growth advantage for tumor progression. Thus, application of LSTM provides for prediction of numerous additional conditional drivers and to reveal hitherto unknown aspects of cancer evolution.

Significance

Cancer is caused by the effects of somatic mutations known as drivers. Although a number of major cancer drivers have been identified, it is suspected that many more comparatively rare and conditional drivers exist, and the interactions between different cancer-associated mutations that might be relevant for tumor progression are not well understood. We applied an advanced neural network approach to learn the sequence of mutations and the mutational burden in colon and lung cancers, and to identify mutations that are associated with individual drivers. A significant ordering of driver mutations is demonstrated, and numerous, previously undetected conditional drivers are identified. These findings broaden the existing understanding of the mechanisms of tumor progression and have implications for therapeutic strategies.
Specific type 1 diabetes risk genes underpin age-at-diagnosis and indicate joint defects in immunity, beta-cell fragility and responses to viral infections in early-onset disease
Authors: Inshaw Jamie R.J. , Cutler Antony J. , Crouch Daniel J.M. , Wicker Linda S. , Todd John A.
Published: March 2019

Objective

Immunohistological analyses of pancreata from patients with type 1 diabetes suggest a stratification of islet pathology of both B and T lymphocyte islet inflammation common in children diagnosed at <7 years (<7 group), whereas B cells are rare in those diagnosed age ≥13 (≥13 group). Based on these observations, we sought to identify differences in genetic susceptibility between these age-at-diagnosis groups, to inform on the aetiology of the most aggressive form of type 1 diabetes that initiates in the first years of life.

Research Design and Methods

Using multinomial logistic regression models, we tested if known type 1 diabetes loci (17 within the HLA region and 55 non-HLA regions) had significantly stronger effect sizes in the <7 group compared to the ≥13 group, using genotype data from 27,075 individuals (18,488 controls, 3,109 cases diagnosed at <7, 3,754 at 7-13 and 1,724 at ≥13).

Results

Six HLA haplotypes/classical alleles and seven non-HLA regions, one of which functions specifically in beta cells (GLIS3), and the other six likely affecting key T cell (IL2RA, IL10, SIRPG, IKZF3, THEMIS), thymus (THEMIS) and B cell development/functions (IKZF3, IL10) or in both immune and beta cells (CTSH) had stronger effects in the <7 group.

Conclusions

In newborn children with the greatest load of certain risk alleles, dysregulated response of immune and beta cells to environmental stresses such as virus infection, combine to cause a rapid loss of insulin production, driving down the age of type 1 diabetes diagnosis.
Impact of 3-dimensional genome organization, guided by cohesin and CTCF looping, on sex-biased chromatin interactions and gene expression in mouse liver
Authors: Matthews Bryan J. , Waxman David J.
Published: March 2019

Background

Sex differences in the transcriptome and epigenome are widespread in mouse liver and are associated with sex-bias in liver disease. Several thousand sex-differential distal enhancers have been identified; however, their links to sex-biased genes and the impact of any sex-differences in nuclear organization, DNA looping, and chromatin interactions are unknown.

Results

To address these issues, we first characterized 1,847 mouse liver genomic regions showing significant sex differential occupancy by cohesin and CTCF, two key 3D nuclear organizing factors. These sex-differential binding sites were largely distal to sex-biased genes, but rarely generated sex-differential TAD (topologically associating domain) or intra-TAD loop anchors. A substantial subset of the sex-biased cohesin-non-CTCF binding sites, but not the sex-biased cohesin-and-CTCF binding sites, overlapped sex-biased enhancers. Cohesin depletion reduced the expression of male-biased genes with distal, but not proximal, sex-biased enhancers by >10-fold, implicating cohesin in long-range enhancer interactions regulating sex-biased genes. Using circularized chromosome conformation capture-based sequencing (4C-seq), we showed that sex differences in distal sex-biased enhancer-promoter interactions are common. Sex-differential chromatin interactions involving sex-biased gene promoters, enhancers, and lncRNAs were associated with sex-biased binding of cohesin and/or CTCF. Furthermore, intra-TAD loops with sex-independent cohesin-and-CTCF anchors conferred sex specificity to chromatin interactions indirectly, by insulating sex-biased enhancer-promoter contacts and by bringing sex-biased genes into closer proximity to sex-biased enhancers.

Conclusions

These findings elucidate how 3-dimensional genome organization contributes to sex differences in gene expression in a non-reproductive tissue through both direct and indirect effects of cohesin and CTCF looping on distal enhancer interactions with sex-differentially expressed genes.
Comparative Analysis of Electrostatic Models for Ligand Docking
Authors: Sartori Geraldo Rodrigues , Nascimento Alessandro S.
Published: March 2019

The precise modeling of molecular interactions remains an important goal among molecular modeling techniques. Some of the challenges in the field include the precise definition of a Hamiltonian for biomolecular systems, together with precise parameters derived from Molecular Mechanics Force Fields, for example. The problem is even more challenging when interaction energies from different species are computed, such as the interaction energy involving a ligand and a protein, given that small differences must be computed from large energies. Here we evaluated the effects of the electrostatic model for ligand binding energy evaluation in the context of ligand docking. For this purpose, a classical Coulomb potential with distance-dependent dielectrics was compared with a Poisson-Boltzmann (PB) model for electrostatic potential computation, based on DelPhi calculations. We found that, although the electrostatic energies were highly correlated for the Coulomb and PB models, the ligand pose and the enrichment of actual ligands against decoy compounds, were improved when binding energies were computed using PB as compared to the Coulomb model. We observed that the electrostatic energies computed with the Coulomb model were, on average, ten times larger than the energies computed with the PB model, suggesting a strong overestimation of the polar interactions in the Coulomb model. We also found that a slightly smoothed Lennard-Jones potential combined with the PB model resulted in a good compromise between ligand sampling and energetic scoring.
A beneficial genomic rearrangement creates multiple versions of calcipressin inC. elegans
Authors: Zhao Yuehui , Wan Jason , Biliya Shweta , Brady Shannon C. , Lee Daehan , Andersen Erik C. , Vannberg Fredrik O. , Lu Hang , McGrath Patrick T.
Published: March 2019

Gene duplication is a major source of genetic novelty and evolutionary adaptation, providing a molecular substrate that can generate biological complexity and diversity (Ohno 1967, Taylor and Raes 2004). Despite an abundance of genomic evidence from extant organisms suggesting the importance of gene duplication, consensus about how they arise and functionally diversify is lacking (Innan and Kondrashov 2010). In the process of studying the adaptation of laboratory strains of C. elegans to new food sources, we identified a recombinant inbred line (RIL) with higher relative fitness and hyperactive exploration behavior compared to either parental strain. Using bulk-segregant analysis and short-read resequencing, we identified a de novo beneficial, complex rearrangement of the rcan-1 gene, which we resolved into five new unique tandem inversion/duplications using Oxford Nanopore long-read sequencing. rcan-1 encodes an ortholog to human RCAN1/DSCR1, which has been implicated as a causal gene for Down syndrome (Fuentes, Genesca et al. 2000). The genomic rearrangement in rcan-1 causes two complete and two truncated versions of the rcan-1 coding region, with a variety of modified promoter and 3’ regions, which ultimately reduce whole-body gene expression. This rearrangement does not phenocopy a loss-of-function allele, which indicates that the rearrangement was necessary for the observed fitness gains. Our results demonstrate that adaptation can occur through unexpectedly complex genetic changes that can simultaneously duplicate and diversify a gene, providing the molecular substrate for future evolutionary change.
A rapid method to determine the bactericidal activity of compounds against non-replicatingMycobacterium tuberculosisat low pH
Authors: Early Julie V. , Mullen Steven , Parish Tanya
Published: March 2019

There is an urgent need for new anti-tubercular agents which can lead to a shortened treatment time by targeting persistent or non-replicating bacilli. In order to assess compound activity against non-replicatingMycobacterium tuberculosis, we developed a method to detect the bactericidal activity of novel compounds within 7 days. Our method uses incubation at low pH in order to induce a non-replicating state. We used a strain ofM. tuberculosisexpressing luciferase; we first confirmed the linear relationship between luminescence and viable bacteria (determined by colony forming units) under our assay conditions. We optimized the assay parameters in 96-well plates in order to achieve a reproducible assay. Our final assay usedM. tuberculosisin phosphate-citrate buffer, pH 4.5 exposed to compounds for 7 days; viable bacteria were determined by luminescence. We recorded the minimum bactericidal concentration at pH 4.5 (MBC4.5) representing >2 logs of kill. We confirmed the utility of the assay with control compounds. The ionophores monensin, niclosamide, and carbonyl cyanide 3-chlorophenylhydrazone and the anit-tubercular drugs pretomanid and rifampicin were active, while several other drugs such as isoniazid, ethambutol, and linezolid were not.
Short-time fractal analysis of biological autoluminescence
Authors: Dlask Martin , Kukal Jaromír , Poplová Michaela , Sovka Pavel , Cifra Michal
Published: March 2019

Biological systems manifest continuous weak autoluminescence, which is present even in the absence of external stimuli. Since this autoluminescence arises from internal metabolic and physiological processes, several works suggested that it could carry information in the time series of the detected photon counts. However, there is little experimental work which would show any difference of this signal from random Poisson noise and some works were prone to artifacts due to lacking or improper reference signals. Here we apply rigorous statistical methods and advanced reference signals to test the hypothesis whether time series of autoluminescence from germinating mung beans display any intrinsic correlations. Utilizing the fractional Brownian bridge that employs short samples of time-series in the method kernel, we suggest that the detected autoluminescence signal from mung beans is not totally random, but it seems to involve a process with a negative memory. Our results contribute to the development of the rigorous methodology of signal analysis of photonic biosignals.
In the mother’s shadow: exploring power dynamics in family business succession
Authors: Ferrari Filippo
Published: March 2019

Purpose

This paper aims to investigate and explain the power dynamics involving the mother (as the founder) and the daughter (as the successor) during the business transmission process.

Design/methodology/approach

This qualitative research was conducted on a sample of Italian family SMEs. The adopted approach is consistent with the narration paradigm, where the biographical features of the participant are investigated to highlight the culture, value systems and other background features.

Findings

This research suggests that if the founder is her mother, the daughter faces further challenges. Findings suggest that during business transmission, it is also important to consider the cultural and contextual factors, such as gender biases, both in the family and in the workplace. This paper seems to suggest that power is important in itself, regardless of the gender of those who exercise it.

Research limitations/implications

Future research should investigate, quantitatively, the same issues considered in this research, to assess the reliability and validity of the evidence discussed here.

Practical implications

This paper suggests how to overcome dysfunctional dynamics in mother–daughter business transmission.

Social implications

Family firms are the most widespread type of firm in the world; as a consequence, systematic failures in business transmission represent a prominent socio-economical problem for policymakers and institutions.

Originality/value

This research shows that in family business, power is not dynamic and does not shift among family members, as suggested by previous research. Even once the mother retires, a stable power hierarchy remains within the family firm.
Women’s ways of leading: the environmental effect
Authors: Dzubinski Leanne , Diehl Amy , Taylor Michelle
Published: March 2019

Purpose

This paper aims to present a model describing how women enact executive leadership, taking into account gendered organizational patterns that may constrain women to perform leadership in context-specific ways.

Design/methodology/approach

This paper discusses gendered organizations, role congruity theory and organizational culture and work context. These strands of theory are interwoven to construct a model describing ways in which executive-level women are constrained to self-monitor based on context.

Findings

The pressure on women to conform to an organization’s executive leadership culture is enormous. Executive women in strongly male-normed executive leadership contexts must exercise strong gendered self-constraint to break through the glass ceiling. Women in strongly male-normed contexts using lessened gendered self-constraint may encounter a glass cliff. Women in gender-diverse-normed contexts may still operate using strong gendered self-constraint due to internalized gender scripts. Only in gender-diverse-normed contexts with lessened gendered-self-restraint can executive women operate from their authentic selves.

Practical implications

Organizational leaders should examine their leadership culture to determine levels of pressure on women to act with gendered self-constraint and to work toward creating change. Women may use the model to make strategic choices regarding whether or how much to self-monitor based on their career aspirations and life goals.

Originality/value

Little has been written on male-normed and gender-diverse-normed contexts as a marker for how executive-level women perform leadership. This paper offers a model describing how different contexts constrain women to behave in specific, gendered ways.
Lucky to reach the top?
Authors: Ottsen Christina Lundsgaard
Published: March 2019

Purpose

As organizations aim to become increasingly diverse, it is important to understand how perspectives of potential future leaders vary across culture and gender. This study aims to advance the understanding of the persistent gender gap in management.

Design/methodology/approach

Samples from the gender-segregated Qatar and the co-ed Denmark present a unique opportunity to investigate the potential effects of gender. Here, 115 Middle Easterners and 121 Scandinavians rated perceived importance of job-related skills, networking upward and serendipity in leadership acquisition.

Findings

Effects of gender showed that compared to men, women across cultures expected that serendipity has less to do with leadership acquisition. Middle Eastern women also showed low expectations regarding networking with people in powerful positions. Nevertheless, both genders showed conviction of meritocracy by rating job-related skills as the most important factor in leadership acquisition. Cross-culturally, Scandinavians presumed job-related skills to be more important than Middle Easterners.

Research limitations/implications

Despite meritocracy beliefs, it appears that gender differences in perceived possibility of leadership acquisition contribute to the gender gap in management. Scandinavian women relied more on networking than Middle Eastern women, but still lacked faith in serendipitous opportunities compared to male peers. Perceived luck enhances achievement motivation. If men rely more on luck than women, then they are more confident in succeeding and more ambitious about pursuit of leadership. Women’s lack of faith in serendipity might affect their career ambitions negatively even in societies emphasizing equality.

Originality/value

This is the first study that directly focuses on gender differences in perception of opportunities for leadership acquisition through serendipity.
Numerical simulation of fatigue crack propagation in mixed-mode (I+II) using the program BemCracker2D
Authors: Leite Pedro G.P. , Gomes Gilberto
Published: March 2019

Purpose

The purpose of this paper is to present the application of the boundary element method (BEM) in linear elastic fracture mechanics for analysis of fatigue crack propagation problems in mixed-mode (I+II) using a robust academic software named BemCracker2D and its graphical interface BemLab2D.

Design/methodology/approach

The methodology consists in calculating elastic stress by conventional BEM and to carry out an incremental analysis of the crack extension employing the dual BEM (DBEM). For each increment of the analysis, the stress intensity factors (SIFs) are computed by the J-Integral technique, the crack growth direction is evaluated by the maximum circumferential stress criterion and the crack growth rate is computed by a modified Paris equation, which takes into account an equivalent SIF to obtain the fracture Modes I and II. The numerical results are compared with the experimental and/or BEM values extracted from the open literature, aiming to demonstrate the accuracy and efficiency of the adopted methodology, as well as to validate the robustness of the programs.

Findings

The paper addresses the numerical simulation of fatigue crack growth. The main contribution of the paper is the introduction of a software for simulating two-dimensional fatigue crack growth problems in mixed-mode (I+II) via the DBEM. The software BemCracker2D coupled to the BemLab2D graphical user interface (GUI), for pre/post-processing, are very complete, efficient and versatile and its does make relevant contributions in the field of fracture mechanics.

Originality/value

The main contribution of the manuscript is the development of a GUI for pre/post-processing of 2D fracture mechanics problems, as well as the object oriented programming implementation. Finally, the main merit is of educational nature.
The effects of residual stresses and strains on lateral-torsional buckling behavior of cold-formed steel channel and built-up I-sections beams
Authors: Kabir Mohammad Zaman , Parvizi Mehdi
Published: March 2019

Purpose

The purpose of this paper is to focus on the influences of residual stresses which were induced during roll-forming sections on lateral-torsional buckling of thin-walled cold-formed steel channel and built-up I-sections beams. Built-up I section is made up of two back-to-back cold-formed channel beams. In this direction, at the primary stage, the roll-forming process of a channel section was simulated in ABAQUS environment and the accuracy of the result was verified with those existing experiments. Residual stresses and strains in both longitudinal and circumferential transverse directions were extracted and considered in the lateral-torsional buckling analysis under uniform end moments. The contribution of the current research is devoted to the numerical simulation of the rolling process in ABAQUS software enabling to restore the remaining stresses and strains for the buckling analysis in the identical software. The results showed that the residual stresses decrease considerably the lateral-torsional buckling strength as they have a major impact on short-span beams for channel sections and larger span for built-up I sections. The obtained moment capacity from the buckling analysis was compared to the predictions by American Iron and Steel Institute design code and it is found to be conservative.

Design/methodology/approach

This paper has explained a numerical study on the roll-forming process of a channel section and member moment capacities related to the lateral-torsional buckling of the rolled form channel and built-up I-sections beams under uniform bending about its major axis. It has also investigated the effects of residual stresses and strains on the behaviour of this buckling mode.

Findings

The residuals decrease the moment capacities of the channel beams and have major effect on shorter spans and also increase the local buckling strength of compression flange. But the residuals have major effect on larger spans for built-up I sections. It could be seen that the ratio of moment (with residuals and without residuals) for singly symmetric sections is more pronounced than doubly symmetric sections. So it is recommended to use doubly symmetric section of cold-formed section beams.

Originality/value

The incorporation of residual stresses and strains in the process of numerical simulation of rolled forming of cold-formed steel sections under end moments is the main contribution of the current work. The effect of residual stresses and strains on the lateral-torsional buckling is, for the first time, addressed in the paper.
Wine attractions at hotels: study of online reviews
Authors: Hsieh Yu-Chin Jerrie , Lee Zui Chih , Yin Ping
Published: March 2019

Purpose

The purpose of this study is to delineate the role of wine at hotels from the customer’s perspective by analyzing New York City hotel reviews posted on TripAdvisor.

Design/methodology/approach

This study used content analysis to study 26,831 wine-relevant reviews that had been posted on TripAdvisor’s New York City hotels by April 12, 2018. Two trained coders quantified and tallied the presence of themes based on the pre-established coding scheme.

Findings

Wine was mentioned in the online reviews in expressing positive, negative or neutral hotel experiences. Of the 877,616 New York City hotel reviews, about 3 per cent contained the keyword “wine.” The three most frequently mentioned wine-related positive experiences were free happy hours, a surprise bottle of complimentary wine and the fun of pairing food and wine. The top three wine-related negative experiences were pricey/expensive/overpriced wine, poor wine list and poor quality of wine. The study found that hotel guests liked wine and that it had become a significant aspect of their lodging experience.

Originality/value

This study adds value to the literature of hotel wines by divulging hotel customers’ wine-related experiences through their online comments and by providing a snapshot of hotel guests’ wine-drinking behavior. The findings can provide an insight for hotels to further the use of wine as a means to enhance guest experience and to generate additional revenue.
How confusion impacts product labeling perceptions
Authors: Fitzgerald M. Paula , Russo Donovan Karen , Kees Jeremy , Kozup John
Published: March 2019

Purpose

Consumer confusion is an often discussed, but seldom investigated, construct central to marketing. This study aims to conceptualize consumer confusion as an intellectual emotion with cognitive and emotional components, and examine it in the context of qualified health claims and conflicting marketplace information.

Design/methodology/approach

A between-subjects experimental design is used to test the hypotheses.

Findings

Structural equation modeling suggests that weak science discussions and conflicting information on dietary supplements evoke consumer confusion. Confusion, in turn, impacts scientific certainty perceptions, product quality and firm credibility. Incorporating confusion measures in theoretical models significantly increases the amount of variance explained in consumer perceptions. Implications are offered for businesses, consumer behaviorists and public policymakers.

Originality/value

It is hard to think about many of marketing’s focal issues (e.g. trademark theory, disclosures and warnings, advertising deception, search and shopping behavior) without using the term confusion. While confusion is central to discussions of these domains, it has evaded focused attention and study. Indeed, no previous research in marketing has directly addressed the experience of consumer confusion per se. The current research fills a gap in the marketing literature by explicitly defining the construct of confusion and offering a measurement approach that is easily adapted to many business/consumer interactions. Furthermore, the authors demonstrate the role of confusion in the context of qualified health claims by showing how conflicting information between health claims, qualifiers and external information can create confusion, and in turn, lead to negative consumer perceptions.