bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure of arylO-demethylase offers molecular insight into a catalytic tyrosine-dependent mechanism
Authors: Kohler Amanda C. , Mills Matthew J. L. , Adams Paul D. , Simmons Blake A. , Sale Kenneth L. 
Published: April 2017

SignificanceModern industrial and agricultural practices generate large quantities of aromatic pollutants; however, these waste products can be converted into fine chemicals, fuels, and plastics through biocatalytic pathways. The bacterial world can inform such utilization strategies as certain strains of soil and marine bacteria metabolize environmentally derived aromatics. Many of these metabolic pathways involve aryl intermediates that require demethylation to facilitate modification and ring opening for assimilation into the tricarboxylic acid (TCA) cycle. Aryl demethylases, which catalyze this reaction, are poorly understood, making their utilization in biotechnology difficult. We provide the structural and mechanistic characterization of a single-domain aryl demethylase, LigM, which employs a tyrosine-dependent mechanism. Insights from this work will inform synthetic biology approaches to convert underutilized aromatics into higher value compounds.
Unveiling the carrier transport mechanism in epitaxial graphene for forming wafer-scale, single-domain graphene
Authors: Bae Sang-Hoon , Zhou Xiaodong , Kim Seyoung , Lee Yun Seog , Cruz Samuel S. , Kim Yunjo , Hannon James B. , Yang Yang , Sadana Devendra K. , Ross Frances M. , Park Hongsik , Kim Jeehwan 
Published: April 2017

Significance
The use of epitaxial graphene has been less favored over the use of chemical vapor deposition (CVD)-grown polycrystalline graphene because graphene formed near SiC vicinal steps accompanies carrier scattering, which makes the practical domain size of epitaxial graphene much smaller than that of CVD-grown graphene. Nonetheless, the origin of carrier scattering at the SiC vicinal steps has not been fully understood. Here, we experimentally reveal that graphene formed at side walls is pristine, and the scattering near the steps mainly originates from the deformation of graphene and partially from stripes of bilayer graphene. This understanding of the origin of scattering allows us to demonstrate large-size single-domain graphene, removing major scattering sources through a layer-resolved transfer.
Biosynthesis of the pyrrolidine protein synthesis inhibitor anisomycin involves novel gene ensemble and cryptic biosynthetic steps
Authors: Zheng Xiaoqing , Cheng Qiuxiang , Yao Fen , Wang Xiaozheng , Kong Lingxin , Cao Bo , Xu Min , Lin Shuangjun , Deng Zixin , Chooi Yit-Heng , You Delin 
Published: April 2017

Significance
Despite significant advances in the prediction of natural product biosynthetic gene clusters (BGCs) from microbial genomes, challenges remain for those belong to the lesser-known classes. Using a bioactivity-guided library screening approach, we have identified a BGC encoding the biosynthesis of anisomycin, an important pyrrolidine-containing protein synthesis inhibitor. The biosynthetic pathway is distinct from known bacterial alkaloid pathways and involves a class of natural product backbone biosynthesis genes encoding an α-keto acid-incorporating transketolase. A cryptic but crucial glycosylation, unexpected transaminations, and a multistep pyrrolidine-forming reaction catalyzed by a single enzyme are also required to complete the assembly of the core benzylpyrrolidine scaffold. These findings open up new avenues for genomics-guided natural product discovery and engineering of pyrrolidine antibiotics.
Evidence of low-density and high-density liquid phases and isochore end point for water confined to carbon nanotube
Authors: Nomura Kentaro , Kaneko Toshihiro , Bai Jaeil , Francisco Joseph S. , Yasuoka Kenji , Zeng Xiao Cheng 
Published: April 2017

Significance
Bulk water is known for its rich phase behavior, including 18 crystalline phases and 3 amorphous phases. Although computer simulations have uncovered coexistence of metastable low- and high-density liquid water below the freezing point, experimental evidence is still lacking because of the predicted coexistence below 230 K. Here, we show simulation evidence that, inside an isolated carbon nanotube with a diameter of 1.25 nm, both low- and high-density liquid water states can be detected near ambient temperature (278–292 K) and above ambient pressure. In the temperature–pressure phase diagram, the low- and high-density liquid phases are separated by hexagonal ice nanotube phase. The latter has already been observed in the laboratory.
Modeling Otolith Weight using Fish Age and Length: Applications to Age Determination
Authors: Hanson S. Dale , Stafford Craig P. 
Published: April 2017

AbstractRelationships among otolith weight and age have been explored widely as cost‐effective means to predict age. However, otolith weight is influenced by both fish age and somatic growth, making it necessary to partition these confounding effects to best use otolith weight to predict age. We used several hatchery strains of Lake Trout Salvelinus namaycush that varied in capture season, year, location, and mean size at stocking to develop a maximum likelihood model of otolith weight as complementary but independent functions of age (mg/year) and fish length (mg/mm). Once these relationships were established, we determined age probabilities for each fish based on their measurements. Our best model included age and somatic growth components, with cumulative mean temperature as a variable to scale for seasonal differences in otolith accretion. For fish between 3 and 19 years of age, otolith weight increased by 1.16 mg/year, with an additional somatic growth component of 0.62 × exp(fish length × 0.0038) mg/mm. We correctly assigned age to 60% of the age‐3 fish, but this decreased to about 10% among the oldest age‐classes; however, predicted age residuals approximated normal distributions within each age‐class. The model was robust to seasonal and annual variation, but somatic growth differences among some strain and stocking‐size groupings resulted in modal aging biases of ±1 year. Given the stability in otolith weight components arising from fish age and somatic growth, we suggest that modeling otolith weight using reader age estimates offers a new quality assurance/quality control tool to assess whether reader ages support the widely documented properties of otolith growth. When otolith weight and fish length are more informative of age, our model may also be useful in estimating age composition data similar to an age–length key.Received December 19, 2016; accepted March 20, 2017 Published online May 26, 2017
Severe asthma
Authors: Shah Anand , Menzies-Gow Andrew 
Published: April 2017

Abstract
Poorly controlled asthma is a common reason for referral to the respiratory clinic, and the majority of cases can be managed effectively by ensuring the correct diagnosis and ensuring good compliance with inhaled therapy. However, severe asthma affects up to 10% of patients with asthma and is associated with substantial morbidity and mortality, along with significant health-care costs from both inpatient treatment and lost work days. This chapter covers two cases of difficult-to-control asthma and highlights the role of detailed investigations when asthma control is not straightforward. It will cover the diagnostic criteria for allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization and discuss the role of omalizumab in managing severe asthma.
Chronic obstructive pulmonary disease
Authors: Jaffer Amina , Patel Anant , Hurst John 
Published: April 2017

Abstract
This chapter discusses the case of a 70-year-old man with his first presentation of chronic obstructive pulmonary disease. This case is used as a basis to explore and describe the diagnosis, investigation, and management of this condition. The chapter includes the evidence base and relative guidelines that support current practice, as well as highlighting useful learning points and providing expert opinion. The role of lung volume reduction surgery is discussed, and its potential benefits in selected patients highlighted. Phenotypic variability within chronic obstructive pulmonary disease is increasingly recognized, and this is discussed, including the implications on current management and future research.
Intensive care unit and ventilation
Authors: Garner Justin , Treacher David 
Published: April 2017

Abstract
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by rapidly developing hypoxaemic respiratory failure and bilateral pulmonary infiltrates on chest X-ray. ALI/ARDS are a relatively frequent diagnosis in protracted-stay patients in the intensive care unit. The pathology is a non-specific response to a wide variety of insults. Impaired gas exchange, ventilation-perfusion mismatch, and reduced compliance ensue. Mechanical ventilation is the mainstay of management, along with treatment of the underlying cause. Mortality remains very high at around 40%. The condition is challenging to treat. Injury to the lungs, indistinguishable from that of ARDS, has been attributed to the use of excessive tidal volumes, pressures, and repeated opening and collapsing of alveoli. Lung-protective strategies aim to minimize the effects of ventilator-induced lung injury. Use of low tidal volume ventilation has been shown to improve mortality. Emerging ventilatory therapies include high-frequency oscillatory ventilation and extracorporeal membrane oxygenation.
Narcolepsy: still sleepy on CPAP
Authors: Walder Dave , Reading Paul 
Published: April 2017

Abstract
Sleep disorders are an increasingly common reason for referral to the respiratory clinic, and our understanding of the different aetiologies is increasing. The commonest sleep disorder is sleep apnoea, but other sleep disorders can cause similar symptoms. Narcolepsy is a neurological disorder that affects the brain’s ability to regulate the normal sleep-wake cycle and often presents with similar symptoms to obstructive sleep apnoea, daytime hypersomnolence, and disturbed night-time sleeping but is largely underdiagnosed. This chapter discusses a patient who presented with symptoms of daytime somnolence and witnessed apnoeas and details the investigations required for a diagnosis of narcolepsy. It covers the more specialized sleep studies required for a clinical diagnosis and the treatment options available for patients with this condition.
Pulmonary disease caused by non-tuberculous mycobacteria
Authors: Stowell Janet , Breen Ronan 
Published: April 2017

Abstract
This chapter describes a case of Mycobacterium malmoense in a male ex-smoker with chronic obstructive pulmonary disease. The approaches to a diagnosis of pulmonary non-tuberculous mycobacterial disease are discussed, including key laboratory features and associated radiological changes. The factors influencing the decision to treat and treatment regimen selected are reviewed, along with evidence from landmark trials regarding drug combinations and the role of surgery in managing non-tuberculous mycobacterial disease. This case was complicated by a secondary diagnosis of invasive aspergillosis, and the challenges of treating non-tuberculous mycobacteria and Aspergillus concurrently are highlighted. Non-tuberculous mycobacterial infection in HIV-positive patients can behave differently to non-tuberculous mycobacterial disease in immunocompetent individuals. Restoring immunocompetence is key to the success of non-tuberculous mycobacterial treatment in these individuals, but beware Mycobacterium avium complex-related immune restoration inflammatory syndrome.
Swine ‘flu’ in pregnancy
Authors: Almond Mark H , Griffiths Mark J 
Published: April 2017

Abstract
Influenza viruses are a significant cause of morbidity and mortality globally, resulting in severe illness in 3-5 million people and death in up to 500,000 during epidemic years. In March 2009, a novel H1N1 virus emerged in Mexico, spreading rapidly around the globe and achieving pandemic status within 3 months. Although it is now generally considered that the 2009 pandemic resulted in mild disease in most individuals, serious complications still occurred, with 12,000 deaths by mid-February 2010 in the United States alone. Risk factors for severe disease included asthma, cardiac disease, immunosuppression, pregnancy, diabetes mellitus, and obesity. The chapter outlines the case of a young pregnant female who presented with an influenza-like illness and subsequently developed acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. The origins, presentation, diagnosis, complications, and management of pandemic influenza are discussed, in addition to a summary of the pulmonary physiology and pathology of pregnancy.
Transplant
Authors: Barrett Jessica , Carby Martin 
Published: April 2017

Abstract
Since the first successful lung transplant in 1981, tens of thousands of operations have been performed across the world. Yet despite significant technical advances, mortality is the highest of any solid organ transplant. Most patients will have a major complication within the first 5 years of the operation. These are best managed in transplant centres. However, a working knowledge of the presentation and initial management is essential for a respiratory physician. Although the rate of complications remains high, more than 80% of patients with surviving transplants report no limitation of activity at 1, 3, and 5 years. Developments in surgical technique have reduced immediate complications, and immunosuppressive regimens continue to improve. However, the incidence of obliterative bronchiolitis remains high and is responsible for the majority of graft failures.
The molten glass sewing machine
Authors: Brun P.-T. , Inamura Chikara , Lizardo Daniel , Franchin Giorgia , Stern Michael , Houk Peter , Oxman Neri 
Published: April 2017

We present a fluid-instability-based approach for digitally fabricating geometrically complex uniformly sized structures in molten glass. Formed by mathematically defined and physically characterized instability patterns, such structures are produced via the additive manufacturing of optically transparent glass, and result from the coiling of an extruded glass thread. We propose a minimal geometrical model—and a methodology—to reliably control the morphology of patterns, so that these building blocks can be assembled into larger structures with tailored functionally and optically tunable properties.
This article is part of the themed issue ‘Patterning through instabilities in complex media: theory and applications’.
Oblique wrinkles
Authors: Carfagna M. , Destrade M. , Gower A. L. , Grillo A. 
Published: April 2017

We prove theoretically that when a soft solid is subjected to an extreme deformation, wrinkles can form on its surface at an angle that is oblique to a principal direction of stretch. These oblique wrinkles occur for a strain that is smaller than the one required to obtain wrinkles normal to the direction of greatest compression. We go on to explain why they will probably never be observed in real-world experiments.This article is part of the themed issue ‘Patterning through instabilities in complex media: theory and applications.’
The dynamics of folding instability in a constrained Cosserat medium
Authors: Gourgiotis Panos A. , Bigoni Davide 
Published: April 2017

Different from Cauchy elastic materials, generalized continua, and in particular constrained Cosserat materials, can be designed to possess extreme (near a failure of ellipticity) orthotropy properties and in this way to model folding in a three-dimensional solid. Following this approach, folding, which is a narrow zone of highly localized bending, spontaneously emerges as a deformation pattern occurring in a strongly anisotropic solid. How this peculiar pattern interacts with wave propagation in the time-harmonic domain is revealed through the derivation of an antiplane, infinite-body Green’s function, which opens the way to integral techniques for anisotropic constrained Cosserat continua. Viewed as a perturbing agent, the Green’s function shows that folding, emerging near a steadily pulsating source in the limit of failure of ellipticity, is transformed into a disturbance with wavefronts parallel to the folding itself. The results of the presented study introduce the possibility of exploiting constrained Cosserat solids for propagating waves in materials displaying origami patterns of deformation.
This article is part of the themed issue ‘Patterning through instabilities in complex media: theory and applications.’
Wrinkling instabilities in soft bilayered systems
Authors: Budday Silvia , Andres Sebastian , Walter Bastian , Steinmann Paul , Kuhl Ellen 
Published: April 2017

Wrinkling phenomena control the surface morphology of many technical and biological systems. While primary wrinkling has been extensively studied, experimentally, analytically and computationally, higher-order instabilities remain insufficiently understood, especially in systems with stiffness contrasts well below 100. Here, we use the model system of an elastomeric bilayer to experimentally characterize primary and secondary wrinkling at moderate stiffness contrasts. We systematically vary the film thickness and substrate prestretch to explore which parameters modulate the emergence of secondary instabilities, including period-doubling, period-tripling and wrinkle-to-fold transitions. Our experiments suggest that period-doubling is the favourable secondary instability mode and that period-tripling can emerge under disturbed boundary conditions. High substrate prestretch can suppress period-doubling and primary wrinkles immediately transform into folds. We combine analytical models with computational simulations to predict the onset of primary wrinkling, the post-buckling behaviour, secondary bifurcations and the wrinkle-to-fold transition. Understanding the mechanisms of pattern selection and identifying the critical control parameters of wrinkling will allow us to fabricate smart surfaces with tunable properties and to control undesired surface patterns like in the asthmatic airway.
This article is part of the themed issue ‘Patterning through instabilities in complex media: theory and applications.’
On the buckling of elastic rings by external confinement
Authors: Hazel Andrew L. , Mullin Tom 
Published: April 2017

We report the results of an experimental and numerical investigation into the buckling of thin elastic rings confined within containers of circular or regular polygonal cross section. The rings float on the surface of water held in the container and controlled removal of the fluid increases the confinement of the ring. The increased compressive forces can cause the ring to buckle into a variety of shapes. For the circular container, finite perturbations are required to induce buckling, whereas in polygonal containers the buckling occurs through a linear instability that is closely related to the canonical Euler column buckling. A model based on Kirchhoff–Love beam theory is developed and solved numerically, showing good agreement with the experiments and revealing that in polygons increasing the number of sides means that buckling occurs at reduced levels of confinement.
This article is part of the themed issue ‘Patterning through instabilities in complex media: theory and applications.’
Detecting Drug-Target Binding in Cells using Fluorescence Activated Cell Sorting Coupled with Mass Spectrometry Analysis
Authors: Wilson Kris , Webster Scott P , Iredale John P , Zheng Xiaozhong , Homer Natalie Z , Pham Nhan , Auer Manfred , Mole Damian J 
Published: April 2017

AbstractThe assessment of drug-target engagement for determining the efficacy of a compound inside cells remains challenging, particularly for difficult target proteins. Existing techniques are more suited to soluble protein targets. Difficult target proteins include those with challenging in vitro solubility, stability or purification properties that preclude target isolation. Here, we report a novel technique that measures intracellular compound-target complex formation, as well as cellular permeability, specificity and cytotoxicity - the Toxicity-Affinity-Permeability-Selectivity (TAPS) technique. The TAPS assay is exemplified here using human kynurenine 3-monooxygenase (KMO), a challenging intracellular membrane protein target of significant current interest. TAPS confirmed target binding of known KMO inhibitors inside cells. We conclude that the TAPS assay can be used to facilitate intracellular hit validation on most, if not all intracellular drug targets.
De novoVariants in Neurodevelopmental Disorders with Epilepsy
Authors: Heyne Henrike O. , Singh Tarjinder , Stamberger Hannah , Jamra Rami Abou , Caglayan Hande , Craiu Dana , Jonghe Peter De , Guerrini Renzo , Helbig Katherine L. , Koeleman Bobby P. C. , Kosmicki Jack A. , Linnankivi Tarja , May Patrick , Muhle Hiltrud , Møller Rikke S. , Neubauer Bernd A. , Palotie Aarno , Pendziwiat Manuela , Striano Pasquale , Tang Sha , Wu Sitao ,   EuroEPINOMICS RES Consortium, Poduri Annapurna , Weber Yvonne G. , Weckhuysen Sarah , Sisodiya Sanjay M. , Daly Mark , Helbig Ingo , Lal Dennis , Lemke Johannes R. 
Published: April 2017

AbstractEpilepsy is a frequent feature of neurodevelopmental disorders (NDD) but little is known about genetic differences between NDD with and without epilepsy. We analyzedde novovariants (DNV) in 6753 parent-offspring trios ascertained for different NDD. In the subset of 1942 individuals with NDD with epilepsy, we identified 33 genes with a significant excess of DNV, of whichSNAP25andGABRB2had previously only limited evidence for disease association. Joint analysis of all individuals with NDD also implicatedCACNA1Eas a novel disease gene. Comparing NDD with and without epilepsy, we found missense DNV, DNV in specific genes, age of recruitment and severity of intellectual disability to be associated with epilepsy. We further demonstrate to what extent our results impact current genetic testing as well as treatment, emphasizing the benefit of accurate genetic diagnosis in NDD with epilepsy.
Meta-analysis of liver and heart transcriptomic data for functional annotation transfer in mammalian orthologs
Authors: Loren Reyes Pía Francesca , Michoel Tom , Joshi Anagha , Devailly Guillaume 
Published: April 2017

AbstractFunctional annotation transfer across multi-gene family orthologs can lead to functional misannotations. We hypothesised that co-expression network will help predict functional orthologs amongst complex homologous gene families. To explore the use of transcriptomic data available in public domain to identify functionally equivalent ones from all predicted orthologs, we collected genome wide expression data in mouse and rat liver from over 1500 experiments with varied treatments. We used a hyper-graph clustering method to identify clusters of orthologous genes co-expressed in both mouse and rat. We validated these clusters by analysing expression profiles in each species separately, and demonstrating a high overlap. We then focused on genes in 18 homology groups with one-to-many or many-to-many relationships between two species, to discriminate between functionally equivalent and non-equivalent orthologs. Finally, we further applied our method by collecting heart transcriptomic data (over 1400 experiments) in rat and mouse to validate the method in an independent tissue.