bluuebunny/crossref_metadata_2025_split huggingface dataset:
Skepticism and Political Constancy:Richard IIand the Garden Scene as a “Model of State”
Authors: Condren Conal 
Published: September 2016

AbstractMany readers have taken the garden scene inRichard IIand the voice of its Gardener to constitute a relatively straightforward statement of Shakespeare's notions of good government and constancy in political conduct, in stark contrast to the political disorder depicted in the play. I argue, however, that read in the context of the political and moral issues Shakespeare explored, its value or even relevance to his political world is questionable. The choric voice of the Gardener was not necessarily Shakespeare's. The dramatic point may have been to present, without resolving, the dissonance between the Gardener's vision and the imponderables of political conduct lying beyond his tiny realm.
Shakespeare's Politics
Authors: Frazer Elizabeth 
Published: September 2016

AbstractThis paper sets out diverse ways that Shakespeare's dramas can be read politically. Critics and political theorists have often concentrated on what Shakespeare said about politics—whether he was broadly republican or monarchist, protofeminist or a patriarchalist—as well as concentrating on his references to political themes of his day. Focusing on political readings ofMerchant of VeniceandOthello, I argue that, rather, we should pay attention to how Shakespeare plays with numerous styles of political action and role, from statesmanship and the competiton for state office or for sovereignty, to the everyday relations of kinship and friendship that interact with state government and law, and to individuals' struggles against politically established power—patriarchy, class, state law—that constrains or oppresses them. The figure of the Machiavellian political operator, whether acting for good or for ill, is contrasted with the open speaker of truth in public.
“I Ask Your Voices and Your Suffrages”: The Bogus Rome of Peele and Shakespeare'sTitus Andronicus
Authors: Kewes Paulina 
Published: September 2016

AbstractThis essay provides a contextual reading ofTitus Andronicus, paying close attention to the play's collaborative authorship. Peele and Shakespeare are shown to have manufactured a superficially compelling but in reality utterly fake image of the Roman state as an imaginary laboratory for political ideas, especially the elective principle. Topical allusions and deliberate anachronisms encourage the audience to relate the subject matter to the present, viz., late Elizabethan England in the throes of a succession crisis and rent by confessional divisions. Unlike Peele's solo works, which exhibit a potent anti-Catholic bias,Titusremains confessionally elusive. The play invites the audience to reflect on the viability of particular modes of succession without committing itself either way, and shows that it is not institutional structures and processes but those who use and abuse them that make the difference to the state of the polity.
“Something Wicked This Way Comes”: Machiavelli, Macbeth, and the Conquest of Fortuna
Authors: Zuckert Michael P. 
Published: September 2016

AbstractAs in all or almost all Shakespeare plays the opening scenes of Macbeth are key to setting up the problem the play addresses. In his Scottish play Shakespeare uses the opening scenes to set the two main contexts in which the regicide, usurpation, tyranny, and fall of the tyrant occur. The two are, we might say, the earthly or political context and the cosmic or superhuman context represented by the witches. In presenting these two contexts Shakespeare appears to be engaging in a dialogue with Machiavelli's Prince, taking cues from Machiavelli's political analysis on how to understand the political character of Scotland and taking issue with Machiavelli's ultimate agenda of a conquest of Fortuna.
Time and the Problem of Royal Succession in Shakespeare's History Plays
Authors: Cox John D. 
Published: September 2016

AbstractShakespeare's most innovative genre was the history play, because it has no precedent in either classical or medieval tradition. In contrast to the focused teleology of Christian medieval drama, Shakespeare's history plays manifest an implicit idea of history that was secular, political, and open-ended. They emphasize human action in a political arena, where the criterion for success is the ability to act in time, without regard to one's spiritual state. Time determines royal succession, which is the focus of all Shakespeare's history plays, as it was the focus of political concern in England in the 1590s, when the plays were written. His emphasis on time and royal succession distinguishes his implied political theory from the moralism and authoritarianism of official Tudor state doctrine on one hand and from the pragmatism of Machiavelli on the other.
THROUGH ONE OF BOB'S WINDOWS
Authors: Griffiths Paul 
Published: September 2016

A short paper hardly stands in need of an epigraph, but I'm going to give mine one all the same. Here, then, are four lines, a quatrain, using every letter in the alphabet except for the loss of B, O, G, I, L, M, R and E.
What vast wants can fantasy attack?What junk quanta has fantasy attun'd?What zany dad had an ax at hand?As Kant says, what a fuck-up …
Reliable and unproductive? Stereotypes of older employees in corporate and news media
Authors: KROON ANNE C. , VAN SELM MARTINE , ter HOEVEN CLAARTJE L. , VLIEGENTHART RENS 
Published: September 2016

ABSTRACTOlder employees face a severe employability problem, partly because of dominant stereotypes about them. This study investigates stereotypes of older employees in corporate and news media. Drawing on the Stereotype Content Model, we content analysed newspaper coverage and corporate media of 50 large-scale Dutch organisations, published between 2006 and 2013. The data revealed that stereotypical portrayals of older employees are more common in news media than in corporate media and mixed in terms of valence. Specifically, older employees were positively portrayed with regard to warmth stereotypes, such as trustworthiness, but negatively with regard to competence stereotypes, such as technological competence and adaptability. Additionally, stereotypical portrayals that do not clearly belong to warmth or competence dimensions are found, such as the mentoring role stereotype and the costly stereotype. Because competence stereotypes weigh more heavily in employers’ productivity perceptions, these media portrayals might contribute to the employability problem of older employees. We suggest that older employees could benefit from a more realistic media debate about their skills and capacities.
Quantitative risk analysis of the novel H7N9 virus in environments associated with H9 avian influenza virus, Zhejiang province, China
Authors: HE F. , LIN J. F. , WANG X. Y. , LI F. D. , YU Z. , CHEN E. F. 
Published: September 2016

SUMMARYH9 avian influenza virus played a key role during generation of the novel H7N9 virus. A surveillance programme was conducted to assess the H9 virus in relation to the risk of H7N9 virus contamination in the environment. Risk of H7N9 virus contamination in the presence of H9 virus was higher than without (adjusted odds ratio 4·49, 95% confidence interval 3·79–5·31). Adjusted odds ratios of the H7N9 virus associated with co-presence of H9 virus and interacting factors were 4·93 (ruralvs.urban area), 46·80 (live poultry marketsvs. other premises), 6·86 (Huzhouvs.Hangzhou prefecture), 40·67 (year 2015vs.2013), and 9·63 (sewage from cleaning poultryvs.poultry faeces). Regular surveillance on gene variability of H7N9 and H9 viruses should be conducted and extra measures are needed to reduce co-circulation of H7N9 and H9 viruses in the environment.
Transition metal ion FRET uncovers K+ regulation of a neurotransmitter/sodium symporter
Authors: Billesbølle Christian B. , Mortensen Jonas S. , Sohail Azmat , Schmidt Solveig G. , Shi Lei , Sitte Harald H. , Gether Ulrik , Loland Claus J. 
Published: September 2016

AbstractNeurotransmitter/sodium symporters (NSSs) are responsible for Na+-dependent reuptake of neurotransmitters and represent key targets for antidepressants and psychostimulants. LeuT, a prokaryotic NSS protein, constitutes a primary structural model for these transporters. Here we show that K+ inhibits Na+-dependent binding of substrate to LeuT, promotes an outward-closed/inward-facing conformation of the transporter and increases uptake. To assess K+-induced conformational dynamics we measured fluorescence resonance energy transfer (FRET) between fluorescein site-specifically attached to inserted cysteines and Ni2+ bound to engineered di-histidine motifs (transition metal ion FRET). The measurements supported K+-induced closure of the transporter to the outside, which was counteracted by Na+ and substrate. Promoting an outward-open conformation of LeuT by mutation abolished the K+-effect. The K+-effect depended on an intact Na1 site and mutating the Na2 site potentiated K+ binding by facilitating transition to the inward-facing state. The data reveal an unrecognized ability of K+ to regulate the LeuT transport cycle.
Irreversible inhibitors of the 3C protease of Coxsackie virus through templated assembly of protein-binding fragments
Authors: Becker Daniel , Kaczmarska Zuzanna , Arkona Christoph , Schulz Robert , Tauber Carolin , Wolber Gerhard , Hilgenfeld Rolf , Coll Miquel , Rademann Jörg 
Published: September 2016

AbstractSmall-molecule fragments binding to biomacromolecules can be starting points for the development of drugs, but are often difficult to detect due to low affinities. Here we present a strategy that identifies protein-binding fragments through their potential to induce the target-guided formation of covalently bound, irreversible enzyme inhibitors. A protein-binding nucleophile reacts reversibly with a bis-electrophilic warhead, thereby positioning the second electrophile in close proximity of the active site of a viral protease, resulting in the covalent de-activation of the enzyme. The concept is implemented for Coxsackie virus B3 3C protease, a pharmacological target against enteroviral infections. Using an aldehyde-epoxide as bis-electrophile, active fragment combinations are validated through measuring the protein inactivation rate and by detecting covalent protein modification in mass spectrometry. The structure of one enzyme–inhibitor complex is determined by X-ray crystallography. The presented warhead activation assay provides potent non-peptidic, broad-spectrum inhibitors of enteroviral proteases.
Genome-wide association study for acute otitis media in children identifies FNDC1 as disease contributing gene
Authors: van Ingen Gijs , Li Jin , Goedegebure André , Pandey Rahul , Li Yun Rose , March Michael E. , Jaddoe Vincent W. V. , Bakay Marina , Mentch Frank D. , Thomas Kelly , Wei Zhi , Chang Xiao , Hain Heather S. , Uitterlinden André G. , Moll Henriette A. , van Duijn Cornelia M. , Rivadeneira Fernando , Raat Hein , Baatenburg de Jong Robert J. , Sleiman Patrick M. , van der Schroeff Marc P. , Hakonarson Hakon 
Published: September 2016

AbstractAcute otitis media (AOM) is among the most common pediatric diseases, and the most frequent reason for antibiotic treatment in children. Risk of AOM is dependent on environmental and host factors, as well as a significant genetic component. We identify genome-wide significance at a locus on 6q25.3 (rs2932989, Pmeta=2.15 × 10−09), and show that the associated variants are correlated with the methylation status of the FNDC1 gene (cg05678571, P=1.43 × 10−06), and further show it is an eQTL for FNDC1 (P=9.3 × 10−05). The mouse homologue, Fndc1, is expressed in middle ear tissue and its expression is upregulated upon lipopolysaccharide treatment. In this first GWAS of AOM and the largest OM genetic study to date, we identify the first genome-wide significant locus associated with AOM.
Initiating and imaging the coherent surface dynamics of charge carriers in real space
Authors: Rusimova K. R. , Bannister N. , Harrison P. , Lock D. , Crampin S. , Palmer R. E. , Sloan P. A. 
Published: September 2016

AbstractThe tip of a scanning tunnelling microscope is an atomic-scale source of electrons and holes. As the injected charge spreads out, it can induce adsorbed molecules to react. By comparing large-scale ‘before’ and ‘after’ images of an adsorbate covered surface, the spatial extent of the nonlocal manipulation is revealed. Here, we measure the nonlocal manipulation of toluene molecules on the Si(111)-7 × 7 surface at room temperature. Both the range and probability of nonlocal manipulation have a voltage dependence. A region within 5–15 nm of the injection site shows a marked reduction in manipulation. We propose that this region marks the extent of the initial coherent (that is, ballistic) time-dependent evolution of the injected charge carrier. Using scanning tunnelling spectroscopy, we develop a model of this time-dependent expansion of the initially localized hole wavepacket within a particular surface state and deduce a quantum coherence (ballistic) lifetime of ∼10 fs.
Wave-induced loss of ultra-relativistic electrons in the Van Allen radiation belts
Authors: Shprits Yuri Y. , Drozdov Alexander Y. , Spasojevic Maria , Kellerman Adam C. , Usanova Maria E. , Engebretson Mark J. , Agapitov Oleksiy V. , Zhelavskaya Irina S. , Raita Tero J. , Spence Harlan E. , Baker Daniel N. , Zhu Hui , Aseev Nikita A. 
Published: September 2016

AbstractThe dipole configuration of the Earth’s magnetic field allows for the trapping of highly energetic particles, which form the radiation belts. Although significant advances have been made in understanding the acceleration mechanisms in the radiation belts, the loss processes remain poorly understood. Unique observations on 17 January 2013 provide detailed information throughout the belts on the energy spectrum and pitch angle (angle between the velocity of a particle and the magnetic field) distribution of electrons up to ultra-relativistic energies. Here we show that although relativistic electrons are enhanced, ultra-relativistic electrons become depleted and distributions of particles show very clear telltale signatures of electromagnetic ion cyclotron wave-induced loss. Comparisons between observations and modelling of the evolution of the electron flux and pitch angle show that electromagnetic ion cyclotron waves provide the dominant loss mechanism at ultra-relativistic energies and produce a profound dropout of the ultra-relativistic radiation belt fluxes.
Stereoselective alkoxycarbonylation of unactivated C(sp3)–H bonds with alkyl chloroformates via Pd(II)/Pd(IV) catalysis
Authors: Liao Gang , Yin Xue-Song , Chen Kai , Zhang Qi , Zhang Shuo-Qing , Shi Bing-Feng 
Published: September 2016

AbstractSeveral examples on Pd-catalysed carbonylation of methyl C(sp3)–H bonds with gaseous CO via Pd(II)/Pd(0) catalysis have been reported. However, methylene C(sp3)–H carbonylation remains a great challenge, largely due to the lack of reactivity of C–H bonds and the difficulty in CO migratory insertion. Herein, we report the stereoselective alkoxycarbonylation of both methyl and methylene C(sp3)–H bonds with alkyl chloroformates through a Pd(II)/Pd(IV) catalytic cycle. A broad range of aliphatic carboxamides and alkyl chloroformates are compatible with this protocol. In addition, this process is scalable and the directing group could be easily removed under mild conditions with complete retention of configuration.
Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity
Authors: Ooi Wen Fong , Xing Manjie , Xu Chang , Yao Xiaosai , Ramlee Muhammad Khairul , Lim Mei Chee , Cao Fan , Lim Kevin , Babu Deepak , Poon Lai-Fong , Lin Suling Joyce , Qamra Aditi , Irwanto Astrid , Qu Zhengzhong James , Nandi Tannistha , Lee-Lim Ai Ping , Chan Yang Sun , Tay Su Ting , Lee Ming Hui , Davies James O. J. , Wong Wai Keong , Soo Khee Chee , Chan Weng Hoong , Ong Hock Soo , Chow Pierce , Wong Chow Yin , Rha Sun Young , Liu Jianjun , Hillmer Axel M. , Hughes Jim R. , Rozen Steve , Teh Bin Tean , Fullwood Melissa Jane , Li Shang , Tan Patrick 
Published: September 2016

AbstractRegulatory enhancer elements in solid tumours remain poorly characterized. Here we apply micro-scale chromatin profiling to survey the distal enhancer landscape of primary gastric adenocarcinoma (GC), a leading cause of global cancer mortality. Integrating 110 epigenomic profiles from primary GCs, normal gastric tissues and cell lines, we highlight 36,973 predicted enhancers and 3,759 predicted super-enhancers respectively. Cell-line-defined super-enhancers can be subclassified by their somatic alteration status into somatic gain, loss and unaltered categories, each displaying distinct epigenetic, transcriptional and pathway enrichments. Somatic gain super-enhancers are associated with complex chromatin interaction profiles, expression patterns correlated with patient outcome and dense co-occupancy of the transcription factors CDX2 and HNF4α. Somatic super-enhancers are also enriched in genetic risk SNPs associated with cancer predisposition. Our results reveal a genome-wide reprogramming of the GC enhancer and super-enhancer landscape during tumorigenesis, contributing to dysregulated local and regional cancer gene expression.
ANGPTL2 activity in cardiac pathologies accelerates heart failure by perturbing cardiac function and energy metabolism
Authors: Tian Zhe , Miyata Keishi , Kadomatsu Tsuyoshi , Horiguchi Haruki , Fukushima Hiroyuki , Tohyama Shugo , Ujihara Yoshihiro , Okumura Takahiro , Yamaguchi Satoshi , Zhao Jiabin , Endo Motoyoshi , Morinaga Jun , Sato Michio , Sugizaki Taichi , Zhu Shunshun , Terada Kazutoyo , Sakaguchi Hisashi , Komohara Yoshihiro , Takeya Motohiro , Takeda Naoki , Araki Kimi , Manabe Ichiro , Fukuda Keiichi , Otsu Kinya , Wada Jun , Murohara Toyoaki , Mohri Satoshi , Yamashita Jun K. , Sano Motoaki , Oike Yuichi 
Published: September 2016

AbstractA cardioprotective response that alters ventricular contractility or promotes cardiomyocyte enlargement occurs with increased workload in conditions such as hypertension. When that response is excessive, pathological cardiac remodelling occurs, which can progress to heart failure, a leading cause of death worldwide. Mechanisms underlying this response are not fully understood. Here, we report that expression of angiopoietin-like protein 2 (ANGPTL2) increases in pathologically-remodeled hearts of mice and humans, while decreased cardiac ANGPTL2 expression occurs in physiological cardiac remodelling induced by endurance training in mice. Mice overexpressing ANGPTL2 in heart show cardiac dysfunction caused by both inactivation of AKT and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a signalling and decreased myocardial energy metabolism. Conversely, Angptl2 knockout mice exhibit increased left ventricular contractility and upregulated AKT-SERCA2a signalling and energy metabolism. Finally, ANGPTL2-knockdown in mice subjected to pressure overload ameliorates cardiac dysfunction. Overall, these studies suggest that therapeutic ANGPTL2 suppression could antagonize development of heart failure.
A unique RPW8-encoding class of genes that originated in early land plants and evolved through domain fission, fusion, and duplication
Authors: Zhong Yan , Cheng Zong-Ming 
Published: September 2016

AbstractDuplication, lateral gene transfer, domain fusion/fission and de novo domain creation play a key role in formation of initial common ancestral protein. Abundant protein diversities are produced by domain rearrangements, including fusions, fissions, duplications, and terminal domain losses. In this report, we explored the origin of the RPW8 domain and examined the domain rearrangements that have driven the evolution of RPW8-encoding genes in land plants. The RPW8 domain first emerged in the early land plant, Physcomitrella patens, and it likely originated de novo from a non-coding sequence or domain divergence after duplication. It was then incorporated into the NBS-LRR protein to create a main sub-class of RPW8-encoding genes, the RPW8-NBS-encoding genes. They evolved by a series of genetic events of domain fissions, fusions, and duplications. Many species-specific duplication events and tandemly duplicated clusters clearly demonstrated that species-specific and tandem duplications played important roles in expansion of RPW8-encoding genes, especially in gymnosperms and species of the Rosaceae. RPW8 domains with greater Ka/Ks values than those of the NBS domains indicated that they evolved faster than the NBS domains in RPW8-NBSs.
Evaluation of antibody level against Fusobacterium nucleatum in the serological diagnosis of colorectal cancer
Authors: Wang Hai-Fang , Li Lin-Fang , Guo Song-He , Zeng Qiu-Yao , Ning Fen , Liu Wan-Li , Zhang Ge 
Published: September 2016

AbstractFusobacterium nucleatum (F. nucleatum, Fn) is associated with the colorectal cancer (CRC). Fn-infection could induce significant levels of serum Fn-specific antibodies in human and mice. The objective of this study was to identify Fn-infection that elicit a humoral response in patients with CRC and evaluate the diagnostic performance of serum anti-Fn antibodies. In this work, we showed the mean absorbance value of anti-Fn-IgA and -IgG in the CRC group were significantly higher than those in the benign colon disease group and healthy control group (P < 0.001). The sensitivity and specificity of ELISA for the detection of anti-Fn-IgA were 36.43% and 92.71% based on the optimal cut-off. The combination of anti-Fn-IgA and carcino-embryonic antigen (CEA) was better for diagnosing CRC (Sen: 53.10%, Spe: 96.41%; AUC = 0.848). Furthermore, combining anti-Fn-IgA with CEA and carbohydrate antigen 19-9 (CA19-9) (Sen: 40.00%, Spe: 94.22%; AUC = 0.743) had the better ability to classify CRC patients with stages I-II. These results suggested that Fn-infection elicited high level of serum anti-Fn antibodies in CRC patients, and serum anti-Fn-IgA level may be a potential diagnosing biomarker for CRC. Serum anti-Fn-IgA in combination with CEA and CA19-9 increases the sensitivity of detecting early CRC.
Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1
Authors: Yan Naihong , Cheng Lin , Cho Kinsang , Malik Muhammad Taimur A. , Xiao Lirong , Guo Chenying , Yu Honghua , Zhu Ruilin , Rao Rajesh C. , Chen Dong Feng 
Published: September 2016

AbstractSome adult-onset disorders may be linked to dysregulated embryonic development, yet the mechanisms underlying this association remain poorly understood. Congenital retinal degenerative diseases are blinding disorders characterized by postnatal degeneration of photoreceptors, and affect nearly 2 million individuals worldwide, but ∼50% do not have a known mutation, implicating contributions of epigenetic factors. We found that embryonic deletion of the histone methyltransferase (HMT) Ezh2 from all retinal progenitors resulted in progressive photoreceptor degeneration throughout postnatal life, via derepression of fetal expression of Six1 and its targets. Forced expression of Six1 in the postnatal retina was sufficient to induce photoreceptor degeneration. Ezh2, although enriched in the embryonic retina, was not present in the mature retina; these data reveal an Ezh2-mediated feed-forward pathway that is required for maintaining photoreceptor homeostasis in the adult and suggest novel targets for retinal degeneration therapy.