bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Risk of Hospital-AcquiredClostridium DifficileInfection With Proton Pump Inhibitor Use: A Meta-Analysis
Authors: Arriola Vanessa , Tischendorf Jessica , Musuuza Jackson , Barker Anna , Rozelle Jeffrey W. , Safdar Nasia
Published: September 2016

BACKGROUND

Clostridium difficileis the principal infectious cause of antibiotic-associated diarrhea and accounts for 12% of hospital-acquired infections. Recent literature has shown an increased risk ofC. difficileinfection (CDI) with proton pump inhibitor (PPI) use.

OBJECTIVE

To conduct a systematic assessment of the risk of hospital-acquired CDI following exposure to PPI.

METHODS

We searched multiple databases for studies examining the relationship between PPI and hospital-acquired CDI. Pooled odds ratios were generated and assessment for heterogeneity performed.

RESULTS

We found 23 observational studies involving 186,033 cases that met eligibility criteria. Across studies, 10,307 cases of hospital-acquired CDI were reported. Significant heterogeneity was present; therefore, a random effects model was used. The pooled odds ratio was 1.81 (95% CI, 1.52–2.14), favoring higher risk of CDI with PPI use. Significant heterogeneity was present, likely due to differences in assessment of exposure, study population, and definition of CDI.

DISCUSSION

This meta-analysis suggests PPIs significantly increase the risk of hospital-acquired CDI. Given the significant health and economic burden of CDI and the risks of PPI, optimization of PPI use should be included in a multifaceted approach to CDI prevention.

Infect Control Hosp Epidemiol2016;1408–1417
Growth and breakdown of wave packets in a high-speed boundary layer
Authors: Shiplyuk Aleksandr N.
Published: October 2016

The recent study of Laurence et al. (J. Fluid Mech., vol. 797, 2016, pp. 471–503) develops a new Schlieren-based technique for investigating instabilities and transition in hypersonic boundary layers. This method enables pioneering measurements in a reflected-shock wind tunnel of the characteristics of the second mode of instability on a slender cone, within very short time scales (approximately 1 ms). The visualization technique was shown to resolve the structural evolution of individual wave packets. It was revealed that the disturbance strength concentrates near the wall for high-enthalpy conditions.
FACTORS INFLUENCING THE AGRONOMIC PERFORMANCE OF THE ADAPTED YAM MINISETT TECHNIQUE IN NIGERIA – PLANTING DATE AND GENDER OF THE FARMER
Authors: MORSE STEPHEN , McNAMARA NORA
Published: September 2016

This paper describes the results of 3 year's data from farmers using the Adaptive Yam Minisett Technique (AYMT) to produce seed yams in Nigeria. A total of 30 sites were established each year between 2013 and 2015 in the Idah area (Kogi State) of Nigeria and 58 plots in the Amoke area (Benue State) in 2015. Each site had yam setts (80 to 100 g) untreated and treated with a pesticide ‘dip’ prior to planting and farmers (male and female) were free to select the variety and manage the sites as they wished. In line with previous research, the results suggest that treatment does increase the weight of tubers produced by a sett but not necessarily the number of tubers. Varietal differences were also observed. For the first time, the results suggest that the time of planting does have a significant impact on seed tuber weight, with later planting leading to small tubers. Also, the gender of the farmer had an impact on some of the agronomic variables, with male owners of the site generally producing more and larger tubers per sett planted and sprouted than female owners. Various mechanisms for the latter are discussed in the paper.
Pope Innocent III, the Fourth Lateran Council, and Frankish Greece and Cyprus
Authors: SCHABEL CHRIS , TSOUGARAKIS NICKIPHOROS I.
Published: September 2016

Although the union between the Latin and Greek Churches was one of Pope Innocent III's career-long ambitions, the limited provisions made by the canons of the Fourth Lateran Council regarding the eastern Churches have led most historians to assume that by the end of his pontificate this matter had been relegated to one of secondary importance and was treated only as an afterthought during the council. By collecting and re-examining the surviving sources, this article shows that considerable time and energy was in fact spent during the council in regulating the affairs of the Churches of former Byzantine lands. The ensuing decisions and legislation formed the basis of the organisation of the Church in much of the Greco-Latin East for at least another three centuries.
The First Bible Printed in England: A Little Known Witness from Late Henrician England
Authors: POLEG EYAL
Published: September 2016

The first Bible to be printed in England was produced in 1535 by the royal printer, and with Henry VIII's initial support. It has attracted little scholarly attention. This first extensive examination traces its creation and early reception as witness to the uncertain course of the English Reformation. Its origins reveal a dependency on continental models, which were then modified to create a book carefully placed between conservatism and reform. Priests, scholars, children and crooks left their marks on the Bible, and advanced digital technology exposes unique evidence for the merging of Latin and English in late Henrician liturgy.
Response of the Endangered red panda Ailurus fulgens fulgens to anthropogenic disturbances, and its distribution in Phrumsengla National Park, Bhutan
Authors: Dendup Pema , Cheng Ellen , Lham Choki , Tenzin Ugyen
Published: September 2016

Across much of Asia protected areas have a dual objective of conserving biodiversity and supporting rural and indigenous livelihoods. For the red panda Ailurus fulgens and other sensitive species of concern, even limited anthropogenic disturbance may influence their use of protected areas. We quantified the prevalence of timber collection and livestock grazing, and their impacts on red panda habitat use, in Phrumsengla National Park, Bhutan. Red pandas used sites with at least 20% bamboo cover, as evidenced by presence of their faecal pellets. They avoided sites disturbed by livestock, regardless of bamboo availability. Timber collection itself was not an important predictor of red panda presence but bamboo may be harvested opportunistically from sites where timber is collected. Conservation efforts for the red panda should not rely on protected areas alone but should explicitly consider and mitigate impacts of anthropogenic disturbances in protected areas.
The IUCN Wild Pig Challenge 2015
Authors: Linkie Matthew , Ng Jasline , Lim Zhi Qi , Lubis Muhammad I. , Rademaker Mark , Meijaard Erik
Published: September 2016

Asian mammal species are facing unprecedented pressures from hunting and habitat conversion. Efforts to mitigate these threats often focus on charismatic large-bodied species, while many other species or even guilds receive less attention, particularly Asian wild pigs. To address this we developed a rapid questionnaire survey and administered it to relevant experts to identify the presence, population trends and conservation needs of Asia's 11 threatened wild pig species. The results highlighted geographical differences within species (e.g. the near collapse of bearded pig populations in Peninsular Malaysia yet their widespread presence on Borneo), and knowledge gaps for many endemic species of the Philippines, notably the Critically Endangered Visayan warty pig Sus cebifrons. To support field-based conservation projects, we identified 66 medium-to-large zoos in Asia, Europe and the USA that house Asian wild pigs and have applicable conservation funding schemes. Our rapid survey method, which yielded 170 wild pig records from across Asia, proved effective in filling many of the existing knowledge gaps, and may be widely applicable in assessing the status and needs of other non-flagship threatened species.
Impeccability and perfect virtue
Authors: HENDERSON LUKE
Published: September 2016

Whatever else a theory of impeccability assumes about the moral life of heavenly agents, it seems to imply something about the type of actions possible for such agents, along with the quality of their moral characters. Regarding these characters, there are many that have argued impeccable and heavenly agents must also be perfectly virtuous agents. Michael Slote has recently argued, however, that perfect virtue is impossible. Assuming Slote's argument is successful, a theory of impeccability that relies on the possibility of perfect virtue would be greatly harmed, even to the point of incoherence. My intent here is to defend the coherence of the doctrine of impeccability, at least as it applies to the moral life of heavenly agents.
Ulysses Is Not the Hero of Troilus and Cressida
Authors: Spiekerman Tim
Published: September 2016

Shakespeare's Troilus and Cressida is a notoriously bleak and problematic play: a dark comedy, a witty tragedy, an X-rated romance. A love story set during the Trojan War, the play appears to treat both love and war with utter cynicism. Ulysses drives the plot, craftily luring a despondent Achilles back onto the battlefield, and exposing Troilus to the betrayal of his beloved Cressida. A world-class manipulator and debunker of love and honor, Ulysses casts a shadow over this sour play, though he seems curiously unaffected by his skeptical outlook. A few critics have argued that Ulysses is the hero of Troilus and Cressida, a clear-sighted philosopher who may well speak for Shakespeare himself. I will argue against that view. I will also suggest that Troilus, if not the hero of this play, is perhaps its only sympathetic character.
Skepticism and Political Constancy:Richard IIand the Garden Scene as a “Model of State”
Authors: Condren Conal
Published: September 2016

Many 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

This 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

This 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

As 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

Shakespeare'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 …
LCO Soloists + NU:NORD, Roundhouse Dorfman Hub, London; Riot Ensemble, St Leonard's Church, London
Authors: Graham Stephen
Published: September 2016

Despite the ever-dwindling pot of public money available to exploratory musicians in the UK and elsewhere, various ensembles are nonetheless busy making hay whilst at least a little sun still shines. In London in the space of only a week or two in the second half of April, for instance, audiences could catch a series of new music recitals given by the Park Lane Group of young musicians, an evening of premieres with the Workers’ Union Ensemble, and concerts by the Riot Ensemble and by the London Contemporary Orchestra Soloists. Other cities, from Glasgow to Birmingham, enjoy a similarly wide range of activity.
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

Older 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.
CIRCULATING MUSICAL KNOWLEDGE IN EARLY SEVENTEENTH-CENTURY GERMANY:MUSICA POETICATREATISES OF JOHANN HERMANN SCHEIN AND MICHAEL ALTENBURG IN THE LIBRARY OF JOHANN CASPAR TROST
Authors: Groote Inga Mai , Hakelberg Dietrich
Published: September 2016

Recent research on the library of Johann Caspar Trost the Elder, organist in Halberstadt, has led to the identification of a manuscript with two unknown treatises on musica poetica, one a lost treatise by Johann Hermann Schein and the other an unknown treatise by Michael Altenburg. Together they offer fresh insights into the learning and teaching of music in the early modern period. The books once owned by Trost also have close connections to his personal and professional life. This article situates the newly discovered manuscript in the framework of book history and Trost’s biography, and discusses the two treatises against the background of contemporary books of musical instruction (Calvisius, Lippius, or Finolt). The historical context of the manuscript, its theoretical sources and its origins all serve to contribute to and further the current understanding of musical education in early modern central Germany. An edition of the treatises is provided.
Neumann-Hoffman Code Evasion and Stripping Method For BeiDou Software-defined Receiver
Authors: Meng Qian , Liu Jian-ye , Zeng Qing-hua , Feng Shao-jun , Chen Rui-zhi
Published: September 2016

The acquisition and tracking strategies of the BeiDou navigation satellite signals are affected by the modulation of Neumann-Hoffman code (NH code), which increases the complexity of receiver baseband signal processing. Based on the analysis of probability statistics of the NH code, a special sequence of incoming signals is proposed to evade the bit transitions caused by the NH code, and an NH Code Evasion and Stripping method (NCES) based on the NH-pre-modulated code is proposed. The NCES can be applied in both 20-bit NH code and 10-bit NH code. The fine acquisition eliminates the impact of NH code on the traditional tracking loop. These methods were verified with a BeiDou PC-based software-defined receiver using the actual sampled signals. Compared with other acquisition schemes which try to determine or ignore the NH code phase, the NCES needs fewer incoming signals and the actual runtime is greatly reduced without sacrificing much time to search in the secondary code dimension, and the success rate of acquisition is effectively improved. An extension of Fast Fourier Transform (FFT)-based parallel code-phase search acquisition gives the NCES an advantage in engineering applications.
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

H9 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.
LIMITS OF FRACTIONAL DERIVATIVES AND COMPOSITIONS OF ANALYTIC FUNCTIONS
Authors: MACGREGOR THOMAS H. , STERNER MICHAEL P.
Published: September 2016

Suppose that the function $f$ is analytic in the open unit disk $\unicode[STIX]{x1D6E5}$ in the complex plane. For each $\unicode[STIX]{x1D6FC}>0$ a function $f^{[\unicode[STIX]{x1D6FC}]}$ is defined as the Hadamard product of $f$ with a certain power function. The function $f^{[\unicode[STIX]{x1D6FC}]}$ compares with the fractional derivative of $f$ of order $\unicode[STIX]{x1D6FC}$. Suppose that $f^{[\unicode[STIX]{x1D6FC}]}$ has a limit at some point $z_{0}$ on the boundary of $\unicode[STIX]{x1D6E5}$. Then $w_{0}=\lim _{z\rightarrow z_{0}}f(z)$ exists. Suppose that $\unicode[STIX]{x1D6F7}$ is analytic in $f(\unicode[STIX]{x1D6E5})$ and at $w_{0}$. We show that if $g=\unicode[STIX]{x1D6F7}(f)$ then $g^{[\unicode[STIX]{x1D6FC}]}$ has a limit at $z_{0}$.
Social Perception of Self-Enhancement Bias and Error
Authors: Heck Patrick R. , Krueger Joachim I.
Published: October 2016

Abstract. How do social observers perceive and judge individuals who self-enhance (vs. not)? Using a decision-theoretic framework, we distinguish between self-enhancement bias and error, where the former comprises both correct and incorrect self-perceptions of being better than average. The latter occurs when a claim to be better than others is found to be false. In two studies, we find that when judging people’s competence, observers are sensitive to the accuracy of self-perception. When judging their morality, however, they tend to respond negatively to any claims of being better than average. These findings are further modulated by the domain of performance (intelligence vs. moral aptitude). Implications for the strategic use of self-enhancement claims are discussed.
The Gravity of Volcanic Eruptions
Authors: Yan Wudan
Published: September 2016

New research suggests that continually monitoring gravity changes near active volcanoes could provide insights into volcanic activity.
Candidates Have Dustup over Climate in First Debate
Authors: Showstack Randy
Published: September 2016

During the first presidential candidate debate Monday, Donald Trump denied saying that climate change is a hoax, but his own tweets show otherwise.
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

Neurotransmitter/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

Small-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

Acute 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

The 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

The 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

Several 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

Regulatory 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

A 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

Duplication, 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

Fusobacterium 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

Some 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.
Investigating Energetic X-Shaped Flares on the Outskirts of A Solar Active Region
Authors: Liu Rui , Chen Jun , Wang Yuming , Liu Kai
Published: September 2016

Typical solar flares display two quasi-parallel, bright ribbons on the chromosphere. In between is the polarity inversion line (PIL) separating concentrated magnetic fluxes of opposite polarity in active regions (ARs). Intriguingly a series of flares exhibiting X-shaped ribbons occurred at the similar location on the outskirts of NOAA AR 11967, where magnetic fluxes were scattered, yet three of them were alarmingly energetic. The X shape, whose center coincided with hard X-ray emission, was similar in UV/EUV, which cannot be accommodated in the standard flare model. Mapping out magnetic connectivities in potential fields, we found that the X morphology was dictated by the intersection of two quasi-separatrix layers, i.e., a hyperbolic flux tube (HFT), within which a separator connecting a double null was embedded. This topology was not purely local but regulated by fluxes and flows over the whole AR. The nonlinear force-free field model suggested the formation of a current layer at the HFT, where the current dissipation can be mapped to the X-shaped ribbons via field-aligned heat conduction. These results highlight the critical role of HFTs in 3D magnetic reconnection and have important implications for astrophysical and laboratory plasmas.
Synthesis, characterization and drug loading property of Monomethoxy-Poly(ethylene glycol)-Poly(ε-caprolactone)-Poly(D,L-lactide) (MPEG-PCLA) copolymers
Authors: Chu BingYang , Zhang Lan , Qu Ying , Chen XiaoXin , Peng JinRong , Huang YiXing , Qian ZhiYong
Published: September 2016

Amphiphilic block copolymers have attracted a great deal of attention in drug delivery systems. In this work, a series of monomethoxy-poly (ethylene glycol)-poly (ε-caprolactone-co-D,L-lactide) (MPEG-PCLA) copolymers with variable composition of poly (ε-caprolactone) (PCL) and poly (D,L-lactide) (PDLLA) were prepared via ring-opening copolymerization of ε-CL and D,L-LA in the presence of MPEG and stannous octoate. The structure and molecular weight were characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The crystallinity, hydrophilicity, thermal stability and hydrolytic degradation behavior were investigated in detail, respectively. The results showed that the prepared amphiphilic MPEG-PCLA copolymers have adjustable properties by altering the composition of PCLA, which make it convenient for clinical applications. Besides, the drug loading properties were also studied. Docetaxel (DTX) could be entrapped in MPEG-PCLA micelles with high loading capacity and encapsulation efficiency. And all lyophilized DTX-loaded MPEG-PCLA micelles except MPEG-PCL micelles were readily re-dissolved in normal saline at 25 °C. In addition, DTX-loaded MPEG-PCLA micelles showed a slightly enhanced antitumor activity compared with free DTX. Furthermore, DTX micelles exhibited a slower and sustained release behavior in vitro, and higher DTX concentration and longer retention time in vivo. The results suggested that the MPEG-PCLA copolymer with the adjustable ratio of PCL to PDLLA may be a promising drug delivery carrier for DTX.
Evidence for Direct Control of Virulence and Defense Gene Circuits by the Pseudomonas aeruginosa Quorum Sensing Regulator, MvfR
Authors: Maura Damien , Hazan Ronen , Kitao Tomoe , Ballok Alicia E. , Rahme Laurence G.
Published: September 2016

Pseudomonas aeruginosa defies eradication by antibiotics and is responsible for acute and chronic human infections due to a wide variety of virulence factors. Currently, it is believed that MvfR (PqsR) controls the expression of many of these factors indirectly via the pqs and phnAB operons. Here we provide strong evidence that MvfR may also bind and directly regulate the expression of additional 35 loci across the P. aeruginosa genome, including major regulators and virulence factors, such as the quorum sensing (QS) regulators lasR and rhlR, and genes involved in protein secretion, translation, and response to oxidative stress. We show that these anti-oxidant systems, AhpC-F, AhpB-TrxB2 and Dps, are critical for P. aeruginosa survival to reactive oxygen species and antibiotic tolerance. Considering that MvfR regulated compounds generate reactive oxygen species, this indicates a tightly regulated QS self-defense anti-poisoning system. These findings also challenge the current hierarchical regulation model of P. aeruginosa QS systems by revealing new interconnections between them that suggest a circular model. Moreover, they uncover a novel role for MvfR in self-defense that favors antibiotic tolerance and cell survival, further demonstrating MvfR as a highly desirable anti-virulence target.
Breast Cancer Cell Invasion into a Three Dimensional Tumor-Stroma Microenvironment
Authors: Truong Danh , Puleo Julieann , Llave Alison , Mouneimne Ghassan , Kamm Roger D. , Nikkhah Mehdi
Published: September 2016

In this study, to model 3D chemotactic tumor-stroma invasion in vitro, we developed an innovative microfluidic chip allowing side-by-side positioning of 3D hydrogel-based matrices. We were able to (1) create a dual matrix architecture that extended in a continuous manner, thus allowing invasion from one 3D matrix to another and (2) establish distinct regions of tumor and stroma cell/ECM compositions, with a clearly demarcated tumor invasion front, thus allowing us to quantitatively analyze progression of cancer cells into the stroma at a tissue or single-cell level. We showed significantly enhanced cancer cell invasion in response to a transient gradient of epidermal growth factor (EGF). 3D tracking at the single-cell level displayed increased migration speed and persistence. Subsequently, we analyzed changes in expression of EGF receptors, cell aspect ratio and protrusive activity. These findings show the unique ability of our model to quantitatively analyze 3D chemotactic invasion, both globally by tracking the progression of the invasion front and at the single-cell level by examining changes in cellular behavior and morphology using high-resolution imaging. Taken together, we have shown a novel model recapitulating 3D tumor-stroma interactions for studies of real-time cell invasion and morphological changes within a single platform.
The Evolution of Generosity in the Ultimatum Game
Authors: Hintze Arend , Hertwig Ralph
Published: September 2016

When humans fail to make optimal decisions in strategic games and economic gambles, researchers typically try to explain why that behaviour is biased. To this end, they search for mechanisms that cause human behaviour to deviate from what seems to be the rational optimum. But perhaps human behaviour is not biased; perhaps research assumptions about the optimality of strategies are incomplete. In the one-shot anonymous symmetric ultimatum game (UG), humans fail to play optimally as defined by the Nash equilibrium. However, the distinction between kin and non-kin—with kin detection being a key evolutionary adaption—is often neglected when deriving the “optimal” strategy. We computationally evolved strategies in the UG that were equipped with an evolvable probability to discern kin from non-kin. When an opponent was not kin, agents evolved strategies that were similar to those used by humans. We therefore conclude that the strategy humans play is not irrational. The deviation between behaviour and the Nash equilibrium may rather be attributable to key evolutionary adaptations, such as kin detection. Our findings further suggest that social preference models are likely to capture mechanisms that permit people to play optimally in an evolutionary context. Once this context is taken into account, human behaviour no longer appears irrational.
Exercise protects against methamphetamine-induced aberrant neurogenesis
Authors: Park Minseon , Levine Harry , Toborek Michal
Published: September 2016

While no effective therapy is available for the treatment of methamphetamine (METH)-induced neurotoxicity, aerobic exercise is being proposed to improve depressive symptoms and substance abuse outcomes. The present study focuses on the effect of exercise on METH-induced aberrant neurogenesis in the hippocampal dentate gyrus in the context of the blood-brain barrier (BBB) pathology. Mice were administered with METH or saline by i.p. injections for 5 days with an escalating dose regimen. One set of mice was sacrificed 24 h post last injection of METH and the remaining animals were either subjected to voluntary wheel running (exercised mice) or remained in sedentary housing (sedentary mice). METH administration decreased expression of tight junction (TJ) proteins and increased BBB permeability in the hippocampus. These changes were preserved post METH administration in sedentary mice and were associated with the development of significant aberrations of neural differentiation. Exercise protected against these effects by enhancing the protein expression of TJ proteins, stabilizing the BBB integrity and enhancing the neural differentiation. In addition, exercise protected against METH-induced systemic increase in inflammatory cytokine levels. These results suggest that exercise can attenuate METH-induced neurotoxicity by protecting against the BBB disruption and related microenvironmental changes in the hippocampus.