bluuebunny/crossref_metadata_2025 huggingface dataset:
Children's identification of questions from rising terminal pitch
Authors: SAINDON MATHIEU R. , TREHUB SANDRA E. , SCHELLENBERG E. GLENN , VAN LIESHOUT PASCAL
Published: September 2015

Young children are slow to master conventional intonation patterns in their yes/no questions, which may stem from imperfect understanding of the links between terminal pitch contours and pragmatic intentions. In Experiment 1, five- to ten-year-old children and adults were required to judge utterances as questions or statements on the basis of intonation alone. Children eight years of age or younger performed above chance levels but less accurately than adult listeners. To ascertain whether the verbal content of utterances interfered with young children's attention to the relevant acoustic cues, low-pass filtered versions of the same utterances were presented to children and adults in Experiment 2. Low-pass filtering reduced performance comparably for all age groups, perhaps because such filtering reduced the salience of critical pitch cues. Young children's difficulty in differentiating declarative questions from statements is not attributable to basic perceptual difficulties but rather to absent or unstable intonation categories.
Using financial incentives to motivate conservation of an at-risk species on private lands
Authors: RAMSDELL C. PAXTON , SORICE MICHAEL G. , DWYER ANGELA M.
Published: September 2015

Financial incentives have become a core component of private lands conservation programmes because of their ability to motivate stewardship behaviour. Concern exists about the durability of stewardship behaviours after payments end. Payments for performance may impact farmers' current and future engagement with an incentive programme to protect an at-risk ground-nesting grassland bird. Farmer motivations for participating in the programme, as well as their intention to continue the programme if the financial incentive no longer existed, were quantified. Although farmers did not report a high level of current involvement in the programme, most reported they would continue at a similar or higher level of engagement if the payments ended. These outcomes were related to their perception that their participation was driven by their internal motivation to help rather than the desire to obtain the financial reward. The perception that their behaviour was self-directed was positively influenced by the flexibility surrounding landowners’ engagement with the programme, a feeling of competence and achievement, and a feeling of connectedness to the organization implementing the programme. The success of conservation incentive programmes over the long term can be enhanced by explicitly accounting for the needs of landowners in programme design and administration.
Submarine geomorphology and sea floor processes along the coast of Vestfold Hills, East Antarctica, from multibeam bathymetry and video data
Authors: O’Brien Philip E. , Smith Jodie , Stark Jonathan S. , Johnstone Glenn , Riddle Martin , Franklin Dennis
Published: September 2015

A survey of nearshore areas in the Vestfold Hills, Antarctica, using high-resolution multibeam swath bathymetry provided both a detailed digital bathymetric model and information on sediment acoustic backscatter. Combined with underwater video transects and sediment sampling, these data were used to identify and map geomorphic units. Six geomorphic units identified in the survey region include: rocky outcrops, basins, pediments, valleys, scarps and embayments. In addition to geomorphic units, the data revealed sedimentary features that provide insights into post-glacial sediment transport and erosion in the area. Ice keel pits and scours are common, and sea floor channels, scour depressions and sand ribbons indicate transport and deposition by wind-driven currents and oceanographic circulation. Gullies and sediment lobes observed on steep slopes indicate mass movement of sediment. Some of these processes have not been directly observed to date, but their effectiveness in shaping the modern sea floor is clearly indicated by the sea floor mapping data. The embayments preserve a mantle of boulder sand probably deposited by cold-based glaciers which were flanked by faster-flowing ice in adjoining regions.
Not always variable: Probing the vernacular grammar
Authors: D'Arcy Alexandra , Tagliamonte Sali A.
Published: September 2015

Written and spoken language are known to differ substantially (Biber, 1988; 1995; Biber, Johansson, Leech, Conrad, & Finegan, 1999). Standard written language is highly uniform and governed by prescription, whereas the vernacular is most revealing of structured heterogeneity (Weinreich, Labov, & Herzog, 1968). We focus on four English morphosyntactic variables that problematize assumptions about the nature of variation in the vernacular: the genitive, the comparative, the dative, and relative pronouns. Each is characterized in casual speech by functional divides that reflect discrete configurations of variant use. After detailing the patterning of these variables in speech, we explore a characteristic arguably shared by each: its historical pathway into the language, where analogy and prestige were powerful motivations for variant choice. We suggest that this combination of systemic and social factors contributed to the nature of these variables in the vernacular grammar. Furthermore, we advocate for greater scrutiny of written and spoken data and the outcomes of change from above and below within each register. The type of innovation and its trajectory may affect the nature of the emergent variable grammar.
Gender and language change in Old Norse sentential negatives
Authors: Blaxter Tam
Published: September 2015

One consistent finding across sociolinguistic studies is the tendency for female speakers to lead in ongoing change. Different explanations have been proposed for this and a key method of testing these explanations is to identify whether the pattern occurs in the languages of a wider range of societies than have been studied thus far. Historical societies are relatively understudied in this regard, but undertaking variationist research into gender in historical varieties presents many challenges. One way to overcome these is to examine variation internal to fiction data. This paper presents an analysis of the effect of gender on the adverb selected for sentential negation in Old Norse prose fiction. It finds that female characters lead consistently in this change over time. In doing so, it demonstrates the feasibility of using fiction data when examining the effect of gender in historical varieties such as Old Norse.
Community rules and speaker behavior: Individual adherence to group constraints on (ING)
Authors: Forrest Jon
Published: September 2015

This paper investigates the degree to which individual speakers follow the morphosyntactic hierarchy governing grammatical constraints on (ING) in the Southern U.S. city of Raleigh, North Carolina. (ING) was used as the variable of study for its well-studied internal constraints and comparability to previous studies on the internal constraints oft/ddeletion. A lexical category constraint hierarchy for the community was determined via multivariate mixed-effects statistical models, and each speaker's (ING) pattern was compared to this hierarchy. Results show maintenance in grammatical constraints even when taking phonological factors into account, unlike some work ont/ddeletion. Uniformity exists across speakers with respect to the ordering of internal constraints despite the overall decline in rates of –inover time, but constraint weights (expressed as log odds) vary significantly from speaker to speaker, with no correlates to social or internal factors. These results have consequences for representation of individuals in terms of an aggregate pattern, questioning the consistency of factor weight values at the speaker level despite consistent ordering of constraints.
Introduction: The agents, acts and attitudes of supererogation
Authors: Cowley Christopher
Published: September 2015

I confess to finding the term ‘supererogation’ ugly and unpronounceable. I am also generally suspicious of technical terms in moral philosophy, since they are vulnerable to self-serving definition and counter-definition, to the point of obscuring whether there is a single phenomenon about which to disagree. It was surely not accidental that J.O. Urmson, in his classic 1958 article that launched the contemporary Anglophone debate, eschewed the technical term in favour of the more familiar concepts of saints and heroes. Since then, however, the term Supererogation has bedded down to encompass a number of more or less clear-cut philosophical debates, one of which concerns precisely the extent to which saintliness and heroism exhaust the supererogatory. And it has to be admitted that the word ‘saint’ has certain theological connotations that might be misleading in a secular philosophical discussion (in this volume, only Wynn and Drummond-Young invoke theological ideas), while the word ‘hero’ has potentially limiting associations with knights and soldiers and other forms of testosterone-driven accomplishment.
Can Virtue Ethics Account for Supererogation?
Authors: Heyd David
Published: September 2015

In his classical article, ‘Saints and Heroes’, James Urmson single-handedly revived the idea of supererogation from it astonishingly long post-Reformation slumber. During the first two decades after its publication, Urmson's challenge was taken up almost exclusively by either utilitarians or deontologists of some sort. On the face of it, neither classical utilitarianism nor Kant's categorical imperative makes room for action which is better than the maximizing requirement, on the one hand, or beyond the requirement of duty, on the other. Nevertheless, both utilitarians and Kantians, as well as deontic logicians, offered more flexible and sophisticated versions of their respective theories which could accommodate supererogatory action. In my 1982 book on supererogation I tried to address the question whether virtue ethics could capture that new category of actions which are praiseworthy though not strictly required. But the focus of my discussion was mostly Aristotle (and Seneca) and accordingly more interpretive in nature. However, that was just before the tremendous surge of interest in virtue ethics and the vast literature debating the merits of agent-based vs. action-based approaches in moral theory. It turned out that fitting supererogation into virtue-based moral theory proved to be a more difficult task than doing so in consequentialist and deontological theories. Some argued that supererogation could nevertheless be accounted for in aretaic terms; others held that it could not and that this fact attested to either a theoretical weakness – even if not a refutation – of virtue-based ethics, or to the incoherence of the concept of supererogation.
Disjunctive duties and supererogatory sets of actions
Authors: Brinkmann Matthias
Published: September 2015

James Urmson famously claimed that all ethical theories which only operate with the three deontic categories of the required, the optional, and the forbidden were ‘totally inadequate to the facts of morality’ because they fail to recognise a fourth category of actions, which we can call the supererogatory. Supererogatory actions should be seen as ‘meritorious non-duty’, as something which is good but in no sense required. A number of examples can be provided to make the existence of such a realm outside duty plausible: the soldier throwing herself on a live hand grenade to save her companions, the torture victim who forgives her tormentors even though they do not regret, or the doctor who voluntarily travels to a war zone to treat the wounded.
Saints, Heroes and Moral Necessity
Authors: Archer Alfred
Published: September 2015

During The Second World War somewhere between fifty thousand and five hundred thousand people risked their lives, and often the lives of their families, to help rescue Jews from Nazi persecution. These acts included helping Jews sustain their lives in the face of persecution, escape from incarceration centers, maintain an underground existence and escape the country. Their acts were clearly morally worthy, yet given the actual and potential costs involved, many of these acts seem to go beyond what could be morally demanded of agents in that situation.
Adopting roles: Generosity and Presumptuousness
Authors: Stout Rowland
Published: September 2015

An understanding of generosity must be central to an understanding of our moral nature, yet there is no good philosophical account of generosity. This is exemplified in Aristotle's Nicomachean Ethics, where interesting accounts of liberality (using your wealth well) and magnificence (spending large amounts of money well) are provided in Book IV, but none of generosity. Hutcheson and Hume were interested in benevolence, but benevolence is not the same thing as generosity either. For Hume, benevolence is ‘desire of the happiness of the person belov'd, and an aversion to his misery.’ (Treatise, 2.2.9.3) So, acting benevolently, for Hume, is acting from this sentiment for the sake of someone else's wellbeing. Picking up litter that somebody else has dropped is not benevolent on this account, but I think it may count as generous behaviour. And conversely, I will argue later that benevolent actions that are presumptuous and intrusive are not generous.
A dose–response meta-analysis reveals an association between vitamin B12and colorectal cancer risk
Authors: Sun Nai-Hui , Huang Xuan-Zhang , Wang Shuai-Bo , Li Yuan , Wang Long-Yi , Wang Hong-Chi , Zhang Chang-Wang , Zhang Cong , Liu Hong-Peng , Wang Zhen-Ning
Published: September 2015

Objective

The current meta-analysis evaluated the association between vitamin B12intake and blood vitamin B12level and colorectal cancer (CRC) risk.

Design

The PubMed and EMBASE databases were searched. A dose–response analysis was performed with generalized least squares regression, with the relative risk (RR) and 95 % CI as effect values.

Setting

The meta-analysis included seventeen studies.

Subjects

A total of 10 601 patients.

Results

The non-linear dose–response relationship between total vitamin B12intake and CRC risk was insignificant (P=0·690), but the relationship between dietary vitamin B12intake and CRC risk was significant (P<0·001). Every 4·5 μg/d increment in total and dietary vitamin B12intake was inversely associated with CRC risk (total intake: RR=0·963; 95 % CI 0·928, 0·999; dietary intake: RR=0·914; 95 % CI 0·856, 0·977). The inverse association between vitamin B12intake and CRC risk was also significant when vitamin B12intake was over a dosage threshold, enhancing the non-linear relationship. The non-linear dose–response relationship between blood vitamin B12level and CRC risk was insignificant (P=0·219). There was an insignificant association between every 150 pmol/l increment in blood vitamin B12level and CRC risk (RR=1·023; 95 % CI 0·881, 1·187).

Conclusions

Our meta-analysis indicates that evidence supports the use of vitamin B12for cancer prevention, especially among populations with high-dose vitamin B12intake, and that the association between CRC risk and total vitamin B12intake is stronger than between CRC risk and dietary vitamin B12intake only.
Elemental Distribution in Multilayer Systems by Laser-Assisted Atom Probe Tomography with Various Analysis Directions
Authors: Kubota Masaki , Takamizawa Hisashi , Shimizu Yasuo , Nozawa Yasuko , Ebisawa Naoki , Toyama Takeshi , Ishida Yoichi , Yanagiuchi Katsuaki , Inoue Koji , Nagai Yasuyoshi
Published: September 2015

Elemental distributions in a magnetic multilayer system with the structure Si substrate/Ta/NiFe/Ru/CoFeB/Ru/NiFe were studied using atom probe tomography (APT) along different analysis directions. The distributions of Ru and B atoms, which require a high evaporation field, were strongly influenced by the APT analysis direction. In particular, B in the CoFeB layer appeared near the interface with the lower Ru layer when the analysis was anti-parallel to the film growth direction, while B atoms were observed at the other side of the CoFeB layer when the analysis was parallel to the film growth direction. Moreover, when the analysis was perpendicular to the film growth direction, a homogenous distribution of B atoms was found within the CoFeB layer. Owing to this B behavior, the underlying Ru layer was affected in both of these analysis directions. In APT measurements of such a multilayer system composed of a stack of different evaporation field materials, evaluation of the elemental distribution around interfaces should be performed from more than one analysis direction.
EC – Bed: Linen European Communities – Anti-dumping Duties on Imports of Cotton-Type Bed Linen from India
Authors: Janow Merit E. , Staiger Robert W.
Published: September 2015

As comprehensively argued elsewhere in this volume,1 the WTO's antidumping provisions reflect political compromises that mask an underlying lack of consensus on the value and purpose of an antidumping regime at the national level. This is an old story that has been long argued in academic and policy circles. What is noteworthy recently is the significant increase in the use of trade remedies, especially by developing economies. As a result, while the post-Uruguay Round period is generally marked by greater economic openness resulting from various forms of trade liberalization, the use of trade remedies is no longer primarily the province of OECD economies. Indeed, the introduction and use of trade remedies is proliferating around the world.2
US – Export Restraints: United States – Measures Treating Export Restraints as Subsidies
Authors: Janow Merit E. , Staiger Robert W.
Published: September 2015

This study examines the dispute brought before the World Trade Organization (WTO) concerning the United States – Measures Treating Export Restraints as Subsidies (WT/DS 194), euphemistically referred to herein as US – Export Restraints. In this dispute, Canada challenged the US treatment of export restraints under US countervailing duty law and practice. The principal legal focus was therefore on the WTO Subsidies and Countervailing Measures (SCM) Agreement. This is one of a handful of WTO cases where the complainant (Canada) was not challenging the application of a governmental measure (by the US here) but rather the WTO consistency of existing legal measures. Essentially, Canada claimed that certain US legislation along with established practice by the US Department of Commerce constitute a violation of US obligations under the SCM Agreement.
European Communities – Anti-Dumping Duties on Imports of Cotton-Type Bed Linen from India (AB-2000-13, WT/DS141/AB/R:DSR 2003: III, 965): Recourse to Article 21.5 of the DSU by India
Authors: Grossman Gene M. , Sykes Alan O.
Published: September 2015

This chapter addresses the dispute brought to the World Trade Organization (WTO) by India concerning anti-dumping duties imposed by the European Communities (EC) on cotton-type bed linen. An earlier complaint brought by India challenged the anti-dumping duties on a number of points, including the EC practice of “zeroing” for the computation of dumping margins (which had the effect of assigning a negative dumping margin a weight of zero when computing a weighted average dumping margin). India prevailed in that dispute, and the EC responded with Council Regulation (EC) No. 1644/2001, amending the original anti-dumping measure on bed linen from India. India was of the view that the amended measure did not comply with EC obligations under the WTO Anti-dumping Agreement, and brought the proceeding under Art. 21.5 of the DSU that is the subject of this chapter.
European Community – Antidumping Duties on Malleable Cast Iron Tube or Pipe Fittings from Brazil (WT/DS219/AB/R: DSR 2003:VI, 2613)
Authors: Horn Henrik , Mavroidis Petros C.
Published: September 2015

This chapter addresses the Appellate Body (AB) report on European Community – Antidumping Duties on Malleable Cast Iron Tube or Pipe Fittings from Brazil. The underlying Panel determination was appealed by the complainant Brazil only. Following the approach it took before the Panel, Brazil raised a number of issues concerning the antidumping investigation by the European Community (EC).
United States – Definitive Safeguard Measures on Imports of Certain Steel Products (WT/DS259; WT/DS252; WT/DS248; WT/DS249; WT/DS251; WT/DS258; WT/DS254; WT/DS253: DSR 2003:VII, 3117)
Authors: Grossman Gene M. , Sykes Alan O.
Published: September 2015

Since the inception of the WTO, safeguard measures have regularly been the subject of dispute settlement proceedings. The latest in this chain of disputes concerns the definitive safeguard measures imposed by the United States on a wide range of steel products in 2002.

The safeguards investigation of steel imports was initiated under the US law by the US International Trade Commission (USITC) at the request of the United States Trade Representative (USTR) in June, 2001. The request covered four broad categories of steel products, which were divided into 33 categories by the USITC for purposes of data collection. Ultimately, the USITC defined 27 separate “industries” producing steel products within the scope of the investigation. For each of these industries, the USITC proceeded to determine whether imports had increased, and if so, whether increased imports were a substantial cause of serious injury or threat of injury. This analysis resulted in negative determinations for 15 industries, affirmative determinations for eight industries, and “divided” determinations (a 3–3 vote) for four industries.
Japan – Measures Affecting the Importation of Apples (AB-2003-4): One Bad Apple? (DS245/AB/R): A Comment
Authors: Neven Damien J. , Weiler Joseph H.H.
Published: September 2015

This chapter reviews the decision by the Appellate Body (AB) regarding measures affecting the importation of apples in Japan. Section 2 of the chapter presents some background facts. Section 3 considers the Sanitary and Phytosanitary (SPS) agreement and emphasizes the fact that it imposes a discipline on risk-reducing measures even in the absence of discrimination or protectionism. Section 4 discusses how the evaluation of risk-reducing measures can be undertaken in the context of the SPS agreement. Our discussion focuses on two issues: the scope of the mandate given to the adjudicators and the standard of review that they should apply. We emphasize the difficulty of the task faced by the adjudicators, namely to distinguish between determining the level of risk that a country will find optimal to support (which cannot be challenged) and determining whether risk-reducing measures are necessary to achieve the chosen level of risk. We further observe that the common methodology used by Panels, namely to evaluate the existence of risk in the absence of risk-reducing measures, has limited applicability.
Partizipation traumatisierter Kinder und Jugendlicher bei vorläufigen Schutzmaßnahmen (Inobhutnahme, §42 SGB VIII)
Authors: Rücker Stefan , Büttner Peter , Fegert Jörg , Petermann Franz
Published: September 2015

Zusammenfassung. Fragestellung: Die Studie analysiert wichtige Variablen des Settings der Inobhutnahme und erfasst Traumabelastungen. Methodik: 52 Kinder und Jugendliche mit Inobhutnahmeerfahrung wurden einer Online-Befragung im sozialen Netzwerk Facebook unterzogen. Dabei wurden indikationsbildende, verlaufs- sowie traumabezogene Belastungen erfasst. Ergebnisse: In mehr als jedem zweiten Fall berichten Kinder und Jugendliche, während der Inobhutnahme an wichtigen Entscheidungen nicht beteiligt gewesen zu sein, die Hälfte wollte im Anschluss an die Maßnahme nicht ins Elternhaus zurück. Kinder und Jugendliche ohne Rückkehrwunsch zeichnen sich gegenüber solchen mit Rückkehrwunsch durch schwerste körperliche und emotionale Vernachlässigung sowie durch extreme körperliche Misshandlungen aus. Dennoch werden die Betroffenen vielfach gegen ihren Wunsch in das Elternhaus zurückgeführt. Schlussfolgerungen: Im Setting der Inobhutnahme sollten Kinder und Jugendliche dringend stärker in wichtige Entscheidungen einbezogen werden; ihr Wunsch hinsichtlich des künftigen Lebensortes (Elternhaus vs. nicht Elternhaus) muss stärkere Berücksichtigung finden. Kindern, die gegen ihren Wunsch ins Elternhaus zurückkehren müssen, droht eine fortgesetzte Traumatisierung.
Echoskopie
Authors: Dietrich Christoph F. , Hocke Michael , Braden Barbara
Published: September 2015

Zusammenfassung. Die Nutzung kleiner und kleinster portabler Ultraschalleinheiten steht zurzeit noch an ihrem Anfang. Die Wertigkeit dieser Geräte wurde jedoch in der Kardiologie, Gynäkologie und Gastroenterologie bereits untersucht. Eine weitere Verbesserung der Bildqualität und des Angebotes ist zu erwarten. Sehr wahrscheinlich werden in Zukunft mehr und mehr Ärztinnen und Ärzte diese tragbaren Kitteltascheninstrumente als eine Art Stethoskop zum Nutzen ihrer Patienten einsetzen. Die «European Federation of Societies of Ultrasound in Medicine and Biology» (EFSUMB) definierte dieses Vorgehen als «Echoscopy» (Echoskopie), als eine Form des «point of care ultrasound» (POCUS). Auf der EFSUMB-Website wird Lehrmaterial zu diesem Thema angeboten (www.efsumb.org).
Meertens Receives 2015 Ivan I. Mueller Award for Distinguished Service and Leadership
Authors:   AGU
Published: September 2015

Charles Meertens will receive the 2015 Ivan I. Mueller Award for Distinguished Service and Leadership at the 2015 American Geophysical Union Fall Meeting, to be held 14–18 December in San Francisco, Calif. The award recognizes "major achievements in service and/or leadership to the geodesy community."
Ultrafast optical modification of exchange interactions in iron oxides
Authors: Mikhaylovskiy R.V. , Hendry E. , Secchi A. , Mentink J.H. , Eckstein M. , Wu A. , Pisarev R.V. , Kruglyak V.V. , Katsnelson M.I. , Rasing Th. , Kimel A.V.
Published: September 2015

Ultrafast non-thermal manipulation of magnetization by light relies on either indirect coupling of the electric field component of the light with spins via spin-orbit interaction or direct coupling between the magnetic field component and spins. Here we propose a scenario for coupling between the electric field of light and spins via optical modification of the exchange interaction, one of the strongest quantum effects with strength of 103 Tesla. We demonstrate that this isotropic opto-magnetic effect, which can be called inverse magneto-refraction, is allowed in a material of any symmetry. Its existence is corroborated by the experimental observation of terahertz emission by spin resonances optically excited in a broad class of iron oxides with a canted spin configuration. From its strength we estimate that a sub-picosecond modification of the exchange interaction by laser pulses with fluence of about 1 mJ cm−2 acts as a pulsed effective magnetic field of 0.01 Tesla.
Bloch-like waves in random-walk potentials based on supersymmetry
Authors: Yu Sunkyu , Piao Xianji , Hong Jiho , Park Namkyoo
Published: September 2015

Bloch’s theorem was a major milestone that established the principle of bandgaps in crystals. Although it was once believed that bandgaps could form only under conditions of periodicity and long-range correlations for Bloch’s theorem, this restriction was disproven by the discoveries of amorphous media and quasicrystals. While network and liquid models have been suggested for the interpretation of Bloch-like waves in disordered media, these approaches based on searching for random networks with bandgaps have failed in the deterministic creation of bandgaps. Here we reveal a deterministic pathway to bandgaps in random-walk potentials by applying the notion of supersymmetry to the wave equation. Inspired by isospectrality, we follow a methodology in contrast to previous methods: we transform order into disorder while preserving bandgaps. Our approach enables the formation of bandgaps in extremely disordered potentials analogous to Brownian motion, and also allows the tuning of correlations while maintaining identical bandgaps, thereby creating a family of potentials with ‘Bloch-like eigenstates’.
Antagonistic effects of IL-17 and D-resolvins on endothelial Del-1 expression through a GSK-3β-C/EBPβ pathway
Authors: Maekawa Tomoki , Hosur Kavita , Abe Toshiharu , Kantarci Alpdogan , Ziogas Athanasios , Wang Baomei , Van Dyke Thomas E. , Chavakis Triantafyllos , Hajishengallis George
Published: September 2015

Del-1 is an endothelial cell-secreted anti-inflammatory protein. In humans and mice, Del-1 expression is inversely related to that of IL-17, which inhibits Del-1 through hitherto unidentified mechanism(s). Here we show that IL-17 downregulates human endothelial cell expression of Del-1 by targeting a critical transcription factor, C/EBPβ. Specifically, IL-17 causes GSK-3β-dependent phosphorylation of C/EBPβ, which is associated with diminished C/EBPβ binding to the Del-1 promoter and suppressed Del-1 expression. This inhibitory action of IL-17 can be reversed at the GSK-3β level by PI3K/Akt signalling induced by D-resolvins. The biological relevance of this regulatory network is confirmed in a mouse model of inflammatory periodontitis. Intriguingly, resolvin-D1 (RvD1) confers protection against IL-17-driven periodontal bone loss in a Del-1-dependent manner, indicating an RvD1-Del-1 axis against IL-17-induced pathological inflammation. The dissection of signalling pathways regulating Del-1 expression provides potential targets to treat inflammatory diseases associated with diminished Del-1 expression, such as periodontitis and multiple sclerosis.
Nonlinear spin-wave excitations at low magnetic bias fields
Authors: Bauer Hans G. , Majchrak Peter , Kachel Torsten , Back Christian H. , Woltersdorf Georg
Published: September 2015

Nonlinear magnetization dynamics is essential for the operation of numerous spintronic devices ranging from magnetic memory to spin torque microwave generators. Examples are microwave-assisted switching of magnetic structures and the generation of spin currents at low bias fields by high-amplitude ferromagnetic resonance. Here we use X-ray magnetic circular dichroism to determine the number density of excited magnons in magnetically soft Ni80Fe20 thin films. Our data show that the common model of nonlinear ferromagnetic resonance is not adequate for the description of the nonlinear behaviour in the low magnetic field limit. Here we derive a model of parametric spin-wave excitation, which correctly predicts nonlinear threshold amplitudes and decay rates at high and at low magnetic bias fields. In fact, a series of critical spin-wave modes with fast oscillations of the amplitude and phase is found, generalizing the theory of parametric spin-wave excitation to large modulation amplitudes.
Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer
Authors: Chen Zhong , Lan Xun , Wu Dayong , Sunkel Benjamin , Ye Zhenqing , Huang Jiaoti , Liu Zhihua , Clinton Steven K. , Jin Victor X. , Wang Qianben
Published: September 2015

Glucocorticoids (GCs) have been widely used as coadjuvants in the treatment of solid tumours, but GC treatment may be associated with poor pharmacotherapeutic response or prognosis. The genomic action of GC in these tumours is largely unknown. Here we find that dexamethasone (Dex, a synthetic GC)-regulated genes in triple-negative breast cancer (TNBC) cells are associated with drug resistance. Importantly, these GC-regulated genes are aberrantly expressed in TNBC patients and are associated with unfavourable clinical outcomes. Interestingly, in TNBC cells, Compound A (CpdA, a selective GR modulator) only regulates a small number of genes not involved in carcinogenesis and therapy resistance. Mechanistic studies using a ChIP-exo approach reveal that Dex- but not CpdA-liganded glucocorticoid receptor (GR) binds to a single glucocorticoid response element (GRE), which drives the expression of pro-tumorigenic genes. Our data suggest that development of safe coadjuvant therapy should consider the distinct genomic function between Dex- and CpdA-liganded GR.
Estimation of a biofilm-specific reaction rate: kinetics of bacterial urea hydrolysis in a biofilm
Authors: Connolly James M , Jackson Benjamin , Rothman Adam P , Klapper Isaac , Gerlach Robin
Published: September 2015

Background/Objectives:

Biofilms and specifically urea-hydrolysing biofilms are of interest to the medical community (for example, urinary tract infections), scientists and engineers (for example, microbially induced carbonate precipitation). To appropriately model these systems, biofilm-specific reaction rates are required. A simple method for determining biofilm-specific reaction rates is described and applied to a urea-hydrolysing biofilm.

Methods:

Biofilms were grown in small silicon tubes and influent and effluent urea concentrations were determined. Immediately after sampling, the tubes were thin sectioned to estimate the biofilm thickness profile along the length of the tube. Urea concentration and biofilm thickness data were used to construct an inverse model for the estimation of the urea hydrolysis rate.

Results/Conclusions:

It was found that urea hydrolysis in Escherichia coli MJK2 biofilms is well approximated by first-order kinetics between urea concentrations of 0.003 and 0.221 mol/l (0.186 and 13.3 g/l). The first-order rate coefficient (k1) was estimated to be 23.2±6.2 h−1. It was also determined that advection dominated the experimental system rather than diffusion, and that urea hydrolysis within the biofilms was not limited by diffusive transport. Beyond the specific urea-hydrolysing biofilm discussed in this work, the method has the potential for wide application in cases where biofilm-specific rates must be determined.
Effects of Nanotexture on Electrical Profiling of Single Tumor Cell and Detection of Cancer from Blood in Microfluidic Channels
Authors: Islam Muhymin , Motasim Bellah Mohammad , Sajid Adeel , Raziul Hasan Mohammad , Kim Young-tae , Iqbal Samir M.
Published: September 2015

Microfluidic channels have been implemented to detect cancer cells from blood using electrical measurement of each single cell from the sample. Every cell provided characteristic current profile based on its mechano-physical properties. Cancer cells not only showed higher translocation time and peak amplitude compared to blood cells, their pulse shape was also distinctively different. Prevalent microfluidic channels are plain but we created nanotexture on the channel walls using micro reactive ion etching (micro-RIE). The translocation behaviors of the metastatic renal cancer cells through plain and nanotextured PDMS microchannels showed clear differences. Nanotexture enhanced the cell-surface interactions and more than 50% tumor cells exhibited slower translocation through nanotextured channels compared to plain devices. On the other hand, most of the blood cells had very similar characteristics in both channels. Only 7.63% blood cells had slower translocation in nanotextured microchannels. The tumor cell detection efficiency from whole blood increased by 14% in nanotextured microchannels compared to plain channels. This interesting effect of nanotexture on translocation behavior of tumor cells is important for the early detection of cancer.
Robust bioengineered 3D functional human intestinal epithelium
Authors: Chen Ying , Lin Yinan , Davis Kimberly M. , Wang Qianrui , Rnjak-Kovacina Jelena , Li Chunmei , Isberg Ralph R. , Kumamoto Carol A. , Mecsas Joan , Kaplan David L.
Published: September 2015

Intestinal functions are central to human physiology, health and disease. Options to study these functions with direct relevance to the human condition remain severely limited when using conventional cell cultures, microfluidic systems, organoids, animal surrogates or human studies. To replicate in vitro the tissue architecture and microenvironments of native intestine, we developed a 3D porous protein scaffolding system, containing a geometrically-engineered hollow lumen, with adaptability to both large and small intestines. These intestinal tissues demonstrated representative human responses by permitting continuous accumulation of mucous secretions on the epithelial surface, establishing low oxygen tension in the lumen and interacting with gut-colonizing bacteria. The newly developed 3D intestine model enabled months-long sustained access to these intestinal functions in vitro, readily integrable with a multitude of different organ mimics and will therefore ensure a reliable ex vivo tissue system for studies in a broad context of human intestinal diseases and treatments.
Super-Resolution Imaging Conditions for enhanced Yellow Fluorescent Protein (eYFP) Demonstrated on DNA Origami Nanorulers
Authors: Jusuk Ija , Vietz Carolin , Raab Mario , Dammeyer Thorben , Tinnefeld Philip
Published: September 2015

Photostability is one of the crucial properties of a fluorophore which strongly influences the quality of single molecule-based super-resolution imaging. Enhanced yellow fluorescent protein (eYFP) is one of the most widely used versions of fluorescent proteins in modern cell biology exhibiting fast intrinsic blinking and reversible photoactivation by UV light. Here, we developed an assay for studying photostabilization of single eYFP molecules with respect to fast blinking and demonstrated a 6-fold enhanced photostability of single eYFP molecules with a beneficial influence on the blinking kinetics under oxygen removal and addition of aliphatic thiols (dSTORM-buffer). Conjugation to single stranded DNA and immobilization via DNA hybridization on a DNA origami 12 helix bundle in aqueous solution allowed photophyiscal studies of eYFP at the single-molecule level and at close to physiological conditions. The benefit of improved photophysical properties for localization-based super-resolution microscopy is demonstrated and quantitatively characterized by imaging 12 helix bundle DNA origami nanorulers with binding sites at designed distances of 160 and 100 nm and by imaging microtubules in fixed mammalian Vero cells.
Standardization of the antibody-dependent respiratory burst assay with human neutrophils and Plasmodium falciparum malaria
Authors: Llewellyn David , Miura Kazutoyo , Fay Michael P. , Williams Andrew R. , Murungi Linda M. , Shi Jianguo , Hodgson Susanne H. , Douglas Alexander D. , Osier Faith H. , Fairhurst Rick M. , Diakite Mahamadou , Pleass Richard J. , Long Carole A. , Draper Simon J.
Published: September 2015

The assessment of naturally-acquired and vaccine-induced immunity to blood-stagePlasmodium falciparummalaria is of long-standing interest. However, the field has suffered from a paucity ofin vitroassays that reproducibly measure the anti-parasitic activity induced by antibodies in conjunction with immune cells. Here we optimize the antibody-dependent respiratory burst (ADRB) assay, which assesses the ability of antibodies to activate the release of reactive oxygen species from human neutrophils in response toP. falciparumblood-stage parasites. We focus particularly on assay parameters affecting serum preparation and concentration and importantly assess reproducibility. Our standardized protocol involves testing each serum sample in singlicate with three independent neutrophil donors and indexing responses against a standard positive control of pooled hyper-immune Kenyan sera. The protocol can be used to quickly screen large cohorts of samples from individuals enrolled in immuno-epidemiological studies or clinical vaccine trials and requires only 6 μL of serum per sample. Using a cohort of 86 samples, we show that malaria-exposed individuals induce higher ADRB activity than malaria-naïve individuals. The development of the ADRB assay complements the use of cell-independent assays in blood-stage malaria, such as the assay of growth inhibitory activity and provides an important standardized cell-based assay in the field.
Shape-controlled synthesis and influence of W doping and oxygen nonstoichiometry on the phase transition of VO2
Authors: Chen Ru , Miao Lei , Liu Chengyan , Zhou Jianhua , Cheng Haoliang , Asaka Toru , Iwamoto Yuji , Tanemura Sakae
Published: September 2015

Monoclinic VO2(M) in nanostructure is a prototype material for interpreting correlation effects in solids with fully reversible phase transition and for the advanced applications to smart devices. Here, we report a facile one-step hydrothermal method for the controlled growth of single crystalline VO2(M/R) nanorods. Through tuning the hydrothermal temperature, duration of the hydrothermal time and W-doped level, single crystalline VO2(M/R) nanorods with controlled aspect ratio can be synthesized in large quantities and the crucial parameter for the shape-controlled synthesis is the W-doped content. The dopant greatly promotes the preferential growth of (110) to form pure phase VO2(R) nanorods with high aspect ratio for the W-doped level = 2.0 at% sample. The shape-controlled process of VO2(M/R) nanorods upon W-doping are systematically studied. Moreover, the phase transition temperature (Tc) of VO2 depending on oxygen nonstoichiometry is investigated in detail.
M1 Muscarinic Receptor Deficiency Attenuates Azoxymethane-Induced Chronic Liver Injury in Mice
Authors: Rachakonda Vikrant , Jadeja Ravirajsinh N. , Urrunaga Nathalie H. , Shah Nirish , Ahmad Daniel , Cheng Kunrong , Twaddell William S. , Raufman Jean-Pierre , Khurana Sandeep
Published: September 2015

Cholinergic nervous system regulates liver injury. However, the role of M1 muscarinic receptors (M1R) in modulating chronic liver injury is uncertain. To address this gap in knowledge we treated M1R-deficient and WT mice with azoxymethane (AOM) for six weeks and assessed liver injury responses 14 weeks after the last dose of AOM. Compared to AOM-treated WT mice, M1R-deficient mice had attenuated liver nodularity, fibrosis and ductular proliferation, α-SMA staining and expression of α1 collagen, Tgfβ-R, Pdgf-R, Mmp-2, Timp-1 and Timp-2. In hepatocytes, these findings were associated with reductions of cleaved caspase-3 staining and Tnf-α expression. In response to AOM treatment, M1R-deficient mice mounted a vigorous anti-oxidant response by upregulating Gclc and Nqo1 expression and attenuating peroxynitrite generation. M1R-deficient mouse livers had increased expression of Trail-R2, a promotor of stellate cell apoptosis; dual staining for TUNNEL and α-SMA revealed increased stellate cells apoptosis in livers from M1R-deficient mice compared to those from WT. Finally, pharmacological inhibition of M1R reduced H2O2-induced hepatocyte apoptosis in vitro. These results indicate that following liver injury, anti-oxidant response in M1R-deficient mice attenuates hepatocyte apoptosis and reduces stellate cell activation, thereby diminishing fibrosis. Therefore, targeting M1R expression and activation in chronic liver injury may provide therapeutic benefit.
Protective role of ALDH2 against acetaldehyde-derived DNA damage in oesophageal squamous epithelium
Authors: Amanuma Yusuke , Ohashi Shinya , Itatani Yoshiro , Tsurumaki Mihoko , Matsuda Shun , Kikuchi Osamu , Nakai Yukie , Miyamoto Shin’ichi , Oyama Tsunehiro , Kawamoto Toshihiro , Whelan Kelly A. , Nakagawa Hiroshi , Chiba Tsutomu , Matsuda Tomonari , Muto Manabu
Published: September 2015

Acetaldehyde is an ethanol-derived definite carcinogen that causes oesophageal squamous cell carcinoma (ESCC). Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that eliminates acetaldehyde and impairment of ALDH2 increases the risk of ESCC. ALDH2 is produced in various tissues including the liver, heart and kidney, but the generation and functional roles of ALDH2 in the oesophagus remain elusive. Here, we report that ethanol drinking increased ALDH2 production in the oesophagus of wild-type mice. Notably, levels of acetaldehyde-derived DNA damage represented by N2-ethylidene-2′-deoxyguanosine were higher in the oesophagus of Aldh2-knockout mice than in wild-type mice upon ethanol consumption. In vitro experiments revealed that acetaldehyde induced ALDH2 production in both mouse and human oesophageal keratinocytes. Furthermore, the N2-ethylidene-2′-deoxyguanosine levels increased in both Aldh2-knockout mouse keratinocytes and ALDH2-knockdown human keratinocytes treated with acetaldehyde. Conversely, forced production of ALDH2 sharply diminished the N2-ethylidene-2′-deoxyguanosine levels. Our findings provide new insight into the preventive role of oesophageal ALDH2 against acetaldehyde-derived DNA damage.
Micelle PCR reduces chimera formation in 16S rRNA profiling of complex microbial DNA mixtures
Authors: Boers Stefan A. , Hays John P. , Jansen Ruud
Published: September 2015

16S rRNA gene profiling has revolutionized the field of microbial ecology. Many researchers in various fields have embraced this technology to investigate bacterial compositions of samples derived from many different ecosystems. However, it is important to acknowledge the current limitations and drawbacks of 16S rRNA gene profiling. Although sample handling, DNA extraction methods and the choice of universal 16S rRNA gene PCR primers are well known factors that could seriously affect the final results of microbiota profiling studies, inevitable amplification artifacts, such as chimera formation and PCR competition, are seldom appreciated. Here we report on a novel micelle based amplification strategy, which overcomes these limitations via the clonal amplification of targeted DNA molecules. Our results show that micelle PCR drastically reduces chimera formation by a factor of 38 (1.5% vs. 56.9%) compared with traditional PCR, resulting in improved microbial diversity estimates. In addition, compartmentalization during micelle PCR prevents PCR competition due to unequal amplification rates of different 16S template molecules, generating robust and accurate 16S microbiota profiles required for comparative studies (e.g. longitudinal surveys).
Background-free in-vivo Imaging of Vitamin C using Time-gateable Responsive Probe
Authors: Song Bo , Ye Zhiqing , Yang Yajie , Ma Hua , Zheng Xianlin , Jin Dayong , Yuan Jingli
Published: September 2015

Sensitive optical imaging of active biomolecules in the living organism requires both a molecular probe specifically responsive to the target and a high-contrast approach to remove the background interference from autofluorescence and light scatterings. Here, a responsive probe for ascorbic acid (vitamin C) has been developed by conjugating two nitroxide radicals with a long-lived luminescent europium complex. The nitroxide radical withholds the probe on its “off” state (barely luminescent), until the presence of vitamin C will switch on the probe by forming its hydroxylamine derivative. The probe showed a linear response to vitamin C concentration with a detection limit of 9.1 nM, two orders of magnitude lower than that achieved using electrochemical methods. Time-gated luminescence microscopy (TGLM) method has further enabled real-time, specific and background-free monitoring of cellular uptake or endogenous production of vitamin C and mapping of vitamin C in living Daphnia magna. This work suggests a rational design of lanthanide complexes for background-free small animal imaging of biologically functional molecules.
Novel lithium-nitrogen compounds at ambient and high pressures
Authors: Shen Yanqing , Oganov Artem R. , Qian Guangri , Zhang Jin , Dong Huafeng , Zhu Qiang , Zhou Zhongxiang
Published: September 2015

Using ab initio evolutionary simulations, we predict the existence of five novel stable Li-N compounds at pressures from 0 to 100 GPa (Li13N, Li5N, Li3N2, LiN2and LiN5). Structures of these compounds contain isolated N atoms, N2dimers, polyacetylene-like N chains and N5rings, respectively. The structure of Li13N consists of Li atoms and Li12N icosahedra (with N atom in the center of the Li12icosahedron) – such icosahedra are not described by Wade-Jemmis electron counting rules and are unique. Electronic structure of Li-N compounds is found to dramatically depend on composition and pressure, making this system ideal for studying metal-insulator transitions. For example, the sequence of lowest-enthalpy structures of LiN3shows peculiar electronic structure changes with increasing pressure: metal-insulator-metal-insulator. This work also resolves the previous controversies of theory and experiment on Li2N2.