bluuebunny/crossref_metadata_2025 huggingface dataset:
Square superlattice pattern with discharge holes due to direction-selective surface discharges in dielectric barrier discharge
Authors: Mi Yanlin , Dong Lifang , Liu Binbin , Sun Haoyang , Huang Jiayu , Han Rong , Cui Yiqian , Hao Fang , Liu Fucheng , Pan Yuyang
Published: December 2018

We report a square superlattice pattern with discharge holes due to direction-selective surface discharges (SDs) in a dielectric barrier discharge system for the first time. The instantaneous images with an exposure time of 10 μs (half cycle of voltage) taken using a high-speed video camera show that the directions of surface discharges (SDs) of the small spots are selective, which are different from the directions of SDs of the large spots diffused in all directions. In each positive half cycle of voltage, the graphs captured using an intensified charge-coupled device show that the large spot discharges after the small spots and locates at the center of the square formed by the SDs induced by small spots but not their cross point. In each negative half cycle of voltage, the large spots discharge before the small spot and press the SD of the small spot to stretch along the midperpendicular of two adjacent large spots. In a word, the direction-selective surface discharges play a crucial role for the formation of the pattern with the discharge holes in the dielectric barrier discharge system.
Effects of wave potential on electron holes in thermal and superthermal space plasmas
Authors: Aravindakshan Harikrishnan , Kakad Amar , Kakad Bharati
Published: December 2018

Observations from various interplanetary and other spacecraft missions evince that superthermal distributions are omnipresent in the solar wind and near Earth's plasma environment. These observations confirm the presence of coherent bipolar electric field pulses. In phase space, these electric field structures are observed as electron holes (EHs) or ion holes. Trapping of particles in a potential well causes the formation of such structures and is generally studied using the Bernstein-Greene-Kruskal approach. The literature on these structures encompasses the trapped electron distribution function and physically plausible regions. In this paper, we focus on the effects of the width and amplitude of wave potential on electron trapping in thermal and superthermal plasmas. It can be observed that both an increase in the width and the amplitude of wave potential cause an augmentation in the trapping of particles. The amplitude plays a dominant role in the trapping of maximum energetic particles, whereas the width plays a role in deciding the density of particles at the center of the EHs. We found that there exists an upper limit for the stability region of EHs defined by the width-amplitude relation. Additionally, it is noticed that the superthermal plasma does not impose restriction on the presence of electron holes with a width less than the electron Debye length.
Self-screening induced abnormal stability of ferroelectric phase in GeTe ultrathin films
Authors: Wang Xiaojie , Zhou Lingjun , Feng Jinlong , Wang Sheng , Qian Hang , Tong Hao , Miao Xiangshui
Published: December 2018

A stable ferroelectric phase or Curie temperature (Tc) above room temperature is essential for ferroelectric devices. However, the fast Tc drop of ferroelectric thin films has become a vital factor inhibiting the scaling down of ferroelectric devices. Many efforts have been made to slow down the Tc drop in conventional insulating ferroelectric thin films, but they are costly and complex. A semiconducting ferroelectric, GeTe, is proposed in this letter, which shows an abnormal stability of the ferroelectric phase as the film thickness decreases to as thin as 3 nm. The ferroelectric Curie temperatures of GeTe thin films with different thicknesses have been studied using variable-temperature Raman measurements. The self-screening process of free carriers provided by intrinsic Ge vacancies in GeTe films plays an important role in cancelling the depolarization field according to first principles calculations and results in an abnormal stability of ferroelectricity in ultrathin GeTe films. Self-screening by free carriers in GeTe unravels that the ferroelectric phase could remain stable in low dimension semiconducting ferroelectrics. These results provide a straightforward solution for high density ferroelectric devices and show promising application of semiconducting ferroelectrics in large current ferroelectric diodes.
A comparison of surface hopping approaches for capturing metal-molecule electron transfer: A broadened classical master equation versus independent electron surface hopping
Authors: Miao Gaohan , Ouyang Wenjun , Subotnik Joseph
Published: December 2018

Within a generalized Anderson-Holstein model, we investigate electron transfer rates using two different surface hopping algorithms: a broadened classical master equation (BCME) and independent electron surface hopping (IESH). We find that for large enough bandwidth and density of one electron states, and in the presence of external friction, the IESH results converge to the BCME results for impurity-bath model systems, recovering both relaxation rates and equilibrium populations. Without external friction, however, the BCME and IESH results can strongly disagree, and preliminary evidence suggests that IESH does not always recover the correct equilibrium state. Finally, we also demonstrate that adding an electronic thermostat to IESH does help drive the metallic substrate to the correct equilibrium state, but this improvement can sometimes come at the cost of worse short time dynamics. Overall, our results should be of use for all computational chemists looking to model either gas phase scattering or electrochemical dynamics at a metal interface.
Torsionally induced exciton localization and decoherence in π-conjugated polymers
Authors: Barford William , Mannouch Jonathan R.
Published: December 2018

We develop a model of excitons coupled to the rotational motion of monomers to study the torsionally induced relaxation and decoherence of excitons in π-conjugated polymers. The model assumes that the monomer units are described by elastically uncoupled harmonic oscillators and that there is a linear exciton-roton coupling. Although the rotational degrees of freedom are much slower than the exciton, so that the adiabatic approximation is generally expected to be valid, we also investigate possible quantized roton corrections via coupled time evolving block decimation-Ehrenfest equations of motion. For the relaxation of the lowest-excited exciton, we find that (1) for a polymer chain with a ground state spiral torsional conformation, the equilibrium angular displacement of each monomer is proportional to the difference of the exciton bond-orders on the neighboring bridging bonds. Consequently, this displacement vanishes in the long chain limit and a classical (Landau) exciton-polaron is not formed. (2) For a polymer chain with a ground state staggered torsional conformation, the equilibrium angular displacement of each monomer is proportional to the sum of the exciton bond-orders on the neighboring bridging bonds. Consequently, there is significant angular displacement and local planarization causing exciton density localization. A classical (Landau) exciton-polaron is formed where the staggered angular displacement is proportional to the exciton density. (3) Generally, in the adiabatic limit, the decay of off-diagonal long-range order (i.e., exciton decoherence) mirrors the localization of the exciton density. However, quantum corrections to the rotational motion alter this adiabatic prediction because of correlated exciton-roton dynamics within the first rotational half-period. In particular, exciton-polaron quasiparticle formation causes more rapid and oscillatory exciton decoherence and slower exciton density localization.
Relation between fermionic and qubit mean fields in the electronic structure problem
Authors: Ryabinkin Ilya G. , Genin Scott N. , Izmaylov Artur F.
Published: December 2018

For quantum computing applications, the electronic Hamiltonian for the electronic structure problem needs to be unitarily transformed into a qubit form. We found that mean-field procedures on the original electronic Hamiltonian and on its transformed qubit counterpart can give different results. We establish conditions of when fermionic and qubit mean fields provide the same or different energies. In cases when the fermionic mean-field (Hartree–Fock) approach provides an accurate description (electronic correlation effects are small), the choice of molecular orbitals for the electron Hamiltonian representation becomes the determining factor in whether the qubit mean-field energy will be equal to or higher than that of the fermionic counterpart. In strongly correlated cases, the qubit mean-field approach has a higher chance to undergo symmetry breaking and lower its energy below the fermionic counterpart.
Isochronal superposition and density scaling of the α-relaxation from pico- to millisecond
Authors: Hansen Henriette Wase , Frick Bernhard , Capaccioli Simone , Sanz Alejandro , Niss Kristine
Published: December 2018

The relaxation dynamics in two van der Waals bonded liquids and one hydrogen-bonding molecular liquid are studied as a function of pressure and temperature by incoherent neutron scattering using simultaneous dielectric spectroscopy. The dynamics are studied in a range of alpha relaxation times from pico- to milliseconds, primarily in the equilibrium liquid state. In this range, we find that isochronal superposition and density scaling work not only for the two van der Waals liquids but also for the hydrogen-bonding liquid, though the density scaling exponent is much smaller for the latter. Density scaling and isochronal superposition are seen to break down for intra-molecular dynamics when it is separated in time from the alpha relaxation, in close agreement with previous observations from molecular dynamics simulations.
Modular path integral methodology for real-time quantum dynamics
Authors: Makri Nancy
Published: December 2018

In a recent communication [N. Makri, J. Chem. Phys. 148, 101101 (2018)], it was shown that the locality of interactions in many systems of interest allows a decomposition of the path integral and its evaluation via sequential linking of the paths of relatively small “modules” (e.g., chemical groups or monomers). The present paper describes the modular path integral methodology for simulating dynamical properties by propagating the density matrix in real time. The procedure is first presented for the simple topology of a single-file arrangement of units interacting via nearest neighbor couplings and subsequently extended to the calculation of two-particle correlations in arrays that may also contain some long-range interactions, to the treatment of systems with side chains or cyclic structures, to the simulation of internal dynamics in long organic molecules, and to the modifications required for coupling of one or several units of a system to dissipative environments. Illustrative applications to the dynamics of interacting two-level-systems are presented.
Towards on-chip mid infrared photonic aerosol spectroscopy
Authors: Singh Robin , Su Peter , Kimerling Lionel , Agarwal Anu , Anthony Brian W.
Published: December 2018

We propose an on-chip mid-infrared (MIR) photonic spectroscopy platform for aerosol characterization to obtain highly discriminatory information on the chemistry of aerosol particles. Sensing of aerosols is crucial for various environmental, climatic, warfare threat detection, and pulmonary healthcare applications. Currently, chemical characterization of aerosols is performed using FTIR spectroscopy, yielding chemical fingerprinting because most of the vibrational and rotational transitions of chemical molecules fall in the IR range, and Raman spectroscopy. Both techniques use free space bench-top geometries. Here, we propose miniaturized on-chip MIR photonics-based aerosol spectroscopy consisting of a broadband spiral-waveguide sensor that significantly enhances the particle-light interaction to improve sensitivity. The spiral waveguides are made of a chalcogenide glass material (Ge23Sb7S70) which shows a broad transparency over the IR range (1–10 μm). We demonstrate the sensing of N-methyl aniline-based aerosol particles with the device. We anticipate that the sensor will readily complement existing photonic resonator-based particle sizing and counting techniques to develop a unified framework for on-chip integrated photonic aerosol spectroscopy.
Improvement of response time in GAGG:Ce scintillation crystals by magnesium codoping
Authors: Tamulatis G. , Dosovitskiy G. , Gola A. , Korjik M. , Mazzi A. , Nargelas S. , Sokolov P. , Vaitkevičius A.
Published: December 2018

Dynamics of the population of the excited Ce states responsible for the luminescence response time in Gd3Al2Ga3O12:Ce scintillating crystals is studied by revealing the dynamics of nonequilibrium carriers in the picosecond domain. Optical pump and probe technique exploiting selective excitation of structural units of the crystal and probing the induced absorption as a function of time and spectral position is exploited. A fast response within a few picoseconds due to the absorption by holes at Gd ions and by electrons occupying the first excited state of Ce ions with the intracenter relaxation time of 500 fs are identified. Trapping of nonequilibrium electrons during their migration through the matrix to the emitting Ce ions are shown to be responsible for the slow component in the population of the excited Ce state. Elimination of the slow component is evidenced even at Mg codoping as low as 10 ppm. The elimination correlates with the acceleration of the response in coincidence time resolution experiments showing potential of GAGG:Ce, Mg in medical and high-energy physics applications.
Hierarchical transitions in multiplex adaptive networks of oscillatory units
Authors: Maslennikov Oleg V. , Nekorkin Vladimir I.
Published: December 2018

In this work, we consider two-layer multiplex networks of coupled Stuart-Landau oscillators. The first layer contains oscillators with amplitude heterogeneity and all-to-all adaptive links, while the second layer contains identical oscillators all-to-all coupled by links with constant weights. The links between different layers are adaptive and organized in a one-to-one manner. We study the evolution of one-layer and two-layer networks depending on intra- and interlayer coupling strengths and show hierarchical transitions between oscillatory and quenched regimes.
Conservation and restoration in peopled landscapes in Oceania: opportunities and challenges
Authors: Wittmer Heiko U. , Anton Victor , Gruber Monica A. M. , Ireland Luke , Linklater Wayne , Russell James C. , Shanahan Danielle F.
Published: December 2018

While the role of humans in causing high rates of species extinctions worldwide is well established, philosophies and opinions as to how to mitigate the current biodiversity loss are once again hotly debated topics. At the centre of the debate are differences in opinions regarding the value and the best methods of conserving and restoring biodiversity in peopled landscapes. Here we synthesise information from different case studies from Oceania that demonstrate how biodiversity conservation in peopled landscapes will require different, and often novel, socio-ecological approaches. We draw special attention to the importance of prioritising human dimensions in the conservation of different ecosystems, ranging from highly modified urban areas to largely intact wilderness areas. Particularly, we explore the importance of understanding motivations to conserve biodiversity, implementing well designed conservation actions, both socially and ecologically, and involving different stakeholders in the design and implementation of conservation projects. On the basis of our synthesis, we suggest that conservation in peopled landscapes in Oceania offers great opportunities for community involvement, including traditional landowners, in all aspects of conservation planning and implementation. Where uncertainties regarding the suitability of established management strategies exist, novel guidelines should be based on the best available ecological and social evidence to avoid potential negative outcomes.
Introduction: Structuring thought, externalizing structure
Authors: Rita Manzini M.
Published: December 2018

The articles collected in this volume bear witness to the important role played by studies on language variation, specifically on Romance microvariation, in the development of formal approaches to language. Leonardo M. Savoia is a central figure in this endeavor, in the twin fields of phonology and morphosyntax. In this introductory chapter, I will briefly put research into (micro)variation in Romance and other language families in the context of the recent theoretical debate in generative grammar. Despite Savoia’s unrivalled expertise in field work and the prodigious number of data we owe to him, especially on Italian and Albanian varieties, it is only within a theoretical setting that his work is truly appreciated. I will conclude each section by illustrating how the themes explored therein resonate in the several contributions to the volume.
Objects and subjects in the left periphery
Authors: Belletti Adriana
Published: December 2018

A parallel is highlighted between the linguistic behavior of young Italian-speaking children as emerged in recent experimental work (Belletti and Manetti 2017) with comparative data from other Romance languages such as Balearic Catalan and (previous stages of) Spanish in the domain of a-Topics. A possible path from a-Topics to DOM is drawn, building on previous proposals in Belletti (2017a). a-Marking of topics concerns direct object DPs. A proposal is sketched out as to why subject DPs could not be a-marked when they are also topics in terms of a possibly conflicting requirement arising from the simultaneous satisfaction of both the Topic criterion with a-marking and the Subject criterion (in the sense of Rizzi 2006).
Clitic stress allomorphy in Sardinian
Authors: Bafile Laura , Lai Rosangela
Published: December 2018

Sardinian displays stress shifts under cliticisation with imperative and gerund verb forms. Stress shift is related to the type and number of clitics associated to the host. Across the range of dialectal variation, three different stress shift patterns are attested. We will argue that Sardinian data supports the approach whereby stress shift variation cannot be regarded either as the result of purely prosodic rules or as the consequence of different syntactic feature-checking properties of the clause. The analysis here proposed accounts for stress placement as an allomorphy that is partly determined by phonological conditions.
Clitics and vowel epenthesis
Authors: Garzonio Jacopo , Rossi Silvia
Published: December 2018

Syncope and epenthesis have been treated as two closely related phenomena in traditional accounts: what syncope destroys, epenthesis restores. In this paper we present some cases of vowel epenthesis in the verbal domain in some Northern Emilian varieties where both syncope and epenthesis are rather restricted. It will be shown that apparently free alternations in some arhizotonic forms, like lizì vs. alzì ‘you.pl read’, are to be considered as the result of two different grammars. Only in one of these there is allomorphy of verb stems triggered by the interaction of morphosyntactic configurations, and morphophonological and phonotactic constraints.
Unstable personal pronouns in Northern Logudorese
Authors: Loporcaro Michele , Romagnoli Serena , Wild Mario
Published: December 2018

This paper deals with some Logudorese dialects of Northern Sardinia, whose nominal and pronominal morphology has been variously reshaped due to contact with Gallurese/Sassarese. While many of the data discussed here were addressed in the previously available literature, we draw on first-hand fieldwork data to show that further simplification in the system of personal pronouns has taken place (Sènnori) or is presently ongoing (Luras), resulting in an overall trend towards loss of marking of the gender contrast, everywhere in the plural, at times also in the singular. In particular in the case of Luras, we show that this rearrangement is taking place through a kaleidoscope of subtly differing individual variants.
Object clitics for subject clitics in Francoprovençal and Piedmontese
Authors: Roberts Ian
Published: December 2018

This article illustrates and analyses the intricate phenomenon of OCL-for-SCL, found in certain varieties of Franco-Provençal Valdôtain and Piedmontese. This phenomenon, which at first sight appears highly unusual, reflects operations of morphophonological realisation of the kind developed in the context of the theory of Distributed Morphology such as fission and fusion, amply attested elsewhere in the world’s languages. In a further section, the contexts for enclisis to past participles are discussed. Following Roberts (2016), this leads to the proposal of the implicational scale ‘complement to restructuring verb > complement to auxiliary > complement to causative’. This can be described this in terms of degrees of ‘transparency’ which in turn may translate into structural ‘size’.
Dialects and neuroscience
Authors: Grimaldi Mirko
Published: December 2018

Dialectal variation has been constanly at the core of linguistic investigation. On the base of the few neurophysiological studies that explored dialectal data, this article examines if and how dialectal variation may contribute to the advancing of the neurobiology of language. Evidence suggest that the neural investigation of allophonic variation generated by phonological rules is very useful for the progress of the neurobiology of language. Also, all kinds of parametric variations characterizing dialects are well suited to this aim. Finally, I outline some general and detailed questions that need to be addressed making use of a new methodology: the oscillatory rhythms approach.
Some Celto-Albanian isoglosses and their implications
Authors: Trumper John
Published: December 2018

Çabej (1969) originally posited a small number of Albanian-Celtic-Germanic isoglosses. Apart from a more detailed discussion of besa and njerí, we highlight in greater depth the areal diffusion of the I-E diffusion of Albanoid bërrakë, e blertë, brī and dritë. We add in-depth observations on the Celto-Albanian binomial ardracht (Old Irish) – dritë (Albanoid), where the Celtic terms involved are traceable to Gaulish dercos and uodercos of texts and inscriptions. Such isoglosses are developed here and tend to substantiate Hamp’s view that the Albanoid Urheimat was originally Central-North Europe rather than its present day Mediterranean Heimat.
Are Sardinian vocatives perfectly regular?
Authors: Floricic Franck , Molinu Lucia
Published: December 2018

The aim of this contribution is to honor Leonardo Savoia with some reflections concerning a topic which has received little attention until recent years: the case of Vocatives. If according to D’Alessandro & Van Oostendorp (2016: 78) Vocatives are perfectly regular, typological data show on the other hand that in many languages this is not the case. More specifically, we present and discuss the question of the shape of the Vocatives found in Logudorese Sardinian. We shall bring new data that confirm the view expressed among others in the seminal work of Uspensky & Zhivov (1977) and Floricic (2002, 2011), according to which Vocatives are in many respects exceptional.
Boriding behaviour of titanium alloys with different crystalline structures
Authors: Kara Gokhan , Purcek Gencaga
Published: December 2018

The objective of this study is to investigate the boriding behaviour of titanium implant materials on the basis of their crystalline structure and chemical composition. α-type Cp-Ti, α +  β type Ti-6Al-4V and β-type Ti-45Nb alloys have been borided by the powder-pack boriding technique at temperatures between 850 and 1200°C. The X-ray diffraction, GDOES and SEM analysis demonstrated that boride layers on Cp-Ti and Ti-6Al-4V alloy mainly composed of TiB2 and TiB phases, whereas Ti-45Nb alloy consists of the mixture of TiB2.NbB2 and TiB phases. Boride layers on Ti-45Nb alloy grew uniformly and the highest boride layer thickness of 72.1  μm was obtained on this alloy among the others. Activation energies of boron in monolithic layer of Cp-Ti and Ti-6Al-4V alloy were determined to be 214.5 and 231.8  kJ/mol, respectively. Activation energies in monolithic and total boride layers on Ti-45Nb were determined to be 228.5 and 145.8  kJ/mol, respectively.
Bobbin tool friction stir welding: a review
Authors: Fuse Kishan , Badheka Vishvesh
Published: December 2018

Friction stir welding is a solid-state welding technique for joining similar and dissimilar material. Bobbin tool friction stir welding (BTFSW) is a variant of the conventional friction stir welding process (CFSW). Compared with conventional FSW, BTFSW eliminates all limitations of CFSW using a two shoulders configuration. Now, the need has arisen to review the work done on BTFSW to provide broader aspects of the technique to researchers. This paper aims at providing comprehensive insight on the BTFSW. The paper pays critical attention to tool material selection, design features of shoulder and pin surfaces, microstructure evolution, mechanical characterisation, derivatives, and challenges in this technique. Further, welding defects and future scope of BTFSW are also addressed in this paper.
Regulatory light chain phosphorylation augments length-dependent contraction in PTU-treated rats
Authors: Breithaupt Jason J. , Pulcastro Hannah C. , Awinda Peter O. , DeWitt David C. , Tanner Bertrand C.W.
Published: December 2018

Force production by actin–myosin cross-bridges in cardiac muscle is regulated by thin-filament proteins and sarcomere length (SL) throughout the heartbeat. Prior work has shown that myosin regulatory light chain (RLC), which binds to the neck of myosin heavy chain, increases cardiac contractility when phosphorylated. We recently showed that cross-bridge kinetics slow with increasing SLs, and that RLC phosphorylation amplifies this effect, using skinned rat myocardial strips predominantly composed of the faster α-cardiac myosin heavy chain isoform. In the present study, to assess how RLC phosphorylation influences length-dependent myosin function as myosin motor speed varies, we used a propylthiouracil (PTU) diet to induce >95% expression of the slower β-myosin heavy chain isoform in rat cardiac ventricles. We measured the effect of RLC phosphorylation on Ca2+-activated isometric contraction and myosin cross-bridge kinetics (via stochastic length perturbation analysis) in skinned rat papillary muscle strips at 1.9- and 2.2-µm SL. Maximum tension and Ca2+ sensitivity increased with SL, and RLC phosphorylation augmented this response at 2.2-µm SL. Subtle increases in viscoelastic myocardial stiffness occurred with RLC phosphorylation at 2.2-µm SL, but not at 1.9-µm SL, thereby suggesting that RLC phosphorylation increases β-myosin heavy chain binding or stiffness at longer SLs. The cross-bridge detachment rate slowed as SL increased, providing a potential mechanism for prolonged cross-bridge attachment to augment length-dependent activation of contraction at longer SLs. Length-dependent slowing of β-myosin heavy chain detachment rate was not affected by RLC phosphorylation. Together with our previous studies, these data suggest that both α- and β-myosin heavy chain isoforms show a length-dependent activation response and prolonged myosin attachment as SL increases in rat myocardial strips, and that RLC phosphorylation augments length-dependent activation at longer SLs. In comparing cardiac isoforms, however, we found that β-myosin heavy chain consistently showed greater length-dependent sensitivity than α-myosin heavy chain. Our work suggests that RLC phosphorylation is a vital contributor to the regulation of myocardial contractility in both cardiac myosin heavy chain isoforms.
Novel pfkelch13 Gene Polymorphism Associates With Artemisinin Resistance in Eastern India
Authors: Das Sabyasachi , Manna Subhankar , Saha Bhaskar , Hati Amiya Kumar , Roy Somenath
Published: December 2018

Background

Artesunate-sulfadoxine-pyrimethamine (ASSP) is the frontline artemisinin combination therapy (ACT) in India. Random, irrational, subtherapeutic artemisinin doses and self-medication with ACT along with predominance of sulfadoxine-pyrimethamine resistance parasite invoked a strong possibility of emerging artemisinin-resistant malaria parasites.

Methods

This study involved 226 patients with uncomplicated Plasmodium falciparum infection who had successfully completed the 42 days follow-up after ASSP combination therapy from April 2014 to January 2016. We assessed the ASSP treatment efficacy by evaluating parasite clearance half-life, pfkelch13, and other (pfdhfr, pfdhps, pfmdr1, pfcrt) gene mutations and survival of parasites as detected by an ex vivo ring-stage survival assay (RSA).

Findings

Slow-clearing infections with longer parasite clearance half-lives (>5 hours) were observed in 12% isolates. Cure rate after ASSP treatment was declining to about 84.1%. ASSP failure was recorded in 15.9% (early treatment failure, 7.9%; late treatment failure, 7.9%) of isolates. In sum, 24 patients (10.6%) had parasite clearance half-lives greater than 5 hours with pfkelch13 polymorphism after 441 codon; in 15 of those patients (6.6%), parasites had not cleared by 72 hours after initiation of therapy. Median ex vivo ring-stage survival rate of these isolates was very high (12.2%; 95% confidence interval [CI], 10.9–13.8) from that of cured patients (0.9%; 95% CI, 0.09–1.07). Of these 15 patients, 13 patients had pfkelch13 G625R polymorphism, whereas 2 patients contained R539T polymorphism. As per the World Health Organization guideline, these 15 isolates were true artemisinin-resistant isolates.

Interpretation

Identification of artemisinin-resistant isolates in India together with new mutations and increasing combination therapy failures blow alarms for urgent malaria control.
Reproductive Homeostasis and Senescence in Drosophila melanogaster
Authors: Curtsinger James W
Published: December 2018

The homeostatic properties of reproduction in aging female Drosophila melanogaster are investigated. Classic studies based on cohort analysis suggest that homeostatic capacity declines gradually as daily oviposition rates decline in aging flies. Analysis at the level of individuals gives a very different picture: reproductive homeostasis remains relatively constant for most of adult life until a critical point when oviposition either ceases entirely or continues in dysregulated fashion. The collapse of homeostatic capacity is abrupt. Enhanced homeostasis is associated with increased lifetime fecundity and improved prospects for survival. The fractal concept of lacunarity can be used to parameterize the “roughness” of individual fecundity trajectories and is inversely related to homeostatic capacity.
Whole-genome sequence of the oriental lung fluke Paragonimus westermani
Authors: Oey Harald , Zakrzewski Martha , Narain Kanwar , Devi K Rekha , Agatsuma Takeshi , Nawaratna Sujeevi , Gobert Geoffrey N , Jones Malcolm K , Ragan Mark A , McManus Donald P , Krause Lutz
Published: December 2018

Background

Foodborne infections caused by lung flukes of the genus Paragonimus are a significant and widespread public health problem in tropical areas. Approximately 50 Paragonimus species have been reported to infect animals and humans, but Paragonimus westermani is responsible for the bulk of human disease. Despite their medical and economic importance, no genome sequence for any Paragonimus species is available.

Results

We sequenced and assembled the genome of P. westermani, which is among the largest of the known pathogen genomes with an estimated size of 1.1 Gb. A 922.8 Mb genome assembly was generated from Illumina and Pacific Biosciences (PacBio) sequence data, covering 84% of the estimated genome size. The genome has a high proportion (45%) of repeat-derived DNA, particularly of the long interspersed element and long terminal repeat subtypes, and the expansion of these elements may explain some of the large size. We predicted 12,852 protein coding genes, showing a high level of conservation with related trematode species. The majority of proteins (80%) had homologs in the human liver fluke Opisthorchis viverrini, with an average sequence identity of 64.1%. Assembly of the P. westermani mitochondrial genome from long PacBio reads resulted in a single high-quality circularized 20.6 kb contig. The contig harbored a 6.9 kb region of non-coding repetitive DNA comprised of three distinct repeat units. Our results suggest that the region is highly polymorphic in P. westermani, possibly even within single worm isolates.

Conclusions

The generated assembly represents the first Paragonimus genome sequence and will facilitate future molecular studies of this important, but neglected, parasite group.
Annotation of the Giardia proteome through structure-based homology and machine learning
Authors: Ansell Brendan R E , Pope Bernard J , Georgeson Peter , Emery-Corbin Samantha J , Jex Aaron R
Published: December 2018

Background

Large-scale computational prediction of protein structures represents a cost-effective alternative to empirical structure determination with particular promise for non-model organisms and neglected pathogens. Conventional sequence-based tools are insufficient to annotate the genomes of such divergent biological systems. Conversely, protein structure tolerates substantial variation in primary amino acid sequence and is thus a robust indicator of biochemical function. Structural proteomics is poised to become a standard part of pathogen genomics research; however, informatic methods are now required to assign confidence in large volumes of predicted structures.

Aims

Our aim was to predict the proteome of a neglected human pathogen, Giardia duodenalis, and stratify predicted structures into high- and lower-confidence categories using a variety of metrics in isolation and combination.

Methods

We used the I-TASSER suite to predict structural models for ~5,000 proteins encoded in G. duodenalis and identify their closest empirically-determined structural homologues in the Protein Data Bank. Models were assigned to high- or lower-confidence categories depending on the presence of matching protein family (Pfam) domains in query and reference peptides. Metrics output from the suite and derived metrics were assessed for their ability to predict the high-confidence category individually, and in combination through development of a random forest classifier.

Results

We identified 1,095 high-confidence models including 212 hypothetical proteins. Amino acid identity between query and reference peptides was the greatest individual predictor of high-confidence status; however, the random forest classifier outperformed any metric in isolation (area under the receiver operating characteristic curve = 0.976) and identified a subset of 305 high-confidence-like models, corresponding to false-positive predictions. High-confidence models exhibited greater transcriptional abundance, and the classifier generalized across species, indicating the broad utility of this approach for automatically stratifying predicted structures. Additional structure-based clustering was used to cross-check confidence predictions in an expanded family of Nek kinases. Several high-confidence-like proteins yielded substantial new insight into mechanisms of redox balance in G. duodenalis—a system central to the efficacy of limited anti-giardial drugs.

Conclusion

Structural proteomics combined with machine learning can aid genome annotation for genetically divergent organisms, including human pathogens, and stratify predicted structures to promote efficient allocation of limited resources for experimental investigation.
Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study
Authors: Jiang Xia , Dimou Niki L , Al-Dabhani Kawthar , Lewis Sarah J , Martin Richard M , Haycock Philip C , Gunter Marc J , Key Timothy J , Eeles Rosalind A , Muir Kenneth , Neal David , Giles Graham G , Giovannucci Edward L , Stampfer Meir , Pierce Brandon L , Schildkraut Joellen M , Warren Andersen Shaneda , Thompson Deborah , Zheng Wei , Kraft Peter , Tsilidis Konstantinos K ,   PRACTICAL, CRUK, BPC3, CAPS and PEGASUS consortia
Published: December 2018

Background

Observational studies have suggested an association between circulating vitamin D concentrations [25(OH)D] and risk of breast and prostate cancer, which was not supported by a recent Mendelian randomization (MR) analysis comprising 15 748 breast and 22 898 prostate-cancer cases. Demonstrating causality has proven challenging and one common limitation of MR studies is insufficient power.

Methods

We aimed to determine whether circulating concentrations of vitamin D are causally associated with the risk of breast and prostate cancer, by using summary-level data from the largest ever genome-wide association studies conducted on vitamin D (N = 73 699), breast cancer (Ncase = 122 977) and prostate cancer (Ncase = 79 148). We constructed a stronger instrument using six common genetic variants (compared with the previous four variants) and applied several two-sample MR methods.

Results

We found no evidence to support a causal association between 25(OH)D and risk of breast cancer [OR per 25 nmol/L increase, 1.02 (95% confidence interval: 0.97–1.08), P = 0.47], oestrogen receptor (ER)+ [1.00 (0.94–1.07), P = 0.99] or ER− [1.02 (0.90–1.16), P = 0.75] subsets, prostate cancer [1.00 (0.93–1.07), P = 0.99] or the advanced subtype [1.02 (0.90–1.16), P = 0.72] using the inverse-variance-weighted method. Sensitivity analyses did not reveal any sign of directional pleiotropy.

Conclusions

Despite its almost five-fold augmented sample size and substantially improved statistical power, our MR analysis does not support a causal effect of circulating 25(OH)D concentrations on breast- or prostate-cancer risk. However, we can still not exclude a modest or non-linear effect of vitamin D. Future studies may be designed to understand the effect of vitamin D in subpopulations with a profound deficiency.
Long-term outcomes of patients with stable coronary disease and chronic kidney dysfunction: 10-year follow-up of the Medicine, Angioplasty, or Surgery Study II Trial
Authors: Lima Eduardo Gomes , Charytan David M , Hueb Whady , de Azevedo Diogo Freitas Cardoso , Garzillo Cibele Larrosa , Favarato Desiderio , Linhares Filho Jaime Paula Pessoa , Martins Eduardo Bello , Batista Daniel Valente , Rezende Paulo Cury , Hueb Alexandre Ciappina , Ramires José Antonio Franchini , Kalil Filho Roberto
Published: December 2018

Background

Chronic kidney disease (CKD) is associated with a worse prognosis in patients with stable coronary artery disease (CAD); however, there is limited randomized data on long-term outcomes of CAD therapies in these patients. We evaluated long-term outcomes of CKD patients with CAD who underwent randomized therapy with medical treatment (MT) alone, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG).

Methods

Baseline estimated glomerular filtration rate (eGFR) was obtained in 611 patients randomized to one of three therapeutic strategies in the Medicine, Angioplasty, or Surgery Study II trial. Patients were categorized in preserved renal function and mild or moderate CKD groups depending on their eGFR (≥90, 89–60 and 59–30 mL/min/1.73 m2, respectively). The primary clinical endpoint, a composite of overall death and myocardial infarction, and its individual components were analyzed using proportional hazards regression (Clinical Trial registration information: http://www.controlled-trials.com. Registration number: ISRCTN66068876).

Results

Of 611 patients, 112 (18%) had preserved eGFR, 349 (57%) mild dysfunction and 150 (25%) moderate dysfunction. The primary endpoint occurred in 29.5, 32.4 and 44.7% (P = 0.02) for preserved eGFR, mild CKD and moderate CKD, respectively. Overall mortality incidence was 18.7, 23.8 and 39.3% for preserved eGFR, mild CKD and moderate CKD, respectively (P = 0.001). For preserved eGFR, there was no significant difference in outcomes between therapies. For mild CKD, the primary event rate was 29.4% for PCI, 29.1% for CABG and 41.1% for MT (P = 0.006) [adjusted hazard ratio (HR) = 0.26, 95% confidence interval (CI) 0.07–0.88; P = 0.03 for PCI versus MT; and adjusted HR = 0.48; 95% CI 0.31–0.76; P = 0.002 for CABG versus MT]. We also observed higher mortality rates in the MT group (28.6%) compared with PCI (24.1%) and CABG (19.0%) groups (P = 0.015) among mild CKD subjects (adjusted HR = 0.44, 95% CI 0.25–0.76; P = 0.003 for CABG versus MT; adjusted HR = 0.56, 95% CI 0.07–4.28; P = 0.58 for PCI versus MT). Results were similar with moderate CKD group but did not achieve significance.

Conclusions

Coronary interventional therapy, both PCI and CABG, is associated with lower rates of events compared with MT in mild CKD patients >10 years of follow-up. More study is needed to confirm these benefits in moderate CKD.
Labour’s declining share of national income in Ireland and Denmark: the national specificities of structural change
Authors: Flaherty Eoin , Riain Seán Ó
Published: December 2018

The share of national income going to workers has decreased steadily across Europe since the 1980s. This apparently uniform decrease in labour’s share conceals differences amongst states however—in ‘liberal’ Ireland, this fall has been drastic, while that of ‘social democratic’ Denmark has been moderate. This article presents a parallel time series analysis of institutional and structural factors shaping labour’s share in Ireland and Denmark. Our results show that factors common to the study of variation in labour’s share operate in different ways in different countries, both in magnitude and causal mechanism. We find that stressors such as global trade, foreign investment and high-tech growth produce different effects in each location. Equally, protections such as unionization, leftist cabinets and welfare spending display contradictory effects in both locations. We conclude that ‘power resource’ models of labour share should be supplemented with comparative approaches that emphasize how institutionalized socio-political logics mediate returns to labour.
Evaluation of a Quality Improvement Intervention That Eliminated Routine Use of Opioids After Cesarean Delivery
Authors: Holland Erica , Bateman Brian T. , Cole Naida , Taggart Ashley , Robinson Laura A. , Sugrue Ronan , Xu Xinling , Robinson Julian N.
Published: December 2018

OBJECTIVE:

To evaluate the effects of eliminating the routine use of oral opioids for postcesarean delivery analgesia on postcesarean opioid consumption.

METHODS:

At a tertiary care center, we implemented a quality improvement intervention among faculty practice patients undergoing cesarean delivery, which consisted of 1) eliminating routine ordering of oral opioids after cesarean delivery, 2) implementing guidelines for ordering a short course of opioids when deemed necessary, and 3) coupling opioid prescribing at discharge to patterns of opioid use in-hospital combined with shared decision-making. All patients, both before and after the intervention, were administered neuraxial opioids and scheduled acetaminophen and nonsteroidal antiinflammatory medications in the absence of contraindications. The primary outcome was the percentage of women who used any opioids postoperatively in-hospital. Secondary outcomes included the percentage of women discharged with a prescription for opioids, the quantity of opioids used in-hospital, pain scores, satisfaction, opioid-related side effects, and opioid prescriptions ordered in the 6 weeks after delivery. The effects of this intervention were assessed based on a chart review of patient data and a survey of patients in the 12 weeks before and 12 weeks after the intervention.

RESULTS:

We evaluated the records of 191 postcesarean delivery patients before and 181 after the intervention. Less than half of women used oral opioids in-hospital after the intervention, 82 (45%) compared with 130 (68%) before (P<.001). However, there was no change in pain scores or overall satisfaction with pain relief. Postintervention, only 40% of patients were discharged with prescriptions for opioids compared with 91% of patients before the intervention (P<.001).

CONCLUSION:

Eliminating routine ordering of oral opioids after cesarean delivery is associated with a significant decrease in opioid consumption while maintaining the same levels of pain control and patient satisfaction. Oral opioids are not needed by a large proportion of women after cesarean delivery.
Novel immunological and clinical insights in vascularized composite allotransplantation
Authors: Kollar Branislav , Pomahac Bohdan , Riella Leonardo V.
Published: December 2018

Purpose of review

Vascularized composite allotransplantation (VCA) is a promising approach to restore the quality of life of carefully selected patients that suffered extensive injury. Although acute rejection occurs very frequently, still little is known about the specific characteristics of the VCA immune response. This review aims to highlight the current development in the field of VCA concerning the immunobiology and management of upper extremity and face transplant recipients.

Recent findings

T-cell mediated rejection is the predominant mechanism of allograft injury in VCA. As current histological classification does not differentiate types of rejection, novel evidence using NanoString has determined a molecular signature that helps identify antibody-mediated rejection in comparison to T-cell mediated rejection. Additionally, long-term follow-up of VCA patients progressively reveals various features of chronic rejection, and novel immunosuppressive approaches such as costimulation blockade found its way into immunosuppressive regimens of VCA recipients, unraveling its potential benefits as well as limitations. Finally, novel noninvasive biomarkers were recently evaluated and showed promise to differentiate the severity of acute rejection, and consequently, the intensity of treatment required.

With growing knowledge about the immunobiology in VCA, novel approaches to immunosuppressive therapy and immune monitoring will help better manage patients and improve long-term VCA outcomes.