bluuebunny/crossref_metadata_2025 huggingface dataset:
Ring defects in n-type Czochralski-grown silicon: A high spatial resolution study using Fourier-transform infrared spectroscopy, micro-photoluminescence, and micro-Raman
Authors: Basnet Rabin , Sun Chang , Wu Huiting , Nguyen Hieu T. , Rougieux Fiacre Emile , Macdonald Daniel
Published: December 2018

We investigated ring defects induced by a two-step anneal in n-type Czochralski-grown silicon wafers using a combination of high spatial resolution Fourier Transform Infrared Spectroscopy (FTIR), micro-photoluminescence (PL) mapping, and micro-Raman mapping. Through FTIR measurements, we show the inhomogeneous loss in interstitial oxygen with a positive correlation with the inverse lifetime. Using high-resolution micro-PL mapping, we are able to distinguish individual recombination-active oxygen precipitates within the rings with a decreasing density from the center to the edge of the sample. The radial inhomogeneity of the oxygen precipitates is likely to be related to variations in the distribution of grown-in defects. We also demonstrate that micro-Raman mapping reveals the oxygen precipitates without the smearing effects of carrier diffusion that are present in micro-PL mapping.
Vapor density and electron density determination during high-current anode phenomena in vacuum arcs
Authors: Khakpour A. , Methling R. , Franke St. , Gortschakow S. , Uhrlandt D.
Published: December 2018

This paper presents time and space resolved results of spectroscopic measurements in a vacuum circuit breaker experiment during high-current anode modes, i.e., anode spot type 1, anode spot type 2, and anode plume. Excited state densities for Cu I, Cu II, and Cu III transitions are determined during anode spot type 1 and type 2 as well as for the anode plume. Temporal evolution of excited state densities and Cu neutral gas densities are also determined during anode spot type 1 and type 2, which show that the Cu density in front of the anode during anode spot type 2 is about 6 times higher compared to anode spot type 1. Electron densities are also determined during both types of anode spot using Stark broadening. The electron densities during anode spot type 2 are remarkably higher than during anode spot type 1.
Wide-range and accurate particle sizing using extended interferometric particle imaging technique
Authors: Xu Jie , Ge Baozhen , Lu Qieni
Published: December 2018

Accurate measurement of particles of a wide size range is generally difficult in interferometric particle imaging (IPI). We propose an extended IPI technique with double or multiple imaging systems of different scattering angles and polarizations to achieve a wider measurable size range. The effects of particle size, scattering angle, polarization, and the comprehensive parameters of the imaging system on fringe patterns are thoroughly discussed. In the case of measuring water droplets, the measurable size range of the extended IPI enlarges to 10 μm-1 mm, with high-quality fringe patterns favoring the accuracy of measurement. The relative deviations of extracted diameters are no greater than 9%, demonstrating good accuracy of the particle sizing using the extended IPI technique.
A generalised Landau-Lifshitz fluctuating hydrodynamics model for concurrent simulations of liquids at atomistic and continuum resolution
Authors: Korotkin I. A. , Karabasov S. A.
Published: December 2018

A new hybrid molecular dynamics–hydrodynamics method based on the analogy with two-phase flows is implemented that takes into account the feedback of molecular dynamics on hydrodynamics consistently. The consistency is achieved by deriving a discrete system of fluctuating hydrodynamic equations whose solution converges to the locally averaged molecular dynamics field exactly in terms of the locally averaged fields. The new equations can be viewed as a generalisation of the classical continuum Landau-Lifshitz fluctuating hydrodynamics model in statistical mechanics to include a smooth transition from large-scale continuum hydrodynamics that obeys a Gaussian statistics to all-atom molecular dynamics. Similar to the classical Landau-Lifshitz fluctuating hydrodynamics model, the suggested generalised Landau-Lifshitz fluctuating hydrodynamics equations are too complex for analytical solution; hence, a computational scheme for solving these equations is suggested. The scheme is implemented in a popular open-source molecular dynamics code GROMACS (GROningen MAchine for Chemical Simulations), and numerical examples are provided for liquid argon simulations under equilibrium conditions and under macroscopic flow effects.
Atomic resolution of interface diffusing in short-period InAs/GaSb superlattice
Authors: Cui J. , Yao Y. , Jiang D. W. , Wang G. W. , Wang Y. G. , Shen X. , Yu R. C.
Published: December 2018

High-angle annular dark-field (HAADF) and electron energy loss spectroscopy in a Cs-corrected scanning transmission electron microscope were utilized for characterizing the interfacial chemical structure of the short-period InAs/GaSb superlattices with atomic resolution. The interfacial features determined from HAADF image contrasts and elemental composition profiles demonstrated that each interface width remains below 4.8 monolayers for all elements, while InAs-on-GaSb interfaces are sharper than GaSb-on-InAs interfaces. Tensile mapping revealed that the In and Sb diffusion at the interface may influence more than the other two elements and modulate the realistic lattice in the sublayers.
Acceptor levels of the carbon vacancy in 4H-SiC: Combining Laplace deep level transient spectroscopy with density functional modeling
Authors: Capan Ivana , Brodar Tomislav , Coutinho José , Ohshima Takeshi , Markevich Vladimir P. , Peaker Anthony R.
Published: December 2018

We provide direct evidence that the broad Z1/2 peak, commonly observed by conventional deep level transient spectroscopy in as-grown and at high concentrations in radiation damaged 4H-SiC, has two components, namely, Z1 and Z2, with activation energies for electron emissions of 0.59 and 0.67 eV, respectively. We assign these components to Z1/2=→Z1/2−+e−→Z1/20+2e− transition sequences from negative-U ordered acceptor levels of carbon vacancy (VC) defects at hexagonal/pseudo-cubic sites, respectively. By employing short filling pulses at lower temperatures, we were able to characterize the first acceptor level of VC on both sub-lattice sites. Activation energies for electron emission of 0.48 and 0.41 eV were determined for Z1(−/0) and Z2(−/0) transitions, respectively. Based on trap filling kinetics and capture barrier calculations, we investigated the two-step transitions from neutral to doubly negatively charged Z1 and Z2. Positions of the first and second acceptor levels of VC at both lattice sites, as well as (=/0) occupancy levels, were derived from the analysis of the emission and capture data.
Deformation of a surfactant-laden viscoelastic droplet in a uniaxial extensional flow
Authors: Panigrahi Devi Prasad , Das Sayan , Chakraborty Suman
Published: December 2018

The present study deals with the effect of surfactant distribution on the deformation of a viscoelastic droplet suspended in another viscoelastic medium, subjected to a uniaxial extensional flow. Under the assumption of negligible fluid inertia and small shape deformation, an asymptotic approach is adopted to solve the flow field. The Oldroyd-B model is used to represent both the carrier and droplet phases. The dynamics of the droplet is studied for the limiting cases of surface diffusion as well as surface convection mode of surfactant transport. The presence of an imposed flow results in a non-uniform distribution of surfactants which generates a surface tension gradient or Marangoni stress that is significantly found to affect the deformation of a viscoelastic droplet. The present analysis is performed for the general scenario where either of the phases may exhibit Newtonian or viscoelastic behavior. Upon comparison with the special case where both the phases are Newtonian, noteworthy differences in the effect of Marangoni stress on the dynamics of droplets are observed. It is found that increase in the Marangoni stress along the droplet surface reduces the effect of viscoelasticity on the shape deformation of the droplet. It is also found that a critical viscosity ratio can be defined for a viscoelastic droplet at which the effect of Marangoni stress on its shape deformation is the maximum.
Tri-carbon defects in carbon doped GaN
Authors: Irmscher K. , Gamov I. , Nowak E. , Gärtner G. , Zimmermann F. , Beyer F. C. , Richter E. , Weyers M. , Tränkle G.
Published: December 2018

Carbon doped GaN crystals grown by hydride vapor phase epitaxy have been investigated using mid-infrared and near-ultraviolet absorption spectroscopy. Two local vibrational modes (LVMs) at 1679 cm−1 and 1718 cm−1 as well as an absorption shoulder in front of the band edge absorption of GaN are discovered, all of which increase in intensity with the carbon concentration. The LVMs are similar in wavenumber position to an LVM formerly observed in carbon-rich AlN crystals and unambiguously assigned to a tri-carbon defect. Together with the polarization dependence of the LVMs, we conclude that in GaN the underlying defects are two crystallographically inequivalent configurations of each three nearest neighbor carbon atoms. The strength of both the infrared and ultraviolet absorption features implies concentrations of the underlying defects of the same order as the total carbon concentration. Hence, the tri-carbon defects contribute to the UV absorption and possess deep energy levels in GaN.
Terahertz wave emission from a liquid water film under the excitation of asymmetric optical fields
Authors: Jin Qi , Dai Jianming , E Yiwen , Zhang Xi-Cheng
Published: December 2018

Liquid water excited by intense two-color laser pulses radiates electromagnetic waves at terahertz frequencies. Compared with one-color excitation, two-orders of magnitude enhanced terahertz energy are observed by using asymmetric optical excitation with the same total excitation pulse energy and focusing geometry. Modulation of the terahertz field is achieved via the coherent control approach. We find that modulated and unmodulated terahertz energies have, respectively, quadratic and linear dependence on the laser pulse energy. This work, as part of terahertz aqueous photonics, paves an alternative way of studying laser-liquid interactions and developing intense terahertz sources.
On the magnetohydrodynamic limits of the ideal two-fluid plasma equations
Authors: Shen Naijian , Li Yuan , Pullin D. I. , Samtaney Ravi , Wheatley Vincent
Published: December 2018

The two-fluid plasma equations describing a magnetized plasma, originating from truncating moments of the Vlasov-Boltzmann equation, are increasingly used to describe an ion-electron plasma whose transport phenomena occur on a time scale slower and a length scale longer than those of particle collisions. A similar treatment under more stringent constraints gives the single-fluid magnetohydrodynamic (MHD) equations for low-frequency macroscopic processes. Since both stem from kinetic theory, the two-fluid plasma and MHD equations are necessarily related to each other. Such a connection is often established via ad hoc physical reasoning without a firm analytical foundation. Here, we perform a sequence of formal expansions for the dimensionless ideal two-fluid plasma equations with respect to limiting values of the speed-of-light c, the ion-to-electron mass ratio M, and the plasma skin depth dS. Several different closed systems of equations result, including separate systems for each limit applied in isolation and those resulting from limits applied in combination, which correspond to the well-known Hall-MHD and single-fluid ideal MHD equations. In particular, it is shown that while the zeroth-order description corresponding to the c→∞ limit, with M and dS fixed, is strictly charge neutral, it nonetheless uniquely determines the perturbation charge non-neutrality at the first order. Furthermore, the additional M→∞ limit is found to be not required to obtain the single-fluid MHD equations despite being essential for the Hall-MHD system. The hierarchy of systems presented demonstrates how plasmas can be appropriately modeled in situations where only one of the limits applies, which lie in the parameter space in between where the two-fluid plasma and Hall-MHD models are appropriate.
Communication: Strong-interaction limit of an adiabatic connection in Hartree-Fock theory
Authors: Seidl Michael , Giarrusso Sara , Vuckovic Stefan , Fabiano Eduardo , Gori-Giorgi Paola
Published: December 2018

We show that the leading term in the strong-interaction limit of the adiabatic connection that has as weak-interaction expansion the Møller-Plesset perturbation theory can be fully determined from a functional of the Hartree-Fock density. We analyze this functional and highlight similarities and differences with the strong-interaction limit of the density-fixed adiabatic connection case of Kohn-Sham density functional theory.
Total cross section measurements for electron scattering from dichloromethane
Authors: Lozano A. I. , Álvarez L. , Blanco F. , Brunger M. J. , García G.
Published: December 2018

Using our magnetically confined electron transmission apparatus, we report the results of total cross sections (TCSs) for electron scattering from dichloromethane (CH2Cl2). The energy range of this study is 1–300 eV. Wherever possible, the present data are compared to earlier measured TCSs of Wan et al. [J. Chem. Phys. 94, 1865 (1991)] and Karwasz et al. [Phys. Rev. A 59, 1341 (1999)] and to the corresponding theoretical independent atom model with screening corrected additivity rule and interference term (IAM-SCAR+I) results of Krupa et al. [Phys. Rev. A 97, 042702 (2018)] and a spherical complex optical potential formulation calculation of Naghma et al. [J. Electron Spectrosc. Relat. Phenom. 193, 48 (2014)]. Within their respective uncertainties, the present TCS and those of Karwasz et al. are found to be in very good agreement over their common energy range. However, agreement with the results of Wan et al. is quite poor. The importance of the experimentally inherent ‘missing angle’ effect (see later) on the measured TCS is investigated and found to be significant at the lower energies studied. Indeed, when this effect is accounted for, agreement between our measured TCSs and the corrected IAM-SCAR+I+rotations calculation results are, for energies above about 3 eV, in good accord (to better than 8%). Finally, we observe two σ* shape resonances, consistent with the earlier electron transmission spectroscopy results of Burrow et al. [J. Chem. Phys. 77, 2699 (1982)], at about 2.8 eV and 4.4 eV incident electron energy, in our measured TCS.
Detection of Nicotine and Nicotine Metabolites in Units of Banked Blood
Authors: Wiencek Joesph R , Gehrie Eric A , Keiser Amaris M , Szklarski Penny C , Johnson-Davis Kamisha L , Booth Garrett S
Published: December 2018

Objectives

To determine the concentrations of nicotine and nicotine metabolites in RBC units as a means to estimate the point prevalence of exposure within the healthy donor pool.

Methods

Segments from 105 RBC units were tested for the presence of nicotine, cotinine, or trans-3ʹ-hydroxycotinine by liquid chromatography–tandem mass spectrometry.

Results

Of the 20 (19%) units that contained detectable concentrations of nicotine, cotinine, or trans-3ʹ-hydroxycotinine, 19 (18.1%) contained concentrations consistent with the use of a nicotine-containing product within 48 hours of specimen collection. One RBC unit contained nicotine concentrations consistent with passive exposure.

Conclusions

Chemicals from nicotine-containing products are detectable within the US RBC supply. Further investigation is needed to determine the risks of transfusion-associated exposure to nicotine and other tobacco-associated chemicals among vulnerable patient populations such as neonates.
Product Matrix Processes as Limits of Random Plane Partitions
Authors: Borodin Alexei , Gorin Vadim , Strahov Eugene
Published: December 2018

We consider a random process with discrete time formed by squared singular values of products of truncations of Haar-distributed unitary matrices. We show that this process can be understood as a scaling limit of the Schur process, which gives determinantal formulas for (dynamical) correlation functions and a contour integral representation for the correlation kernel. The relation with the Schur processes implies that the continuous limit of marginals for q-distributed plane partitions coincides with the joint law of squared singular values for products of truncations of Haar-distributed random unitary matrices. We provide structural reasons for this coincidence that may also extend to other classes of random matrices.
Hasse Principle for Rost Motives
Authors: Borovoi Mikhail , Semenov Nikita , Zhykhovich Maksim
Published: December 2018

We prove a Hasse principle for binary direct summands of the Chow motive of a smooth projective quadric $Q$ over a number field $F$. Besides, we show that such summands are twists of Rost motives. In the case when $F$ has at most one real embedding we describe a complete motivic decomposition of $Q$.
Milton, Buchanan, and King Arthur
Authors: Ng Su Fang
Published: December 2018

Arthur appears in a range of Milton’s works, including the late poetry, though his attitude to Arthur shifted drastically in the course of his career, from a heroic subject suitable for an epic in Epitaphium Damonis (1640) to a figure tainted by tyranny in Paradise Regained (1671). This shift is not simply the consequence of Milton coming to doubt the veracity of Geoffrey of Monmouth’s Historia regum Britanniae. Rather, his understanding of Arthur was shaped by an engagement with the works of humanist George Buchanan. Buchanan’s Rerum Scotiarum historiae, one of Milton’s sources for the History of Britain, was among a number of hostile rewritings of Arthur as illegitimate by Scottish historians and chroniclers to resist English claims of suzerainty over Scotland. Sympathetic to Buchanan’s theories of popular sovereignty and tyrannicide, Milton had to contend with his anti-Galfridian attacks while not wholly embracing a Scottish perspective. Milton’s reception of Buchanan is part of a longstanding Anglo-Scottish debate over Arthur.
Crime, Intimidation, and Whistleblowing: A Theory of Inference from Unverifiable Reports
Authors: Chassang Sylvain , Miquel Gerard Padró I
Published: December 2018

We consider a game between a principal, an agent, and a monitor in which the principal would like to rely on messages by the monitor (the potential whistleblower) to target intervention against a misbehaving agent. The difficulty is that the agent can credibly threaten to retaliate against the monitor in the event of an intervention. In this setting, intervention policies that are responsive to the monitor’s message provide informative signals to the agent, which can be used to target threats efficiently. Principals that are too responsive to information shut down communication channels. Successful intervention policies must therefore garble the information provided by monitors and cannot be fully responsive. We show that policy evaluation on the basis of non-verifiable whistleblower messages is feasible under arbitrary incomplete information provided policy design takes into account that messages are endogenous.
Ethics Committees
Authors: McCarty Catherine A. , Barnes Robert , Thomas Monica , Sande Jonathan , Ouellette Annette
Published: December 2018

Healthcare ethics committees can be valuable resources but are largely underutilized by nurses. The purpose of this project was to review ethics concerns and educational needs of nurses in a large, integrated healthcare delivery system. Seven themes were identified: organizational issues, nonbeneficial care, withdrawing life-sustaining therapies, discharge disposition, challenging patients and families, communication with physicians, and capacity versus competence. A process was then developed to better engage nurses in ethical discussions.
Management of Surgical Incisions Using Incisional Negative-Pressure Therapy
Authors: Schlosser Kathryn A. , Otero Javier , Lincourt Amy , Augenstein Vedra A.
Published: December 2018

Use of negative-pressure therapy (NPT) is a well-established therapy for chronic, open, contaminated wounds, promoting formation of granulation tissue and healing. The application of NPT after primary closure (ie, incisional NPT) has also been shown to reduce surgical site infection and surgical site occurrence in high-risk procedures across multiple disciplines. Incisional NPT is believed to decrease edema and shear stress, promote angiogenesis and lymphatic drainage, and increase vascular flow and scar formation. Incisional NPT may be considered when there is a high risk of surgical site occurrence or surgical site infection, particularly in procedures with nonautologous implants, such as hernia mesh or other permanent prosthetics. Here we discuss the proposed physiologic mechanism as demonstrated in animal models and review clinical outcomes across multiple specialties.
Management of Closed Incisions Using Negative-Pressure Wound Therapy in Orthopedic Surgery
Authors: Agarwal Animesh
Published: December 2018

Negative-pressure wound therapy (NPWT) has been a major advance in the management of open wounds, especially in orthopedic trauma surgery. Due to the success of NPWT, surgeons began using NPWT on closed incisions as a way to help prevent surgical wound dehiscence, especially in at-risk patients for wound problems. It has been well established that obesity, diabetes mellitus, and smoking in addition to other comorbidities increase the risk of wound dehiscence and surgical site infections in orthopedic patients. This article reviews the current literature and provides an overview on the use of NPWT on closed incisions in orthopedic trauma procedures and joint arthroplasty.
The impact of rule changes on the number and severity of injuries in the NFL
Authors: Sheth Suril B , Anandayuvaraj Dharun , Patel Saumil S
Published: December 2018

Injuries in the National Football League (NFL) are a concern for reasons of performance, revenue, and player health. In particular, recent discoveries highlighting the long-term repercussions of concussions has drawn popular attention to the violence of the sport of American football and shone a bright light on the NFL's efforts to reduce injuries and their long-term impact. While studies have largely focused on the impact of injuries on players' long-term health, there has been less independent work on the evolution of injuries, namely in how the number and extent of injuries have changed over the years and what role, if any, the NFL has played in improving these figures by changing the rules or by improving protective gear technology. Here, we studied injuries from eight seasons 2010-2017, i.e. and address the impact of major rule changes that were enacted in the NFL in 2013 and 2016. We classified injuries into three major categories: arm, leg, and head, i.e. concussions. From publicly available weekly injury reports provided by each team in the NFL, we calculated the number of players who were seriously injured enough to miss at least one game of the season, and the severity of the injuries sustained, as evaluated by the number of games of the season the injured player had to sit out. The 2013 rule changes did not significantly reduce the number of players who suffered a head injury and had to sit out at least one game, and had no impact on leg or arm injuries either. Following the 2016 rule changes, we observed no change in the number of players who got injured but a significant increase in the severity of all three injury types in the two full seasons that followed. Overall, the NFL's efforts to reduce injuries and their severity have had little success, and our findings suggest instead that rule changes or technological changes cannot curb the violence and danger present in the game today.
Data paper: FoRAGE (Functional Responses from Around the Globe in all Ecosystems) database: a compilation of functional responses for consumers and parasitoids
Authors: Uiterwaal Stella F. , Lagerstrom Ian T. , Lyon Shelby R. , DeLong John P.
Published: December 2018

Functional responses - the relationships between consumer foraging rate and resource (prey) density - provide key insights into consumer-resource interactions and predation mechanics while also being a major contributor to population dynamics and food web structure. We present a global database of standardized functional response parameters extracted from the published literature. We refit the functional responses with a Type II model using standardized methods and report the fitted parameters along with data on experimental conditions, consumer and resource taxonomy and type, as well as the habitat and dimensionality of the foraging interaction. The consumer and resource species covered here are taxonomically diverse, from protozoans filtering algae to wasps parasitizing moth larvae to wolves hunting moose. The FoRAGE database (doi:10.5063/F17H1GTQ) is a living data set that will be updated periodically as new functional responses are published.
Transcriptional activation of DBP by hnRNP K facilitates circadian rhythm
Authors: Kwon Paul Kwangho , Lee Kyung-Ha , Kim Ji-hyung , Tae Sookil , Ham Seokjin , Kim Hyo-Min , Choi Jung-Hyun , Jeong Young-Hun , Kim Sung Wook , Yi Hee , Ku Hyun-Ok , Roh Tae-Young , Lim Chunghun , Kim Kyong-Tai
Published: December 2018

D-site albumin promoter binding protein (DBP) supports the rhythmic transcription of downstream genes, in part by displaying high-amplitude cycling of its own transcripts compared to other circadian clock genes. However, the underlying mechanism remains elusive. Here, we demonstrated that poly(C) motif within DBP proximal promoters, in addition to an E-box element, provoked the transcriptional activation through increased RNA polymerase 2 (Pol2) recruitment by inducing higher chromatin accessibility. We also clarified that heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a key regulator that binds to the poly(C) motif on single-stranded DNAs in vitro. Chromatin immunoprecipitation further confirmed the expression-dependent and rhythmic binding of hnRNP K which was inhibited through its cytosolic localization mediated by time-dependent ERK activation. Knockdown of hnRNP K triggered low-amplitude mRNA rhythms in DBP and other core clock genes through transcriptional or post-transcriptional regulation. Finally, transgenic depletion of aDrosophilahomolog of hnRNP K in circadian pacemaker neurons lengthened 24-hour periodicity in free-running locomotor behaviors. Taken together, our results provide new insights into the function of hnRNP K as a transcriptional amplifier of DBP, which acts rhythmically through its intracellular localization by the ERK phosphorylation and as an mRNA stabilizer along with its physiological significance in circadian rhythms ofDrosophila.

Significance Statement

In the case of mood disorders and the aging process, the mRNA expression and amplitude level of clock genes, including DBP, were reported to be diminished. However, the reason behind this decrease of clock gene amplitude and expression level remained unclear. Through this study, we revealed the regulatory mechanism behind the expression of clock genes, especially of DBP mRNA expression. In addition, we discovered that hnRNP K regulates more core clock genes than what we have previously known, such as Clock and Periods. Finally, we demonstrated the physiological significance of hnRNP K in Drosophila through its RNAi line model. Hence, our findings show the regulatory mechanism of circadian rhythm that may provide insight on mood disorder and aging process.
Long-range single-molecule mapping of chromatin accessibility in eukaryotes
Authors: Shipony Zohar , Marinov Georgi K. , Swaffer Matthew P. , Sinott-Armstrong Nasa A. , Skotheim Jan M. , Kundaje Anshul , Greenleaf William J.
Published: December 2018

Active regulatory elements in eukaryotes are typically characterized by an open, nucleosome-depleted chromatin structure; mapping areas of open chromatin has accordingly emerged as a widely used tool in the arsenal of modern functional genomics. However, existing approaches for profiling chromatin accessibility are limited by their reliance on DNA fragmentation and short read sequencing, which leaves them unable to provide information about the state of chromatin on larger scales or reveal coordination between the chromatin state of individual distal regulatory elements. To address these limitations, we have developed a method for profiling accessibility of individual chromatin fibers at multi-kilobase length scale (SMAC-seq, or Single-Molecule long-read Accessible Chromatin mapping sequencing assay), enabling the simultaneous, high-resolution, single-molecule assessment of the chromatin state of distal genomic elements. Our strategy is based on combining the preferential methylation of open chromatin regions by DNA methyltransferases (CpG and GpC 5-methylcytosine (5mC) and N6-methyladenosine (m6A) enzymes) and the ability of long-read single-molecule nanopore sequencing to directly read out the methylation state of individual DNA bases. Applying SMAC-seq to the budding yeast Saccharomyces cerevisiae, we demonstrate that aggregate SMAC-seq signals match bulk-level accessibility measurements, observe single-molecule protection footprints of nucleosomes and transcription factors, and quantify the correlation between the chromatin states of distal genomic elements.
From Metapopulation to Metacommunity and the Complications of Community Structure
Authors: Hajian-Forooshani Zachary , Schmitt Lauren , Medina Nicholas , Vandermeer John
Published: December 2018

The metacommunity, as it evolved from Levin's metapopulation, provides a framework to consider the spatial organization of species interactions. Arguably the most fundamental feature of metapopulations and metacommunities are that demes are connected via migration. An important result from Levin's metapopulation work - that increasing migration lowers regional extinction probability - is often incorporated into conceptions of metacommunities. We first use a toy model to show how this result from Levin's metapopulation does not necessarily hold when considering community interactions in a metacommunity context. We also report results from a metacommunity field experiment conducted with a tropical terrestrial leaf litter community and show that migration induces the extinction of predators in the metacommunity. Our result corroborates the findings of a prior metacommunity experiment in a temperate terrestrial leaf litter community. The concordance between these experiments even with vastly different communities highlights the importance of considering trophic and non-trophic community structure to understand metacommunity dynamics.
Higher-order epistatic networks underlie the evolutionary fitness landscape of a xenobiotic-degrading enzyme
Authors: Yang Gloria , Anderson Dave W , Baier Florian , Dohmen Elias , Hong Nansook , Carr Paul D , Kamerlin Shina Caroline Lynn , Jackson Colin J , Bornberg-Bauer Erich , Tokuriki Nobuhiko
Published: December 2018

Characterizing the adaptive landscapes that encompass the emergence of novel enzyme functions can provide molecular insights into both enzymatic and evolutionary mechanisms. Here, we combine ancestral protein reconstruction with biochemical, structural, and mutational analyses to characterize the functional evolution of methyl-parathion hydrolase (MPH), a xenobiotic organophosphate-degrading enzyme. We identify five mutations that are necessary and sufficient for the evolution of MPH from an ancestral dihydrocoumarin hydrolase. In-depth analyses of the adaptive landscapes encompassing this evolutionary transition revealed that a complex interaction network, defined in part by higher-order epistasis, determined the adaptive pathways that were available. By also characterizing the adaptive landscapes in terms of their functional activity towards three other OP substrates, we reveal that subtle differences in substrate substituents drastically alter the enzyme’s epistatic network by changing its intramolecular interactions. Our work suggests that the mutations function collectively to enable substrate recognition via subtle structural repositioning.
The ecnA antitoxin is not only important for human pathogens: Evidences of its role in the plant pathogen Xathomonas citri subsp. citri
Authors: Granato Laís Moreira , Picchi Simone Cristina , Andrade Maxuel de Oliveira , Martins Paula Maria Moreira , Takita Marco Aurélio , Machado Marcos A , de Souza Alessandra Alves
Published: December 2018

Xathomonas citri subsp. citri causes citrus canker disease worldwide in most commercial varieties of citrus. Its transmission occurs mainly through wind-driven rain. Once on the leaf X. citri can epiphytically survive forming biofilm, which enhances persistence of the bacteria to different environmental stresses and play an important role in the early stages of host infection. Therefore, the study of genes involved in biofilm formation has been an important step towards the understanding of the bacterial strategy to survive and infect the plant host. In this work we show that ecnAB a Toxin-Antitoxin (TA) system, previously identified only in human bacterial pathogen, is conserved in many Xanthomonas spp. In general TA systems consist of a pair of genes in operon that encodes a stable toxin and an unstable antitoxin that, under normal conditions, binds to the toxin and blocks its activity. On the other hand, under stress the antitoxin is degraded, allowing the toxin to act decreasing cell growth and metabolism. When normal growth conditions are re-established, the antitoxin is produced, blocking the toxin and allowing the cells to grow. Thus, this mechanism represents an important bacterial strategy of survival under stress conditions. In this work, we show that in X. citri ecnAB is regulated by quorum sensing and it is involved in important processes such as biofilm formation, EPS production, and motility. In addition, we show that ecnAB plays a role in X. citri survival and virulence in plant host.
Non-helical Helicobacter pylori show altered gland colonization and elicit less gastric pathology during chronic infection
Authors: Martinez Laura E , O'Brien Valerie P , Leverich Christina , Knoblaugh Sue E , Salama Nina R
Published: December 2018

Half of all humans harbor Helicobacter pylori in their stomachs. Helical cell shape is thought to facilitate H. pylori's ability to bore into the protective mucus layer in a corkscrew-like motion, thus enhancing colonization of the stomach. H. pylori cell shape mutants show impaired colonization of the mouse stomach, highlighting the importance of cell shape in infection. To gain a deeper understanding of how helical cell morphology promotes host colonization by H. pylori, we used 3D-confocal microscopy to visualize the clinical isolate PMSS1 and an isogenic straight rod mutant (Dcsd6) within thick longitudinal mouse stomach sections and performed volumetric image analysis to quantify the number of bacteria residing within corpus and antral glands in addition to measuring total colony forming units (CFU). We found that straight rods show attenuation during acute colonization of the stomach (one day or one week post-infection) as measured by total CFU. Our quantitative imaging revealed that wild-type bacteria extensively colonized antral glands at one week post-infection, while csd6 mutants showed variable colonization of the antrum at this timepoint. During chronic infection (one or three months post-infection), total CFU were highly variable, but similar for wild-type and straight rods. Both wild-type and straight rods persisted and expanded in corpus glands during chronic infection. However, the straight rods showed reduced inflammation and disease progression. Thus, helical cell shape contributes to tissue interactions that promote inflammation during chronic infection, in addition to facilitating niche acquisition during acute infection.
Microcapsuled entomopathogenic fungus against fire ants
Authors: Qiu Hua-Long , Fox Eduardo G P , Zhao Dan-Yang , Xu Jin-Zhu , Qin Chang-Sheng
Published: December 2018

A new microencapsulation method of Metarhizium anisopliae based on gelatin (GE) and gum arabic (GA) is presented. Conditions to produce spheres 35-50 μm relied on 1% wall material, GE:GA ratio 1:1–1:2, core:wall ratio 1:1, under pH 4.0, 35-50°C and 500-700 r/min agitation. Microcapsulation provided protection against UV and longer shelf life as compared to unencapsulated conidia. The obtained preparation proved active against the red imported fire ant Solenopsis invicta.
Estimating the probable cause of recurrence in Plasmodium vivax malaria: relapse, reinfection or recrudescence?
Authors: Taylor Aimee R , Watson James A , Chu Cindy S , Puaprasert Kanokpich , Duanguppama Jureeporn , Day Nicholas P J , Nosten Francois , Neafsey Daniel E , Buckee Caroline O , Imwong Mallika , White Nicholas J
Published: December 2018

Background: Relapse of Plasmodium vivax infection is the main cause of vivax malaria in many parts of Asia. However at the individual patient level, recurrence of a blood stage infection following treatment within the endemic area can be either a relapse (from dormant liver-stage parasites), a recrudescence (blood-stage treatment failure), or a reinfection (following a new mosquito inoculation). Each requires a different prevention strategy, but previously they could not be distinguished reliably. Time-of-event and genetic data provide complimentary information about the cause of P. vivax recurrence, but the optimum approach to genotyping and analysis remains uncertain.
Methods: Individual-level data from two large drug trials in acute vivax malaria patients (Vivax History: VHX; Best Primaquine Dose: BPD) conducted on the Thailand-Myanmar border with follow-up of one year were pooled (n=1299). A total of 710 isolates from both acute and recurrent P. vivax episodes were genotyped using 3-9 highly polymorphic microsatellite markers. These pooled data were analyzed using a novel population statistical model incorporating an assessment of genetic relatedness, treatment drug administered, and the time-to-recurrence.
Results: 99% of genotyped recurrences in individuals who did not receive primaquine (n=365) were estimated to be relapses. In comparison, 14% of genotyped recurrences (n=121) were estimated to be relapses following high-dose supervised primaquine. By comparing episodes across individuals (90194 comparisons), the false-positive rate of relapse identification using genetic data alone was estimated to be 2.2%. We estimated the true failure rate after high-dose primaquine (7mg/kg total dose) to be 2.6% in this epidemiological context, substantially lower the reinfection unadjusted estimate of 12%. Simulation studies show that 9 highly polymorphic microsatellite markers suffice to discriminate between recurrence states. Drug exposures reflected by plasma carboxy-primaquine concentrations were not predictive of treatment failure, but did identify non-adherence.
Conclusion: Using this novel statistical model, relapse of P. vivax malaria could be distinguished reliably from reinfection. This showed that in this population supervised high-dose primaquine could avert up to 99% of relapses. In low transmission settings, microsatellite genotyping combined with time-to event data can accurately discriminate between the different causes of recurrent P. vivax malaria.
Spatiotemporal Integration in Plant Tropisms
Authors: Meroz Yasmine , Bastien Renaud , Mahadevan L
Published: December 2018

Tropisms, growth-driven responses to environmental stimuli, cause plant organs to respond in space and time and reorient themselves. Classical experiments from nearly a century ago reveal that plant shoots respond to the integrated history of light and gravity stimuli rather than just responding instantaneously. We introduce a temporally non-local response function for the dynamics of shoot growth formulated as an integro-differential equation whose solution allows us to qualitatively reproduce experimental observations associated with intermittent and unsteady stimuli. Furthermore, an analytic solution for the case of a pulse light stimulus expresses the response function as function of experimentally tractable variables for the phototropic response of Arabidopsis hypocotyls. All together, our model enables us to predict tropic responses to time-varying stimuli, manifested in temporal integration phenomena, and sets the stage for the incorporation of additional effects such as multiple stimuli, gravitational sagging etc.
Systems-level network modeling of Small Cell Lung Cancer subtypes identifies master regulators and destabilizers
Authors: Wooten DJ , Maddox SF , Tyson DR , Liu Q , Lim JS , Lopez CF , Sage J , Quaranta V
Published: December 2018

Adopting a systems approach, we devise a general workflow to define actionable subtypes in human cancers. Applied to small cell lung cancer (SCLC), the workflow identifies four subtypes based on global gene expression patterns and ontologies. Three correspond to known subtypes, while the fourth is a previously undescribed neuroendocrine variant (NEv2). Tumor deconvolution with subtype gene signatures shows that all of the subtypes are detectable in varying proportions in human and mouse tumors. To understand how multiple stable subtypes can arise within a tumor, we infer a network of transcription factors and develop BooleaBayes, a minimally-constrained Boolean rule-fitting approach.In silicoperturbations of the network identify master regulators and destabilizers of its attractors. Specific to NEv2, BooleaBayes predicts ELF3 and NR0B1 as master regulators of the subtype, and TCF3 as a master destabilizer. Since the four subtypes exhibit differential drug sensitivity, with NEv2 consistently least sensitive, these findings may lead to actionable therapeutic strategies that consider SCLC intratumoral heterogeneity. Our systems-level approach should generalize to other cancer types.
Climatic limits for the present European distribution of hornbeam (Carpinus betulus), with special reference to Ukraine
Authors: Tytar Volodymyr
Published: December 2018

In this study, we used a ecological niche modeling approach to detect the importance of diverse climatic parameters in controlling the distribution of forest tree species, exemplified by the common hornbeam (Carpinus betulus L.), with special reference to Ukraine from where digitized data on the species has been scarce. In Ukraine populations of this tree species are found on the edge of its home range and are exposed to extreme climate conditions. The main objectives of the present study were to model the European-wide ecological niche of the common hornbeam and investigate primary climatic factors that control the potential distribution of this tree in Ukraine. Using an ecological niche modeling approach, we consider having reliably modeled the European-wide bioclimatic niche of the common hornbeam for predicting the response of species geographical distribution to climate. Most contributing to the model was the mean monthly PET (potential evapotranspiration) of the coldest quarter, continentality and annual PET. In terms of the Most Limiting Factor, in Ukraine continentality is crucial throughout the majority of the country.
Cytoplasmic self-organization established by internal lipid membranes in the interplay with either actin or microtubules
Authors: Tang Sindy K. Y. , Renz Malte , Shemesh Tom , Driscoll Meghan , Lippincott-Schwartz Jennifer
Published: December 2018

Cells harbor an intrinsic organization of their components. Specific protein structures, as the centrosome, have been described master regulators of cell organization. In the absence of these key elements, however, cytoplasmic selforganization has nevertheless been observed. Cytoplasmic self-organization was postulated to arise from the interaction of microtubules with molecular motors on lipid membrane surfaces.

Here, we show that lipid membranes are capable of organizing both major cytoskeletal systems, microtubules and actin, even if one or the other cytoskeletal system is completely paralyzed. A microfluidic droplet system and Xenopus oocyte extracts enabled us to build an artificial cell and study minimal requirements for cellular self-organization. Mathematical modeling reveals the interaction of lipid membranes with any filament system through molecular motors as a universal principle of cytoplasmic self-organization. Both cytoskeletal systems form mechanisms to establish robust 2-dimensional selforganization and self-centering. Pharmacologic inhibition of the cytoskeletal network systems helps dissect specific contributions of each network in the interplay with lipid membranes with regards to 2- and 3-dimensional organization, time and length scale of cytoplasmic organization and the degree of concentration of the centered elements. While microtubules provide 3-dimensional polarity, actin filaments ensure fast and dense compaction and long-range organization.
Interactions between non-structured domains of FG- and non-FG-nucleoporins coordinate the ordered assembly of the nuclear pore complex in mitosis
Authors: Konishi Hide A. , Yoshimura Shige H.
Published: December 2018

In this study, we examined how channel-forming subunits of the nuclear pore complex (NPC) are assembled into a selective channel within a highly structured scaffold ring during post-mitotic assembly. We focused on non-structured domains of the scaffold Nups and performed in vitro self-assembled particle assays with those derived from channel-forming FG-Nups. We found that non-structured domains of ELYS and Nup35N interacted with channel-forming FG-Nups to form a self-assembled particle. Sequential addition of FG-Nups into the scaffold particle revealed that ELYS, which initiates post-mitotic NPC reassembly, interacts with early assembling FG-Nups (Nups98 and 153) but not middle stage-assembling FG-Nups (Nups58 and 62). Nup35, which assembles between the early and middle stages, facilitated the assembly of Nup62 into the early assembling Nups both in vitro and in vivo. These results demonstrate that ELYS and Nup35 have a role of facilitator in the ordered assembly of channel-forming FG-Nups during mitosis.