bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of vonoprazan and proton pump inhibitors for eradication of Helicobacter pylori
Authors: Shinozaki Satoshi , Nomoto Hiroaki , Kondo Yoshie , Sakamoto Hirotsugu , Hayashi Yoshikazu , Yamamoto Hironori , Lefor Alan Kawarai , Osawa Hiroyuki
Published: May 2016

Alternative eradication therapies for Helicobacter pylori infection are needed because of an increasing failure rate over the past decade. The aim of this study was to determine if vonoprazan, a new potassium‐competitive acid blocker, showed superiority to existing proton pump inhibitors for primary eradication of H. pylori in routine clinical practice. Data for 573 patients who underwent primary H. pylori eradication therapy were retrospectively reviewed. Regimens included clarithromycin 200 mg, amoxicillin 750 mg, and an acid‐suppressing drug [lansoprazole 30 mg (LAC), rabeprazole 10 mg (RAC), esomeprazole 20 mg (EAC), or vonoprazan 20 mg (VAC)] twice daily for 1 week. Eradication was successful in 73% (419/573) of patients using intention‐to‐treat (ITT) analysis and 76% (419/549) of patients in per‐protocol (PP) analysis. The VAC group had a significantly superior eradication rate compared with the LAC and RAC groups in ITT (VAC 83%, LAC 66% and RAC 67%, p < 0.01) and PP analysis (VAC 85%, LAC 69% and RAC 70%, p < 0.01), and had a similarly high eradication rate to the EAC group (83% in ITT and 87% in PP). Although the eradication rate in the VAC and EAC groups was not significantly higher than in the LAC and RAC groups in patients with mild gastric atrophy with both ITT and PP analyses, it was significantly higher in patients with severe gastric atrophy (p < 0.01). The VAC group had a significantly higher H. pylori eradication rate than the LAC and RAC groups, and a > 80% eradication rate regardless of the degree of atrophy.
Recent changes in the Norske Øer Ice Barrier, coastal Northeast Greenland
Authors: Sneed William A. , Hamilton Gordon S.
Published: May 2016

In Northeast Greenland, the Norske Øer Ice Barrier (NØIB) abuts Nioghalvfjerdsfjorden (79N) and Zachariae Isstrøm (ZI), two floating outlets of the Northeast Greenland Ice Stream. NØIB is an extensive region of perennially fast sea ice, which varies in size from year to year, but with complete breakup a rare event in the 20th century. It reportedly broke up in the 1950s and was seen to break up in 1997. Since 2000 the NØIB has broken up during 11 of the last 14 summers. The forcings driving the increased frequency of ice barrier breakup are poorly understood, and it is not clear if the breakup is a purely local phenomenon or an indicator of regional changes in the ocean and atmosphere. Here we use a logistic regression statistical model to show that the odds of breakup are linked to June positive degree days and July wind speeds at a nearby weather station. It is too soon to know if subtle changes detected on 79N and ZI in the last decade are connected to breakups of the NØIB but, if they are, it suggests a complex interaction between the atmosphere, ocean and outlet glaciers in this part of Greenland.
Modeling hydraulic fracture of glaciers using continuum damage mechanics
Authors: MOBASHER MOSTAFA E. , DUDDU RAVINDRA , BASSIS JEREMY N. , WAISMAN HAIM
Published: May 2016

The presence of water-filled crevasses is known to increase the penetration depth of crevasses and this has been hypothesized to play an important role controlling iceberg calving rate. Here, we develop a continuum-damage-based poro-mechanics formulation that enables the simulation of water-filled basal and surface crevasse propagation. The formulation incorporates a scalar isotropic damage variable into a Maxwell-type viscoelastic constitutive model for glacial ice, and the effect of the water pressure on fracture propagation using the concept of effective solid stress. We illustrate the model by simulating quasi-static hydrofracture in idealized rectangular slabs of ice in contact with the ocean. Our results indicate that water-filled basal crevasses only propagate when the water pressure is sufficiently large, and that the interaction between simultaneously propagating water-filled surface and basal crevasses can have a mutually positive influence leading to deeper crevasse propagation, which can critically affect glacial stability. Therefore, this study supports the hypothesis that hydraulic fracture is a plausible mechanism for the accelerated breakdown of glaciers.
Genetic differentiation ofLiparus glabrirostris(Curculionidae: Molytinae) populations from the fragmented habitats of the Alps and Carpathian Mountains
Authors: Mitrović M. , Tomanović Ž. , Jakovljević M. , Radović D. , Havelka J. , Stary P.
Published: May 2016

Populations ofLiparus glabrirostris(Curculionidae: Molytinae), a weevil inhabiting higher altitudes of Central Europe, were sampled from 24 localities in the Alps and Carpathian Mountains, and the geographical structuring of genetic variation was analyzed. Comparison of the concatenated mitochondrial cytochrome oxidase subunit I and subunit II sequences revealed consistent genetic divergence between the populations ofL. glabrirostrisfrom different mountain ranges. In phylogenetic analysis using maximum parsimony and median-joining networks, concatenated mitochondrial haplotypes from the Alps and Carpathians clustered as separate lineages, with high bootstrap support. Substantial genetic distances determined between the separated groups ranged from 2.6 to 3.0%, with divergence estimated to have initiated approximately 0.85–0.98 million years ago. The nuclear elongation factor 1α gene was additionally amplified and haplotype analysis showed very low evolutionary divergence (0.2%), with separate clustering as well. The observed divergence suggests that the populations have been isolated for a long time, as a consequence of environmental changes resulting in varying fragmentation of habitats in the Alps and Carpathians, interrupting genetic exchange events and altering the genetic structure ofL. glabrirostrispopulations. On the other hand, comparison of morphological characteristics showed no differences to confirm genetically well differentiated groups of populations. A polymerase chain reaction and restriction fragment length polymorphism-based method was therefore developed to discriminate between the Alpine and Carpathian lineages.
Comparison of different measuring methods for body temperature in lactating cows under different climatic conditions
Authors: Ammer Stefanie , Lambertz Christian , Gauly Matthias
Published: May 2016

The aim of the research described here was to compare different methods of body temperature (BT) measurements in dairy cows. It was hypothesised that reticular temperature (RET) values reflect the physiological status of the animals in an equivalent way to rectal (RT) and vaginal (VT) measurements. RT, VT and RET temperatures of twelve lactating Holstein–Friesian cows were measured over five consecutive days in June and October 2013. While RT and VT were manually measured three times a day, RET was automatically recorded at 10 min intervals using a bolus in the reticulum. For comparison with RT and VT, different RET values were used: single values at the respective recording times (RET-SIN), and mean (RET-MEAN) and median (RET-MED) values of 2 h prior to RT and VT measurements. Overall, body temperatures averaged 38·1 ± 0·6, 38·2 ± 0·4, 38·7 ± 0·9, 38·5 ± 0·7 and 38·7 ± 0·5 °C for RT, VT, RET-SIN, RET-MEAN and RET-MED, respectively. RT and VT were lower than all RET measurements, while RET-SIN and RET-MED were higher than RET-MEAN (P < 0·001). RET-MEAN and RET-MED values were higher in the morning, whereas RT and VT were greatest in the evening (P < 0·001). Overall, records of RT and VT were strongly correlated (r = 0·75; P < 0·001). In contrast to RET-SIN and RET-MEAN, RET-MED was higher correlated to RT and VT. In June, coefficients were higher between all methods than in October. Relation of barn T to RT and VT was stronger when compared to RET measurements. RET-SIN was higher correlated to barn T than RET-MEAN or RET-MED. Correlation between VT and barn T was strongest (r = 0·48; P < 0·001). In summary, RET-MED showed highest correlation with VT and RT. However, single RET measurements (influenced by water or feed intake) can lead to extreme variations and differences to single VT and RT values.
The impact of crossbreeding Egyptian and Italian buffalo on milk yield and composition under subtropical environmental conditions
Authors: Nasr Mohammed AF
Published: May 2016

Buffalo are the second most valuable species in the world for milk production and their milk prices have been based on fat and protein composition. The aim of the paper was to compare the milk yield and composition of pure Egyptian buffalo (EB) and their crosses with the Italian buffalo and to investigate the impact of temperature humidity index (THI) on milk yield and composition under subtropical stressful conditions. 516 lactating buffalo were used (152 EB; 176 F1crosses 50% EB and 50% Italian buffalo and 188 back cross (BC) 75% EB and 25% Italian buffalo). The results revealed that, milk yield (5·79 and 10·32%) and peak yield (6·36 and 7·67%) were significantly higher in F1and BC than in EB, respectively. BC had 7·74 and 3·67% significantly higher daily yield when compared with EB and F1, respectively. EB were robust in the hot condition as the only reduction was in the peak of milk production from 15·02 in low THI to 13·72 kg in high THI, but fat and total solids%, were increased from 5·61 and 16·31 THI in low to 7·01 and 17·59 in high THI, respectively. BC was similar to some extent to EB as their milk was similar to EB under sever hot climate conditions (2331·92 and 2327·50 kg, respectively). A statistically significant reduction in the average daily milk yields was detected only in F1from 10·33 to 8·38 kg in low and high THI level, respectively. The current study showed that BC produced a higher milk with higher daily average milk yield and peak yield with some evidence of robust under sever hot condition which were approximately similar to EB. Thus, it is recommended to encourage the producers to increase the number of BC animals in their farm for improving the milk production to fulfil the demand of Egyptian markets.
The initial value problem in Lagrangian drift kinetic theory
Authors: Burby J. W.
Published: May 2016

Existing high-order variational drift kinetic theories contain unphysical rapidly varying modes that are not seen at low orders. These unphysical modes, which may be rapidly oscillating, damped or growing, are ushered in by a failure of conventional high-order drift kinetic theory to preserve the structure of its parent model’s initial value problem. In short, the (infinite dimensional) system phase space is unphysically enlarged in conventional high-order variational drift kinetic theory. I present an alternative, ‘renormalized’ variational approach to drift kinetic theory that manifestly respects the parent model’s initial value problem. The basic philosophy underlying this alternate approach is that high-order drift kinetic theory ought to be derived by truncating the all-orders system phase-space Lagrangian instead of the usual ‘field$+$particle’ Lagrangian. For the sake of clarity, this story is told first through the lens of a finite-dimensional toy model of high-order variational drift kinetics; the analogous full-on drift kinetic story is discussed subsequently. The renormalized drift kinetic system, while variational and just as formally accurate as conventional formulations, does not support the troublesome rapidly varying modes.
Making Megaliths: Shifting and Unstable Stones in the Neolithic of the Avebury Landscape
Authors: Gillings Mark , Pollard Joshua
Published: May 2016

This paper focuses upon the web of practices and transformations bound up in the extraction and movement of megaliths during the Neolithic of southern Britain. The focus is on the Avebury landscape of Wiltshire, where over 700 individual megaliths were employed in the construction of ceremonial and funerary monuments. Locally sourced, little consideration has been given to the process of acquisition and movement of sarsen stones that make up key monuments such as the Avebury henge and its avenues, attention instead focusing on the middle-distance transportation of sarsen out of this region to Stonehenge. Though stone movements were local, we argue they were far from lacking in significance, as indicated by the subsequent monumentalization of at least two locations from which they were likely acquired. We argue that since such stones embodied place(s), their removal, movement and resetting represented a remarkably dynamic and potentially disruptive reconfiguration of the world as it was known. Megaliths were never inert or stable matter, and we need to embrace this in our interpretative accounts if we are to understand the very different types of monument that emerged in prehistory as a result.
Measurement of the dimensions of food insecurity in developed countries: a systematic literature review
Authors: Ashby Stephanie , Kleve Suzanne , McKechnie Rebecca , Palermo Claire
Published: May 2016

Objective

Food insecurity is a salient health issue comprised of four dimensions – food access, availability, utilization and stability over time. The aim of the present study was to conduct a systematic literature review to identify all multi-item tools that measure food insecurity and explore which of the dimensions they assess.

Design

Five databases were searched (CENTRAL, CINAHL plus, EMBASE, MEDLINE, TRIP) for studies published in English since 1999. Inclusion criteria included human studies using multi-item tools to measure food security and studies conducted in developed countries. Manuscripts describing the US Department of Agriculture Food Security Survey Module, that measures ‘food access’, were excluded due to wide acceptance of the validity and reliability of this instrument. Two authors extracted data and assessed the quality of the included studies. Data were summarized against the dimensions of food insecurity.

Setting

A systematic review of the literature.

Subjects

The majority of tools were developed in the USA and had been used in different age groups and cultures.

Results

Eight multi-item tools were identified. All of the tools assessed the ‘food access’ dimension and two partially assessed the dimensions ‘food utilization’ and ‘stability over time’, respectively. ‘Food availability’ was not assessed by existing tools.

Conclusions

Current tools available for measuring food insecurity are subjective, limited in scope, with a majority assessing only one dimension of food insecurity (access). To more accurately assess the true burden of food insecurity, tools should be adapted or developed to assess all four dimensions of food insecurity.
Epigenetic reprogramming of fallopian tube fimbriae in BRCA mutation carriers defines early ovarian cancer evolution
Authors: Bartlett Thomas E. , Chindera Kantaraja , McDermott Jacqueline , Breeze Charles E. , Cooke William R. , Jones Allison , Reisel Daniel , Karegodar Smita T. , Arora Rupali , Beck Stephan , Menon Usha , Dubeau Louis , Widschwendter Martin
Published: May 2016

The exact timing and contribution of epigenetic reprogramming to carcinogenesis are unclear. Women harbouring BRCA1/2 mutations demonstrate a 30–40-fold increased risk of high-grade serous extra-uterine Müllerian cancers (HGSEMC), otherwise referred to as ‘ovarian carcinomas’, which frequently develop from fimbrial cells but not from the proximal portion of the fallopian tube. Here we compare the DNA methylome of the fimbrial and proximal ends of the fallopian tube in BRCA1/2 mutation carriers and non-carriers. We show that the number of CpGs displaying significant differences in methylation levels between fimbrial and proximal fallopian tube segments are threefold higher in BRCA mutation carriers than in controls, correlating with overexpression of activation-induced deaminase in their fimbrial epithelium. The differentially methylated CpGs accurately discriminate HGSEMCs from non-serous subtypes. Epigenetic reprogramming is an early pre-malignant event integral to BRCA1/2 mutation-driven carcinogenesis. Our findings may provide a basis for cancer-preventative strategies.
Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription
Authors: Kobayashi Eri H. , Suzuki Takafumi , Funayama Ryo , Nagashima Takeshi , Hayashi Makiko , Sekine Hiroki , Tanaka Nobuyuki , Moriguchi Takashi , Motohashi Hozumi , Nakayama Keiko , Yamamoto Masayuki
Published: May 2016

Nrf2 (NF-E2-related factor-2) transcription factor regulates oxidative/xenobiotic stress response and also represses inflammation. However, the mechanisms how Nrf2 alleviates inflammation are still unclear. Here, we demonstrate that Nrf2 interferes with lipopolysaccharide-induced transcriptional upregulation of proinflammatory cytokines, including IL-6 and IL-1β. Chromatin immunoprecipitation (ChIP)-seq and ChIP-qPCR analyses revealed that Nrf2 binds to the proximity of these genes in macrophages and inhibits RNA Pol II recruitment. Further, we found that Nrf2-mediated inhibition is independent of the Nrf2-binding motif and reactive oxygen species level. Murine inflammatory models further demonstrated that Nrf2 interferes with IL6 induction and inflammatory phenotypes in vivo. Thus, contrary to the widely accepted view that Nrf2 suppresses inflammation through redox control, we demonstrate here that Nrf2 opposes transcriptional upregulation of proinflammatory cytokine genes. This study identifies Nrf2 as the upstream regulator of cytokine production and establishes a molecular basis for an Nrf2-mediated anti-inflammation approach.
Direct evidence for charge stripes in a layered cobalt oxide
Authors: Babkevich P. , Freeman P. G. , Enderle M. , Prabhakaran D. , Boothroyd A. T.
Published: May 2016

Recent experiments indicate that static stripe-like charge order is generic to the hole-doped copper oxide superconductors and competes with superconductivity. Here we show that a similar type of charge order is present in La5/3Sr1/3CoO4, an insulating analogue of the copper oxide superconductors containing cobalt in place of copper. The stripe phase we have detected is accompanied by short-range, quasi-one-dimensional, antiferromagnetic order, and provides a natural explanation for the distinctive hourglass shape of the magnetic spectrum previously observed in neutron-scattering measurements of La2−xSrxCoO4 and many hole-doped copper oxide superconductors. The results establish a solid empirical basis for theories of the hourglass spectrum built on short-range, quasi-static, stripe correlations.
Measurements of continuum lowering in solid-density plasmas created from elements and compounds
Authors: Ciricosta O. , Vinko S. M. , Barbrel B. , Rackstraw D. S. , Preston T. R. , Burian T. , Chalupský J. , Cho B. I. , Chung H. -K. , Dakovski G. L. , Engelhorn K. , Hájková V. , Heimann P. , Holmes M. , Juha L. , Krzywinski J. , Lee R. W. , Toleikis S. , Turner J. J. , Zastrau U. , Wark J. S.
Published: May 2016

The effect of a dense plasma environment on the energy levels of an embedded ion is usually described in terms of the lowering of its continuum level. For strongly coupled plasmas, the phenomenon is intimately related to the equation of state; hence, an accurate treatment is crucial for most astrophysical and inertial-fusion applications, where the case of plasma mixtures is of particular interest. Here we present an experiment showing that the standard density-dependent analytical models are inadequate to describe solid-density plasmas at the temperatures studied, where the reduction of the binding energies for a given species is unaffected by the different plasma environment (ion density) in either the element or compounds of that species, and can be accurately estimated by calculations only involving the energy levels of an isolated neutral atom. The results have implications for the standard approaches to the equation of state calculations.
Identification of an activation site in Bak and mitochondrial Bax triggered by antibodies
Authors: Iyer Sweta , Anwari Khatira , Alsop Amber E. , Yuen Wai Shan , Huang David C. S. , Carroll John , Smith Nicholas A. , Smith Brian J. , Dewson Grant , Kluck Ruth M.
Published: May 2016

During apoptosis, Bak and Bax are activated by BH3-only proteins binding to the α2–α5 hydrophobic groove; Bax is also activated via a rear pocket. Here we report that antibodies can directly activate Bak and mitochondrial Bax by binding to the α1–α2 loop. A monoclonal antibody (clone 7D10) binds close to α1 in non-activated Bak to induce conformational change, oligomerization, and cytochrome c release. Anti-FLAG antibodies also activate Bak containing a FLAG epitope close to α1. An antibody (clone 3C10) to the Bax α1–α2 loop activates mitochondrial Bax, but blocks translocation of cytosolic Bax. Tethers within Bak show that 7D10 binding directly extricates α1; a structural model of the 7D10 Fab bound to Bak reveals the formation of a cavity under α1. Our identification of the α1–α2 loop as an activation site in Bak paves the way to develop intrabodies or small molecules that directly and selectively regulate these proteins.
CT-Finder: A Web Service for CRISPR Optimal Target Prediction and Visualization
Authors: Zhu Houxiang , Misel Lauren , Graham Mitchell , Robinson Michael L. , Liang Chun
Published: May 2016

The CRISPR system holds much promise for successful genome engineering, but therapeutic, industrial and research applications will place high demand on improving the specificity and efficiency of this tool. CT-Finder (http://bioinfolab.miamioh.edu/ct-finder) is a web service to help users design guide RNAs (gRNAs) optimized for specificity. CT-Finder accommodates the original single-gRNA Cas9 system and two specificity-enhancing paired-gRNA systems: Cas9 D10A nickases (Cas9n) and dimeric RNA-guided FokI nucleases (RFNs). Optimal target candidates can be chosen based on the minimization of predicted off-target effects. Graphical visualization of on-target and off-target sites in the genome is provided for target validation. Major model organisms are covered by this web service.
A Subject-Specific Acoustic Model of the Upper Airway for Snoring Sounds Generation
Authors: Saha Shumit , Bradley T. Douglas , Taheri Mahsa , Moussavi Zahra , Yadollahi Azadeh
Published: May 2016

Monitoring variations in the upper airway narrowing during sleep is invasive and expensive. Since snoring sounds are generated by air turbulence and vibrations of the upper airway due to its narrowing; snoring sounds may be used as a non-invasive technique to assess upper airway narrowing. Our goal was to develop a subject-specific acoustic model of the upper airway to investigate the impacts of upper airway anatomy, e.g. length, wall thickness and cross-sectional area, on snoring sounds features. To have a subject-specific model for snoring generation, we used measurements of the upper airway length, cross-sectional area and wall thickness from every individual to develop the model. To validate the proposed model, in 20 male individuals, intensity and resonant frequencies of modeled snoring sounds were compared with those measured from recorded snoring sounds during sleep. Based on both modeled and measured results, we found the only factor that may positively and significantly contribute to snoring intensity was narrowing in the upper airway. Furthermore, measured resonant frequencies of snoring were inversely correlated with the upper airway length, which is a risk factor for upper airway collapsibility. These results encourage the use of snoring sounds analysis to assess the upper airway anatomy during sleep.
Mice lacking Programmed cell death-1 show a role for CD8+ T cells in long-term immunity against blood-stage malaria
Authors: Horne-Debets Joshua M. , Karunarathne Deshapriya S. , Faleiro Rebecca J. , Poh Chek Meng , Renia Laurent , Wykes Michelle N.
Published: May 2016

Even after years of experiencing malaria, caused by infection with Plasmodium species, individuals still have incomplete immunity and develop low-density parasitemia on re-infection. Previous studies using the P. chabaudi (Pch) mouse model to understand the reason for chronic malaria, found that mice with a deletion of programmed cell death-1 (PD-1KO) generate sterile immunity unlike wild type (WT) mice. Here we investigated if the mechanism underlying this defect during acute immunity also impacts on long-term immunity. We infected WT and PD-1KO mice with Pch-malaria and measured protection as well as immune responses against re-infections, 15 or 20 weeks after the original infection had cleared. WT mice showed approximately 1% parasitemia compared to sterile immunity in PD-1KO mice on re-infection. An examination of the mechanisms of immunity behind this long-term protection in PD-1KO mice showed a key role for parasite-specific CD8+ T cells even when CD4+ T cells and B cells responded to re-infection. These studies indicate that long-term CD8+ T cell-meditated protection requires consideration for future malaria vaccine design, as part of a multi-cell type response.
Stability of numerous novel potassium chlorides at high pressure
Authors: Zhang Weiwei , Oganov Artem R. , Zhu Qiang , Lobanov Sergey S. , Stavrou Elissaios , Goncharov Alexander F.
Published: May 2016

K-Cl is a simple system displaying all four main types of bonding, as it contains (i) metallic potassium, (ii) elemental chlorine made of covalently bonded Cl2 molecules held together by van der Waals forces and (iii) an archetypal ionic compound KCl. The charge balance rule, assigning classical charges of “+1” to K and “−1” to Cl, predicts that no compounds other than KCl are possible. However, our quantum-mechanical variable-composition evolutionary simulations predict an extremely complex phase diagram, with new thermodynamically stable compounds K3Cl, K2Cl, K3Cl2, K4Cl3, K5Cl4, K3Cl5, KCl3 and KCl7. Of particular interest are 2D-metallic homologs Kn+1Cln, the presence of positively charged Cl atoms in KCl7 and the predicted stability of KCl3 already at nearly ambient pressures at zero Kelvin. We have synthesized cubic "Equation missing" -KCl3 at 40–70 GPa and trigonal "Equation missing" -KCl3 at 20–40 GPa in a laser-heated diamond anvil cell (DAC) at temperature exceeding 2000 K from KCl and Cl2. These phases were identified using in situ synchrotron X-ray diffraction and Raman spectroscopy. Upon unloading to 10 GPa, "Equation missing" -KCl3 transforms to a yet unknown structure before final decomposition to KCl and Cl2 at near-ambient conditions.
Photonic Quantum Networks formed from NV− centers
Authors: Nemoto Kae , Trupke Michael , Devitt Simon J. , Scharfenberger Burkhard , Buczak Kathrin , Schmiedmayer Jörg , Munro William J.
Published: May 2016

In this article we present a simple repeater scheme based on the negatively-charged nitrogen vacancy centre in diamond. Each repeater node is built from modules comprising an optical cavity containing a single NV−, with one nuclear spin from 15N as quantum memory. The module uses only deterministic processes and interactions to achieve high fidelity operations (>99%) and modules are connected by optical fiber. In the repeater node architecture, the processes between modules by photons can be in principle deterministic, however current limitations on optical components lead the processes to be probabilistic but heralded. Our resource-modest repeater architecture contains two modules at each node and the repeater nodes are then connected by entangled photon pairs. We discuss the performance of such a quantum repeater network with modest resources and then incorporate more resource-intense strategies step by step. Our architecture should allow large-scale quantum information networks with existing or near future technology.
Respiratory Syncytial Virus whole-genome sequencing identifies convergent evolution of sequence duplication in the C-terminus of the G gene
Authors: Schobel Seth A. , Stucker Karla M. , Moore Martin L. , Anderson Larry J. , Larkin Emma K. , Shankar Jyoti , Bera Jayati , Puri Vinita , Shilts Meghan H. , Rosas-Salazar Christian , Halpin Rebecca A. , Fedorova Nadia , Shrivastava Susmita , Stockwell Timothy B. , Peebles R. Stokes , Hartert Tina V. , Das Suman R.
Published: May 2016

Respiratory Syncytial Virus (RSV) is responsible for considerable morbidity and mortality worldwide and is the most important respiratory viral pathogen in infants. Extensive sequence variability within and between RSV group A and B viruses and the ability of multiple clades and sub-clades of RSV to co-circulate are likely mechanisms contributing to the evasion of herd immunity. Surveillance and large-scale whole-genome sequencing of RSV is currently limited but would help identify its evolutionary dynamics and sites of selective immune evasion. In this study, we performed complete-genome next-generation sequencing of 92 RSV isolates from infants in central Tennessee during the 2012–2014 RSV seasons. We identified multiple co-circulating clades of RSV from both the A and B groups. Each clade is defined by signature N- and O-linked glycosylation patterns. Analyses of specific RSV genes revealed high rates of positive selection in the attachment (G) gene. We identified RSV-A viruses in circulation with and without a recently reported 72-nucleotide G gene sequence duplication. Furthermore, we show evidence of convergent evolution of G gene sequence duplication and fixation over time, which suggests a potential fitness advantage of RSV with the G sequence duplication.
Interferon-γ and Tumor Necrosis Factor-α Polarize Bone Marrow Stromal Cells Uniformly to a Th1 Phenotype
Authors: Jin Ping , Zhao Yuanlong , Liu Hui , Chen Jinguo , Ren Jiaqiang , Jin Jianjian , Bedognetti Davide , Liu Shutong , Wang Ena , Marincola Francesco , Stroncek David
Published: May 2016

Activated T cells polarize mesenchymal stromal cells (MSCs) to a proinflammatory Th1 phenotype which likely has an important role in amplifying the immune response in the tumor microenvironment. We investigated the role of interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α), two factors produced by activated T cells, in MSC polarization. Gene expression and culture supernatant analysis showed that TNF-α and IFN-γ stimulated MSCs expressed distinct sets of proinflammatory factors. The combination of IFN-γ and TNF-α was synergistic and induced a transcriptome most similar to that found in MSCs stimulated with activated T cells and similar to that found in the inflamed tumor microenvironment; a Th1 phenotype with the expression of the immunosuppressive factors IL-4, IL-10, CD274/PD-L1 and indoleamine 2,3 dioxygenase (IDO). Single cell qRT-PCR analysis showed that the combination of IFN-γ and TNF-α polarized uniformly to this phenotype. The combination of IFN-γ and TNF-α results in the synergist uniform polarization of MSCs toward a primarily Th1 phenotype. The stimulation of MSCs by IFN-γ and TNF-α released from activated tumor infiltrating T cells is likely responsible for the production of many factors that characterize the tumor microenvironment.
Vasoactive Intestinal Peptide modulates trophoblast-derived cell line function and interaction with phagocytic cells through autocrine pathways
Authors: Vota Daiana , Paparini Daniel , Hauk Vanesa , Toro Ayelén , Merech Fatima , Varone Cecilia , Ramhorst Rosanna , Pérez Leirós Claudia
Published: May 2016

Trophoblast cells migrate and invade the decidual stroma in a tightly regulated process to maintain immune homeostasis at the maternal-placental interface during the first weeks of pregnancy. Locally synthesized factors modulate trophoblast cell function and their interaction with maternal leukocytes to promote the silent clearance of apoptotic cells. The vasoactive intestinal peptide (VIP) is a pleiotropic polypeptide with trophic and anti-inflammatory effects in murine pregnancy models. We explored the effect of VIP on two human first trimester trophoblast cell lines, particularly on their migration, invasiveness and interaction with phagocytic cells, and the signalling and regulatory pathways involved. We found that VIP enhanced trophoblast cell migration and invasion through the activation of high affinity VPAC receptors and PKA-CRE signalling pathways. VIP knocked-down trophoblast cells showed reduced migration in basal and leukemic inhibitor factor (LIF)-elicited conditions. In parallel, VIP-silenced trophoblast cells failed to induce the phagocytosis of apoptotic bodies and the expression of immunosuppressant markers by human monocytes. Our results suggest that VIP-mediated autocrine pathways regulate trophoblast cell function and contribute to immune homeostasis maintenance at placentation and may provide new clues for therapeutic intervention in pregnancies complicated by defective deep placentation.
Spider web and silk performance landscapes across nutrient space
Authors: Blamires Sean J. , Tseng Yi-Hsuan , Wu Chung-Lin , Toft Søren , Raubenheimer David , Tso I.-Min
Published: May 2016

Predators have been shown to alter their foraging as a regulatory response to recent feeding history, but it remains unknown whether trap building predators modulate their traps similarly as a regulatory strategy. Here we fed the orb web spider Nephila pilipes either live crickets, dead crickets with webs stimulated by flies, or dead crickets without web stimulation, over 21 days to enforce spiders to differentially extract nutrients from a single prey source. In addition to the nutrients extracted we measured web architectures, silk tensile properties, silk amino acid compositions, and web tension after each feeding round. We then plotted web and silk “performance landscapes” across nutrient space. The landscapes had multiple peaks and troughs for each web and silk performance parameter. The findings suggest that N. pilipes plastically adjusts the chemical and physical properties of their web and silk in accordance with its nutritional history. Our study expands the application of the geometric framework foraging model to include a type of predatory trap. Whether it can be applied to other predatory traps requires further testing.
Implementation of Outstanding Electronic Transport in Polar Covalent Boron Nitride Atomic Chains: another Extraordinary Odd-Even Behaviour
Authors: Xu Xiaodong , Li Weiqi , Liu Linhua , Feng Jikang , Jiang Yongyuan , Tian Wei Quan
Published: May 2016

A theoretical investigation of the unique electronic transport properties of the junctions composed of boron nitride atomic chains bridging symmetric graphene electrodes with point-contacts is executed through non-equilibrium Green’s function technique in combination with density functional theory. Compared with carbon atomic chains, the boron nitride atomic chains have an alternative arrangement of polar covalent B-N bonds and different contacts coupling electrodes, showing some unusual properties in functional atomic electronic devices. Remarkably, they have an extraordinary odd-even behavior of conductivity with the length increase. The rectification character and negative differential resistance of nonlinear current-voltage characteristics can be achieved by manipulating the type of contacts between boron nitride atomic chains bridges and electrodes. The junctions with asymmetric contacts have an intrinsic rectification, caused by stronger coupling in the C-N contact than the C-B contact. On the other hand, for symmetric contact junctions, it is confirmed that the transport properties of the junctions primarily depend on the nature of contacts. The junctions with symmetric C-N contacts have higher conductivity than their C-B contacts counterparts. Furthermore, the negative differential resistances of the junctions with only C-N contacts is very conspicuous and can be achieved at lower bias.
Overexpression of spinach non-symbiotic hemoglobin in Arabidopsis resulted in decreased NO content and lowered nitrate and other abiotic stresses tolerance
Authors: Bai Xuegui , Long Juan , He Xiaozhao , Yan Jinping , Chen Xuanqin , Tan Yong , Li Kunzhi , Chen Limei , Xu Huini
Published: May 2016

A class 1 non-symbiotic hemoglobin family gene, SoHb, was isolated from spinach. qRT-PCR showed that SoHb was induced by excess nitrate, polyethylene glycol, NaCl, H2O2, and salicylic acid. Besides, SoHb was strongly induced by application of nitric oxide (NO) donor, while was suppressed by NO scavenger, nitrate reductase inhibitor, and nitric oxide synthase inhibitor. Overexpression of SoHb in Arabidopsis resulted in decreased NO level and sensitivity to nitrate stress, as shown by reduced root length, fresh weight, the maximum photosystem II quantum ratio of variable to maximum fluorescence (Fv/Fm), and higher malondialdehyde contents. The activities and gene transcription of superoxide dioxidase, and catalase decreased under nitrate stress. Expression levels of RD22, RD29A, DREB2A, and P5CS1 decreased after nitrate treatment in SoHb-overexpressing plants, while increased in the WT plants. Moreover, SoHb-overexpressing plants showed decreased tolerance to NaCl and osmotic stress. In addition, the SoHb-overexpression lines showed earlier flower by regulating the expression of SOC, GI and FLC genes. Our results indicated that the decreasing NO content in Arabidopsis by overexpressing SoHb might be responsible for lowered tolerance to nitrate and other abiotic stresses.
QSAR Accelerated Discovery of Potent Ice Recrystallization Inhibitors
Authors: Briard Jennie G. , Fernandez Michael , De Luna Phil , Woo Tom. K. , Ben Robert N.
Published: May 2016

Ice recrystallization is the main contributor to cell damage and death during the cryopreservation of cells and tissues. Over the past five years, many small carbohydrate-based molecules were identified as ice recrystallization inhibitors and several were shown to reduce cryoinjury during the cryopreservation of red blood cells (RBCs) and hematopoietic stems cells (HSCs). Unfortunately, clear structure-activity relationships have not been identified impeding the rational design of future compounds possessing ice recrystallization inhibition (IRI) activity. A set of 124 previously synthesized compounds with known IRI activities were used to calibrate 3D-QSAR classification models using GRid INdependent Descriptors (GRIND) derived from DFT level quantum mechanical calculations. Partial least squares (PLS) model was calibrated with 70% of the data set which successfully identified 80% of the IRI active compounds with a precision of 0.8. This model exhibited good performance in screening the remaining 30% of the data set with 70% of active additives successfully recovered with a precision of ~0.7 and specificity of 0.8. The model was further applied to screen a new library of aryl-alditol molecules which were then experimentally synthesized and tested with a success rate of 82%. Presented is the first computer-aided high-throughput experimental screening for novel IRI active compounds.
Whole genome sequencing of Gyeongbuk Araucana, a newly developed blue-egg laying chicken breed, reveals its origin and genetic characteristics
Authors: Jeong Hyeonsoo , Kim Kwondo , Caetano-Anollés Kelsey , Kim Heebal , Kim Byung-ki , Yi Jun-Koo , Ha Jae-Jung , Cho Seoae , Oh Dong Yep
Published: May 2016

Chicken, Gallus gallus, is a valuable species both as a food source and as a model organism for scientific research. Here, we sequenced the genome of Gyeongbuk Araucana, a rare chicken breed with unique phenotypic characteristics including flight ability, large body size, and laying blue-shelled eggs, to identify its genomic features. We generated genomes of Gyeongbuk Araucana, Leghorn, and Korean Native Chicken at a total of 33.5, 35.82, and 33.23 coverage depth, respectively. Along with the genomes of 12 Chinese breeds, we identified genomic variants of 16.3 million SNVs and 2.3 million InDels in mapped regions. Additionally, through assembly of unmapped reads and selective sweep, we identified candidate genes that fall into heart, vasculature and muscle development and body growth categories, which provided insight into Gyeongbuk Araucana’s phenotypic traits. Finally, genetic variation based on the transposable element insertion pattern was investigated to elucidate the features of transposable elements related to blue egg shell formation. This study presents results of the first genomic study on the Gyeongbuk Araucana breed; it has potential to serve as an invaluable resource for future research on the genomic characteristics of this chicken breed as well as others.
Controlling Octahedral Rotations in a Perovskite via Strain Doping
Authors: Herklotz A. , Wong A. T. , Meyer T. , Biegalski M. D. , Lee H. N. , Ward T. Z.
Published: May 2016

The perovskite unit cell is the fundamental building block of many functional materials. The manipulation of this crystal structure is known to be of central importance to controlling many technologically promising phenomena related to superconductivity, multiferroicity, mangetoresistivity and photovoltaics. The broad range of properties that this structure can exhibit is in part due to the centrally coordinated octahedra bond flexibility, which allows for a multitude of distortions from the ideal highly symmetric structure. However, continuous and fine manipulation of these distortions has never been possible. Here, we show that controlled insertion of He atoms into an epitaxial perovskite film can be used to finely tune the lattice symmetry by modifying the local distortions, i.e., octahedral bonding angle and length. Orthorhombic SrRuO3 films coherently grown on SrTiO3 substrates are used as a model system. Implanted He atoms are confirmed to induce out-of-plane strain, which provides the ability to controllably shift the bulk-like orthorhombically distorted phase to a tetragonal structure by shifting the oxygen octahedra rotation pattern. These results demonstrate that He implantation offers an entirely new pathway to strain engineering of perovskite-based complex oxide thin films, useful for creating new functionalities or properties in perovskite materials.
Migration mechanism of a GaN bicrystalline grain boundary as a model system
Authors: Lee Sung Bo , Yoo Seung Jo , Kim Young-Min , Kim Jin-Gyu , Han Heung Nam
Published: May 2016

Using in situ high-resolution transmission electron microscopy, we have explored migration mechanism of a grain boundary in a GaN bicrystal as a model system. During annealing at 500 °C, the grain-boundary region underwent a decrease in thickness, which occurred by decomposition or sublimation of GaN during annealing at 500 °C coupled with electron-beam sputtering. The decrease in thickness corresponds to an increase in the driving force for migration, because the migration of the grain boundary was driven by the surface energy difference. As the driving force increased with annealing time, the grain-boundary morphology turned from atomically smooth to rough, which is characterized by kinetic roughening. The observations indicate that a grain boundary exhibits a nonlinear relationship between driving force for migration and migration velocity, in discord with the general presumption that a grain boundary follows a linear relationship.
Embryo Microinjection of Selenomethionine Reduces Hatchability and Modifies Oxidant Responsive Gene Expression in Zebrafish
Authors: Thomas J. K. , Janz D. M.
Published: May 2016

In previous studies we demonstrated that exposure to selenomethionine (SeMet) causes developmental toxicities in zebrafish (Danio rerio). The objectives of this study were to establish a dose-response relationship for developmental toxicities in zebrafish after embryo microinjection of Se (8, 16 or 32 μg/g dry mass of eggs) in the form of SeMet and to investigate potential underlying mechanism(s) of SeMet-induced developmental toxicities. A dose-dependent increase in frequencies of mortality and total deformities and reduced hatchability were observed in zebrafish exposed to excess Se via embryo microinjection. The egg Se concentration causing 20% mortality was then used to investigate transcript abundance of proteins involved in antioxidant protection and methylation. Excess Se exposure modified gene expression of oxidant-responsive transcription factors (nuclear factor erythroid 2-related factornrf2aandnrf2b) and enzymes involved in cellular methylation (methionine adenosyltransferasemat1aandmat2ab) in zebrafish larvae. Notably, excess Se exposure up-regulated transcript abundance of aryl hydrocarbon receptor 2 (ahr2), a signalling pathway involved in the toxicity of dioxin-related compounds. Our findings suggest that oxidative stress or modification of methylation, or a combination of these mechanisms, might be responsible for Se-induced developmental toxicities in fishes.
Proteomic profiling of small-molecule inhibitors reveals dispensability of MTH1 for cancer cell survival
Authors: Kawamura Tatsuro , Kawatani Makoto , Muroi Makoto , Kondoh Yasumitsu , Futamura Yushi , Aono Harumi , Tanaka Miho , Honda Kaori , Osada Hiroyuki
Published: May 2016

Since recent publications suggested that the survival of cancer cells depends on MTH1 to avoid incorporation of oxidized nucleotides into the cellular DNA, MTH1 has attracted attention as a potential cancer therapeutic target. In this study, we identified new purine-based MTH1 inhibitors by chemical array screening. However, although the MTH1 inhibitors identified in this study targeted cellular MTH1, they exhibited only weak cytotoxicity against cancer cells compared to recently reported first-in-class inhibitors. We performed proteomic profiling to investigate the modes of action by which chemically distinct MTH1 inhibitors induce cancer cell death and found mechanistic differences among the first-in-class MTH1 inhibitors. In particular, we identified tubulin as the primary target of TH287 and TH588 responsible for the antitumor effects despite the nanomolar MTH1-inhibitory activity in vitro. Furthermore, overexpression of MTH1 did not rescue cells from MTH1 inhibitor–induced cell death and siRNA-mediated knockdown of MTH1 did not suppress cancer cell growth. Taken together, we conclude that the cytotoxicity of MTH1 inhibitors is attributable to off-target effects and that MTH1 is not essential for cancer cell survival.
QwikMD — Integrative Molecular Dynamics Toolkit for Novices and Experts
Authors: Ribeiro João V. , Bernardi Rafael C. , Rudack Till , Stone John E. , Phillips James C. , Freddolino Peter L. , Schulten Klaus
Published: May 2016

The proper functioning of biomolecules in living cells requires them to assume particular structures and to undergo conformational changes. Both biomolecular structure and motion can be studied using a wide variety of techniques, but none offers the level of detail as do molecular dynamics (MD) simulations. Integrating two widely used modeling programs, namely NAMD and VMD, we have created a robust, user-friendly software, QwikMD, which enables novices and experts alike to address biomedically relevant questions, where often only molecular dynamics simulations can provide answers. Performing both simple and advanced MD simulations interactively, QwikMD automates as many steps as necessary for preparing, carrying out and analyzing simulations while checking for common errors and enabling reproducibility. QwikMD meets also the needs of experts in the field, increasing the efficiency and quality of their work by carrying out tedious or repetitive tasks while enabling easy control of every step. Whether carrying out simulations within the live view mode on a small laptop or performing complex and large simulations on supercomputers or Cloud computers, QwikMD uses the same steps and user interface. QwikMD is freely available by download on group and personal computers. It is also available on the cloud at Amazon Web Services.