bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation of the incidence of MRSA patients: evaluation of a surveillance system using health insurance claim data
Authors: TANIHARA S. , SUZUKI S.
Published: April 2016

Because sentinel surveillance systems cannot obtain information about patients who visit non-sentinel medical facilities, the characteristics of patients identified by these systems may be biased. In this study, we evaluated the representativeness of a methicillin-resistant Staphylococcus aureus (MRSA) surveillance system using health insurance claim (HIC) data, which does not depend on physician notification. We calculated the age-specific incidence of MRSA patients using data from the Japan Nosocomial Infections Surveillance (JANIS) programme, which is based on sentinel surveillance systems, and inpatient HICs submitted to employee health insurance organizations in 2011, and then computed age-specific incidence ratios between the HIC and JANIS data. Age-specific MRSA incidence in both datasets followed J-shaped curves with similar shapes. For all age groups, the ratios between HIC and JANIS data were around 10. These findings indicate that JANIS notification of MRSA cases was not affected by patients’ age.
Convergence, divergence et filiation linguistique: retour à l’étude panlectale de la variation en français
Authors: FAGYAL ZSUZSANNA
Published: April 2016

Les français parlés en milieux minoritaires au Canada sont probablement les français vernaculaires les plus étudiés en sociolinguistique francophone. L’étude comparée des locutions adverbiales de restriction rien que/juste/seulement/seulement que/ne que de Mougeon, Hallion, Bigot, et Papen publiée dans ce volume s'inscrit dans une longue tradition de recherches systématiques sur les structures grammaticales variables en milieux minoritaires, telles que la morphologie de l'auxiliaire aller (Mougeon et al. 1988; 2010), l'usage des futurs analytique et synthétique (Poplack et Turpin 1999, Nadasdi et al. 2003), la neutralisation des formes masculines de tout (Lemieux et Sankoff 1983; Bigot et Papen 2015) et les formes irrégulières de l'imparfait (Hallion Bres 2006; Papen et Bigot 2010), pour ne citer que quelques-uns des aspects les plus étudiés. La présente contribution de Mougeon et ses collègues à l’étude de la restriction dans quatre variétés de français originaires de l'expansion du français vers l'Ouest de la province du Québec possède, néanmoins, une portée bien plus large que la plupart des études préalables.
Introduction
Authors: HERSCHENSOHN JULIA , FAGYAL ZSUZSANNA
Published: April 2016

This volume represents a new and exciting initiative for the Journal of French Language Studies: the publication of its first issue featuring a theme paper with comments and a response to comments. Unlike collections of articles featuring independent contributions to a common research topic, this new platform for scholarly debate focuses on a single paper discussed by a group of experts. Rather than highlighting the diversity of approaches, the goal is to delve into the analysis of one particular research question by soliciting comments, suggestions and critiques of the methodology, the results and the possible implications for future research.
Pediatric & Congenital Electrophysiology Society: building an international paediatric electrophysiology organisation
Authors: Cohen Mitchell , Sanatani Shubhayan , Stephenson Elizabeth , Skinner Jon , Drago Fabrizio , Davis Andrew , Janousek Jan , Rosenthal Eric , Collins Kathryn K. , Triedman John
Published: April 2016

The Pediatric and Congenital Electrophysiology Society (PACES) is a non-profit organisation comprised of individuals dedicated to improving the care of children and young adults with cardiac rhythm disturbances. Although PACES is a predominantly North American-centric organisation, international members have been a part of PACES for the last two decades. This year, PACES expanded its North American framework into a broadly expansive international role. On 12 May, 2015, paediatric electrophysiology leaders from within the United States of America and Canada met with over 30 international paediatric electrophysiologists from 17 countries and five continents discussing measures to (1) expand PACES’ global vision, (2) address ongoing challenges such as limited resource allocation that may be present in developing countries, (3) expand PACES’ governance to include international representation, (4) promote joint international sessions at future paediatric EP meetings, and (5) facilitate a global multi-centre research consortium. This meeting marked the inception of a formal international collaborative spirit in PACES. This editorial addresses some solutions to breakdown the continental silos paediatric electrophysiologists have practiced within; however, there remain ongoing limitations, and future discussions will be needed to continue to move the PACES global international vision forward.
Not all social cleavages are the same: On the relationship between religious diversity and party system fragmentation
Authors: Raymond Christopher D.
Published: April 2016

Most studies examining the relationship between social cleavages and party system fragmentation maintain that higher levels of social diversity lead to greater party system fragmentation. However, most aggregate-level studies focus on one type of social cleavage: ethnic diversity. In order to develop a better understanding of how different cleavages impact electoral competition, this article considers another type of social cleavage: religious diversity. Contrary to previous literature, higher levels of religious diversity provide incentives for cross-religious cooperation, which in turn reduces party system fragmentation. Using a cross-national data set of elections from 1946–2011, the results show that, in contrast to most studies examining the effects of social cleavage diversity on the number of parties, higher religious diversity is associated with lower levels of party system fragmentation.
Wire-medium loaded planar structures: modal analysis, near fields, and radiation features
Authors: Comite Davide , Baccarelli Paolo , Burghignoli Paolo , Galli Alessandro
Published: April 2016

A novel transmission-line model is used for the analysis of planar structures, including wire-medium (WM) slabs with vertically aligned wires. The network formalism allows for an effective determination of the relevant spectral Green's functions, of the modal dispersion equation via transverse resonance, as well as of the far-field radiation pattern produced by simple sources via reciprocity, as opposed to the more cumbersome field-matching approach. Numerical results, validated also against state-of-the-art simulation software, confirm the accuracy and effectiveness of the proposed approach. In particular, modal and radiation features are presented for a class of leaky-wave antennas based on planar WM loaded configurations covered by partially reflecting screens, for which leaky unimodal regimes are achieved by minimizing spurious radiation from the quasi-transverse electromagnetic (TEM) mode.
Twin Anemia Polycythemia Sequence: Current Views on Pathogenesis, Diagnostic Criteria, Perinatal Management, and Outcome
Authors: Tollenaar Lisanne S. A. , Slaghekke Femke , Middeldorp Johanna M. , Klumper Frans J. , Haak Monique C. , Oepkes Dick , Lopriore Enrico
Published: April 2016

Monochorionic twins share a single placenta and are connected with each other through vascular anastomoses. Unbalanced inter-twin blood transfusion may lead to various complications, including twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS). TAPS was first described less than a decade ago, and the pathogenesis of TAPS results from slow blood transfusion from donor to recipient through a few minuscule vascular anastomoses. This gradually leads to anemia in the donor and polycythemia in the recipient, in the absence of twin oligo-polyhydramnios sequence (TOPS). TAPS may occur spontaneously in 3–5% of monochorionic twins or after laser surgery for TTTS. The prevalence of post-laser TAPS varies from 2% to 16% of TTTS cases, depending on the rate of residual anastomoses. Pre-natal diagnosis of TAPS is currently based on discordant measurements of the middle cerebral artery peak systolic velocity (MCA-PSV; >1.5 multiples of the median [MoM] in donors and <1.0 in recipients). Post-natal diagnosis is based on large inter-twin hemoglobin (Hb) difference (>8 g/dL), and at least one of the following: reticulocyte count ratio >1.7 or minuscule placental anastomoses. Management includes expectant management, and intra-uterine blood transfusion (IUT) with or without partial exchange transfusion (PET) or fetoscopic laser surgery. Post-laser TAPS can be prevented by using the Solomon laser surgery technique. Short-term neonatal outcome ranges from isolated inter-twin Hb differences to severe neonatal morbidity and neonatal death. Long-term neonatal outcome in post-laser TAPS is comparable with long-term outcome after treated TTTS. This review summarizes the current knowledge after 10 years of research on the pathogenesis, diagnosis, management, and outcome in TAPS.
Twin-to-Twin Transfusion Syndrome: From Observational Evidence to Randomized Controlled Trials
Authors: Stirnemann Julien J. , Chalouhi Gihad , Ville Yves
Published: April 2016

Fetoscopic surgery is widely accepted as the preferred first-line treatment for twin–twin transfusion syndrome (TTTS). Nonetheless, the broad diffusion of this technique relies on a single multicentric-randomized trial. We hereby question this trial in a post-hoc Bayesian analysis, submitting its results to several scenarios comprising the alternative published non-randomized literature and pessimistic opinions regarding this surgery. Furthermore, we also discuss further refinements in indications, questioning potential alternatives in early stages of the disease.
Spaces That Signal Identity Improve Workplace	Productivity
Authors: Greenaway Katharine H. , Thai Hannibal A. , Haslam S. Alexander , Murphy Sean C.
Published: April 2016

Abstract. The physical spaces we inhabit have a profound impact on psychological functioning. People generally experience positive outcomes in spaces that support important identities and negative outcomes in spaces that threaten those identities. We investigated the effects of working in an ingroup or outgroup space on organizational performance. Participants completed exercises in a simulated work environment as a member of a research education development (RED) work team. The office space was designed to be identity affirming (decorated by a RED team), identity threatening (decorated by a rival business legacy usability and engineering [BLUE] team), or undecorated. Work teams performed better in both ingroup spaces and outgroup spaces than in undecorated spaces. The findings highlight the importance of considering the impact of physical space on psychological functioning in the workplace and beyond.
Paleofires and Models Illuminate Future Fire Scenarios
Authors: Robertson Ann , Githumbi Esther , Colombaroli Daniele
Published: April 2016

Advances in Interdisciplinary Paleofire Research: Data and Model Comparisons for the Past Millennium; Harvard Forest, Petersham, Massachusetts, 27 September to 2 October 2015
Modeling the Effects of Clouds on Climate
Authors: Yan Wudan
Published: April 2016

New research investigates how mixed-phase cloud partitioning and cloud cover compensate each other in GCMs.
Overexpression of human kynurenine-3-monooxygenase protects against 3-hydroxykynurenine-mediated apoptosis through bidirectional nonlinear feedback
Authors: Wilson K , Auer M , Binnie M , Zheng X , Pham N T , Iredale J P , Webster S P , Mole D J
Published: April 2016

Kynurenine 3-monooxygenase (KMO) is a critical regulator of inflammation. The preferred KMO substrate, kynurenine, is converted to 3-hydroxykynurenine (3HK), and this product exhibits cytotoxicity through mechanisms that culminate in apoptosis. Here, we report that overexpression of human KMO with orthotopic localisation to mitochondria creates a metabolic environment during which the cell exhibits increased tolerance for exogenous 3HK-mediated cellular injury. Using the selective KMO inhibitor Ro61-8048, we show that KMO enzyme function is essential for cellular protection. Pan-caspase inhibition with Z-VAD-FMK confirmed apoptosis as the mode of cell death. By defining expression of pathway components upstream and downstream of KMO, we observed alterations in other key kynurenine pathway components, particularly tryptophan-2,3-dioxygenase upregulation, through bidirectional nonlinear feedback. KMO overexpression also increased expression of inducible nitric oxide synthase (iNOS). These changes in gene expression are functionally relevant, because siRNA knockdown of the pathway components kynureninase and quinolinate phosphoribosyl transferase caused cells to revert to a state of susceptibility to 3HK-mediated apoptosis. In summary, KMO overexpression, and importantly KMO activity, have metabolic repercussions that fundamentally affect resistance to cell stress.
Microtubule-dependent balanced cell contraction and luminal-matrix modification accelerate epithelial tube fusion
Authors: Kato Kagayaki , Dong Bo , Wada Housei , Tanaka-Matakatsu Miho , Yagi Yoshimasa , Hayashi Shigeo
Published: April 2016

Connection of tubules into larger networks is the key process for the development of circulatory systems. In Drosophila development, tip cells of the tracheal system lead the migration of each branch and connect tubules by adhering to each other and simultaneously changing into a torus-shape. We show that as adhesion sites form between fusion cells, myosin and microtubules form polarized bundles that connect the new adhesion site to the cells’ microtubule-organizing centres, and that E-cadherin and retrograde recycling endosomes are preferentially deposited at the new adhesion site. We demonstrate that microtubules help balancing tip cell contraction, which is driven by myosin, and is required for adhesion and tube fusion. We also show that retrograde recycling and directed secretion of a specific matrix protein into the fusion-cell interface promote fusion. We propose that microtubule bundles connecting these cell–cell interfaces coordinate cell contractility and apical secretion to facilitate tube fusion.
Entropy-driven formation of chiral nematic phases by computer simulations
Authors: Dussi Simone , Dijkstra Marjolein
Published: April 2016

Predicting the macroscopic chiral behaviour of liquid crystals from the microscopic chirality of the particles is highly non-trivial, even when the chiral interactions are purely entropic in nature. Here we introduce a novel chiral hard-particle model, namely particles with a twisted polyhedral shape and obtain a stable fully entropy-driven cholesteric phase by computer simulations. By slightly modifying the triangular base of the particle, we are able to switch from a left-handed prolate (calamitic) to a right-handed oblate (discotic) cholesteric phase using the same right-handed twisted particle model. Furthermore, we show that not only prolate and oblate chiral nematic phases, but also other novel entropy-driven phases, namely chiral blue phases, chiral nematic phases featuring both twist and splay deformations, chiral biaxial nematic phases with one of the axes twisted, can be obtained by varying particle biaxiality and chirality. Our results allow to identify general guidelines for the stabilization of these phases.
Viviparity stimulates diversification in an order of fish
Authors: Helmstetter Andrew J. , Papadopulos Alexander S. T. , Igea Javier , Van Dooren Tom J. M. , Leroi Armand M. , Savolainen Vincent
Published: April 2016

Species richness is distributed unevenly across the tree of life and this may be influenced by the evolution of novel phenotypes that promote diversification. Viviparity has originated ∼150 times in vertebrates and is considered to be an adaptation to highly variable environments. Likewise, possessing an annual life cycle is common in plants and insects, where it enables the colonization of seasonal environments, but rare in vertebrates. The extent to which these reproductive life-history traits have enhanced diversification and their relative importance in the process remains unknown. We show that convergent evolution of viviparity causes bursts of diversification in fish. We built a phylogenetic tree for Cyprinodontiformes, an order in which both annualism and viviparity have arisen, and reveal that while both traits have evolved multiple times, only viviparity played a major role in shaping the patterns of diversity. These results demonstrate that changes in reproductive life-history strategy can stimulate diversification.
Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity
Authors: Uto Tomofumi , Fukaya Tomohiro , Takagi Hideaki , Arimura Keiichi , Nakamura Takeshi , Kojima Naoya , Malissen Bernard , Sato Katsuaki
Published: April 2016

Dendritic cells (DCs) comprise several subsets that are critically involved in the initiation and regulation of immunity. Clec4A4/DC immunoreceptor 2 (DCIR2) is a C-type lectin receptor (CLR) exclusively expressed on CD8α− conventional DCs (cDCs). However, how Clec4A4 controls immune responses through regulation of the function of CD8α− cDCs remains unclear. Here we show that Clec4A4 is a regulatory receptor for the activation of CD8α− cDCs that impairs inflammation and T-cell immunity. Clec4a4−/−CD8α− cDCs show enhanced cytokine production and T-cell priming following Toll-like receptor (TLR)-mediated activation. Furthermore, Clec4a4−/− mice exhibit TLR-mediated hyperinflammation. On antigenic immunization, Clec4a4−/− mice show not only augmented T-cell responses but also progressive autoimmune pathogenesis. Conversely, Clec4a4−/− mice exhibit resistance to microbial infection, accompanied by enhanced T-cell responses against microbes. Thus, our findings highlight roles of Clec4A4 in regulation of the function of CD8α− cDCs for control of the magnitude and quality of immune response.
Pathological lymphangiogenesis is modulated by galectin-8-dependent crosstalk between podoplanin and integrin-associated VEGFR-3
Authors: Chen Wei-Sheng , Cao Zhiyi , Sugaya Satoshi , Lopez Maria J. , Sendra Victor G. , Laver Nora , Leffler Hakon , Nilsson Ulf J. , Fu Jianxin , Song Jianhua , Xia Lijun , Hamrah Pedram , Panjwani Noorjahan
Published: April 2016

Lymphangiogenesis plays a pivotal role in diverse pathological conditions. Here, we demonstrate that a carbohydrate-binding protein, galectin-8, promotes pathological lymphangiogenesis. Galectin-8 is markedly upregulated in inflamed human and mouse corneas, and galectin-8 inhibitors reduce inflammatory lymphangiogenesis. In the mouse model of corneal allogeneic transplantation, galectin-8-induced lymphangiogenesis is associated with an increased rate of corneal graft rejection. Further, in the murine model of herpes simplex virus keratitis, corneal pathology and lymphangiogenesis are ameliorated in Lgals8−/− mice. Mechanistically, VEGF-C-induced lymphangiogenesis is significantly reduced in the Lgals8−/− and Pdpn−/− mice; likewise, galectin-8-induced lymphangiogenesis is reduced in Pdpn−/− mice. Interestingly, knockdown of VEGFR-3 does not affect galectin-8-mediated lymphatic endothelial cell (LEC) sprouting. Instead, inhibiting integrins α1β1 and α5β1 curtails both galectin-8- and VEGF-C-mediated LEC sprouting. Together, this study uncovers a unique molecular mechanism of lymphangiogenesis in which galectin-8-dependent crosstalk among VEGF-C, podoplanin and integrin pathways plays a key role.
A prolific catalyst for dehydrogenation of neat formic acid
Authors: Celaje Jeff Joseph A. , Lu Zhiyao , Kedzie Elyse A. , Terrile Nicholas J. , Lo Jonathan N. , Williams Travis J.
Published: April 2016

Formic acid is a promising energy carrier for on-demand hydrogen generation. Because the reverse reaction is also feasible, formic acid is a form of stored hydrogen. Here we present a robust, reusable iridium catalyst that enables hydrogen gas release from neat formic acid. This catalysis works under mild conditions in the presence of air, is highly selective and affords millions of turnovers. While many catalysts exist for both formic acid dehydrogenation and carbon dioxide reduction, solutions to date on hydrogen gas release rely on volatile components that reduce the weight content of stored hydrogen and/or introduce fuel cell poisons. These are avoided here. The catalyst utilizes an interesting chemical mechanism, which is described on the basis of kinetic and synthetic experiments.
Direct Copolymerization of CO2 and Diols
Authors: Tamura Masazumi , Ito Kazuki , Honda Masayoshi , Nakagawa Yoshinao , Sugimoto Hiroshi , Tomishige Keiichi
Published: April 2016

Direct polymerization of CO2 and diols is promising as a simple and environmental-benign method in place of conventional processes using high-cost and/or hazardous reagents such as phosgene, carbon monoxide and epoxides, however, there are no reports on the direct method due to the inertness of CO2 and severe equilibrium limitation of the reaction. Herein, we firstly substantiate the direct copolymerization of CO2 and diols using CeO2 catalyst and 2-cyanopyridine promotor, providing the alternating cooligomers in high diol-based yield (up to 99%) and selectivity (up to >99%). This catalyst system is applicable to various diols including linear C4-C10 α,ω-diols to provide high yields of the corresponding cooligomers, which cannot be obtained by well-known methods such as copolymerization of CO2 and cyclic ethers and ring-opening polymerization of cyclic carbonates. This process provides us a facile synthesis method for versatile polycarbonates from various diols and CO2 owing to simplicity of diols modification.
ClusterViSu, a method for clustering of protein complexes by Voronoi tessellation in super-resolution microscopy
Authors: Andronov Leonid , Orlov Igor , Lutz Yves , Vonesch Jean-Luc , Klaholz Bruno P.
Published: April 2016

Super-resolution microscopy (PALM, STORM etc.) provides a plethora of fluorescent signals in dense cellular environments which can be difficult to interpret. Here we describe ClusterViSu, a method for image reconstruction, visualization and quantification of labelled protein clusters, based on Voronoi tessellation of the individual fluorescence events. The general applicability of this clustering approach for the segmentation of super-resolution microscopy data, including for co-localization, is illustrated on a series of important biological objects such as chromatin complexes, RNA polymerase, nuclear pore complexes and microtubules.
Directed dynamical influence is more detectable with noise
Authors: Jiang Jun-Jie , Huang Zi-Gang , Huang Liang , Liu Huan , Lai Ying-Cheng
Published: April 2016

Successful identification of directed dynamical influence in complex systems is relevant to significant problems of current interest. Traditional methods based on Granger causality and transfer entropy have issues such as difficulty with nonlinearity and large data requirement. Recently a framework based on nonlinear dynamical analysis was proposed to overcome these difficulties. We find, surprisingly, that noise can counterintuitively enhance the detectability of directed dynamical influence. In fact, intentionally injecting a proper amount of asymmetric noise into the available time series has the unexpected benefit of dramatically increasing confidence in ascertaining the directed dynamical influence in the underlying system. This result is established based on both real data and model time series from nonlinear ecosystems. We develop a physical understanding of the beneficial role of noise in enhancing detection of directed dynamical influence.
The BET inhibitor OTX015 reactivates latent HIV-1 through P-TEFb
Authors: Lu Panpan , Qu Xiying , Shen Yinzhong , Jiang Zhengtao , Wang Pengfei , Zeng Hanxian , Ji Haiyan , Deng Junxiao , Yang Xinyi , Li Xian , Lu Hongzhou , Zhu Huanzhang
Published: April 2016

None of the currently used anti-HIV-1 agents can effectively eliminate latent HIV-1 reservoirs, which is a major hurdle to a complete cure for AIDS. We report here that a novel oral BET inhibitor OTX015, a thienotriazolodiazepine compound that has entered phase Ib clinical development for advanced hematologic malignancies, can effectively reactivate HIV-1 in different latency models with an EC50 value 1.95–4.34 times lower than JQ1, a known BET inhibitor that can reactivate HIV-1 latency. We also found that OTX015 was more potent when used in combination with prostratin. More importantly, OTX015 treatment induced HIV-1 full-length transcripts and viral outgrowth in resting CD4+ T cells from infected individuals receiving suppressive antiretroviral therapy (ART), while exerting minimal toxicity and effects on T cell activation. Finally, biochemical analysis showed that OTX015-mediated activation of HIV-1 involved an increase in CDK9 occupancy and RNAP II C-terminal domain (CTD) phosphorylation. Our results suggest that the BET inhibitor OTX015 may be a candidate for anti-HIV-1-latency therapies.
Genome-wide CRISPR screen reveals novel host factors required for Staphylococcus aureus α-hemolysin-mediated toxicity
Authors: Virreira Winter Sebastian , Zychlinsky Arturo , Bardoel Bart W.
Published: April 2016

Staphylococcus aureus causes a wide variety of infections and antibiotic resistant strains are a major problem in hospitals. One of the best studied virulence factors of S. aureus is the pore-forming toxin alpha hemolysin (αHL) whose mechanism of action is incompletely understood. We performed a genome-wide loss-of-function screen using CRISPR/Cas9 technology to identify host targets required for αHL susceptibility in human myeloid cells. We found gRNAs for ten genes enriched after intoxication with αHL and focused on the top five hits. Besides a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), the host receptor for αHL, we identified three proteins, Sys1 golgi trafficking protein (SYS1), ADP-ribosylation factor 1 (ARFRP1), and tetraspanin-14 (TSPAN14) which regulate the presentation of ADAM10 on the plasma membrane post-translationally. Interestingly, we also showed that cells lacking sphingomyelin synthase 1 (SGMS1) resist αHL intoxication, but have only a slightly reduced ADAM10 surface expression. SGMS1 regulates lipid raft formation, suggesting that αHL requires these membrane microdomains for attachment and cytotoxicity.
CALHM1 deficiency impairs cerebral neuron activity and memory flexibility in mice
Authors: Vingtdeux Valérie , Chang Eric H. , Frattini Stephen A. , Zhao Haitian , Chandakkar Pallavi , Adrien Leslie , Strohl Joshua J. , Gibson Elizabeth L. , Ohmoto Makoto , Matsumoto Ichiro , Huerta Patricio T. , Marambaud Philippe
Published: April 2016

CALHM1 is a cell surface calcium channel expressed in cerebral neurons. CALHM1 function in the brain remains unknown, but recent results showed that neuronal CALHM1 controls intracellular calcium signaling and cell excitability, two mechanisms required for synaptic function. Here, we describe the generation of Calhm1 knockout (Calhm1−/−) mice and investigate CALHM1 role in neuronal and cognitive functions. Structural analysis revealed that Calhm1−/− brains had normal regional and cellular architecture, and showed no evidence of neuronal or synaptic loss, indicating that CALHM1 deficiency does not affect brain development or brain integrity in adulthood. However, Calhm1−/− mice showed a severe impairment in memory flexibility, assessed in the Morris water maze, and a significant disruption of long-term potentiation without alteration of long-term depression, measured in ex vivo hippocampal slices. Importantly, in primary neurons and hippocampal slices, CALHM1 activation facilitated the phosphorylation of NMDA and AMPA receptors by protein kinase A. Furthermore, neuronal CALHM1 activation potentiated the effect of glutamate on the expression of c-Fos and C/EBPβ, two immediate-early gene markers of neuronal activity. Thus, CALHM1 controls synaptic activity in cerebral neurons and is required for the flexible processing of memory in mice. These results shed light on CALHM1 physiology in the mammalian brain.
Beyond eruptive scenarios: assessing tephra fallout hazard from Neapolitan volcanoes
Authors: Sandri Laura , Costa Antonio , Selva Jacopo , Tonini Roberto , Macedonio Giovanni , Folch Arnau , Sulpizio Roberto
Published: April 2016

Assessment of volcanic hazards is necessary for risk mitigation. Typically, hazard assessment is based on one or a few, subjectively chosen representative eruptive scenarios, which use a specific combination of eruptive sizes and intensities to represent a particular size class of eruption. While such eruptive scenarios use a range of representative members to capture a range of eruptive sizes and intensities in order to reflect a wider size class, a scenario approach neglects to account for the intrinsic variability of volcanic eruptions, and implicitly assumes that inter-class size variability (i.e. size difference between different eruptive size classes) dominates over intra-class size variability (i.e. size difference within an eruptive size class), the latter of which is treated as negligible. So far, no quantitative study has been undertaken to verify such an assumption. Here, we adopt a novel Probabilistic Volcanic Hazard Analysis (PVHA) strategy, which accounts for intrinsic eruptive variabilities, to quantify the tephra fallout hazard in the Campania area. We compare the results of the new probabilistic approach with the classical scenario approach. The results allow for determining whether a simplified scenario approach can be considered valid, and for quantifying the bias which arises when full variability is not accounted for.
Visualizing Current-Dependent Morphology and Distribution of Discharge Products in Sodium-Oxygen Battery Cathodes
Authors: Schröder Daniel , Bender Conrad L. , Osenberg Markus , Hilger André , Manke Ingo , Janek Jürgen
Published: April 2016

Synchrotron X-ray tomography and scanning electron microscopy were applied to elucidate the spatial distribution of discharge product (NaO2) in the carbon cathode of sodium-oxygen batteries. Various batteries were discharged galvanostatically and their cathodes were analyzed. We observe a particle density gradient along the cathode that scales with the current density applied. Besides, we show that the particle size and shape of discharge product strongly depend on current density and on whether the particles are deposited close to the oxygen reservoir or near the separator. We correlate our findings to transport limitations for the supplied oxygen and gain crucial information for optimal operation of sodium-oxygen batteries. Our findings imply that for low current densities pore clogging might occur and that for elevated current densities small high surface area particles with limited electric conductivity form; both phenomena can decrease the available discharge and charge capacity significantly.
Flotation Immunoassay: Masking the Signal from Free Reporters in Sandwich Immunoassays
Authors: Chen Hui , Hagström Anna E. V. , Kim Jinsu , Garvey Gavin , Paterson Andrew , Ruiz-Ruiz Federico , Raja Balakrishnan , Strych Ulrich , Rito-Palomares Marco , Kourentzi Katerina , Conrad Jacinta C. , Atmar Robert L. , Willson Richard C.
Published: April 2016

In this work, we demonstrate that signal-masking reagents together with appropriate capture antibody carriers can eliminate the washing steps in sandwich immunoassays. A flotation immunoassay (FI) platform was developed with horseradish peroxidase chemiluminescence as the reporter system, the dye Brilliant Blue FCF as the signal-masking reagent and buoyant silica micro-bubbles as the capture antibody carriers. Only reporters captured on micro-bubbles float above the dye and become visible in an analyte-dependent manner. These FIs are capable of detecting proteins down to attomole levels and as few as 106 virus particles. This signal-masking strategy represents a novel approach to simple, sensitive and quantitative immunoassays in both laboratory and point-of-care settings.
Bioorthogonal two-component drug delivery in HER2(+) breast cancer mouse models
Authors: Hapuarachchige Sudath , Kato Yoshinori , Artemov Dmitri
Published: April 2016

The HER2 receptor is overexpressed in approximately 20% of breast cancers and is associated with tumorigenesis, metastasis and a poor prognosis. Trastuzumab is a first-line targeted drug used against HER2(+) breast cancers; however, at least 50% of HER2(+) tumors develop resistance to trastuzumab. To treat these patients, trastuzumab-based antibody-drug conjugates (ACDs) have been developed and are currently used in the clinic. Despite their high efficacy, the long circulation half-life and non-specific binding of cytotoxic ADCs can result in systemic toxicity. In addition, standard ADCs do not provide an image-guided mode of administration. Here, we have developed a two-component, two-step, pre-targeting drug delivery system integrated with image guidance to circumvent these issues. In this strategy, HER2 receptors are pre-labeled with a functionalized trastuzumab antibody followed by the delivery of drug-loaded nanocarriers. Both components are cross-linked by multiple bioorthogonal click reactions in situ on the surface of the target cell and internalized as nanoclusters. We have explored the efficacy of this delivery strategy in HER2(+) human breast cancer models. Our therapeutic study confirms the high therapeutic efficacy of the new delivery system, with no significant toxicity.
On oscillatory microstructure during cellular growth of directionally solidified Sn–36at.%Ni peritectic alloy
Authors: Peng Peng , Li Xinzhong , Li Jiangong , Su Yanqing , Guo Jingjie
Published: April 2016

An oscillatory microstructure has been observed during deep-cellular growth of directionally solidified Sn–36at.%Ni hyperperitectic alloy containing intermetallic compounds with narrow solubility range. This oscillatory microstructure with a dimension of tens of micrometers has been observed for the first time. The morphology of this wave-like oscillatory structure is similar to secondary dendrite arms and can be observed only in some local positions of the sample. Through analysis such as successive sectioning of the sample, it can be concluded that this oscillatory microstructure is caused by oscillatory convection of the mushy zone during solidification. And the influence of convection on this oscillatory microstructure was characterized through comparison between experimental and calculations results on the wavelength. Besides, the change in morphology of this oscillatory microstructure has been proved to be caused by peritectic transformation during solidification. Furthermore, the melt concentration increases continuously during solidification of intermetallic compounds with narrow solubility range, which helps formation of this oscillatory microstructure.
Aflatoxin B1 contamination in maize in Europe increases due to climate change
Authors: Battilani P. , Toscano P. , Van der Fels-Klerx H. J. , Moretti A. , Camardo Leggieri M. , Brera C. , Rortais A. , Goumperis T. , Robinson T.
Published: April 2016

Climate change has been reported as a driver for emerging food and feed safety issues worldwide and its expected impact on the presence of mycotoxins in food and feed is of great concern. Aflatoxins have the highest acute and chronic toxicity of all mycotoxins; hence, the maximal concentration in agricultural food and feed products and their commodities is regulated worldwide. The possible change in patterns of aflatoxin occurrence in crops due to climate change is a matter of concern that may require anticipatory actions. The aim of this study was to predict aflatoxin contamination in maize and wheat crops, within the next 100 years, under a +2 °C and +5 °C climate change scenario, applying a modelling approach. Europe was virtually covered by a net, 50 × 50 km grids, identifying 2254 meshes with a central point each. Climate data were generated for each point, linked to predictive models and predictions were run consequently. Aflatoxin B1is predicted to become a food safety issue in maize in Europe, especially in the +2 °C scenario, the most probable scenario of climate change expected for the next years. These results represent a supporting tool to reinforce aflatoxin management and to prevent human and animal exposure.
A study on the evaluation method and recent clinical efficacy of bevacizumab on the treatment of radiation cerebral necrosis
Authors: Zhuang Hongqing , Yuan Xiangkun , Zheng Yi , Li Xubin , Chang Joe Y. , Wang Junjie , Wang Xiaoguang , Yuan Zhiyong , Wang Ping
Published: April 2016

In order to investigate the efficacy of bevacizumab on the treatment of radiation cerebral necrosis, patients who were diagnosed with radiation cerebral necrosis by imaging after stereotactic radiotherapy were collected. Bevacizumab was applied at a dose of 5 mg/kg once every three weeks at least three times. The changes in cerebral necrosis symptoms before and after treatment, the cerebral edema volume, the cerebral necrosis volume, and the changes in magnetic resonance imaging (MRI) strengthening phase signals of cerebral necrosis were used as the first observation point. The side effects of bevacizumab were used as the second observation point. Total of 14 radiation cerebral necrosis patients were treated with bevacizumab between June 2011 and February 2013 were collected. There were 12 symptomatic patients, of whom 10 patients (83.3%) had reduced symptoms. The edema index grades of nine patients (64.29%) improved. The cerebral necrosis volumes of 13 patients (92.86%) decreased. The T1 phase signal strengths of the intracranial enhanced MRIs of 12 patients (85.71%) significantly decreased. The clinical side effects of bevacizumab were mild. In conclusion, Preliminary results showed that treatment of radiation cerebral necrosis using bevacizumab was safe and effective. This treatment measure is worthy of further study.
Qishen Yiqi Drop Pill improves cardiac function after myocardial ischemia
Authors: JianXin Chen , Xue Xu , ZhongFeng Li , Kuo Gao , FeiLong Zhang , ZhiHong Li , Xian Wang , HongCai Shang
Published: April 2016

Myocardial ischemia (MI) is one of the leading causes of death, while Qishen Yiqi Drop Pill (QYDP) is a representative traditional Chinese medicine to treat this disease. Unveiling the pharmacological mechanism of QYDP will provide a great opportunity to promote the development of novel drugs to treat MI. 64 male Sprague-Dawley (SD) rats were divided into four groups: MI model group, sham operation group, QYDP treatment group and Fosinopril treatment group. Echocardiography results showed that QYDP exhibited significantly larger LV end-diastolic dimension (LVEDd) and LV end-systolic dimension (LVEDs), compared with the MI model group, indicating the improved cardiac function by QYDP. 1H-NMR based metabonomics further identify 9 significantly changed metabolites in the QYDP treatment group and the QYDP-related proteins based on the protein-metabolite interaction networks and the corresponding pathways were explored, involving the pyruvate metabolism pathway, the retinol metabolism pathway, the tyrosine metabolism pathway and the purine metabolism pathway, suggesting that QYDP was closely associated with blood circulation. ELISA tests were further employed to identify NO synthase (iNOS) and cathepsin K (CTSK) in the networks. For the first time, our work combined experimental and computational methods to study the mechanism of the formula of traditional Chinese medicine.
Facile Synthesis of Cadmium-Free Zn-In-S:Ag/ZnS Nanocrystals for Bio-Imaging
Authors: Xuan Tong-Tong , Liu Jia-Qing , Yu Cai-Yan , Xie Rong-Jun , Li Hui-Li
Published: April 2016

High quality cadmium-free Zn-In-S:Ag doped-nanocrystals (d-NCs) were synthesized via a simple one-step noninjection route using silver nitrate, indium acetate, zinc acetate, oleylamine, S powder and 1-dodecanethiol as starting materials in an organic phase. The size and optical properties can be effectively tailored by controlling the reaction time, reaction temperature, Ag+ dopant concentration and the molar ratio of In to Zn. The photoluminescence wavelength of as-prepared Zn-In-S:Ag NCs covered a broad visible range from 458 nm to 603 nm. After being passivated by protective ZnS shell, the photoluminescence quantum yield (PLQY) of Zn-In-S:Ag+ /ZnS was greatly improved to 43.5%. More importantly, the initial high PLQY of the obtained core/shell d-NCs in organic media can be preserved when being transferred into the aqueous media via ligand exchange. Finally, high quality Zn-In-S:Ag+ /ZnS d-NCs in aqueous phase were applied as bio-imaging agents for identifying living KB cells.
Differentiating T2 hyperintensity in neonatal white matter by two-compartment model of diffusional kurtosis imaging
Authors: Gao Jie , Li Xianjun , Li Yanyan , Zeng Lingxia , Jin Chao , Sun Qinli , Xu Duan , Yu Bolang , Yang Jian
Published: April 2016

In conventional neonatal MRI, the T2 hyperintensity (T2h) in cerebral white matter (WM) at term-equivalent age due to immaturity or impairment is still difficult to identify. To clarify such issue, this study used the metrics derived from a two-compartment WM model of diffusional kurtosis imaging (WM-DKI), including intra-axonal, extra-axonal axial and radial diffusivities (Da, De,// and De,⊥), to compare WM differences between the simple T2h and normal control for both preterm and full-term neonates, and between simple T2h and complex T2h with hypoxic-ischemic encephalopathy (HIE). Results indicated that compared with control, the simple T2h showed significantly increased De,// and De,⊥, but no significant change in Da in multiple premyelination regions, indicative of expanding extra-axonal diffusion microenvironment; while myelinated regions showed no changes. However, compared with simple T2h, the complex T2h with HIE had decreased Da, increased De,⊥ in both premyelination and myelinated regions, indicative of both intra- and extra-axonal diffusion alterations. While diffusion tensor imaging (DTI) failed to distinguish simple T2h from complex T2h with HIE. In conclusion, superior to DTI-metrics, WM-DKI metrics showed more specificity for WM microstructural changes to distinguish simple T2h from complex T2h with HIE.
Label-free detection of DNA single-base mismatches using a simple reflectance-based optical technique
Authors: Nava G. , Ceccarello E. , Giavazzi F. , Salina M. , Damin F. , Chiari M. , Buscaglia M. , Bellini T. , Zanchetta G.
Published: April 2016

Reflective Phantom Interface, a novel label-free optical technique, allows to detect and quantify the hybridization of DNA oligomers at a surface, easily discriminating single sequence mismatches.
A prebiotic mixture improved Lactobacillus acidophilus and Bifidobacterium animalis gastrointestinal in vitro resistance in petit-suisse
Authors: Padilha Marina , Villarreal Morales Martha Lissete , Vieira Antonio Diogo Silva , Costa Mayra Garcia Maia , Saad Susana Marta Isay
Published: April 2016

Advantageous addition of a prebiotic mixture in petit-suisse cheese, improved the probiotic strains survival under gastrointestinal conditions simulated in vitro throughout 28 days of storage.
Redox-active tetraruthenium metallacycles: reversible release of up to eight electrons resulting in strong electrochromism
Authors: Fink Daniel , Weibert Bernhard , Winter Rainer F.
Published: April 2016

Tetraruthenium macrocycles with 1,4-divinylphenylene and diarylamine-substituted isophthalic acids as the sides display up to eight one-electron redox steps and rich electrochromic behaviour with strong absorptions of the dications in the near infrared and of the tetra- and hexacations at low energies in the visible.
Site-selective chemical cleavage of peptide bonds
Authors: Elashal Hader E. , Raj Monika
Published: April 2016

The methodology selectively modifies serine residues in a peptide chain and cleaves the peptide chain at the site of modification under neutral aqueous buffer conditions. This method exhibits broad substrate scope (24 examples) including peptides with mutations and posttranslational modifications.
Expanding the phosphorus–carbon analogy: formation of an unprecedented 5-phosphasemibullvalene derivative
Authors: Rigo Massimo , Weber Manuela , Müller Christian
Published: April 2016

The selective and quantitative photochemical di-π-methane rearrangement of a phosphabarrelene allows access to the first 5-phosphasemibullvalene derivative.
The chemistry of parent phosphiranide in the coordination sphere of tungsten
Authors: Hao Yanwei , Zhang Chunli , Mei Yanbo , Tian Rongqiang , Duan Zheng , Mathey François
Published: April 2016

The chemistry of the complexed parent phosphiranide is described.
A human exposome framework for guiding risk management and holistic assessment of recycled water quality
Authors: Garner Emily , Zhu Ni , Strom Laurel , Edwards Marc , Pruden Amy
Published: April 2016

In this critical review, we propose that the “human exposome” concept provides guiding principles for water reuse risk management strategies.
Effects of five membered aromatic heterocycles at the meso-position on the electronic properties of 3-pyrrolyl BODIPY
Authors: Sharma Ritambhara , Lakshmi Vellanki , Chatterjee Tamal , Ravikanth Mangalampalli
Published: April 2016

The synthesis, structures and properties of 3-pyrrolyl BODIPYs containing five membered aromatic heterocycles such as pyrrole, thiophene and furan at the meso-position are described.
High thermal stability and high tensile strength terpolyester nanofibers containing biobased monomer: fabrication and characterization
Authors: Lee Hoik , Koo Jun Mo , Sohn Daewon , Kim Ick-Soo , Im Seung Soon
Published: April 2016

Novel nanofibers of a highly heat-resistive biobased terpolyester of isosorbide (ISB), ethylene glycol, 1,4-cyclohexane dimethanol and terephthalic acid (PEICT) were fabricated using electrospinning and their properties were characterized.
Phosphorescent oxygen-sensing and singlet oxygen production by a biosynthetic silk
Authors: Horgan Conor C. , Han Yong-Shen , Trueman Holly , Jackson Colin J. , Sutherland Tara D. , Rapson Trevor D.
Published: April 2016

A recombinant coiled-coil silk was utilised to immobilise heavy-metal-macrocycles which are known to undergo efficient intersystem crossing from the singlet state to the triplet state following excitation with visible light.
Ultra low water adhesive metal surface for enhanced corrosion protection
Authors: Wang Gang , Zeng Zhixiang , Chen Junjun , Xu Mengya , Zhu Jingfang , Liu Shuan , Ren Tianhui , Xue Qunji
Published: April 2016

A superhydrophobic surface with ultra low water adhesive force is fabricated on various metals for enhanced corrosion protection.
Recent advances in the synthesis of benzimidazol(on)es via rearrangements of quinoxalin(on)es
Authors: Mamedov Vakhid A.
Published: April 2016

The review describes all the quinoxaline-benzimidazole rearrangements as a whole and the new quinoxalinone-benzimidazol(on)e rearrangements in particular when exposed to nucleophilic rearrangements which can be used for the synthesis of various biheterocyclic motifs.
Synergistic inhibitory effects of naproxen in combination with magnolol on TPA-induced skin inflammation in mice
Authors: Yue Yuan , Liu Wenfeng , Zhou Wei , Chen Min , Huang Boxin , Zhang Lanyue , Wang Zhenshi , He Yan , Zhang Kun , Zheng Xi , Du Zhiyun
Published: April 2016

A combination of naproxen and magnolol effectively inhibited TPA-induced skin inflammationviablocking PI3K/Akt and PI3K/PKC signaling pathways.
The effect of growing time and Mn concentration on the defect structure of ZnO nanocrystals: X-ray diffraction, infrared and EPR spectroscopy
Authors: Yildirimcan Saadet , Ocakoglu Kasim , Erat Selma , Emen Fatih M. , Repp Sergej , Erdem Emre
Published: April 2016

ZnO nanomaterials was synthesized via a hydrothermal route and characterized with several methods such as XRD, TG/DTA, FT-IR, FE-SEM, TEM and EPR in order to investigate the effect of growing time and Mn doping on the defects which occurred.