bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequence-Specific Modifications Enhance the Broad-Spectrum Antiviral Response Activated by RIG-I Agonists
Authors: Chiang Cindy , Beljanski Vladimir , Yin Kevin , Olagnier David , Ben Yebdri Fethia , Steel Courtney , Goulet Marie-Line , DeFilippis Victor R. , Streblow Daniel N. , Haddad Elias K. , Trautmann Lydie , Ross Ted , Lin Rongtuan , Hiscott John 
Published: May 2015

ABSTRACT

The cytosolic RIG-I (retinoic acid-inducible gene I) receptor plays a pivotal role in the initiation of the immune response against RNA virus infection by recognizing short 5′-triphosphate (5′ppp)-containing viral RNA and activating the host antiviral innate response. In the present study, we generated novel 5′ppp RIG-I agonists of varieous lengths, structures, and sequences and evaluated the generation of the antiviral and inflammatory responses in human epithelial A549 cells, human innate immune primary cells, and murine models of influenza and chikungunya viral pathogenesis. A 99-nucleotide, uridine-rich hairpin 5′pppRNA termed M8 stimulated an extensive and robust interferon response compared to other modified 5′pppRNA structures, RIG-I aptamers, or poly(I·C). Interestingly, manipulation of the primary RNA sequence alone was sufficient to modulate antiviral activity and inflammatory response, in a manner dependent exclusively on RIG-I and independent of MDA5 and TLR3. Both prophylactic and therapeutic administration of M8 effectively inhibited influenza virus and dengue virus replication
in vitro
. Furthermore, multiple strains of influenza virus that were resistant to oseltamivir, an FDA-approved therapeutic treatment for influenza, were highly sensitive to inhibition by M8. Finally, prophylactic M8 treatment
in vivo
prolonged survival and reduced lung viral titers of mice challenged with influenza virus, as well as reducing chikungunya virus-associated foot swelling and viral load. Altogether, these results demonstrate that 5′pppRNA can be rationally designed to achieve a maximal RIG-I-mediated protective antiviral response against human-pathogenic RNA viruses.

IMPORTANCE
The development of novel therapeutics to treat human-pathogenic RNA viral infections is an important goal to reduce spread of infection and to improve human health and safety. This study investigated the design of an RNA agonist with enhanced antiviral and inflammatory properties against influenza, dengue, and chikungunya viruses. A novel, sequence-dependent, uridine-rich RIG-I agonist generated a protective antiviral response
in vitro
and
in vivo
and was effective at concentrations 100-fold lower than prototype sequences or other RNA agonists, highlighting the robust activity and potential clinical use of the 5′pppRNA against RNA virus infection. Altogether, the results identify a novel, sequence-specific RIG-I agonist as an attractive therapeutic candidate for the treatment of a broad range of RNA viruses, a pressing issue in which a need for new and more effective options persists.
Global Diversity within and between Human Herpesvirus 1 and 2 Glycoproteins
Authors: Lamers Susanna L. , Newman Ruchi M. , Laeyendecker Oliver , Tobian Aaron A. R. , Colgrove Robert C. , Ray Stuart C. , Koelle David M. , Cohen Jeffrey , Knipe David M. , Quinn Thomas C. 
Published: May 2015

ABSTRACT
Human herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) are large-genome DNA viruses that establish a persistent infection in sensory neurons and commonly manifest with recurring oral or genital erosions that transmit virus. HSV encodes 12 predicted glycoproteins that serve various functions, including cellular attachment, entry, and egress. Glycoprotein G is currently the target of an antibody test to differentiate HSV-1 from HSV-2; however, this test has shown reduced capacity to differentiate HSV strains in East Africa. Until the recent availability of 26 full-length HSV-1 and 36 full-length HSV-2 sequences, minimal comparative information was available for these viruses. In this study, we use a variety of sequence analysis methods to compare all available sequence data for HSV-1 and HSV-2 glycoproteins, using viruses isolated in Europe, Asia, North America, the Republic of South Africa, and East Africa. We found numerous differences in diversity, nonsynonymous/synonymous substitution rates, and recombination rates between HSV-1 glycoproteins and their HSV-2 counterparts. Phylogenetic analysis revealed that while most global HSV-2 glycoprotein G sequences did not form clusters within or between continents, one clade (supported at 60.5%) contained 37% of the African sequences analyzed. Accordingly, sequences from this African subset contained unique amino acid signatures, not only in glycoprotein G, but also in glycoproteins I and E, which may account for the failure of sensitive antibody tests to distinguish HSV-1 from HSV-2 in some African individuals. Consensus sequences generated in the study can be used to improve diagnostic assays that differentiate HSV-1 from HSV-2 in global populations.

IMPORTANCE
Human herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) are large DNA viruses associated with recurring oral or genital erosions that transmit virus. Up to 12 HSV-1 and HSV-2 glycoproteins are involved in HSV cell entry or are required for viral spread in animals, albeit some are dispensable for replication
in vitro
. The recent availability of comparable numbers of full-length HSV-1 and HSV-2 sequences enabled comparative analysis of gene diversity of glycoproteins within and between HSV types. Overall, we found less glycoprotein sequence diversity within HSV-2 than within the HSV-1 strains studied, while at the same time, several HSV-2 glycoproteins were evolving under less selective pressure. Because HSV glycoproteins are the focus of antibody tests to detect and differentiate between infections with the two strains and are constituents of vaccines in clinical-stage development, these findings will aid in refining the targets for diagnostic tests and vaccines.
Innovations in Undergraduate Science Education: Going Viral
Authors: Hatfull Graham F. 
Published: May 2015

ABSTRACT
Bacteriophage discovery and genomics provides a powerful and effective platform for integrating missions in research and education. Implementation of the Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) program facilitates a broad impact by including a diverse array of schools, faculty, and students. The program generates new insights into the diversity and evolution of the bacteriophage population and presents a model for introducing first-year undergraduate students to discovery-based research experiences.
Shedding of TNF receptor 2 by effector CD8+ T cells by ADAM17 is important for regulating TNF-α availability during influenza infection
Authors: DeBerge Matthew P , Ely Kenneth H , Wright Peter F , Thorp Edward B , Enelow Richard I 
Published: May 2015

Abstract
Elevated levels of solTNFR2 are observed in a variety of human pathophysiological conditions but regulation of TNFR2 levels during disease is not well understood. We found that solTNFR2 levels were increased following influenza infection or live-attenuated influenza virus challenge in mice and humans, respectively. As influenza-specific CD8+ T cells up-regulated expression of TNFR2 after infection in mice, we hypothesized that CD8+ T cells contributed, in part, to solTNFR2 production after influenza infection and were interested in the mechanisms by which CD8+ T cells regulate TNFR2 shedding. Activation of these cells by TCR stimulation resulted in enhanced shedding of TNFR2 that required actin remodeling and lipid raft formation and was dependent on MAPK/ERK signaling. Furthermore, we identified ADAM17 as the protease responsible for TNFR2 shedding by CD8+ T cells, with ADAM17 and TNFR2 required in “cis” for shedding to occur. We observed similar activation thresholds for TNF-α expression and TNFR2 shedding, suggesting that solTNFR2 functioned, in part, to regulate solTNF-α levels. Production of solTNFR2 by activated CD8+ T cells reduced the availability of solTNF-α released by these cells, and TNFR2 blockade during influenza infection in mice enhanced the levels of solTNF-α, supporting this hypothesis. Taken together, this study identifies critical cellular mechanisms regulating TNFR2 shedding on CD8+ T cells and demonstrates that TNFR2 contributes, in part, to the regulation of TNF-α levels during infection.
The measure of disability: Towards an inclusive method for the evaluation of systems of visual communications and infographics
Authors: Bitterman Alex 
Published: May 2015

Abstract
Data, both qualitative and quantitative, which represents the physical, cognitive and situational abilities of the global population are inconsistent and are not centrally collected by any one international source. Moreover, the definition of ‘disability’ is relative and is linked uniquely to culture. This fluidity makes difficult the standardization of a definitive definition of disability, problematic to quantify and the goal of universal design elusive. Some statistical estimates place the number of disabled persons between 20 and 60 per cent of the world population, the normalization and aggregation of disability statistics remains a low priority for most international governing bodies and this gap in knowledge impacts the ability of designers to adequately consider the needs and abilities of all users when designing places, spaces, products, services and systems. This research note puts forth one potential testing model for systems of visual communication and information-based graphics and graphic systems for a universal design identity system as well as a discussion of the results from the first use of this testing model.
1H and 13C NMR and Electrical Conductivity Studies on New Ionic Plastic Crystals of Tetraalkylammonium Tetraethylborate
Authors: Hirakawa Satoru , Honda Hisashi 
Published: May 2015

Abstract
Eight plastic crystals of the types NEt
x
Me(4 − x)BEt4 and NEt
y
Pr(4 − y)BEt4 (x=0–4, y=1–3) were found in a new region of ionic plastic crystals. In this area, globular cations and anions are assembled by weak interactions. Based on the results of solid-state 1H and 13C nuclear magnetic resonance (NMR) measurements, it was revealed that the ions performed isotropic reorientations in the NEt
x
Me(4–x)BEt4 crystals (x=0–4). Additionally, X-ray diffraction (XRD) of these compounds was able to identify the CsCl-type cubic structure. In contrast, the XRD reflections of NEt
y
Pr(4−y)BEt4 (y=1–3) could be successfully fitted by distorted cubic lattices (trigonal symmetry). The NMR line shapes observed in these compounds were explained by overall molecular motions with large amplitudes (pseudo-isotropic reorientations). Differential scanning calorimetry (DSC) spectra of NEt
y
Pr(4 − y)BEt4 (y=1–3) showed a low entropy change (ΔS
mp) of 6–8 J K−1 mol−1 at the melting point. Ionic diffusion was identified by electrical conductivity measurements of NEt
x
Me(4 − x)BEt4 and NEt
y
Pr(4–y)BEt4 (x=0–4, y=1–3). In the case of NPr4BEt4 crystals, ionic diffusion was also detected, although complex powder patterns and large ΔS
mp values were observed by XRD and DSC measurements, respectively.
Synthesis of some new mixed azines, Schiff and Mannich bases of pharmaceutical interest related to isatin
Authors: Afsah Elsayed M. , Elmorsy Saad S. , Abdelmageed Soha M. , Zaki Zaki E. 
Published: May 2015

Abstract
The mixed azines 3a–h and 4 were obtained by treating 3-hydrazonoindolin-2-one (2) with the appropriate aldehyde or dialdehyde. Treatment of 3b or 3c with formaldehyde or glutaric dialdehyde and the appropriate amine afforded the azine Mannich bases 5–7. The condensation of isatin or its N-Mannich base 8 with 1-aminopiperidine, 4-aminomorpholine and 1,4-diaminopiperazine gave 10a–d, 12 and 13. The Mannich bases 14 and 15 were obtained from 10a and 10b. Treatment of 2 with succinic, phthalic and quinolinic anhydride and pyromellitic dianhydride afforded compounds 16, 17a, 17b and 18, respectively. The synthesis of isatin Schiff bases incorporating a benzoylpiperidine, benzoylmorpholine and 1,4-dibezoylpiperazine moiety and their N-Mannich bases was investigated.
On the usefulness and limits of a geographic perspective in dialectology: Arabic and Berber examples
Authors: Taine-Cheikh Catherine 
Published: May 2015

Abstract
Spoken Arabic and Berber show great variety in their pronunciation, as evidenced by dialectology studies. Some researchers have attempted to illustrate this variety using maps of the data collected. In this article, my goal will be to commend their work, but also to highlight the difficulties which arise when a purely geographic perspective is adopted. The choice of discriminant in relation to the possible variation mechanisms will also be broached, as, for the languages under study, spatial dissemination only partially explains the linguistic differences and similarities.
Restrictive relative clauses in the Sorbian languages
Authors: Bartels Hauke , Spiess Gunter 
Published: May 2015

Abstract
This paper is an attempt to provide an overview of the typologically relevant features of restrictive relative clauses with a nominal head in Lower and Upper Sorbian. Its main concern are (1) the semantic distinction characteristic not only of Sorbian, but also of most other Slavonic languages between relative clauses where the head of the clause and its relativized counterpart are coreferential and those which merely indicate that the referent of the head of the clause has the same properties, represents the same type as the referent of its relativized counterpart, (2) the various relativizers used to express this distinction and (3) the relativization strategies as well as the degree of accessibility to relativization involved in each case.
Ionothermal Synthesis of Lanthanide Tetrafluoride Nanoparticles Using Deep Eutectic Solvents
Authors: Furman Benjamin R. , Gutierrez Robert D. , Baker Charles K. 
Published: May 2015

ABSTRACTWe have developed a new method for controlling the size, crystallinity, and polydispersity of 100–2000 nm tetrafluoride phosphor particles. Five polyol-based deep eutectic solvents (DESs) were downselected out of a set of more than 130 candidates. We analyzed their benefits in synthesizing phosphor matrix particles of β-NaYF4, β-NaYbF4, and β-NaGdF4. We produced green (λmax = 540 nm) and blue/UV (λmax = 450 nm) upconverting phosphors in DES using Yb,Er and Yb,Tm codopants, respectively. The blue/UV phosphor reaction was scaled the up to 25 L, yielding nearly 400 g of high-quality, bright photoluminescent, β-phase product under mild conditions. We conclude that polyol-based DES systems offer a uniquely specialized and useful toolkit for phosphor synthesis.
Characterization of Extended Defects Observed in Cadmium Zinc Telluride (CZT) Crystal
Authors: Uba Samuel , Babalola Stephen , Hossain Anwar , James Ralph 
Published: May 2015

ABSTRACTCadmium Zinc Telluride (CZT) semiconductor crystal properties have been studied extensively with a focus on correlations to their radiation detector performance. The need for defect-free CZT crystal is imperative for optimal detector performance. Extended defects like Tellurium (Te) inclusions, twins, sub-grain boundaries, and dislocations are common defects found in CZT crystals; they alter the electrical properties and, therefore, the crystal's response to high energy radiation. In this research we studied the extended defects in CZT crystals from two separate ingots grown using the low-pressure Bridgman technique. We fabricated several detectors cut from wafers of two separate ingots by dicing, lapping, polishing, etching and applying gold metal contacts on the main surfaces of the crystals. Using infrared (IR) transmission microscope we analyzed the defects observed in the CZT detectors, showing three dimensional scans and plot size distributions of Te inclusions, twins and sub-grain boundaries observed in particular regions of the CZT detectors. We characterized electrical properties of the detectors by measuring bulk resistivity and detector response to gamma radiation. We observed that CZT detectors with more extended defects showed poor opto-electrical properties compared to detectors with fewer defects.
Ordering of InGaAs Quantum Dots Grown by Molecular Beam Epitaxy under As2 gas flux
Authors: Benamara Mourad , Mazur Yuriy I. , Lytvyn Peter , Ware Morgan E. , Dorogan Vitaliy , Hu Xian , de Souza Leonardo D. , Marega Euclydes , Theodores Marcio , Marques Gilmar , Salamo Greg 
Published: May 2015

ABSTRACTThe influence of the substrate temperature on the morphology and ordering of InGaAs quantum dots (QD), grown on GaAs (001) wafers by Molecular Beam Epitaxy (MBE) under As2 flux has been studied using Transmission Electron Microscopy (TEM), Atomic Force Microscopy (AFM) and Photoluminescence (PL) measurements. The experimental results show that lateral and vertical orderings occur for temperatures greater than 520°C and that QDs self-organize in a 6-fold symmetry network on (001) surface for T=555°C. Vertical orderings of asymmetric QDs, along directions a few degrees off [001], are observed on a large scale and their formation is discussed.
Colombia de Cara al nuevo regionalismo renovado: La Alianza del Pacífico
Authors: Duarte Herrera Lisbeth Katherine , González Parías Carlos Hernán , Montoya Uribe Diego Alejandro 
Published: May 2015

La Alianza del Pacífico se presenta como un mecanismo de integración regional novedoso, ajustado a ciertas particularidades históricas de la región y de los Estados fundadores. Pero también, como proceso de integración comparte características con ciertas formas del regionalismo, especialmente con el regionalismo abierto característico de los años 90 del siglo XX, por lo cual, la Alianza del pacifico se presenta como un nuevo regionalismo renovado, actualizado y autodenominado de integración profunda. La internacionalización económica por medio de inserción a nuevos mercados, es uno de los elementos que comparten los cuatro Estados fundadores: México, Colombia, Perú y Chile. En su conjunto estos países acaparan más de la mitad del comercio exterior latinoamericano. No obstante, analizando en detalle se observa que países como Perú y especialmente Colombia, se encuentran un poco rezagados en dicha materia con respecto a sus similares de México y Chile, incluso si se mira a otros países de la región. Los acuerdos comerciales y en especial la Alianza del Pacifico se presenta como una importante oportunidad en la estrategia colombiana de internacionalización económica, pero se debe superar el aun aislamiento y dependencia mono exportadora del país, con el fin de maximizar los beneficios potenciales que estos presentan, ya que se evidencia un importante rezago de Colombia en términos comerciales con respectos a los demás miembros de la alianza, especialmente frente a México y Chile.
NOMINAL KAŊ FORM IN BASSE MANDINKA – ITS COGNITIVE MAPPING AND TAXONOMICAL STATUS (PART 1)
Authors: Andrason Alexander 
Published: May 2015

Abstract
The present study, divided into a series of two papers, provides a detailed empirical description and cognitive-grammaticalization analysis of the meaning of a Mandinka verbal expression compounded of the non-verbal predicator be ‘be’, a verbal noun expressing a given action and the postposition kaŋ ‘on, at’ (so-called the Nominal KAŊ form). Method: The author follows the cognitive approach to verbal semantics which consists first of determining the exact range of contextually induced senses and next of unifying such values into a consistent map based upon certain diachronic universals or grammaticalization paths. Results: The synchronic inventory of senses of the Nominal KAŊ form (i.e. progressive, continuous, progressive-iterative, iterative, habitual and durative values) shows that this construction can be mapped using the imperfective path as a template of chaining. This mapping, hypothesized on the ground of synchronic semantic evidence and typological diachronic laws, is next corroborated by the structural properties of the Nominal KAŊ locution, especially by its locative and nominal character. Conclusion: All the evidence enables the author to semantically define the NomKAŊ form as a nonadvanced imperfective path. Part 1: In the first article of the series, the author deals with methodological issues and with an empirical study where he determines the precise extent of the semantic potential of the Nominal KAŊ form.
WORD ORDER AND CONSTITUENCY OF SERIAL VERB CONSTRUCTIONS
Authors: Yang Yongzhong 
Published: May 2015

Abstract
The goal of this paper is to provide a unified account of word order and constituency of serial verb constructions (SVCs) in the framework of generative grammar. It is argued that both SVO-type and SOV-type SVCs follow the Temporal Iconicity, which is associated with the asymmetric nature of syntactic structure, i.e. V1 or VP1 c-commands V2 or VP2 asymmetrically. Based on this argument, an analysis for the derivation of SVCs - Inter-VP Asymmetrical C-command Analysis - is proposed to account for the derivation of SVCs in various languages. It is argued that in the SVC there exists a null predicate and a null argument, the occurrence or non-occurrence of which gives rise to different types of SVCs. Furthermore, left peripheral deletion (LPD) triggers the movement of VP1’s Spec to [Spec IP] and the occurrence of VP2’s Spec as pro, as a result of which VP1 asymmetrically c-commands VP2. Object gapping triggers the ATB movement of VP2 to generate various types of SVCs. The differences between coordinative constructions, pivotal constructions and SVCs lie in their internal structure but not in the verb position.
Size‐exclusion chromatography‐based enrichment of extracellular vesicles from urine samples
Authors: Lozano‐Ramos Inés , Bancu Ioana , Oliveira‐Tercero Anna , Armengol María Pilar , Menezes‐Neto Armando , Portillo Hernando A. Del , Lauzurica‐Valdemoros Ricardo , Borràs Francesc E. 
Published: May 2015

Renal biopsy is the gold‐standard procedure to diagnose most of renal pathologies. However, this invasive method is of limited repeatability and often describes an irreversible renal damage. Urine is an easily accessible fluid and urinary extracellular vesicles (EVs) may be ideal to describe new biomarkers associated with renal pathologies. Several methods to enrich EVs have been described. Most of them contain a mixture of proteins, lipoproteins and cell debris that may be masking relevant biomarkers. Here, we evaluated size‐exclusion chromatography (SEC) as a suitable method to isolate urinary EVs. Following a conventional centrifugation to eliminate cell debris and apoptotic bodies, urine samples were concentrated using ultrafiltration and loaded on a SEC column. Collected fractions were analysed by protein content and flow cytometry to determine the presence of tetraspanin markers (CD63 and CD9). The highest tetraspanin content was routinely detected in fractions well before the bulk of proteins eluted. These tetraspanin‐peak fractions were analysed by cryo‐electron microscopy (cryo‐EM) and nanoparticle tracking analysis revealing the presence of EVs.When analysed by sodium dodecyl sulphate–polyacrylamide gel electrophoresis, tetraspanin‐peak fractions from urine concentrated samples contained multiple bands but the main urine proteins (such as Tamm–Horsfall protein) were absent. Furthermore, a preliminary proteomic study of these fractions revealed the presence of EV‐related proteins, suggesting their enrichment in concentrated samples. In addition, RNA profiling also showed the presence of vesicular small RNA species.To summarize, our results demonstrated that concentrated urine followed by SEC is a suitable option to isolate EVs with low presence of soluble contaminants. This methodology could permit more accurate analyses of EV‐related biomarkers when further characterized by ‐omics technologies compared with other approaches.