bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual transcriptome sequencing reveals resistance of TLR4 ligand-activated bone marrow-derived macrophages to inflammation mediated by the BET inhibitor JQ1
Authors: Das Amitabh , Chai Jin Choul , Yang Chul-su , Lee Young Seek , Das Nando Dulal , Jung Kyoung Hwa , Chai Young Gyu 
Published: November 2015

AbstractPersistent macrophage activation is associated with the expression of various pro-inflammatory genes, cytokines and chemokines, which may initiate or amplify inflammatory disorders. A novel synthetic BET inhibitor, JQ1, was proven to exert immunosuppressive activities in macrophages. However, a genome-wide search for JQ1 molecular targets has not been undertaken. The present study aimed at evaluating the anti-inflammatory function and underlying genes that are targeted by JQ1 in LPS-stimulated primary bone marrow-derived macrophages (BMDMs) using global transcriptomic RNA sequencing and quantitative real-time PCR. Among the annotated genes, transcriptional sequencing of BMDMs that were treated with JQ1 revealed a selective effect on LPS-induced gene expression in which the induction of cytokines/chemokines, interferon-stimulated genes and prominent (transcription factors) TFs was suppressed. Additionally, we found that JQ1 reduced the expression of previously unidentified genes that are important in inflammation. Importantly, these inflammatory genes were not affected by JQ1 treatment alone. Furthermore, we confirmed that JQ1 reduced cytokines/chemokines in the supernatants of LPS treated BMDMs. Moreover, the biological pathways and gene ontology of the differentially expressed genes were determined in the JQ1 treatment of BMDMs. These unprecedented results suggest that the BET inhibitor JQ1 is a candidate for the prevention or therapeutic treatment of inflammatory disorders.
Correlation between band gap, dielectric constant, Young’s modulus and melting temperature of GaN nanocrystals and their size and shape dependences
Authors: Lu Haiming , Meng Xiangkang 
Published: November 2015

AbstractWith structural miniaturization down to the nanoscale, the detectable parameters of materials no longer remain constant but become tunable. For GaN nanocrystals example, the band gap increases while the dielectric constant, Young’s modulus and melting temperature decrease with decreasing the solid size. Herein, we developed the models to describe the size and shape dependences of these seemingly uncorrelated parameters for GaN nanocrystals, based on our established thermodynamic model for cohesive energy of metallic nanocrystals. Consistency between our theoretical predictions and the corresponding experimental or simulated results confirms the accuracy of the developed models and indicates the essentiality of cohesive energy in describing the effects of size and shape on the physicochemical properties of different low-dimensional systems.
Graphene Based Waveguide Polarizers: In-Depth Physical Analysis and Relevant Parameters
Authors: de Oliveira Rafael E. P. , de Matos Christiano J. S. 
Published: November 2015

AbstractOptical polarizing devices exploiting graphene embedded in waveguides have been demonstrated in the literature recently and both the TE- and TM-pass behaviors were reported. The determination of the passing polarization is usually attributed to graphene’s Fermi level (and, therefore, doping level), with, however, no direct confirmation of this assumption provided. Here we show, through numerical simulation, that rather than graphene’s Fermi level, the passing polarization is determined by waveguide parameters, such as the superstrate refractive index and the waveguide’s height. The results provide a consistent explanation for experimental results reported in the literature. In addition, we show that with an accurate graphene modeling, a waveguide cannot be switched between TE pass and TM pass via Fermi level tuning. Therefore, the usually overlooked contribution of the waveguide design is shown to be essential for the development of optimized TE- or TM-pass polarizers, which we show to be due to the control it provides on the fraction of the electric field that is tangential to graphene.
Role of P38 MAPK on MMP Activity in Photothrombotic Stroke Mice as Measured using an Ultrafast MMP Activatable Probe
Authors: Chang Di , Wang Yuan-Cheng , Bai Ying-Ying , Lu Chun-Qiang , Xu Ting-Ting , Zhu Lei , Ju Shenghong 
Published: November 2015

AbstractMatrix metalloproteinases (MMPs) exert a dual effect in ischemic stroke and thus represent an ideal target for detection and therapy. However, to date, all clinical trials of MMP inhibitors have failed and alternative drug candidates and therapeutic targets are urgently required. Nonetheless, further investigations are limited by the lack of non-invasive imaging techniques. Here, we report a novel, fast and ultrasensitive MMP activatable optical imaging probe for the dynamic visualization of MMP activity in photothrombotic stroke mice. This probe provides a significant signal enhancement in as little as 15 min, with the highest signal intensity occurring at 1 h post-injection and shows high sensitivity in measuring MMP activity alterations, which makes it specifically suitable for the real-time visualization of MMP activity and drug discovery in preclinical research. Moreover, using this probe, we successfully demonstrate that the regulation of the p38 mitogen-activated protein kinase (MAPK) signal pathway is capable of modulating MMP activity after stroke, revealing a novel regulatory mechanism of postischemic brain damage and overcoming the limitations of traditional therapeutic strategies associated with MMP inhibitors by using a non-invasive molecular imaging method.
CMV promoter mutants with a reduced propensity to productivity loss in CHO cells
Authors: Moritz Benjamin , Becker Peter B. , Göpfert Ulrich 
Published: November 2015

AbstractThe major immediate-early promoter and enhancer of the human cytomegalovirus (hCMV-MIE) is one of the most potent DNA elements driving recombinant gene expression in mammalian cells. Therefore, it is widely employed not only in research but also in large-scale industrial applications, e.g. for the production of therapeutic antibodies in Chinese hamster ovary cells (CHO). As we have reported previously, multi-site methylation of hCMV-MIE is linked to productivity loss in permanently transfected CHO cells lines. In particular, the cytosine located 179 bp upstream of the transcription start site (C-179) is frequently methylated. Therefore, our objective was to study whether mutation of C-179 and other cytosines within hCMV-MIE might lessen the instability of transgene expression. We discovered that the single mutation of C-179 to G can significantly stabilise the production of recombinant protein under control of hCMV-MIE in permanently transfected CHO cells.
Crystallization pathways of liquid-bcc transition for a model iron by fast quenching
Authors: Pan Shao-Peng , Feng Shi-Dong , Qiao Jun-Wei , Wang Wei-Min , Qin Jing-Yu 
Published: November 2015

AbstractWe report simulations on the local structural evolution in the liquid-bcc transition of a model iron. Fourteen main Voronoi polyhedra are chosen as the representatives of short-range orders (SROs) and their transformations during crystallization are also investigated. Thus, the crystallization pathways for the main SROs are drawn. Our results also show that the transformations between two SROs in the crystallization pathways can be classified into two categories, first the enlargement of coordination number, second the transformation of local symmetry from five-fold to four-fold. The former reduces the potential energy while the latter increases it. It is found that the potential energy cannot decease monotonously whatever crystallization pathway is chosen to transform the icosahedral SRO to bcc SRO. Therefore, the latter transformation might provide the energy barrier of crystallization. We propose two transformation styles among SROs. All the transformations in the crystallization pathways can be achieved according to the styles. Moreover, the two transformation styles indicates that the bcc structure is more similar to liquid than other crystals. That might be the reason why the first phase nucleated during a rapid cooling process should be bcc crystal.
Combined Mapping of Multiple clUsteriNg ALgorithms (COMMUNAL): A Robust Method for Selection of Cluster Number, K
Authors: Sweeney Timothy E. , Chen Albert C. , Gevaert Olivier 
Published: November 2015

AbstractIn order to discover new subsets (clusters) of a data set, researchers often use algorithms that perform unsupervised clustering, namely, the algorithmic separation of a dataset into some number of distinct clusters. Deciding whether a particular separation (or number of clusters, K) is correct is a sort of ‘dark art’, with multiple techniques available for assessing the validity of unsupervised clustering algorithms. Here, we present a new technique for unsupervised clustering that uses multiple clustering algorithms, multiple validity metrics and progressively bigger subsets of the data to produce an intuitive 3D map of cluster stability that can help determine the optimal number of clusters in a data set, a technique we call COmbined Mapping of Multiple clUsteriNg ALgorithms (COMMUNAL). COMMUNAL locally optimizes algorithms and validity measures for the data being used. We show its application to simulated data with a known K and then apply this technique to several well-known cancer gene expression datasets, showing that COMMUNAL provides new insights into clustering behavior and stability in all tested cases. COMMUNAL is shown to be a useful tool for determining K in complex biological datasets and is freely available as a package for R.
Cellular miR-130b inhibits replication of porcine reproductive and respiratory syndrome virus in vitro and in vivo
Authors: Li Liwei , Gao Fei , Jiang Yifeng , Yu Lingxue , Zhou Yanjun , Zheng Hao , Tong Wu , Yang Shen , Xia Tianqi , Qu Zehui , Tong Guangzhi 
Published: November 2015

AbstractMicroRNAs (miRNAs) can impact viral infections by binding to sequences with partial complementarity on viral RNA transcripts, usually resulting in the repression of virus replication. In the present study, we identified a potential binding site for miR-130 in the 5′ untranslated region (bps 155-162) of the porcine reproductive and respiratory syndrome virus (PRRSV) genome. We found that the delivery of multiple miR-130 family mimics, especially miR-130b, resulted in inhibition of PRRSV replication in vitro. miR-130 was effective in inhibiting the replication of multiple type 2 PRRSV strains, but not against vSHE, a classical type 1 strain. miR-130 over-expression did not induce IFN-α or TNF-α expression in either uninfected or PRRSV-infected porcine alveolar macrophages. Results from luciferase reporter assays indicated that miR-130 directly targeted the PRRSV 5′ UTR. Intranasal inoculation of piglets with miR-130b exhibited antiviral activity in vivo and partially protected piglets from an otherwise lethal challenge with HP-PRRSV strain vJX143. Overall, these results demonstrate the importance of the miR-130 family in modulating PRRSV replication and also provide a scientific basis for using cellular miRNAs in anti-PRRSV therapies.
Immature myeloid Gr-1+ CD11b+ cells from lipopolysaccharide-immunosuppressed mice acquire inhibitory activity in the bone marrow and migrate to lymph nodes to exert their suppressive function
Authors: Landoni Veronica I. , Martire-Greco Daiana , Rodriguez-Rodrigues Nahuel , Chiarella Paula , Schierloh Pablo , Isturiz Martin A. , Fernández Gabriela C. 
Published: November 2015

Secondary infections due to post-sepsis immunosuppression are a major cause of death in patients with sepsis. Repetitive inoculation of increasing doses of lipopolysaccharide (LPS) into mice mimics the immunosuppression associated with sepsis. Myeloid-derived suppressor cells (MDSCs, Gr-1+ CD11b+) are considered a major component of the immunosuppressive network, interfering with T-cell responses in many pathological conditions. We used LPS-immunosuppressed (IS) mice to address whether MDSCs acquired their suppressive ability in the bone marrow (BM) and whether they could migrate to lymph nodes (LNs) to exert their suppressive function. Our results showed that Gr-1+ CD11b+ cells of IS mice already had the potential to inhibit T-cell proliferation in the BM. Moreover, soluble factors present in the BM from IS mice were responsible for inducing this inhibitory ability in control BM cells. In addition, migration of Gr-1+ CD11b+ to LNs in vivo was maximal when cells obtained from the BM of IS mice were inoculated into an IS context. In this regard, we found chemoattractant activity in cell-free LN extracts (LNEs) from IS mice and an increased expression of the LN-homing chemokine receptor C–C chemokine receptor type 7 (CCR7) in IS BM Gr-1+ CD11b+ cells. These results indicate that Gr-1+ CD11b+ cells found in BM from IS mice acquire their suppressive activity in the same niche where they are generated, and migrate to LNs to exert their inhibitory role. A better understanding of MDSC generation and/or regulation of factors able to induce their inhibitory function may provide new and more effective tools for the treatment of sepsis-associated immunosuppression.
The dorsal anterior cingulate cortex is selective for pain: Results from large-scale reverse inference
Authors: Lieberman Matthew D. , Eisenberger Naomi I. 
Published: November 2015

Significance
No neural region has been associated with more conflicting accounts of its function than the dorsal anterior cingulate cortex (dACC), with claims that it contributes to executive processing, conflict monitoring, pain, and salience. However, these claims are based on forward inference analysis, which is the wrong tool for making such claims. Using Neurosynth, an automated brainmapping database, we performed reverse inference analyses to explore the best psychological account of dACC function. Although forward inference analyses reproduced the findings that many processes activate the dACC, reverse inference analyses demonstrated that the dACC is selective for pain and that pain-related terms were the single best reverse inference for this region. This finding has implications for our understanding of pain and distress-related psychological disorders.
Some reflections on verbs with clitic increase
Authors: García Fernández Luis 
Published: November 2015

In this paper we will address the different values of se, one of the classic problems in Spanish grammar. Specifically, we will talk about the clitic which in the usual descriptions has no argumental value and is non-referential: the clitic sometimes called the reflexive-intensive and more recently the aspectual. We will also examine the clitic which appears with a number of verbs of motion and has also been termed aspectual. As we are dealing with a paradigmatic use of se, we will use the term “clitic increase” in order not to give the impression that we are dealing with a specific problem of the form se. This study is set out as follows: in Section 1 we introduce the two structures to be analysed. The first, is the use with transitive verbs, what we might call prototypical (comerse la paella ([to eat up the paella]) and the second deals with intransitive verbs. In Section 2, verbs of motion with clitic increase are analysed, the more relevant grammatical properties are described and a constant meaning is assigned to the appearance of the clitic. This leads us to a proposal for syntactic analysis in which the clitic is the head of the VoiceP. Then, in Section 3, we review the main properties of the first structure type and we show that our analysis also takes these into consideration. In 4, we consider the question of whether the differences introduced by the appearance of the clitic should be explained by lexicon or grammar. We end with conclusions and bibliography.
Romance object-experiencer verbs
Authors: Kailuweit Rolf 
Published: November 2015

The present paper deals with Romance Objective-Experiencer verbs (OE-verbs). I will show that the different subclasses fit into a continuum between a causative and an unaccusative pole. In order to describe their varying syntactic behaviour, a finer-grained analysis of the subevents they denote will elucidate that a traditional approach following the Vendler-Dowty classes of aktionsart will reach its limit when it comes to OE-verbs. My claim is that case assignment to the experiencer does not straightforwardly follow from the aktionsart class, but from the activity contrast between the two arguments of the verb. The presence or absence of causativity explains the differentiation between two types of ­experiencer: (a) a more passive causatively affected experiencer and (b) a less passive experiencer undergoing a change of state in a particular situation without being affected by an external causer. In addition, we find a third type of OE-verb: prototypically unaccustative (ergative) verbs, such as verbs of liking, which select a more active experiencer expressing a subjective judgement. These three types constitute prototypical categories with fuzzy edges. Romance languages differ in the way they code the three types at the lexical level and at the level of the constructional inventory. The results can be formalized following the activity hierarchy approach (Kailuweit 2013).
Denominal parasynthesis and inchoativity from both lexical-semantic and aspectual points of view
Authors: Merchán Aravid Nuria 
Published: November 2015

The present paper deals with a specific verb class: parasynthetic denominal verbs with an inchoative meaning. Analyzing them requires connecting two notions that belong to different linguistic analysis levels: the morphological mechanism of denominal parasynthesis – a particular word formation process starting from a noun – and the semantic notion of inchoativity – which expresses a change of state in the notional subject. This relation is especially productive with affixes such as a- and em-/en-, and with the verbal endings -ar, -ecer and -ear. The aim of this survey is twofold: on the one hand, to show how the study of the conceptualization base in the resulting structure makes it possible to establish different groups of denominal parasynthetic verbs; and, on the other hand, to determine the aspectual characteristics of inchoative denominal parasynthetic verbs so as to try to identify the aspectual class to which they could belong. The outcome is a proposal of characterization and classification that fills the gap concerning inchoative parasynthetic denominal verbs, since they have not been systematically analyzed in Spanish grammars so far.
Inferring divertor plasma properties from hydrogen Balmer and Paschen series spectroscopy in JET-ILW
Authors: Lomanowski B.A. , Meigs A.G. , Sharples R.M. , Stamp M. , Guillemaut C. 
Published: November 2015

Abstract
A parametrised spectral line profile model is formulated to investigate the diagnostic scope for recovering plasma parameters from hydrogenic Balmer and Paschen series spectroscopy in the context of JET-ILW divertor plasmas. The separate treatment of Zeeman and Stark contributions in the line model is tested against the PPP-B code which accounts for their combined influence on the spectral line shape. The proposed simplified model does not fully reproduce the Stark–Zeeman features for the α and β transitions, but good agreement is observed in the line width and wing profiles, especially for n  >  5. The line model has been applied to infer radial density profiles in the JET-ILW divertor with generally good agreement between the D

,

,

,

and

lines for high recycling and detached conditions. In an L-mode detached plasma pulse the Langmuir probe measurements typically underestimated the density by a factor 2–3 and overestimated the electron temperature by a factor of 5–10 compared to spectroscopically derived values. The line model is further used to generate synthetic high-resolution spectra for low-n transitions to assess the potential for parameter recovery using a multi-parametric fitting technique. In cases with 4 parameter fits with a single Maxwellian neutral temperature component the D

line yields the best results with parameter estimates within 10% of the input values. For cases with 9 parameter fits inclusive of a multi-component neutral velocity distribution function the quality of the fits is degraded. Simultaneous fitting of the D

and

profiles improves the fit quality significantly, highlighting the importance of complementary spectroscopic measurements for divertor plasma emission studies.
Analyzing synergistic and non-synergistic interactions in signalling pathways using Boolean Nested Effect Models
Authors: Pirkl Martin , Hand Elisabeth , Kube Dieter , Spang Rainer 
Published: November 2015

Abstract
Motivation: Understanding the structure and interplay of cellular signalling pathways is one of the great challenges in molecular biology. Boolean Networks can infer signalling networks from observations of protein activation. In situations where it is difficult to assess protein activation directly, Nested Effect Models are an alternative. They derive the network structure indirectly from downstream effects of pathway perturbations. To date, Nested Effect Models cannot resolve signalling details like the formation of signalling complexes or the activation of proteins by multiple alternative input signals. Here we introduce Boolean Nested Effect Models (B-NEM). B-NEMs combine the use of downstream effects with the higher resolution of signalling pathway structures in Boolean Networks.
Results: We show that B-NEMs accurately reconstruct signal flows in simulated data. Using B-NEM we then resolve BCR signalling via PI3K and TAK1 kinases in BL2 lymphoma cell lines.
Availability and implementation: R code is available at https://github.com/MartinFXP/B-NEM (github). The BCR signalling dataset is available at the GEO database (http://www.ncbi.nlm.nih.gov/geo/) through accession number GSE68761.
Contact: martin-franz-xaver.pirkl@ukr.de, Rainer.Spang@ukr.de
Supplementary information: Supplementary data are available at Bioinformatics online.
Periodic mass extinctions and the Planet X model reconsidered
Authors: Whitmire Daniel P. 
Published: November 2015

Abstract
The 27 Myr period in the fossil extinction record has been confirmed in modern data bases dating back 500 Myr, which is twice the time interval of the original analysis from 30 years ago. The surprising regularity of this period has been used to reject the Nemesis model. A second model based on the Sun's vertical Galactic oscillations has been challenged on the basis of an inconsistency in period and phasing. The third astronomical model originally proposed to explain the periodicity is the Planet X model in which the period is associated with the perihelion precession of the inclined orbit of a trans-Neptunian planet. Recently, and unrelated to mass extinctions, a trans-Neptunian super-Earth planet has been proposed to explain the observation that the inner Oort cloud objects Sedna and 2012VP113 have perihelia that lie near the ecliptic plane. In this Letter, we reconsider the Planet X model in light of the confluence of the modern palaeontological and outer Solar system dynamical evidence.