bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPR/gRNA-directed synergistic activation mediator (SAM) induces specific, persistent and robust reactivation of the HIV-1 latent reservoirs
Authors: Zhang Yonggang , Yin Chaoran , Zhang Ting , Li Fang , Yang Wensheng , Kaminski Rafal , Fagan Philip Regis , Putatunda Raj , Young Won-Bin , Khalili Kamel , Hu Wenhui 
Published: November 2015

AbstractCurrent antiretroviral therapy does not eliminate the integrated and transcriptionally silent HIV-1 provirus in latently infected cells. Recently, a “shock and kill” strategy has been extensively explored to eradicate the HIV-1 latent reservoirs for a permanent cure of AIDS. The therapeutic efficacy of currently used agents remains disappointing because of low efficiency, non-specificity and cellular toxicity. Here we present a novel catalytically-deficient Cas9-synergistic activation mediator (dCas9-SAM) technology to selectively, potently and persistently reactivate the HIV-1 latent reservoirs. By screening 16 MS2-mediated single guide RNAs, we identified long terminal repeat (LTR)-L and O that surround the enhancer region (-165/-145 for L and -92/-112 for O) and induce robust reactivation of HIV-1 provirus in HIV-1 latent TZM-bI epithelial, Jurkat T lymphocytic and CHME5 microglial cells. This compulsory reactivation induced cellular suicide via toxic buildup of viral proteins within HIV-1 latent Jurkat T and CHME5 microglial cells. These results suggest that this highly effective and target-specific dCas9-SAM system can serve as a novel HIV-latency-reversing therapeutic tool for the permanent elimination of HIV-1 latent reservoirs.
Comprehensive analysis of transcriptome and metabolome analysis in Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma
Authors: Murakami Yoshiki , Kubo Shoji , Tamori Akihiro , Itami Saori , Kawamura Etsushi , Iwaisako Keiko , Ikeda Kazuo , Kawada Norifumi , Ochiya Takahiro , Taguchi Y-h 
Published: November 2015

AbstractIntrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are liver originated malignant tumors. Of the two, ICC has the worse prognosis because it has no reliable diagnostic markers and its carcinogenic mechanism is not fully understood. The aim of this study was to integrate metabolomics and transcriptomics datasets to identify variances if any in the carcinogenic mechanism of ICC and HCC. Ten ICC and 6 HCC who were resected surgically, were enrolled. miRNA and mRNA expression analysis were performed by microarray on ICC and HCC and their corresponding non-tumor tissues (ICC_NT and HCC_NT). Compound analysis was performed using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Principle component analysis (PCA) revealed that among the four sample groups (ICC, ICC_NT, HCC and HCC_NT) there were 14 compounds, 62 mRNAs and 17 miRNAs with two distinct patterns: tumor and non-tumor and ICC and non-ICC. We accurately (84.38%) distinguished ICC by the distinct pattern of its compounds. Pathway analysis using transcriptome and metabolome showed that several pathways varied between tumor and non-tumor samples. Based on the results of the PCA, we believe that ICC and HCC have different carcinogenic mechanism therefore knowing the specific profile of genes and compounds can be useful in diagnosing ICC.
The role of N-glycans and the C-terminal loop of the subunit rBAT in the biogenesis of the cystinuria-associated transporter
Authors: Rius Mònica , Sala Laura , Chillarón Josep 
Published: November 2015

The transport system b0,+ mediates reabsorption of dibasic amino acids and cystine in the kidney. It is made up of two disulfide-linked membrane subunits: the carrier, b0,+AT and the helper, rBAT (related to b0,+ amino acid transporter). rBAT mutations that impair biogenesis of the transporter cause type I cystinuria. It has been shown that upon assembly, b0,+AT prevents degradation and promotes folding of rBAT; then, rBAT traffics b0,+AT from the endoplasmic reticulum (ER) to the plasma membrane. The role of the N-glycans of rBAT and of its C-terminal loop, which has no homology to any other sequence, in biogenesis of system b0,+ is unknown. In the present study, we studied these points. We first identified the five N-glycans of rBAT. Elimination of the N-glycan Asn575, but not of the others, delayed transporter maturation, as measured by pulse chase experiments and endoglycosidase H assays. Moreover, a transporter with only the N-glycan Asn575 displayed similar maturation compared with wild-type, suggesting that this N-glycan was necessary and sufficient to achieve the maximum rate of transporter maturation. Deletion of the rBAT C-terminal disulfide loop (residues 673–685) prevented maturation and prompted degradation of the transporter. Alanine-scanning mutagenesis uncovered loop residues important for stability and/or maturation of system b0,+. Further, double-mutant cycle analysis showed partial additivity of the effects of the Asn679 loop residue and the N-glycan Asn575 on transporter maturation, indicating that they may interact during system b0,+ biogenesis. These data highlight the important role of the N-glycan Asn575 and the C-terminal disulfide loop of rBAT in biogenesis of the rBAT-b0,+AT heterodimer.
Evaluation of Functional Outcomes after Stapes Surgery in Patients with Clinical Otosclerosis in a Teaching Institution
Authors: Souza José , Bento Ricardo , Pereira Larissa , Ikari Liliane , Souza Stephanie , Della Torre Ana , Fonseca Anna 
Published: November 2015

Introduction Otosclerosis is a primary disease of the temporal bone that leads to stapes ankylosis. Hearing loss is the main symptom. Treatment includes surgery, medical treatment, and sound amplification therapy alone or in combination.
Objective To evaluate the functional outcomes of patients with clinical diagnosis of otosclerosis undergoing primary stapes surgery in a teaching institution.
Method Retrospective descriptive study.
Results A total of 210 ears of 163 patients underwent stapes surgery. Of the 163 patients, 116 (71.2%) underwent unilateral surgery and 47 (28.8%) underwent bilateral surgery. Six of the 210 operated ears had obliterative otosclerosis. The average preoperative and postoperative air–bone gap was 32.06 and 4.39 dB, respectively. The mean preoperative and postoperative bone conduction threshold was 23.17 and 19.82 dB, respectively. A total of 184 (87.6%) ears had a residual air–bone gap <10 dB, and 196 (93.3%) had a residual air–bone gap ≤15 dB. Two patients (0.95%) had severe sensorineural hearing loss.
Conclusion Stapes surgery showed excellent functional hearing outcomes in this study. This surgery may be performed in educational institutions with the supervision of experienced surgeons.
Divinely Generic: Bible Translation and the Semiotics of Circulation
Authors: MacLochlainn Scott 
Published: November 2015

AbstractIn this article I examine the practice of Bible translation and the underlying sets of Christian ideologies regarding the commensurability of linguistic forms. Based on ethnographic research conducted at a biannual Bible translation workshop in Mindoro, Philippines, in 2013, during which the Bible was translated into three Mangyan languages, I argue that the degree to which the actual linguistic forms in the scriptures are divinely inspired often exists as an irresolvable semiotic problem for Bible translators. To this end, I discuss the means through which the Holy Spirit is taken as an essential mediator between the fallible work of Christian translators and the Bible as a language-instantiated form of God’s presence. I show how the employment of “generic” language by Christian translators enables them to mirror and circulate the divine universality of scriptural meaning in earthly form. I propose that generic language can be viewed as a site in which multiple and often conflicting claims of language universality and purity are present.
Rereading Sacrifice: The Semiosis of Blood
Authors: Janowitz Naomi 
Published: November 2015

AbstractBlood gains many distinct meanings from different modes of classification, some of which are calibrated by the representational capacities of sacrifice. The Priestly source from Hebrew scriptures and the early Jewish text Second Maccabees both reread ancient sacrifice traditions, articulating new meanings for blood as part of the transformation from a temple-based locative system of animal sacrifice to a utopian decentered model of human self-sacrifice. The Priestly writers created a new semiosis of blood as the purifying essence of temple sacrifice. Second Maccabees offers a temple-replacement ideology with one foot in the locative notion of temple, and the other in suffering and martyrdom—displaced animal sacrifice—as the path to an individual afterlife. Its new meanings for blood are stimulated by conflict over two competing locative systems (foreign and native) and the need to, even while renewing, ultimately replace the temple cult.
Tropes of Slang
Authors: Agha Asif 
Published: November 2015

AbstractThis article describes a class of speech varieties whose members have traditionally been called “slang” or “argot” in a large and long-standing literature. Despite the size of this literature, the characteristics of these speech varieties have remained obscure to those who purport to study them. The thing called “slang” has traditionally been reduced to the repertoires that count as samples of the thing without attention to either (a) the reflexive processes through which samples of the thing come to be differentiated from other discursive behaviors or (b) the social-interpersonal processes through which slang expressions undergo change in form and significance for different members of a language community. This article examines these reflexive social processes by considering examples from a large number of languages and historical periods. It offers a comparative framework for studying the forms of social life that such discursive behaviors enable or displace.
Neuromuscular Blocking Agent Cisatracurium Attenuates Lung Injury by Inhibition of Nicotinic Acetylcholine Receptor-α1
Authors: Fanelli Vito , Morita Yasumasa , Cappello Paola , Ghazarian Mirna , Sugumar Bina , Delsedime Luisa , Batt Jane , Ranieri V. Marco , Zhang Haibo , Slutsky Arthur S. 
Published: November 2015

AbstractAbstract
In rodent models of acute lung injury, neuromuscular blocking agents protected against ventilator-induced lung injury through their antiinflammatory properties mediated by blockade of the nicotinic acetylcholine receptor α1. This protective effect was not due to improved ventilator synchrony, and the reduced cytokine release could be mimicked ex vivo through knockdown of nicotinic acetylcholine receptor α1 expression.

Background
Neuromuscular blocking agents (NMBAs) bind the nicotinic acetylcholine receptor α1 (nAChRα1) that also contributes to inflammatory signaling. Thus, the author hypothesized that the use of NMBA mitigates lung injury by improving ventilator synchrony and decreasing inflammatory responses.

Methods
Lung injury was induced by intratracheal instillation of hydrogen chloride in rats that were randomized to receive no NMBA with evidence of asynchronous ventilation (noNMBA/aSYNC, n = 10); no NMBA with synchronous ventilation (noNMBA/SYNC, n = 10); cisatracurium (CIS, n = 10); or pancuronium (PAN, n = 10). Mechanical ventilation was set at a tidal volume of 6 ml/kg and positive end-expiratory pressure 8 cm H2O for 3 h. Human lung epithelial, endothelial, and CD14+ cells were challenged with mechanical stretch, lipopolysaccharide, lung lavage fluids (bronchoalveolar lavage fluid), or plasma obtained from patients (n = 5) with acute respiratory distress syndrome, in the presence or absence of CIS or small-interfering RNA and small hairpin RNA to attenuate the cell expression of nAChRα1.

Results
The use of CIS and PAN improved respiratory compliance (7.2 ± 0.7 in noNMBA/aSYNC, 6.6 ± 0.5 in noNMBA/SYNC, 5.9 ± 0.3 in CIS, and 5.8 ± 0.4 cm H2O/l in PAN; P < 0.05), increased Pao
2 (140 ± 54, 209 ± 46, 269 ± 31, and 269 ± 54 mmHg, respectively, P < 0.05), and decreased the plasma levels of tumor necrosis factor-α (509 ± 252 in noNMBA, 200 ± 74 in CIS, and 175 ± 84 pg/ml in PAN; P < 0.05) and interleukin-6 (5789 ± 79, 1608 ± 534, and 2290 ± 315 pg/ml, respectively; P < 0.05). The use of CIS and PAN or silencing the receptor nAChRα1 resulted in decreased cytokine release in the human cells in response to a variety of stimuli mentioned earlier.

Conclusions
The use of NMBA is lung protective through its antiinflammatory properties by blocking the nAChRα1.
A tracking and summarization system for online Chinese news topics
Authors: Chang Hsien-Tsung , Liu Shu-Wei , Mishra Nilamadhab 
Published: November 2015

Purpose
– The purpose of this paper is to design and implement new tracking and summarization algorithms for Chinese news content. Based on the proposed methods and algorithms, the authors extract the important sentences that are contained in topic stories and list those sentences according to timestamp order to ensure ease of understanding and to visualize multiple news stories on a single screen.

Design/methodology/approach
– This paper encompasses an investigational approach that implements a new Dynamic Centroid Summarization algorithm in addition to a Term Frequency (TF)-Density algorithm to empirically compute three target parameters, i.e., recall, precision, and F-measure.

Findings
– The proposed TF-Density algorithm is implemented and compared with the well-known algorithms Term Frequency-Inverse Word Frequency (TF-IWF) and Term Frequency-Inverse Document Frequency (TF-IDF). Three test data sets are configured from Chinese news web sites for use during the investigation, and two important findings are obtained that help the authors provide more precision and efficiency when recognizing the important words in the text. First, the authors evaluate three topic tracking algorithms, i.e., TF-Density, TF-IDF, and TF-IWF, with the said target parameters and find that the recall, precision, and F-measure of the proposed TF-Density algorithm is better than those of the TF-IWF and TF-IDF algorithms. In the context of the second finding, the authors implement a blind test approach to obtain the results of topic summarizations and find that the proposed Dynamic Centroid Summarization process can more accurately select topic sentences than the LexRank process.

Research limitations/implications
– The results show that the tracking and summarization algorithms for news topics can provide more precise and convenient results for users tracking the news. The analysis and implications are limited to Chinese news content from Chinese news web sites such as Apple Library, UDN, and well-known portals like Yahoo and Google.

Originality/value
– The research provides an empirical analysis of Chinese news content through the proposed TF-Density and Dynamic Centroid Summarization algorithms. It focusses on improving the means of summarizing a set of news stories to appear for browsing on a single screen and carries implications for innovative word measurements in practice.
Understanding information seeking in digital libraries: antecedents and consequences
Authors: Zha Xianjin , Wang Wentao , Yan Yalan , Zhang Jinchao , Zha Daochen 
Published: November 2015

Purpose
– The purpose of this paper is to explore the antecedents of information seeking in digital libraries from the perspectives of the Technology Acceptance Model and flow experience, as well as the consequences from the perspectives of self-efficacy in getting information and individual performance.

Design/methodology/approach
– A research model is developed and tested using questionnaires and, partial least squares structural equation modeling.

Findings
– The effect of flow experience on information seeking in digital libraries is the largest one. Meanwhile, flow experience fully mediates the effects of ease of use and usefulness on information seeking in digital libraries which further leads to self-efficacy in getting information and individual performance.

Practical implications
– Librarians should help users to experience more stable and sustainable flow by providing dependable, prompt, personalized and professional service to them. Librarians should try their best to provide diversified user training so as to guide potential users to seek information in digital libraries.

Originality/value
– This study contributes to the theoretical development of the structural model exploring information seeking in digital libraries, presenting a new view for digital library research and practice alike.
The benefit of context for facial-composite construction
Authors: Skelton Faye C. , Frowd Charlie D. , Speers Kathryn E 
Published: November 2015

Purpose
– The purpose of this paper is to investigate whether the presence of a whole-face context during facial composite production facilitates construction of facial composite images.

Design/methodology/approach
– In Experiment 1, constructors viewed a celebrity face and then developed a facial composite using PRO-fit software in one of two conditions: either the full-face was visible while facial features were selected, or only the feature currently being selected. The composites were named by different participants. The authors then replicated the study using a more forensically valid procedure: in Experiment 2 non-football fans viewed an image of a premiership footballer and 24 hours later constructed a composite of the face with a trained software operator. The resulting composites were named by football fans.

Findings
– In both studies, the presence of the facial context promoted more identifiable facial composites.

Research limitations/implications
– Current composite software was deployed in a conventional and unconventional way to demonstrate the importance of facial context.

Practical implications
– Results confirm that composite software should have the whole-face context visible to witnesses throughout construction. Although some software systems do this, there remain others that present features in isolation and these findings show that these systems are unlikely to be optimal.

Originality/value
– This is the first study to demonstrate the importance of a full-face context for the construction of facial composite images. Results are valuable to police forces and developers of composite software.
A criterion of crazing density for the residual life assessment of PMMA during creep
Authors: Gao Zongzhan , Li Qinghai , Wang Yi 
Published: November 2015

Purpose
– A series of creep experiments were carried out to study a new criterion for creep residual life assessment of PMMA (MDYB-10) with various stresses level at room temperature. A macroscopical creep life model based on abundant experiments results was researched first. The model included three phases which are described by the Chen theory, Norton formula and exponential expression, respectively. The paper aims to discuss these issues.

Design/methodology/approach
– During the creep experiments, the simple optical testing instrument was used to observe the crazing initiation and quantify the crazing damage density in the specimens.

Findings
– It was shown that the initiation time of crazing damage depended on the stress level, and the crazing damage density increased non-linearly with experiment time. The crazing initiation time equation and damage density equations were expressed.

Originality/value
– Comprehensive consideration of the creep life model and crazing density evolution equation, a new criterion for creep residual life assessment was introduced. The criterion could be applied to assess the residual life for MDYB-10 by measuring the crazing damage density.
Enriched rearing environment and wild genetic background can enhance survival and disease resistance of salmonid fishes during parasite epidemics
Authors: Karvonen Anssi , Aalto‐Araneda Mariella , Virtala Anna‐Maija , Kortet Raine , Koski Perttu , Hyvärinen Pekka 
Published: November 2015

Summary

The importance and volume of aquaculture is increasing world‐wide. Rearing practices play a key role in determining growth rate, survival and disease resistance in aquaculture fishes. Recent evidence suggests that in comparison with a standard stimulus‐poor rearing environment, an enriched or variable rearing environment has significant positive effects on several traits underlying growth and well‐being of fish. However, the effect of enriched rearing on one of the most important threats for aquaculture development, occurrence of parasitic infections, remains unknown.

We used surveillance data of experimental salmonid populations of wild and hatchery origin under semi‐natural parasite exposure to explore effects of enriched rearing on outbreaks of important aquaculture pathogens and associated fish mortalities in production‐scale fish densities. We also conducted controlled parasite exposures to investigate if enriched rearing reduces susceptibility of fish to infection in comparison with standard rearing conditions.

We found evidence of enriched rearing influencing survival and disease resistance of aquaculture fish during parasite epidemics. Essentially, populations from enriched rearing had a higher survival rate, lower parasite occurrence and greater resistance to most infections compared to fish held in standard rearing conditions. Similarly, fish of wild genetic background had lower mortality during some of the epidemics compared to fish of hatchery origin. However, we also demonstrate significant variation in these patterns and in some cases a tendency for opposite effects of enriched rearing and genetic background depending on the fish species and nature of the epidemic.

Synthesis and applications. Our results suggest that parasitic infections and epidemics can be managed through enriched rearing conditions. This may have important implications for economically and ecologically sustainable parasite and disease prevention strategies in aquaculture.
A framework for estimating the sensitivity of eDNA surveys
Authors: Furlan Elise M. , Gleeson Dianne , Hardy Christopher M. , Duncan Richard P. 
Published: November 2015

AbstractImperfect sensitivity, or imperfect detection, is a feature of all survey methods that needs to be accounted for when interpreting survey results. Detection of environmental DNA (eDNA) is increasingly being used to infer species distributions, yet the sensitivity of the technique has not been fully evaluated. Sensitivity, or the probability of detecting target DNA given it is present at a site, will depend on both the survey method and the concentration and dispersion of target DNA molecules at a site. We present a model to estimate target DNA concentration and dispersion at survey sites and to estimate the sensitivity of an eDNA survey method. We fitted this model to data from a species‐specific eDNA survey for Oriental weatherloach, Misgurnus anguillicaudatus, at three sites sampled in both autumn and spring. The concentration of target DNA molecules was similar at all three sites in autumn but much higher at two sites in spring. Our analysis showed the survey method had ≥95% sensitivity at sites where target DNA concentrations were ≥11 molecules per litre. We show how these data can be used to compare sampling schemes that differ in the number of field samples collected per site and number of PCR replicates per sample to achieve ≥95% sensitivity at a given target DNA concentration. These models allow researchers to quantify the sensitivity of eDNA survey methods to optimize the probability of detecting target species, and to compare DNA concentrations spatially and temporarily.