bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of ggplot2 to Pharmacometric Graphics
Authors: Ito K , Murphy D 
Published: October 2013

Visualization is a powerful mechanism for extracting information from data. ggplot2 is a contributed visualization package in the R programming language, which creates publication‐quality statistical graphics in an efficient, elegant, and systematic manner. This article summarizes key features of the package with examples from pharmacometrics and pointers to available resources for learning ggplot2.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e79; doi:10.1038/psp.2013.56; advance online publication 16 October 2013
Structural basis for a class of nanomolar influenza A neuraminidase inhibitors
Authors: Kerry Philip S. , Mohan Sankar , Russell Rupert J. M. , Bance Nicole , Niikura Masahiro , Pinto B. Mario 
Published: October 2013

AbstractThe influenza virus neuraminidase (NA) is essential for the virus life cycle. The rise of resistance mutations against current antiviral therapies has increased the need for the development of novel inhibitors. Recent efforts have targeted a cavity adjacent to the catalytic site (the 150-cavity) in addition to the primary catalytic subsite in order to increase specificity and reduce the likelihood of resistance. This study details structural and in vitro analyses of a class of inhibitors that bind uniquely in both subsites. Crystal structures of three inhibitors show occupation of the 150-cavity in two distinct and novel binding modes. We believe these are the first nanomolar inhibitors of NA to be characterized in this way. Furthermore, we show that one inhibitor, binding within the catalytic site, offers reduced susceptibility to known resistance mutations via increased flexibility of a pendant pentyloxy group and the ability to pivot about a strong hydrogen-bonding network.
Magneto-electric Nanoparticles to Enable Field-controlled High-Specificity Drug Delivery to Eradicate Ovarian Cancer Cells
Authors: Guduru Rakesh , Liang Ping , Runowicz Carolyn , Nair Madhavan , Atluri Venkata , Khizroev Sakhrat 
Published: October 2013

AbstractThe nanotechnology capable of high-specificity targeted delivery of anti-neoplastic drugs would be a significant breakthrough in Cancer in general and Ovarian Cancer in particular. We addressed this challenge through a new physical concept that exploited (i) the difference in the membrane electric properties between the tumor and healthy cells and (ii) the capability of magneto-electric nanoparticles (MENs) to serve as nanosized converters of remote magnetic field energy into the MENs' intrinsic electric field energy. This capability allows to remotely control the membrane electric fields and consequently trigger high-specificity drug uptake through creation of localized nano-electroporation sites. In in-vitro studies on human ovarian carcinoma cell (SKOV-3) and healthy cell (HOMEC) lines, we applied a 30-Oe d.c. field to trigger high-specificity uptake of paclitaxel loaded on 30-nm CoFe2O4@BaTiO3 MENs. The drug penetrated through the membrane and completely eradicated the tumor within 24 hours without affecting the normal cells.
Electromechanics in MoS2 and WS2: nanotubes vs. monolayers
Authors: Ghorbani-Asl Mahdi , Zibouche Nourdine , Wahiduzzaman Mohammad , Oliveira Augusto F. , Kuc Agnieszka , Heine Thomas 
Published: October 2013

AbstractThe transition-metal dichalcogenides (TMD) MoS2 and WS2 show remarkable electromechanical properties. Strain modifies the direct band gap into an indirect one and substantial strain even induces an semiconductor-metal transition. Providing strain through mechanical contacts is difficult for TMD monolayers, but state-of-the-art for TMD nanotubes. We show using density-functional theory that similar electromechanical properties as in monolayer and bulk TMDs are found for large diameter TMD single- (SWNT) and multi-walled nanotubes (MWNTs). The semiconductor-metal transition occurs at elongations of 16%. We show that Raman signals of the in-plane and out-of-plane lattice vibrations depend significantly and linearly on the strain, showing that Raman spectroscopy is an excellent tool to determine the strain of the individual nanotubes and hence monitor the progress of nanoelectromechanical experiments in situ. TMD MWNTs show twice the electric conductance compared to SWNTs and each wall of the MWNTs contributes to the conductance proportional to its diameter.
Genome-wide methylated CpG island profiles of melanoma cells reveal a melanoma coregulation network
Authors: Li Jian-Liang , Mazar Joseph , Zhong Cuncong , Faulkner Geoffrey J. , Govindarajan Subramaniam S. , Zhang Zhan , Dinger Marcel E. , Meredith Gavin , Adams Christopher , Zhang Shaojie , Mattick John S. , Ray Animesh , Perera Ranjan J. 
Published: October 2013

AbstractMetastatic melanoma is a malignant cancer with generally poor prognosis, with no targeted chemotherapy. To identify epigenetic changes related to melanoma, we have determined genome-wide methylated CpG island distributions by next-generation sequencing. Melanoma chromosomes tend to be differentially methylated over short CpG island tracts. CpG islands in the upstream regulatory regions of many coding and noncoding RNA genes, including, for example, TERC, which encodes the telomerase RNA, exhibit extensive hypermethylation, whereas several repeated elements, such as LINE 2 and several LTR elements, are hypomethylated in advanced stage melanoma cell lines. By using CpG island demethylation profiles and by integrating these data with RNA-seq data obtained from melanoma cells, we have identified a co-expression network of differentially methylated genes with significance for cancer related functions. Focused assays of melanoma patient tissue samples for CpG island methylation near the noncoding RNA gene SNORD-10 demonstrated high specificity.
MAS promoter regulation: a role for Sry and tyrosine nitration of the KRAB domain of ZNF274 as a feedback mechanism
Authors: Prokop Jeremy W. , Rauscher Frank J. , Peng Hongzhuang , Liu Yuanjie , Araujo Fabiano C. , Watanabe Ingrid , Reis Fernando M. , Milsted Amy 
Published: October 2013

The ACE2 (angiotensin-converting enzyme 2)/Ang-(1–7) [angiotensin-(1–7)]/MAS axis of the RAS (renin–angiotensin system) has emerged as a pathway of interest in treating both cardiovascular disorders and cancer. The MAS protein is known to bind to and be activated by Ang-(1–7); however, the mechanisms of this activation are just starting to be understood. Although there are strong biochemical data regarding the regulation and activation of the AT1R (angiotensin II type 1 receptor) and the AT2R (angiotensin II type 2 receptor), with models of how AngII (angiotensin II) binds each receptor, fewer studies have characterized MAS. In the present study, we characterize the MAS promoter and provide a potential feedback mechanism that could compensate for MAS degradation following activation by Ang-(1–7). Analysis of ENCODE data for the MAS promoter revealed potential epigenetic control by KRAB (Krüppel-associated box)/KAP-1 (KRAB-associated protein-1). A proximal promoter construct for the MAS gene was repressed by the SOX [SRY (sex-determining region on the Y chromosome) box] proteins SRY, SOX2, SOX3 and SOX14, of which SRY is known to interact with the KRAB domain. The KRAB–KAP-1 complex can be tyrosine-nitrated, causing the dissociation of the KAP-1 protein and thus a potential loss of epigenetic control. Activation of MAS can lead to an increase in nitric oxide, suggesting a feedback mechanism for MAS on its own promoter. The results of the present study provide a more complete view of MAS regulation and, for the first time, suggest biochemical outcomes for nitration of the KRAB domain.
Lipreading in School-Age Children: The Roles of Age, Hearing Status, and Cognitive Ability
Authors: Tye-Murray Nancy , Hale Sandra , Spehar Brent , Myerson Joel , Sommers Mitchell S. 
Published: October 2013

Purpose
The study addressed three research questions: Does lipreading improve between the ages of 7 and 14 years? Does hearing loss affect the development of lipreading? How do individual differences in lipreading relate to other abilities?

Method
Forty children with normal hearing (NH) and 24 with hearing loss (HL) were tested using 4 lipreading instruments plus measures of perceptual, cognitive, and linguistic abilities.

Results
For both groups, lipreading performance improved with age on all 4 measures of lipreading, with the HL group performing better than the NH group. Scores from the 4 measures loaded strongly on a single principal component. Only age, hearing status, and visuospatial working memory were significant predictors of lipreading performance.

Conclusions
Results showed that children's lipreading ability is not fixed but rather improves between 7 and 14 years of age. The finding that children with HL lipread better than those with NH suggests experience plays an important role in the development of this ability. In addition to age and hearing status, visuospatial working memory predicts lipreading performance in children, just as it does in adults. Future research on the developmental time-course of lipreading could permit interventions and pedagogies to be targeted at periods in which improvement is most likely to occur.
Eye-Tracking Measures Reveal How Changes in the Design of Aided AAC Displays Influence the Efficiency of Locating Symbols by School-Age Children Without Disabilities
Authors: Wilkinson Krista M. , O’Neill Tara , McIlvane William J. 
Published: October 2013

Purpose
Many individuals with communication impairments use aided augmentative and alternative communication (AAC) systems involving letters, words, or line drawings that rely on the visual modality. It seems reasonable to suggest that display design should incorporate information about how users attend to and process visual information. The organization of AAC symbols can influence the speed and accuracy with which children select a target symbol on a display. This research examined why some displays facilitate responding.

Method
Eye-tracking technology recorded point-of-gaze while children without disabilities engaged in a visual search task with 2 AAC displays. In 1 display, symbols sharing an internal color were clustered together. In the other display, like-colored symbols were distributed. Dependent measures were (a) latency to fixate on the target compared with distracters and (b) the number of fixations to target and distracters.

Results
Participants were significantly slower to fixate on the target when like-colored symbols were distributed; there was a significant increase in the number of fixations to distracters that did not share color with the target.

Conclusions
Efficient search was related to minimizing fixations to nonrelevant distracters. Vulnerability to distraction can be a significant problem in individuals with disabilities who use AAC. Minimizing the intrusion of such distraction may, therefore, be of importance in AAC display design.
Modeling Mechanisms of Persisting and Resolving Delay in Language Development
Authors: Thomas Michael S. C. , Knowland V. C. P. 
Published: October 2013

Purpose
In this study, the authors used neural network modeling to investigate the possible mechanistic basis of developmental language delay and to test the viability of the hypothesis that persisting delay and resolving delay lie on a mechanistic continuum with normal development.

Method
The authors used a population modeling approach to study individual rates of development in 1,000 simulated individuals acquiring a notional language domain (in this study, represented by English past tense). Variation was caused by differences in internal neurocomputational learning parameters as well as the richness of the language environment. An early language delay group was diagnosed, and individual trajectories were then traced.

Results
Quantitative variations in learning mechanisms were sufficient to produce persisting delay and resolving delay subgroups in similar proportions to empirical observations. In the model, persisting language delay was caused by limitations in processing capacity, whereas resolving delay was caused by low plasticity. Richness of the language environment did not predict the emergence of persisting delay but did predict the final ability levels of individuals with resolving delay.

Conclusion
Mechanistically, it is viable that persisting delay and resolving delay are only quantitatively different. There may be an interaction between environmental factors and outcome groups, with individuals who have resolving delay being influenced more by the richness of the language environment.
Bilinguals Use Language-Specific Articulatory Settings
Authors: Wilson Ian , Gick Bryan 
Published: October 2013

PurposePrevious work has shown that monolingual French and English speakers use distinctarticulatory settings,the underlying articulatory posture of a language. In the present article, the authors report on an experiment in which they investigated articulatory settings in bilingual speakers. The authors first tested the hypothesis that in order to sound native-like, bilinguals must use distinct, language-specific articulatory settings in monolingual mode. The authors then tested the hypothesis that in bilingual mode, a bilingual individual's articulatory setting is identical to the monolingual-mode setting of 1 of his or her languages.MethodEight French–English bilinguals each read 90 English and 90 French sentences, and the authors measured their interspeech posture (ISP) using optical tracking of the lips and jaw and ultrasound imaging of the tongue.ResultsResults show that bilingual speakers who are perceived as native in both languages exhibit distinct, language-specific ISPs, and those who are not perceived as native in one or more languages do not. In bilingual mode, bilinguals use an ISP that is equivalent to the monolingual-mode ISP of their currently most used language. The most balanced bilingual used a French lip ISP but an English tongue-tip ISP.ConclusionResults support the claim that bilinguals who sound native in each of their languages have distinct articulatory settings for each language.Supplemental Materialhttps://doi.org/10.23641/asha.6170441
Native contacts determine protein folding mechanisms in atomistic simulations
Authors: Best Robert B. , Hummer Gerhard , Eaton William A. 
Published: October 2013

Significance
Understanding the mechanism by which proteins fold to their native structure is a central problem in protein science. Clearly, interactions between residues that are in contact in the folded state (native interactions) are likely to be important for folding, but, in principle, nonnative interactions may play a role. Here, we use recently published microsecond to millisecond all-atom molecular dynamics simulations of proteins folding and unfolding to show, remarkably, that nonnative contacts are irrelevant to the mechanism of folding in most cases. This statistical analysis would be very difficult to perform by experiment. Although this is a limited set of proteins, the results nonetheless strongly support coarse-grained theoretical and simulation models of folding in which only native contacts are energetically favorable.
FFAS-3D: improving fold recognition by including optimized structural features and template re-ranking
Authors: Xu Dong , Jaroszewski Lukasz , Li Zhanwen , Godzik Adam 
Published: October 2013

Abstract
Motivation: Homology detection enables grouping proteins into families and prediction of their structure and function. The range of application of homology-based predictions can be significantly extended by using sequence profiles and incorporation of local structural features. However, incorporation of the latter terms varies a lot between existing methods, and together with many examples of distant relations not recognized even by the best methods, suggests that further improvements are still possible.
Results: Here we describe recent improvements to the fold and function assignment system (FFAS) method, including adding optimized structural features (experimental or predicted), ‘symmetrical’ Z-score calculation and re-ranking the templates with a neural network. The alignment accuracy in the new FFAS-3D is now 11% higher than the original and comparable with the most accurate template-based structure prediction algorithms. At the same time, FFAS-3D has high success rate at the Structural Classification of Proteins (SCOP) family, superfamily and fold levels. Importantly, FFAS-3D results are not highly correlated with other programs suggesting that it may significantly improve meta-predictions. FFAS-3D does not require 3D structures of the templates, as using predicted features instead of structure-derived does not lead to the decrease of accuracy. Because of that, FFAS-3D can be used for databases other than Protein Data Bank (PDB) such as Protein families database or Clusters of orthologous groups thus extending its applications to functional annotations of genomes and protein families.
Availability and implementation: FFAS-3D is available at http://ffas.godziklab.org.
Contact: adam@godziklab.org
Supplementary Information: Supplementary data are available at Bioinformatics online.
Comment on ‘Bayesian parentage analysis with systematic accountability of genotyping error, missing data and false matching’
Authors: Anderson Eric C. , Ng Thomas C. 
Published: October 2013

Abstract
Summary: We show the software SOLOMON is improved by using the likelihood ratio instead of an ad hoc statistic.
Code: github.com/eriqande/solidmon/releases/tag/v0.1-bioinformatics
Contact: eric.anderson@noaa.gov
The Top-Down Revitalization of Corsican: Considering the Reversal of a Language Shift in the Linguistic and Semiotic Landscapes of Ajaccio
Authors: Blackwood Robert 
Published: October 2013

Abstract
The Linguistic Landscape (LL) is being used creatively in different ways to examine language practices in multilingual communities, and a sister subdiscipline, semiotic landscapes, is emerging to include non-language elements to help better understand attitudes towards languages where two or more varieties are in competition. This article seeks to establish the extent to which the LL contributes to ‘top-down’ language revitalization, a perspective normally overlooked in favour of ‘bottom-up’ language activism. Assessing the presence and absence of the Italo-Romance language of Corsican in the French town of Ajaccio, the regional capital of Corsica, I exploit recent developments in LL studies, as well as research on language commodification, to evaluate the extent to which top-down agents revitalize a minorized language by placing it in the LL.
Deciphering the Responses of Root Border-Like Cells of Arabidopsis and Flax to Pathogen-Derived Elicitors
Authors: Plancot Barbara , Santaella Catherine , Jaber Rim , Kiefer-Meyer Marie Christine , Follet-Gueye Marie-Laure , Leprince Jérôme , Gattin Isabelle , Souc Céline , Driouich Azeddine , Vicré-Gibouin Maïté 
Published: October 2013

Abstract
Plant pathogens including fungi and bacteria cause many of the most serious crop diseases. The plant innate immune response is triggered upon recognition of microbe-associated molecular patterns (MAMPs) such as flagellin22 and peptidoglycan. To date, very little is known of MAMP-mediated responses in roots. Root border cells are cells that originate from root caps and are released individually into the rhizosphere. Root tips of Arabidopsis (Arabidopsis thaliana) and flax (Linum usitatissimum) release cells known as “border-like cells.” Whereas root border cells of pea (Pisum sativum) are clearly involved in defense against fungal pathogens, the function of border-like cells remains to be established. In this study, we have investigated the responses of root border-like cells of Arabidopsis and flax to flagellin22 and peptidoglycan. We found that both MAMPs triggered a rapid oxidative burst in root border-like cells of both species. The production of reactive oxygen species was accompanied by modifications in the cell wall distribution of extensin epitopes. Extensins are hydroxyproline-rich glycoproteins that can be cross linked by hydrogen peroxide to enhance the mechanical strength of the cell wall. In addition, both MAMPs also caused deposition of callose, a well-known marker of MAMP-elicited defense. Furthermore, flagellin22 induced the overexpression of genes involved in the plant immune response in root border-like cells of Arabidopsis. Our findings demonstrate that root border-like cells of flax and Arabidopsis are able to perceive an elicitation and activate defense responses. We also show that cell wall extensin is involved in the innate immunity response of root border-like cells.
Proteome Analysis of Peroxisomes from Etiolated Arabidopsis Seedlings Identifies a Peroxisomal Protease Involved in β-Oxidation and Development
Authors: Quan Sheng , Yang Pingfang , Cassin-Ross Gaëlle , Kaur Navneet , Switzenberg Robert , Aung Kyaw , Li Jiying , Hu Jianping 
Published: October 2013

AbstractPlant peroxisomes are highly dynamic organelles that mediate a suite of metabolic processes crucial to development. Peroxisomes in seeds/dark-grown seedlings and in photosynthetic tissues constitute two major subtypes of plant peroxisomes, which had been postulated to contain distinct primary biochemical properties. Multiple in-depth proteomic analyses had been performed on leaf peroxisomes, yet the major makeup of peroxisomes in seeds or dark-grown seedlings remained unclear. To compare the metabolic pathways of the two dominant plant peroxisomal subtypes and discover new peroxisomal proteins that function specifically during seed germination, we performed proteomic analysis of peroxisomes from etiolated Arabidopsis (Arabidopsis thaliana) seedlings. The detection of 77 peroxisomal proteins allowed us to perform comparative analysis with the peroxisomal proteome of green leaves, which revealed a large overlap between these two primary peroxisomal variants. Subcellular targeting analysis by fluorescence microscopy validated around 10 new peroxisomal proteins in Arabidopsis. Mutant analysis suggested the role of the cysteine protease RESPONSE TO DROUGHT21A-LIKE1 in β-oxidation, seed germination, and growth. This work provides a much-needed road map of a major type of plant peroxisome and has established a basis for future investigations of peroxisomal proteolytic processes to understand their roles in development and in plant interaction with the environment.