bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR01: H-RasG12V overexpression in the central nervous system leads to expansion of oligodendrocyte precursor cells and neural crest cells
Authors: Distel Martin , Traver David 
Published: May 2015

Abstract
Somatic mutations in Ras proto-oncogenes have been found in a large number of different cancers. In addition, germline mutations in the H-Ras gene have been shown to be the causative genetic alteration underlying Costello Syndrome (CS). Costello Syndrome belongs to the large group of Ras/MAPK pathway diseases commonly termed Rasopathies. CS patients exhibit craniofacial and cardiac abnormalities, mental retardation and are prone to develop cancers including neural crest derived neoplasias.
Since Costello Syndrome is a rare disease, the effects of H-RasG12V expression on the development of the central nervous system remain largely uncharacterized. Towards this goal, we have established a zebrafish model suitable for live imaging and cost-effective drug screening. Using the Gal4/UAS system we have enforced expression of H-RasG12V in the central nervous system starting at early neurulation stages. H-RasG12V expressing embryos develop hyperplasia of the forebrain and the spinal cord and show an outgrowth in the dorsal tail region around 3 days post fertilization (dpf). In situ hybridisation revealed an increase in oligodendrocyte precursor cells, similar to what has been reported for zebrafish neurofibromin 1 mutants. In addition, cells expressing the neural crest markers Sox10 and FoxD3 accumulate lateral to the neural tube and notochord. Time-lapse imaging revealed that H-RasG12V expressing cells indeed migrate out of the spinal cord. This migration was ectopic, occuring several hours after normal neural crest migration. Furthermore, coinciding with the accumulation of neural crest like cells around the neural tube, the intersomitic vasculature hyperbranches to form new blood vessels towards domains of H-RasG12V expressing cells.
Taking advantage of the early onset and obvious phenotypes in our H-RasG12V overexpression model we performed a pilot drug screen to identify potential therapeutic compounds for Costello Syndrome. We found the Mek1/Mek2 inhibitor PD98059 successfully inhibited hyperplasia of the forebrain and the spinal cord, with normal numbers of oligodendrocyte precursor cells and neural crest cells. Thus, this zebrafish model will be a valuable tool to further investigate the mechanisms underlying CNS- abnormalities of Costello Syndrome patients, including the formation of neural crest derived neoplasias and will be useful to identify therapies against this disease.
This abstract is also presented as Poster A3.
Citation Format: Martin Distel, David Traver. H-RasG12V overexpression in the central nervous system leads to expansion of oligodendrocyte precursor cells and neural crest cells. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr PR01.
Abstract PR08: Drugging MYCN protein stability through an allosteric transition in Aurora kinase A
Authors: Gustafson W. Clay , Meyerowitz Justin G. , Nekritz Erin A. , Charron Elise , Matthay Katherine K. , Hertz Nicholas T. , Eilers Martin , Shokat Kevan M. , Weiss William A. 
Published: May 2015

Abstract
MYC family proteins represent a critical node in oncogenesis across a wide range of pediatric and adult cancers. This is particularly true in neuroblastoma, where amplification of MYCN confers an especially poor prognosis. Proteolytic degradation of MYCN protein is regulated in part by a kinase-independent function of Aurora Kinase A. We describe a class of allosteric inhibitors that disrupts the native conformation of Aurora A and causes degradation of MYCN protein across MYCN-expressing neuroblastoma cell lines. We compare co-crystal structures with structure-activity relationships across multiple inhibitors and chemotypes to delineate an Aurora A conformation-specific effect on proteolytic degradation of MYCN protein, which is driven markedly by conformation disrupting inhibitors, and impacted more modestly by current clinical Aurora Kinase A inhibitors, which disrupt the kinase structure less efficiently. Using functional assays of apoptosis, cell cycle, and proliferation we further define a distinct MYCN-specific effect distinguishing it from simple inhibition of mitosis by conventional Aurora kinase inhibitors. This new class of conformation disrupting inhibitors, which block stabilizing interactions between Aurora A and MYCN, represents a novel strategy to target MYCN-driven cancers.
This abstract is also presented as Poster B46.
Citation Format: W. Clay Gustafson, Justin G. Meyerowitz, Erin A. Nekritz, Elise Charron, Katherine K. Matthay, Nicholas T. Hertz, Martin Eilers, Kevan M. Shokat, William A. Weiss. Drugging MYCN protein stability through an allosteric transition in Aurora kinase A. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr PR08.
Adapting the Crossmodal Congruency Task for Measuring the Limits of Visual–Tactile Interactions Within and Between Groups
Authors: Poole Daniel , Poole Daniel , Couth Samuel , Poole Daniel , Couth Samuel , Gowen Emma , Poole Daniel , Couth Samuel , Gowen Emma , Warren Paul A. , Poole Daniel , Couth Samuel , Gowen Emma , Warren Paul A. , Poliakoff Ellen 
Published: May 2015

The crossmodal congruency task (CCT) is a commonly used paradigm for measuring visual–tactile interactions and how these may be influenced by discrepancies in space and time between the tactile target and visual distractors. The majority of studies which have used this paradigm have neither measured, nor attempted to control, individual variability in unisensory (tactile) performance. We have developed a version of the CCT in which unisensory baseline performance is constrained to enable comparisons within and between participant groups. Participants were instructed to discriminate between single and double tactile pulses presented to their dominant hand, at their own approximate threshold level. In Experiment 1, visual distractors were presented at −30 ms, 100 ms, 200 ms and 400 ms stimulus onset asynchronies. In Experiment 2, ipsilateral visual distractors were presented 0 cm, 21 cm, and 42 cm vertically from the target hand, and 42 cm in a symmetrical, contralateral position. Distractors presented −30 ms and 0 cm from the target produced a significantly larger congruency effect than at other time points and spatial locations. Thus, the typical limits of visual–tactile interactions were replicated using a version of the task in which baseline performance can be constrained. The usefulness of this approach is supported by the observation that tactile thresholds correlated with self-reported autistic traits in this non-clinical sample. We discuss the suitability of this adapted version of the CCT for measuring visual–tactile interactions in populations where unisensory tactile ability may differ within and between groups.
Visuotactile Temporal Recalibration Transfers Across Different Locations
Authors: Ho Hao Tam , Ho Hao Tam , Orchard-Mills Emily , Ho Hao Tam , Orchard-Mills Emily , Alais David 
Published: May 2015

Following prolonged exposure to audiovisual asynchrony, an observer’s point of subjective simultaneity (PSS) shifts in the direction of the leading modality. It has been debated whether other sensory pairings, such as vision and touch, lead to a similar temporal recalibration, and if so, whether the internal timing mechanism underlying lag visuotactile adaptation is centralised or distributed. To address these questions, we adapted observers to vision- and tactile-leading visuotactile asynchrony on either their left or right hand side in different blocks. In one test condition, participants performed a simultaneity judgment on the adapted side (unilateral) and in another they performed a simultaneity judgment on the non-adapted side (contralateral). In a third condition, participants adapted concurrently to equal and opposite asynchronies on each side and were tested randomly on either hand (bilateral opposed). Results from the first two conditions show that observers recalibrate to visuotactile asynchronies, and that the recalibration transfers to the non-adapted side. These findings suggest a centralised recalibration mechanism not linked to the adapted side and predict no recalibration for the bilateral opposed condition, assuming the adapted effects were equal on each side. This was confirmed in the group of participants that adapted to vision- and tactile-leading asynchrony on the right and left hand side, respectively. However, the other group (vision-leading on the left and tactile-leading on the right) did show a recalibration effect, suggesting a distributed mechanism. We discuss these findings in terms of a hybrid model that assumes the co-existence of a centralised and distributed timing mechanism.
Applying a Neighborhood Fractions Sampling Approach as a Diagnostic Tool
Authors: Nachamkin Jason E. , Schmidt Jerome 
Published: May 2015

Abstract
The fractions skill score (FSS) belongs to a class of spatial neighborhood techniques that measures forecast skill from samples of gridded forecasts and observations at increasing spatial scales. Each sample contains the fraction of the predicted and observed quantities that exist above a threshold value. Skill is gauged by the rate that the observed and predicted fractions converge with increasing scale. In this study, neighborhood sampling is applied to diagnose the performance of high-resolution (1.67 km) precipitation forecasts over central Florida. Reliability diagrams derived from the spatial fractions indicate that the FSS can be influenced by small, low-predictability events. Further tests indicate the FSS is subtly affected by samples from points on and near the grid boundaries. Inclusion of these points tends to reduce the magnitude and sensitivity of the FSS, especially at large scales. An attempt to mine data from the set of neighborhood fractions was moderately successful at obtaining descriptive information about the precipitation fields. The width of the distribution of the fractions at each scale provided information concerning forecast resolution and sharpness. The rate at which the distribution of the fractions converged toward the domain mean with increasing scale was found to be sensitive to the uniformity of coverage of precipitation through the domain. Generally, the 6-h forecasts possessed greater spatial skill than those at 12 h. High-FSS values at 12 h were mostly associated with evenly distributed precipitation patterns, while the 6-h forecasts also performed well for several nonuniform cases.
Serodiagnosis ofMycobacterium abscessuscomplex infection in cystic fibrosis
Authors: Qvist Tavs , Pressler Tania , Taylor-Robinson David , Katzenstein Terese L. , Høiby Niels 
Published: May 2015

Early signs of pulmonary disease withMycobacterium abscessuscomplex (MABSC) can be missed in patients with cystic fibrosis (CF). A serological method could help stratify patients according to risk. The objective of this study was to test the diagnostic accuracy of a novel method for investigating IgG activity against MABSC.A prospective study of all patients attending the Copenhagen CF Centre was conducted by culturing for MABSC during a 22-month period and then screening patients with an anti-MABSC IgG ELISA. Culture-positive patients had stored serum examined for antibody kinetics before and after culture conversion.307 patients had 3480 respiratory samples cultured and were then tested with the anti-MABSC IgG ELISA. Patients with MABSC pulmonary disease had median anti-MABSC IgG levels six-fold higher than patients with no history of infection (434versus64 ELISA units; p<0.001). The test sensitivity was 95% (95% CI 74–99%) and the specificity was 73% (95% CI 67–78%). A diagnostic algorithm was constructed to stratify patients according to risk.The test accurately identified patients with pulmonary disease caused by MABSC and was suited to be used as a complement to mycobacterial culture.
Tolstoy's oak tree metaphor: depression, recovery and psychiatric 'spiritual ecology’
Authors: Holmes Jeremy 
Published: May 2015

SummaryTolstoy's life and work illustrate resilience, the transcendence of trauma and the enduring impact of childhood loss. I have chosen the famous oak tree passage from War and Peace to illustrate recovery from the self-preoccupation of depression and the theme of ‘eco-spirituality’ – the idea that post-depressive connectedness and love apply not just to significant others but also to nature and the environment.
The Figure of the Prostitute, Tajdid, and Masculinity in Anticolonial Literature of Iraq
Authors: Bahoora Haytham 
Published: May 2015

Abstract
In the Iraqi literary production of the 1940s and 1950s, the figure of the woman prostitute appeared repeatedly, signaling a crisis in the ways Iraqi men imagined and articulated the contours of women’s liberation. Through an examination of works by Jabra Ibrahim Jabra, Fuʾad al-Takarli, and Badr Shakir al-Sayyab, this article argues that the innovative aesthetic forms and themes adopted by men writers and their dedication to political and cultural renewal (tajdid) and social reform used the figure of the prostitute to articulate a vision of women’s liberation that emphasized secular, urban, and middle-class notions of domesticity and respectability. The literary prostitute was a marginal figure used to envision a new era of women’s rights through her exclusion and excision from the imagined national future. The instrumentalization of the figure of the prostitute in Iraqi literary production revealed the limits of representation of the masculine imagination.
Poetry and Diplomacy in the Zuozhuan
Authors: Li Wai-Yee 
Published: May 2015

Abstract
Zuozhuan (ca. fourth century BC) records many instances of statesmen who recite or chant odes ( fushi), mostly from the extant Shijing, to convey their political vision, policy recommendation, or diplomatic finesse. This essay examines the implications of this confluence of poetry and diplomacy. Scholars have focused on fushi as seamless political communication, the celebration of a common cultural heritage, and the formalization of ritual judgment. I discuss how the practice of fushi negotiates political and cultural differences. How does it bear on the distinction of “Chinese” and “barbarians”? How does it define the struggle for supremacy, push for political advantage, and cover up weakness? Does the manipulation of meanings and interpretations indicate anxieties about the power of ritual propriety to correct political failures?
Nobody's Genre, Everybody's Song:SanquSongs and the Expansion of the Literary Sphere in Yuan China
Authors: Sieber Patricia 
Published: May 2015

AbstractThis article examines two key texts from early fourteenth-century Hangzhou to explore how they shaped the process of textualization of a new genre, the so-called sanqu songs. The article argues that both of these texts, the seminal anthology of the genre, the Yangchun baixue, and the first biographical compendium, the Lugui bu, sought to uncouple social status from literary reputation to varying degrees. The article suggests that the anthology made a case for a universalist poetic practice open to diasporic and Chinese writers, while the biographical collection took a more localist approach focused on urban Chinese writers. Taken together, they illustrate that the realm of songwriting in Yuan China constituted a contested discursive space that should not be solely understood in ethnic terms but can be enriched through the analytical perspectives of diaspora, cosmopolitanism, and urban culture.
Assessing the Potential Adoption and Usefulness of Concurrent, Action-Oriented,
Electronic Adverse Drug Event Triggers Designed for the Outpatient Setting
Authors: Mull Hillary J. , Rosen Amy K. , Shimada Stephanie L. , Rivard Peter E. , Nordberg Brian , Long Brenna , Hoffman Jennifer M. , Leecaster Molly , Savitz Lucy A. , Shanahan Christopher W. , Helwig Amy , Nebeker Jonathan R. 
Published: May 2015

Background: Adverse drug event (ADE) detection is an important priority for
patient safety research. Trigger tools have been developed to help identify ADEs. In
previous work we developed seven concurrent, action-oriented, electronic trigger
algorithms designed to prompt clinicians to address ADEs in outpatient
care.Objectives: We assessed the potential adoption and usefulness of the seven triggers
by testing the positive predictive validity and obtaining stakeholder input.Methods: We
adapted ADE triggers, “bone marrow toxin - white blood cell count (BMT‑WBC),” “bone
marrow toxin - platelet (BMT-platelet),” “potassium raisers,” “potassium reducers,”
“creatinine,” “warfarin,” and “sedative hypnotics,” with logic to suppress flagging
events with evidence of clinical intervention and applied the triggers to 50,145
patients from three large health care systems. Four pharmacists assessed trigger
positive predictive value (PPV) with respect to ADE detection (conservatively excluding
ADEs occurring during clinically appropriate care) and clinical usefulness (i.e.,
whether the trigger alert could change care to prevent harm). We measured agreement
between raters using the free kappa and assessed positive PPV for the trigger’s
detection of harm, clinical usefulness, and both. Stakeholders from the participating
health care systems rated the likelihood of trigger adoption and the perceived ease of
implementation.Findings: Agreement between pharmacist raters was moderately high for
each ADE trigger (kappa free > 0.60). Trigger PPVs for harm ranged from 0
(Creatinine, BMT-WBC) to 17 percent (potassium raisers), while PPV for care change
ranged from 0 (WBC) to 60 percent (Creatinine). Fifteen stakeholders rated the triggers.
Our assessment identified five of the seven triggers as good candidates for
implementation: Creatinine, BMT-Platelet, Potassium Raisers, Potassium Reducers, and
Warfarin.Conclusions: At least five outpatient ADE triggers performed well and merit
further evaluation in outpatient clinical care. When used in real time, these triggers
may promote care changes to ameliorate patient harm.
RNA-seq-Based Gene Annotation and Comparative Genomics of Four Fungal Grass Pathogens in the GenusZymoseptoriaIdentify Novel Orphan Genes and Species-Specific Invasions of Transposable Elements
Authors: Grandaubert Jonathan , Bhattacharyya Amitava , Stukenbrock Eva H 
Published: May 2015

AbstractThe fungal pathogen Zymoseptoria tritici (synonym Mycosphaerella graminicola) is a prominent pathogen of wheat. The reference genome of the isolate IPO323 is one of the best-assembled eukaryotic genomes and encodes more than 10,000 predicted genes. However, a large proportion of the previously annotated gene models are incomplete, with either no start or no stop codons. The availability of RNA-seq data allows better predictions of gene structure. We here used two different RNA-seq datasets, de novo transcriptome assemblies, homology-based comparisons, and trained ab initio gene callers to generate a new gene annotation of Z. tritici IPO323. The annotation pipeline was also applied to re-sequenced genomes of three closely related species of Z. tritici: Z. pseudotritici, Z. ardabiliae, and Z. brevis. Comparative analyses of the predicted gene models using the four Zymoseptoria species revealed sets of species-specific orphan genes enriched with putative pathogenicity-related genes encoding small secreted proteins that may play essential roles in virulence and host specificity. De novo repeat identification allowed us to show that few families of transposable elements are shared between Zymoseptoria species while we observe many species-specific invasions and expansions. The annotation data presented here provide a high-quality resource for future studies of Z. tritici and its sister species and provide detailed insight into gene and genome evolution of fungal plant pathogens.
Identification of Reproduction-Related Gene Polymorphisms Using Whole Transcriptome Sequencing in the Large White Pig Population
Authors: Fischer Daniel , Laiho Asta , Gyenesei Attila , Sironen Anu 
Published: May 2015

Abstract
Recent developments in high-throughput sequencing techniques have enabled large-scale analysis of genetic variations and gene expression in different tissues and species, but gene expression patterns and genetic variations in livestock are not well-characterized. In this study, we have used high-throughput transcriptomic sequencing of the Finnish Large White to identify gene expression patterns and coding polymorphisms within the breed in the testis and oviduct. The main objective of this study was to identify polymorphisms within genes that are highly and specifically expressed in male and/or female reproductive organs. The differential expression (DE) analysis underlined 1234 genes highly expressed in the testis and 1501 in the oviduct. Furthermore, we used a novel in-house R-package hoardeR for the identification of novel genes and their orthologs, which underlined 55 additional DE genes based on orthologs in the human, cow, and sheep. Identification of polymorphisms in the dataset resulted in a total of 29,973 variants, of which 10,704 were known coding variants. Fifty-seven nonsynonymous SNPs were present among genes with high expression in the testis and 67 were present in the oviduct, underlining possible influential genes for reproduction traits. Seven genes (PGR, FRAS1, TCF4, ADAT1, SPAG6, PIWIL2, and DNAH8) with polymorphisms were highlighted as reproduction-related based on their biological function. The expression and SNPs of these genes were confirmed using RT-PCR and Sanger sequencing. The identified nonsynonymous mutations within genes highly expressed in the testis or oviduct provide a list of candidate genes for reproduction traits within the pig population and enable identification of biomarkers for sow and boar fertility.
Judgment of Nasolabial Esthetics in Cleft Lip and Palate is Not Influenced by Overall Facial Attractiveness
Authors: Kocher Katharina , Kowalski Piotr , Kolokitha Olga-Elpis , Katsaros Christos , Fudalej Piotr S. 
Published: May 2015

Objective To determine whether judgment of nasolabial esthetics in cleft lip and palate (CLP) is influenced by overall facial attractiveness. Design Experimental study. Setting University of Bern, Switzerland. Subjects and Methods Seventy-two fused images (36 of boys, 36 of girls) were constructed. Each image comprised (1) the nasolabial region of a treated child with complete unilateral CLP (UCLP) and (2) the external facial features, i.e., the face with masked nasolabial region, of a noncleft child. Photographs of the nasolabial region of six boys and six girls with UCLP representing a wide range of esthetic outcomes, i.e., from very good to very poor appearance, were randomly chosen from a sample of 60 consecutively treated patients in whom nasolabial esthetics had been rated in a previous study. Photographs of external facial features of six boys and six girls without UCLP with various esthetics were randomly selected from patients' files. Eight lay raters evaluated the fused images using a 100-mm visual analogue scale. Method reliability was assessed by reevaluation of fused images after >1 month. A regression model was used to analyze which elements of facial esthetics influenced the perception of nasolabial appearance. Results Method reliability was good. A regression analysis demonstrated that only the appearance of the nasolabial area affected the esthetic scores of fused images (coefficient −11.44; P < .001; R2 = 0.464). The appearance of the external facial features did not influence perceptions of fused images. Conclusion Cropping facial images for assessment of nasolabial appearance in CLP seems unnecessary. Instead, esthetic evaluation can be performed on images of full faces.