bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative High-Throughput Identification of Drugs as Modulators of Human Constitutive Androstane Receptor
Authors: Lynch Caitlin , Zhao Jinghua , Huang Ruili , Xiao Jingwei , Li Linhao , Heyward Scott , Xia Menghang , Wang Hongbing 
Published: May 2015

AbstractThe constitutive androstane receptor (CAR, NR1I3) plays a key role in governing the transcription of numerous hepatic genes that involve xenobiotic metabolism/clearance, energy homeostasis and cell proliferation. Thus, identification of novel human CAR (hCAR) modulators may not only enhance early prediction of drug-drug interactions but also offer potentially novel therapeutics for diseases such as metabolic disorders and cancer. In this study, we have generated a double stable cell line expressing both hCAR and a CYP2B6-driven luciferase reporter for quantitative high-throughput screening (qHTS) of hCAR modulators. Approximately 2800 compounds from the NIH Chemical Genomics Center Pharmaceutical Collection were screened employing both the activation and deactivation modes of the qHTS. Activators (115) and deactivators (152) of hCAR were identified from the primary qHTS, among which 10 agonists and 10 antagonists were further validated in the physiologically relevant human primary hepatocytes for compound-mediated hCAR nuclear translocation and target gene expression. Collectively, our results reveal that hCAR modulators can be efficiently identified through this newly established qHTS assay. Profiling drug collections for hCAR activity would facilitate the prediction of metabolism-based drug-drug interactions and may lead to the identification of potential novel therapeutics.
Layer dependence and gas molecule absorption property in MoS2 Schottky diode with asymmetric metal contacts
Authors: Yoon Hyong Seo , Joe Hang-Eun , Jun Kim Sun , Lee Hee Sung , Im Seongil , Min Byung-Kwon , Jun Seong Chan 
Published: May 2015

AbstractSurface potential measurement on atomically thin MoS2 flakes revealed the thickness dependence in Schottky barriers formed between high work function metal electrodes and MoS2 thin flakes. Schottky diode devices using mono- and multi- layer MoS2 channels were demonstrated by employing Ti and Pt contacts to form ohmic and Schottky junctions respectively. Characterization results indicated n-type behavior of the MoS2 thin flakes and the devices showed clear rectifying performance. We also observed the layer dependence in device characteristics and asymmetrically enhanced responses to NH3 and NO2 gases based on the metal work function and the Schottky barrier height change.
A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer
Authors: Al-Tassan Nada A. , Whiffin Nicola , Hosking Fay J. , Palles Claire , Farrington Susan M. , Dobbins Sara E. , Harris Rebecca , Gorman Maggie , Tenesa Albert , Meyer Brian F. , Wakil Salma M. , Kinnersley Ben , Campbell Harry , Martin Lynn , Smith Christopher G. , Idziaszczyk Shelley , Barclay Ella , Maughan Timothy S. , Kaplan Richard , Kerr Rachel , Kerr David , Buchanan Daniel D. , Win Aung Ko , Hopper John , Jenkins Mark , Lindor Noralane M. , Newcomb Polly A. , Gallinger Steve , Conti David , Schumacher Fred , Casey Graham , Dunlop Malcolm G. , Tomlinson Ian P. , Cheadle Jeremy P. , Houlston Richard S. 
Published: May 2015

AbstractGenome-wide association studies (GWAS) of colorectal cancer (CRC) have identified 23 susceptibility loci thus far. Analyses of previously conducted GWAS indicate additional risk loci are yet to be discovered. To identify novel CRC susceptibility loci, we conducted a new GWAS and performed a meta-analysis with five published GWAS (totalling 7,577 cases and 9,979 controls of European ancestry), imputing genotypes utilising the 1000 Genomes Project. The combined analysis identified new, significant associations with CRC at 1p36.2 marked by rs72647484 (minor allele frequency [MAF] = 0.09) near CDC42 and WNT4 (P = 1.21 × 10−8, odds ratio [OR] = 1.21 ) and at 16q24.1 marked by rs16941835 (MAF = 0.21, P = 5.06 × 10−8; OR = 1.15) within the long non-coding RNA (lncRNA) RP11-58A18.1 and ~500 kb from the nearest coding gene FOXL1. Additionally we identified a promising association at 10p13 with rs10904849 intronic to CUBN (MAF = 0.32, P = 7.01 × 10-8; OR = 1.14). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CRC. Additionally, our analysis further demonstrates that imputation can be used to exploit GWAS data to identify novel disease-causing variants.
Continuous de novo biosynthesis of haem and its rapid turnover to bilirubin are necessary for cytoprotection against cell damage
Authors: Takeda Taka-aki , Mu Anfeng , Tai Tran Tien , Kitajima Sakihito , Taketani Shigeru 
Published: May 2015

AbstractIt is well known that haem serves as the prosthetic group of various haemoproteins that function in oxygen transport, respiratory chain and drug metabolism. However, much less is known about the functions of the catabolites of haem in mammalian cells. Haem is enzymatically degraded to iron, carbon monoxide (CO) and biliverdin, which is then converted to bilirubin. Owing to difficulties in measuring bilirubin, however, the generation and transport of this end product remain unclear despite its clinical importance. Here, we used UnaG, the recently identified bilirubin-binding fluorescent protein, to analyse bilirubin production in a variety of human cell lines. We detected a significant amount of bilirubin with many non-blood cell types, which was sensitive to inhibitors of haem metabolism. These results suggest that there is a basal level of haem synthesis and its conversion into bilirubin. Remarkably, substantial changes were observed in the bilirubin generation when cells were exposed to stress insults. Since the stress-induced cell damage was exacerbated by the pharmacological blockade of haem metabolism but was ameliorated by the addition of biliverdin and bilirubin, it is likely that the de novo synthesis of haem and subsequent conversion to bilirubin play indispensable cytoprotective roles against cell damage.
Optical pumping and readout of bismuth hyperfine states in silicon for atomic clock applications
Authors: Saeedi K. , Szech M. , Dluhy P. , Salvail J.Z. , Morse K.J. , Riemann H. , Abrosimov N.V. , Nötzel N. , Litvinenko K.L. , Murdin B.N. , Thewalt M.L.W. 
Published: May 2015

AbstractThe push for a semiconductor-based quantum information technology has renewed interest in the spin states and optical transitions of shallow donors in silicon, including the donor bound exciton transitions in the near-infrared and the Rydberg, or hydrogenic, transitions in the mid-infrared. The deepest group V donor in silicon, bismuth, has a large zero-field ground state hyperfine splitting, comparable to that of rubidium, upon which the now-ubiquitous rubidium atomic clock time standard is based. Here we show that the ground state hyperfine populations of bismuth can be read out using the mid-infrared Rydberg transitions, analogous to the optical readout of the rubidium ground state populations upon which rubidium clock technology is based. We further use these transitions to demonstrate strong population pumping by resonant excitation of the bound exciton transitions, suggesting several possible approaches to a solid-state atomic clock using bismuth in silicon, or eventually in enriched 28Si.
Method of preparing an equimolar DNA mixture for one-step DNA assembly of over 50 fragments
Authors: Tsuge Kenji , Sato Yukari , Kobayashi Yuka , Gondo Maiko , Hasebe Masako , Togashi Takashi , Tomita Masaru , Itaya Mitsuhiro 
Published: May 2015

AbstractIn the era of synthetic biology, techniques for rapidly constructing a designer long DNA from short DNA fragments are desired. To realize this, we attempted to establish a method for one-step DNA assembly of unprecedentedly large numbers of fragments. The basic technology is the Ordered Gene Assembly in Bacillus subtilis (OGAB) method, which uses the plasmid transformation system of B. subtilis. Since this method doesn’t require circular ligation products but needs tandem repeat ligation products, the degree of deviation in the molar concentration of the material DNAs is the only determinant that affects the efficiency of DNA assembly. The strict standardization of the size of plasmids that clone the DNA block and the measurement of the block in the state of intact plasmid improve the reliability of this step, with the coefficient of variation of the molar concentrations becoming 7%. By coupling this method with the OGAB method, one-step assembly of more than 50 DNA fragments becomes feasible.
Laser Shock Peening on Zr-based Bulk Metallic Glass and Its Effect on Plasticity: Experiment and Modeling
Authors: Cao Yunfeng , Xie Xie , Antonaglia James , Winiarski Bartlomiej , Wang Gongyao , Shin Yung C. , Withers Philip J. , Dahmen Karin A. , Liaw Peter K. 
Published: May 2015

AbstractThe Zr-based bulk metallic glasses (BMGs) are a new family of attractive materials with good glass-forming ability and excellent mechanical properties, such as high strength and good wear resistance, which make them candidates for structural and biomedical materials. Although the mechanical behavior of BMGs has been widely investigated, their deformation mechanisms are still poorly understood. In particular, their poor ductility significantly impedes their industrial application. In the present work, we show that the ductility of Zr-based BMGs with nearly zero plasticity is improved by a laser shock peening technique. Moreover, we map the distribution of laser-induced residual stresses via the micro-slot cutting method and then predict them using a three-dimensional finite-element method coupled with a confined plasma model. Reasonable agreement is achieved between the experimental and modeling results. The analyses of serrated flows reveal plentiful and useful information of the underlying deformation process. Our work provides an easy and effective way to extend the ductility of intrinsically-brittle BMGs, opening up wider applications of these materials.
‘Dying of the Fifth Act’: Corneille's (Un)Natural Deaths
Authors: Harris Joseph 
Published: May 2015

Abstract

Generally speaking, deaths in tragedy involve murder or suicide. This article brings together a handful of disparate cases, from within Corneille's dramatic work, of deaths that do not fit into this typical tragic schema. Such deaths held something of a fascination for Corneille throughout his career: between his comedy
L'Illusion comique
(1635) and his swansong tragedy
Suréna
(1674), four of his female characters die of a broken heart, and one man is struck down by a lethal haemorrhage. Although these ‘(un)natural deaths’ clearly compromise
vraisemblance
, the very backbone of seventeenth-century dramaturgy, Corneille is also keen to harness their potential benefits as a source of dramatic, ethical, or emotional effect. This article traces the various techniques that Corneille adopts in order to integrate such causally problematic deaths into his plays. As I argue, although Corneille never settles for a single strategy (sometimes refusing to re-use even techniques he deems successful), he increasingly tends to draw on his rhetorical skills to ‘prepare’ these potentially awkward deaths on a thematic or poetic level. This becomes most poignantly clear at the end of his final tragedy
Suréna
, which reworks elements of his earlier ‘(un)natural deaths’ to unexpectedly elegiac effect.
Descemet Stripping Automated Endothelial Keratoplasty for Endothelial Dysfunction in Xeroderma Pigmentosum: A Clinicopathological Correlation and Review of Literature
Authors: Vira Divya , Fernandes Merle , Mittal Ruchi 
Published: May 2015

Abstract:
Xeroderma pigmentosum (XP) mainly affects the ocular surface; however, endothelial damage may also occur. We would like to report changes in the endothelial–Descemet layer and review the literature on similar findings in patients with XP, including the role of Descemet stripping automated endothelial keratoplasty (DSAEK) in the management of a 21-year-old man who presented with nonresolving corneal edema in the right eye after excision biopsy for conjunctival intraepithelial neoplasia. His best-corrected visual acuity (BCVA) was 20/200 in the right eye and 20/20 in the left eye. On general examination, there was patchy hyperpigmentation of the exposed areas of skin suggestive of XP. On examination of the right eye, there was stromal edema involving the exposed half of cornea. The left eye appeared normal. Pachymetry readings were 860 and 600 μm in the right and left eye, respectively. Descemet stripping automated endothelial keratoplasty was performed for endothelial dysfunction and the stripped endothelium, and Descemet membrane (DM) was sent for histopathologic evaluation. Postoperatively, the donor lenticule was well apposed and the overlying stromal edema resolved. The patient achieved a BCVA of 20/30 in the right eye without progression of corneal scarring at 1-year follow-up. In the meanwhile, however, the left eye developed corneal edema. Histopathology revealed gross attenuation of endothelial cells with uniform thickness of the DM. Corneal endothelial dysfunction in XP is amenable to treatment with DSAEK.
The Cf-4 receptor-like protein associates with the BAK1 receptor-like kinase to initiate receptor endocytosis and plant immunity
Authors: Postma Jelle , Liebrand Thomas W. H. , Bi Guozhi , Evrard Alexandre , Bye Ruby R. , Mbengue Malick , Joosten Matthieu H. A. J. , Robatzek Silke 
Published: May 2015

SummaryThe first layer of plant immunity is activated by cell surface receptor-like kinases (RLKs) and proteins (RLPs) that detect infectious pathogens. Constitutive interaction with the RLK SUPPRESSOR OF BIR1 (SOBIR1) contributes to RLP stability and kinase activity. As RLK activation requires transphosphorylation with a second associated RLK, it remains elusive how RLPs initiate downstream signaling. To address this, we investigated functioning of Cf RLPs that mediate immunity of tomato againstCladosporium fulvum.We employed live-cell imaging and co-immunoprecipitation in tomato andNicotiana benthamianato investigate the requirement of associated kinases for Cf activity and ligand-induced subcellular trafficking of Cf-4.Upon elicitation with the matching effector ligands Avr4 and Avr9, BRI1-ASSOCIATED KINASE 1 (BAK1) associates with Cf-4 and Cf-9. Furthermore, Cf-4 that interacts with SOBIR1 at the plasma membrane, is recruited to late endosomes after elicitation. Significantly, BAK1 is required for Avr4-triggered endocytosis, effector-triggered defenses in Cf-4 plants and resistance of tomato againstC. fulvum.Our observations indicate that RLP-mediated immune signaling and endocytosis require ligand-induced recruitment of BAK1, reminiscent of BAK1 interaction and subcellular fate of the FLAGELLIN SENSING 2 RLK. This reveals that diverse classes of cell surface immune receptors share common requirements for signaling initiation and endocytosis.
Rust fungal effectors mimic host transit peptides to translocate into chloroplasts
Authors: Petre Benjamin , Lorrain Cécile , Saunders Diane G.O. , Duplessis Sébastien , Kamoun Sophien 
Published: May 2015

SUMMARYParasite effector proteins target various host cell compartments to alter host processes and promote infection. How effectors cross membrane-rich interfaces to reach these compartments is a major question in effector biology. Growing evidence suggests that effectors use molecular mimicry to subvert host cell machinery for protein sorting. We recently identified CTP1 (chloroplast-targetedprotein 1), a candidate effector from the poplar leaf rust fungusMelampsora larici-populinathat carries a predicted transit peptide and accumulates in chloroplasts. Here, we show that the CTP1 transit peptide is necessary and sufficient for accumulation in the stroma of chloroplasts, and is cleaved after translocation. CTP1 is part of aMelampsora-specific family of polymorphic secreted proteins whose members translocate and are processed in chloroplasts in a N-terminal signal-dependent manner. Our findings reveal that fungi have evolved effector proteins that mimic plant-specific sorting signals to traffic within plant cells.
Attention selectively gates afferent signal transmission to area V4
Authors: Grothe Iris , Rotermund David , Neitzel Simon David , Mandon Sunita , Ernst Udo Alexander , Kreiter Andreas Kurt , Pawelzik Klaus Richard 
Published: May 2015

AbstractSelective attention causes visual cortical neurons to act as if only one of multiple stimuli are within their receptive fields. This suggests that attention employs a, yet unknown, neuronal gating mechanism for transmitting only the information that is relevant for the current behavioral context. We introduce an experimental paradigm to causally investigate this putative gating and the mechanism underlying selective attention by determining the signal availability of two time-varying stimuli in local field potentials of V4 neurons. We find transmission of the low frequency (<20Hz) components only from the attended visual input signal and that the higher frequencies from both stimuli are attenuated. A minimal model implementing routing by synchrony replicates the attentional gating effect and explains the spectral transfer characteristics of the signals. It supports the proposal that selective gamma-band synchrony subserves signal routing in cortex and further substantiates our experimental finding that attention selectively gates signals already at the level of afferent synaptic input.
Impacts of climate change on agro-ecological landscapes in the coastal area of the Thai Binh province (Vietnam) using the Delphi technique
Authors: Trinh Hai Le , An Thinh Nguyen , Anh Tuan Tran , Dinh Cham Dao , The Anh Luu , Luu Thu Thuy Hoang , Manh Ha Nguyen , Quoc Bao Tran , Van Huong Le , Dinh Khanh Uong , Thi Mai Bui , Phuc Tuan Tong , Hai Hoang , Truong Quang Hai 
Published: May 2015

Purpose– This paper aims to facilitate the joint assessment of issues related to the agricultural systems, i.e. agriculture, aquaculture and climate change (CC) response strategies, in the coastal districts with a panel of stakeholders; and to evaluate the level of agreement on the topics under consideration and potentially identify the most promising approaches to assessing CC affecting agricultural systems in the area and identify relevant and adequate response strategies.Design/methodology/approach– Stakeholder Delphi technique – its assessment is an interactive method of qualitative research used to facilitate the interactive participation of varied and conceivably hierarchical and antagonistic stakeholder groups.Findings– The most important result for the province is that the impact of climate change on agro-ecological landscapes (poverty and near river areas) is the duration of cold weather, more frequent and extreme. Moreover, Kendall’s W test gave a score of 0.547, which indicates a “strong” stakeholder agreement and the “confidence in ranks” being “high” in Thai Binh (Vietnam).Originality/value– The scientific results in this study are intended to serve as relevant knowledge-inputs and direct contributions to capacity-building for the local partners (stakeholders and local authorities). These local partners are engaged in policy-making and effective planning and implementation of climate response measures in the districts in the province of Thai Binh.
From barriers to bridges: approaching accessibility in course design
Authors: Varonis Evangeline Marlos 
Published: May 2015

Purpose
– The purpose of this paper is to explore how the principles of universal design can be implemented by faculty and course designers to help give all learners access to equivalent information. It describes how information communication technologies can create barriers to information access, particularly when course content is rich in multimedia, but also how such technologies can be utilized to creates bridges to accessible content through designing for accessibility from the outset.

Design/methodology/approach
– This paper offers a brief review of current international guidelines and US legislation related to information communication technologies in higher education. It documents the challenge of meeting these best practices and legal mandates, as evidenced by recent legal cases in the USA resulting from inaccessible course content in higher education. Finally, it describes how universal design can enhance accessibility for individuals with visual, hearing, motor, and cognitive impairments and provides concrete suggestions for making content more accessible to all learners, not just those with disabilities.

Findings
– Given the challenges of creating accessible content that provides equivalent information to all learners, faculty and course designers can implement the principles of Universal Design to enhance the learning environment for all students and ensure they are in compliance with guidelines and regulations. Such compliance is facilitated by emerging standards for accessible content and emerging technologies for making content accessible to all without the need for special accommodations.

Originality/value
– This paper focusses on concrete approaches to achieving accessibility in higher education, a matter of increasing concern for moral reasons (it is the right thing to do) and for legal reasons given recent lawsuits.
Bringing the national interlending system into the local document supply process – a Swedish case study
Authors: Gavel Ylva 
Published: May 2015

Purpose
– The purpose of this paper is to describe how systems automating the local document supply process (such as integrated library systems and ILL management systems) can be integrated with systems automating regional document requesting (interlending). This is illustrated with a case study of DocFlow, an ILL management system developed in-house at Karolinska Institutet and its integration with Libris, the national interlending system in Sweden.

Design/methodology/approach
– The present paper describes how system integration between Libris and DocFlow was accomplished in practice. It also discusses various aspects of integration between systems offering automation of document supply.

Findings
– Integration between local document supply workflows and regional document request flows may involve techniques such as import of outgoing and incoming interlending requests, synchronization of status values between systems, exchange of messages between systems and quick links to the native interfaces of external systems.

Practical implications
– The paper brings up various aspects to consider when developing or procuring a system for the local management of ILL workflows.

Originality/value
– The paper may provide a deeper understanding of system integration, as it applies to the document supply process.