bluuebunny/crossref_metadata_2025_split huggingface dataset:
King Lear, Heartbreak House, and the Dynamics of Inertia
Authors: Gamboa Brett 
Published: May 2015

ABSTRACT
In light of its fragmented dramaturgy and contemporary concerns, on the one hand, and its extensive debt to the structures and characters of Shakespeare's King Lear, on the other, Heartbreak House deserves consideration as both Shaw's most experimental and most derivative play. Such a paradox was familiar to Shaw, but the tension between the play's modernity and its classical inheritance may obscure Shaw's insights into Shakespeare's dramaturgy and the uses he made of them. In fact, the most urgently modern aspects of Heartbreak House are not its references to airships or dynamite but its absorption and adaptation of a theory of tragedy implicit in Lear: namely, that through temporal and emotional endurance, inertia, and a deliberate unwillingness to make good on implicit contracts established with audiences, a play can deepen engagement with the plot by creating doubt about its continuance. Shaw's play opens up modernity to us less by what it chooses to represent than by its strategies for structuring audience anticipation and disappointment, strategies that represent the play's chief inheritance from Lear. As a result, Shakespeare's influence is rather more constitutive of than contrary to Shaw's modernity.
Geneva—or the Failure of Rationalism
Authors: Zorn Christa 
Published: May 2015

ABSTRACT
Shaw's farcical representation of Hitler in his late play, Geneva, has been criticized as inadequate and inappropriate, since he mocks democratic institutions as powerless while letting the dictator get away with his self-serving agenda. But if we read Geneva as an experiment with modernist strategies, rather than as a play in the realist tradition, we discover that Shaw is making interesting new assumptions about historical discourse that are buried in the unrecognized inner frames and deeper structures of this late play. Shaw seems to envision political discourse in which specific positions are no longer confined to individual speakers, but are disseminated throughout a public sphere that is not just based on rational judgment. Instead, Shaw's dramatic devices direct us to the less visible and less reasonable forces in public discourse as well as to the mythic and irrational forces behind political power.
Mineração de dados: aplicações, ferramentas, tipos de aprendizado e outros subtemas
Authors: Carvalho Deborah Ribeiro , Dallagassa Marcelo Rosano 
Published: June 2015

Especialistas na área de mineração de dados apresentam conceitos, características, limites e potencialidades da mineração de dados, incluindo indicação de ferramentas disponíveis, relações com a inteligência artificial, e implicações de seu uso na área de business intelligence.
Un piratage énonciatif signé La Rédaction ? Le cas Valérie par Valérie (2008)
Authors: Farah Alain 
Published: June 2015

L’ouvrage Valérie par Valérie paraît en 2008 aux éditions Al Dante/Questions théoriques. Il porte la signature de La Rédaction, collectif dont la paternité est attribuée à Christophe Hanna. Ce livre contient le témoignage d’une ancienne figure de la téléréalité, phagocyté par la parole, le ton et les préoccupations d’un « nègre ». À travers cette narration indécidable se dévoilent les rouages d’un procédé de piratage de l’écriture, en même temps qu’émerge une mise en question du statut d’auteur, voire de l’acte créateur lui-même. Présentant l’écrivain comme un rédacteur, et l’écriture comme un agencement de fragments glanés au fil de ponctions et de vols, Valérie par Valérie actualise ainsi l’attaque dirigée par Isidore Ducasse contre la fétichisation de la signature auctoriale.
Determination of GPCR Phosphorylation Status: Establishing a Phosphorylation Barcode
Authors: Prihandoko Rudi , Bradley Sophie J. , Tobin Andrew B. , Butcher Adrian J. 
Published: June 2015

AbstractG protein−coupled receptors (GPCRs) are rapidly phosphorylated following agonist occupation in a process that mediates receptor uncoupling from its cognate G protein, a process referred to as desensitization. In addition, this process provides a mechanism by which receptors can engage with arrestin adaptor molecules and couple to downstream signaling pathways. The importance of this regulatory process has been highlighted recently by the understanding that ligands can direct receptor signaling along one pathway in preference to another, the phenomenon of signaling bias that is partly mediated by the phosphorylation status or phosphorylation barcode of the receptor. Methods to determine the phosphorylation status of a GPCR in vitro and in vivo are necessary to understand not only the physiological mechanisms involved in GPCR signaling, but also to fully examine the signaling properties of GPCR ligands. This unit describes detailed methods for determining the overall phosphorylation pattern on a receptor (the phosphorylation barcode), as well as mass spectrometry approaches that can define the precise sites that become phosphorylated. These techniques, coupled with the generation and characterization of receptor phosphorylation‐specific antibodies, provide a full palate of techniques necessary to determine the phosphorylation status of any given GPCR subtype. © 2015 by John Wiley & Sons, Inc.
Rodent Models of Amyotrophic Lateral Sclerosis
Authors: Philips Thomas , Rothstein Jeffrey D. 
Published: June 2015

AbstractAmyotrophic Lateral Sclerosis (ALS) is a motor neuron disease affecting upper and lower motor neurons in the central nervous system. Patients with ALS develop extensive muscle wasting and atrophy leading to paralysis and death 3 to 5 years after disease onset. The condition may be familial (fALS 10%) or sporadic ALS (sALS, 90%). The large majority of fALS cases are due to genetic mutations in the Superoxide dismutase 1 gene (SOD1, 15% of fALS) and repeat nucleotide expansions in the gene encoding C9ORF72 (∼40% to 50% of fALS and ∼10% of sALS). Studies suggest that ALS is mediated through aberrant protein homeostasis (i.e., ER stress and autophagy) and/or changes in RNA processing (as in all non‐SOD1‐mediated ALS). In all of these cases, animal models suggest that the disorder is mediated non‐cell autonomously, i.e., not only motor neurons are involved, but glial cells including microglia, astrocytes, and oligodendrocytes, and other neuronal subpopulations are also implicated in the pathogenesis. Provided in this unit is a review of ALS rodent models, including discussion of their relative advantages and disadvantages. Emphasis is placed on correlating the model phenotype with the human condition and the utility of the model for defining the disease process. Information is also presented on RNA processing studies in ALS research, with particular emphasis on the newest ALS rodent models. © 2015 by John Wiley & Sons, Inc.
Overview of Genetically Engineered Mouse Models of Papillary and Anaplastic Thyroid Cancers: Enabling Translational Biology for Patient Care Improvement
Authors: Charles Roch‐Philippe 
Published: June 2015

AbstractThe prognosis from thyroid cancer subtypes in humans covers a spectrum from “cured at almost 90%” to “100% lethal.” Invasive and poorly differentiated forms of thyroid cancer are among the most aggressive human cancers, and there are few effective therapeutic options. Genetically engineered mice, based on mutations observed in patients, can accurately recapitulate the human disease and its progression, providing invaluable tools for the preclinical evaluation of novel therapeutic approaches. This overview details models developed to date as well as their uses for identifying novel anticancer agents. © 2015 by John Wiley & Sons, Inc.
Proteasomes: Isolation and Activity Assays
Authors: Li Yanjie , Tomko Robert J. , Hochstrasser Mark 
Published: June 2015

AbstractIn eukaryotes, damaged or unneeded proteins are typically degraded by the ubiquitin‐proteasome system. In this system, the protein substrate is often first covalently modified with a chain of ubiquitin polypeptides. This chain serves as a signal for delivery to the 26S proteasome, a 2.5‐MDa, ATP‐dependent multisubunit protease complex. The proteasome consists of a barrel‐shaped 20S core particle (CP) that is capped on one or both of its ends by a 19S regulatory particle (RP). The RP is responsible for recognizing the substrate, unfolding it, and translocating it into the CP for destruction. Here we describe simple, one‐step purifications scheme for isolating the 26S proteasome and its 19S RP and 20S CP subcomplexes from the yeast Saccharomyces cerevisiae, as well as assays for measuring ubiquitin‐dependent and ubiquitin‐independent proteolytic activity in vitro. © 2015 by John Wiley & Sons, Inc.
In Vitro Analysis of the Very‐Low Density Lipoprotein Export from the Trans‐Golgi Network
Authors: Siddiqi Shadab A. 
Published: June 2015

AbstractThe movement of mature VLDL particles from the TGN to the plasma membrane (PM) is a complex physiological process that plays a critical role in hepatic lipid homeostasis. However, the molecular mechanisms regulating these intracellular transport events had not been studied until recently because of the lack of appropriate molecular assays and techniques. This unit provides a detailed description of cell‐free approaches and techniques to study the TGN‐to‐PM transport of the mature VLDL at the molecular level. A major emphasis is placed on the preparation and purification of sub‐cellular organelles because the success of in vitro assays for the vesicle formation and fusion depends on the quality of the isolated TGN, hepatic PM and hepatic cytosol. A number of critical factors that control the formation of mature VLDL‐containing vesicle, the PG‐VTV, from the TGN and their subsequent targeting to and fusion with the hepatic PM have been discussed. © 2015 by John Wiley & Sons, Inc.
Identification and Characterization of Tunneling Nanotubes for Intercellular Trafficking
Authors: Abounit Saïda , Delage Elise , Zurzolo Chiara 
Published: June 2015

AbstractTunneling nanotubes (TNTs) are thin membranous channels providing direct cytoplasmic connection between remote cells. They are commonly observed in different cell cultures and increasing evidence supports their role in intercellular communication and pathogen transfer. However, the study of TNTs presents several pitfalls (e.g., difficulty in preserving such delicate structures, possible confusion with other protrusions, structural and functional heterogeneity, etc.) and therefore requires thoroughly designed approaches. The methods described in this unit represent a guideline for the characterization of TNTs (or TNT‐like structures) in cell culture. Specifically, optimized protocols to (1) identify TNTs and the cytoskeletal elements present inside them; (2) evaluate TNT frequency in cell culture; (3) unambiguously distinguish them from other cellular connections or protrusions; and (4) monitor their formation in living cells are provided. Finally, this unit describes how to assess TNT‐mediated cell‐to‐cell transfer of cellular components, which is a fundamental criterion for identifying functional TNTs. © 2015 by John Wiley & Sons, Inc.
Variability and trends in global drought
Authors: McCabe Gregory J. , Wolock David M. 
Published: June 2015

AbstractMonthly precipitation (P) and potential evapotranspiration (PET) from the CRUTS3.1 data set are used to compute monthly P minus PET (PMPE) for the land areas of the globe. The percent of the global land area with annual sums of PMPE less than zero are used as an index of global drought (%drought) for 1901 through 2009. Results indicate that for the past century %drought has not changed, even though global PET and temperature (T) have increased. Although annual global PET and T have increased, annual global P also has increased and has mitigated the effects of increased PET on %drought.
A decline in Arctic Ocean mercury suggested by differences in decadal trends of atmospheric mercury between the Arctic and northern midlatitudes
Authors: Chen Long , Zhang Yanxu , Jacob Daniel J. , Soerensen Anne L. , Fisher Jenny A. , Horowitz Hannah M. , Corbitt Elizabeth S. , Wang Xuejun 
Published: June 2015

AbstractAtmospheric mercury (Hg) in the Arctic shows much weaker or insignificant annual declines relative to northern midlatitudes over the past decade (2000–2009) but with strong seasonality in trends. We use a global ocean‐atmosphere model of Hg (GEOS‐Chem) to simulate these observed trends and determine the driving environmental variables. The atmospheric decline at northern midlatitudes can largely be explained by decreasing North Atlantic oceanic evasion. The midlatitude atmospheric signal propagates to the Arctic but is countered by rapid Arctic warming and declining sea ice, which suppresses deposition and promotes oceanic evasion over the Arctic Ocean. The resulting simulation implies a decline of Hg in the Arctic surface ocean that we estimate to be −0.67% yr−1 over the study period. Rapid Arctic warming and declining sea ice are projected for future decades and would drive a sustained decline in Arctic Ocean Hg, potentially alleviating the methylmercury exposure risk for northern populations.
Chemical weathering and long‐term CO2 consumption in the Ayeyarwady and Mekong river basins in the Himalayas
Authors: Manaka Takuya , Otani Souya , Inamura Akihiko , Suzuki Atsushi , Aung Thura , Roachanakanan Raywadee , Ishiwa Takeshige , Kawahata Hodaka 
Published: June 2015

AbstractThe role of terrestrial river systems in the global carbon cycle on a long timescale has been a subject of interest, especially in the context of past climate changes such as the global cooling in the Cenozoic. The discharges of water and carbon into the ocean from the Himalayan watersheds are among the highest in the world. However, there are few reliable geochemical data from the Ayeyarwady River. This study focused on reevaluating chemical weathering in the Himalayan watersheds based on samples taken from the Ayeyarwady, Mekong, and Chao Phraya Rivers and on chemical analysis of the composition of dissolved substances in these rivers. Comparisons of water quality showed that, unlike in previous studies, the total alkalinity budgets of the Ayeyarwady are dominated by carbonate rather than silicate weathering. Long‐term CO2 consumption by silicate weathering in the Ayeyarwady is estimated to be only 63–145 × 109 mol yr−1, which is only 10% of the previous estimate. Our results also suggest that the total Himalayan watersheds account for only about 10% of the total global CO2 consumption by silicate weathering. Although we need further studies, chemical weathering and associated CO2 uptake in the Himalayas likely played a lesser role in long‐term global cooling in the past than previously appreciated.
Tissue‐Specific Regulation of Oncogene Expression Using Cre‐Inducible ROSA26 Knock‐In Transgenic Mice
Authors: Carofino Brandi L. , Justice Monica J. 
Published: June 2015

AbstractCre‐inducible mouse models are often utilized for the spatial and temporal expression of oncogenes. With the wide number of Cre recombinase lines available, inducible transgenesis represents a tractable approach to achieve discrete oncogene expression. Here, we describe a protocol for targeting Cre‐inducible genes to the ubiquitously expressed ROSA26 locus. Gene targeting provides several advantages over standard transgenic techniques, including a known site of integration and previously characterized pattern of expression. Historically, an inherent instability of ROSA26 targeting vectors has hampered the efficiency of developing ROSA26 knock‐in lines. In this protocol, we provide individual steps for utilizing Gateway recombination for cloning as well as detailed instructions for screening targeted ES cell clones. By following this protocol, one can achieve germline transmission of a ROSA26 knock‐in line within several months. © 2015 by John Wiley & Sons, Inc.
Olfactory identification deficits and increased mortality in the community
Authors: Devanand Davangere P. , Lee Seonjoo , Manly Jennifer , Andrews Howard , Schupf Nicole , Masurkar Arjun , Stern Yaakov , Mayeux Richard , Doty Richard L. 
Published: June 2015

ObjectiveTo examine the association between odor identification deficits and future mortality in a multiethnic community cohort of older adults.MethodsParticipants were evaluated with the 40‐item University of Pennsylvania Smell Identification Test (UPSIT). Follow‐up occurred at 2‐year intervals with information on death obtained from informant interviews and the National Death Index.ResultsDuring follow‐up (mean = 4.1 years, standard deviation = 2.6), 349 of 1,169 (29.9%) participants died. Participants who died were more likely to be older (p < 0.001), be male (p < 0.001), have lower UPSIT scores (p < 0.001), and have a diagnosis of dementia (p < 0.001). In a Cox model, the association between lower UPSIT score and mortality (hazard ratio [HR] = 1.07 per point interval, 95% confidence interval [CI] = 1.05–1.08, p < 0.001) persisted after controlling for age, gender, education, ethnicity, language, modified Charlson medical comorbidity index, dementia, depression, alcohol abuse, head injury, smoking, body mass index, and vision and hearing impairment (HR = 1.05, 95% CI = 1.03–1.07, p < 0.001). Compared to the fourth quartile with the highest UPSIT scores, HRs for mortality for the first, second, and third quartiles of UPSIT scores were 3.81 (95% CI = 2.71–5.34), 1.75 (95% CI = 1.23–2.50), and 1.58 (95% CI = 1.09–2.30), respectively. Participant mortality rate was 45% in the lowest quartile of UPSIT scores (anosmia) and 18% in the highest quartile of UPSIT scores.InterpretationImpaired odor identification, particularly in the anosmic range, is associated with increased mortality in older adults even after controlling for dementia and medical comorbidity. Ann Neurol 2015;78:401–411
Sulfated Carbon Quantum Dots as Efficient Visible‐Light Switchable Acid Catalysts for Room‐Temperature Ring‐Opening Reactions
Authors: Li Haitao , Sun Chenghua , Ali Muataz , Zhou Fengling , Zhang Xinyi , MacFarlane Douglas R. 
Published: June 2015

AbstractAcid catalytic processes play a classic and important role in modern organic synthesis. How well the acid can be controlled often plays the key role in the controllable synthesis of the products with high conversion yield and selectivity. The preparation of a novel, photo‐switchable solid‐acid catalyst based on carbon quantum dots is described. The carbon quantum dots are decorated with small amounts of hydrogensulfate groups and thus exhibit a photogenerated acidity that produces a highly efficient acid catalysis of the ring opening of epoxides with methanol and other primary alcohols. This reversible, light‐switchable acidity is shown to be due to photoexcitation and charge separation in the carbon quantum dots, which create an electron withdrawing effect from the acidic groups. The catalyst is easily separated by filtration, and we demonstrate multiple cycles of its recovery and reuse.
Pd‐Catalyzed Regioselective Activation of gem‐Difluorinated Cyclopropanes: A Highly Efficient Approach to 2‐Fluorinated Allylic Scaffolds
Authors: Xu Jun , Ahmed Ebrahim‐Alkhalil , Xiao Bin , Lu Qian‐Qian , Wang Yun‐Long , Yu Chu‐Guo , Fu Yao 
Published: June 2015

AbstractAn unprecedented Pd‐catalyzed regioselective activation of gem‐difluorinated cyclopropanes induced by CC bond cleavage is reported. It provides a general and efficient access to a variety of 2‐fluoroallylic amines, ethers, esters, and alkylation products in high Z‐selectivity, which are important skeletons in many biologically active molecules. In addition, the transformation represents the first general application of gem‐difluorinated cyclopropanes as reaction partners in transition‐metal‐catalyzed cross‐coupling reaction.
Highly Efficient Glutathione Peroxidase and Peroxiredoxin Mimetics Protect Mammalian Cells against Oxidative Damage
Authors: Bhowmick Debasish , Srivastava Shubhi , D'Silva Patrick , Mugesh Govindasamy 
Published: June 2015

AbstractNovel isoselenazoles with high glutathione peroxidase (GPx) and peroxiredoxin (Prx) activities provide remarkable cytoprotection to human cells, mainly by exhibiting antioxidant activities in the presence of cellular thiols. The cytotoxicity of the isoselenazoles is found to be significantly lower than that of ebselen, which is being clinically evaluated by several groups for the treatment of reperfusion injuries and stroke, hearing loss, and bipolar disorder. The compounds reported in this paper have the potential to be used as therapeutic agents for disorders mediated by reactive oxygen species.
One‐Step Synthesis of Self‐Supported Nickel Phosphide Nanosheet Array Cathodes for Efficient Electrocatalytic Hydrogen Generation
Authors: Wang Xiaoguang , Kolen'ko Yury V. , Bao Xiao‐Qing , Kovnir Kirill , Liu Lifeng 
Published: June 2015

AbstractNickel phosphide is an emerging low‐cost, earth‐abundant catalyst that can efficiently reduce water to generate hydrogen. However, the synthesis of nickel phosphide catalysts usually involves multiple steps and is laborious. Herein, a convenient and straightforward approach to the synthesis of a three‐dimensional (3D) self‐supported biphasic Ni5P4‐Ni2P nanosheet (NS) array cathode is presented, which is obtained by direct phosphorization of commercially available nickel foam using phosphorus vapor. The synthesized 3D Ni5P4‐Ni2P‐NS array cathode exhibits outstanding electrocatalytic activity and long‐term durability toward the hydrogen evolution reaction (HER) in acidic medium. The fabrication procedure reported here is scalable, showing substantial promise for use in water electrolysis. More importantly, the approach can be readily extended to synthesize other self‐supported transition metal phosphide HER cathodes.
Advances in affinity ligand‐functionalized nanomaterials for biomagnetic separation
Authors: Fields Conor , Li Peng , O'Mahony James J. , Lee Gil U. 
Published: June 2015

ABSTRACTThe downstream processing of proteins remains the most significant cost in protein production, and is largely attributed to rigorous chromatographic purification protocols, where the stringency of purity for biopharmaceutical products sometimes exceeds 99%. With an ever burgeoning biotechnology market, there is a constant demand for alternative purification methodologies, to ameliorate the dependence on chromatography, while still adhering to regulatory concerns over product purity and safety. In this article, we present an up‐to‐date view of bioseparation, with emphasis on magnetic separation and its potential application in the field. Additionally, we discuss the economic and performance benefits of synthetic ligands, in the form of peptides and miniaturized antibody fragments, compared to full‐length antibodies. We propose that adoption of synthetic affinity ligands coupled with magnetic adsorbents, will play an important role in enabling sustainable bioprocessing in the future. Biotechnol. Bioeng. 2016;113: 11–25. © 2015 Wiley Periodicals, Inc.