bluuebunny/crossref_metadata_2025_split huggingface dataset:
Titus Andronicus
Authors: Wells Stanley 
Published: May 2017

Abstract
Titus Andronicus, the least highly regarded and most obviously dated of all Shakespeare’s plays, nevertheless has fine passages offering opportunities for great acting. It is also Shakespeare’s most Senecan play, the first of the tragedies not to be based on English history. ‘Titus Andronicus’ explains that most scholars accept the view that Shakespeare wrote it in collaboration with George Peele. The play was a great popular success in its time and, although set in Ancient Rome, its story is not based on recorded history. Its double revenge plot is artfully devised to incorporate numerous horrifying, but theatrically effective and sometimes deeply moving, episodes, written mostly in highly rhetorical blank verse.
Macbeth
Authors: Wells Stanley 
Published: May 2017

Abstract
When Macbeth was first seen, around 1606, its subject matter was highly topical. King James I was on the throne. The use of the supernatural, and of conventions associated with the contemporary theatre such as people speaking in verse, soliloquies, asides, witches, ghosts, a dumb show, and a severed head was very much of its time. ‘Macbeth’ explains that the text of the play known today, the shortest of Shakespeare’s tragedies, is believed to be an adaptation by Thomas Middleton. Although Macbeth is a historical tragedy, it is also a kind of parable that can easily be related to very different areas of human life.
Timon of Athens
Authors: Wells Stanley 
Published: May 2017

Abstract
Timon of Athens is an unfinished, abandoned text co-written by William Shakespeare and Thomas Middleton. The curiously skeletal text is well worthy of resuscitation for its powerful rhetoric, acute social satire, and the hauntingly beautiful poetry of its later scenes. ‘Timon of Athens’ describes the play as a two-part parable. In the first part, Timon, a wealthy and generous Greek nobleman, realizes that the people he calls his friends are mercenary sycophants who care only for his money. In the second part, Timon exiles himself from Athens and lives as a hermit, cursing mankind, receiving visits from the people he had previously called friends, and eventually seeking refuge in death.
Sulforaphane suppresses PRMT5/MEP50 function in epidermal squamous cell carcinoma leading to reduced tumor formation
Authors: Saha Kamalika , Fisher Matthew L , Adhikary Gautam , Grun Daniel , Eckert Richard L 
Published: May 2017

Abstract
Protein arginine methyltransferase 5 (PRMT5) cooperates with methylosome protein 50 (MEP50) to arginine methylate histone H3 and H4 to silence gene expression, and increased PRMT5 activity is associated with enhanced cancer cell survival. We have studied the role of PRMT5 and MEP50 in epidermal squamous cell carcinoma. We show that knockdown of PRMT5 or MEP50 results in reduced H4R3me2s formation, and reduced cell proliferation, invasion, migration and tumor formation. We further show that treatment with sulforaphane (SFN), a cancer preventive agent derived from cruciferous vegetables, reduces PRMT5 and MEP50 level and H4R3me2s formation, and this is associated with reduced cell proliferation, invasion and migration. The SFN-dependent reduction in PRMT5 and MEP50 level requires proteasome activity. Moreover, SFN-mediated responses are partially reversed by forced PRMT5 or MEP50 expression. SFN treatment of tumors results in reduced MEP50 level and H4R3me2s formation, confirming that that SFN impacts this complex in vivo. These studies suggest that the PRMT5/MEP50 is required for tumor growth and that reduced expression of this complex is a part of the mechanism of SFN suppression of tumor formation.
How Self-Control Shapes the Meaning of Choice
Authors: Sela Aner , Berger Jonah , Kim Joshua 
Published: May 2017

Abstract
Self-control is an important driver of choice, but might it also change choice’s meaning, making it seem less indicative of preference? Decades of research suggest that preference and choice are often intertwined. Choice often originates from one’s preferences. As a result, choice is often seen as a reflection of preference, leading people to infer their preferences by observing their own choices. We suggest that self-control attenuates this process. Because self-control often overrides personal desires in favor of external constraints, norms, and long-term considerations, we propose that self-control is associated with a sense of attenuated correspondence between choice and individual preference. Five experiments suggest that when the notion of self-control is salient, people are less likely to see their choices as reflecting their preferences or to infer preference from previous choices. As a result, evoking the notion of self-control attenuates the tendency to view choice as indicative of preference, even in contexts unrelated to where self-control was originally evoked. Thus, self-control shapes not only choice itself, but also the perceived meaning of choice.
Adjacent Segment Degeneration After Anterior Cervical Discectomy and Fusion With an Autologous Iliac Crest Graft: A Magnetic Resonance Imaging Study of 59 Patients With a Mean Follow-up of 27 Years
Authors: Burkhardt Benedikt W , Simgen Andreas , Wagenpfeil Gudrun , Reith Wolfgang , Oertel Joachim M 
Published: May 2017

Abstract

BACKGROUND
Anterior cervical decompression and fusion (ACDF) is a widely accepted surgical technique for the treatment of degenerative disc disease. ACDF is associated with adjacent segment degeneration (ASD).

OBJECTIVE
To assess whether physiological aging of the spine would overcome ASD by comparing adjacent to adjoining segments more than 18 yr after ACDF.

METHODS
Magnetic resonance imaging of 59 (36 male, 23 female) patients who underwent ACDF was performed to assess degeneration. The mean follow-up was 27 yr (18-45 yr). Besides measuring the disc height, a 5-step grading system (segmental degeneration index [SDI]) including disc signal intensity, anterior and posterior disc protrusion, narrowing of the disc space, and foraminal stenosis was used to assess the grade of adjacent and adjoining segments.

RESULTS
The SDI of cranial and caudal adjacent segments was significantly higher compared to adjoining segments (P < .001). The disc height of cranial and caudal adjacent segments was significantly lower compared to adjoining segments (P < .001, P < .01). The SDI of adjacent segments in patients with repeat cervical procedure was significantly higher than in patients without repeat procedure (P = .02, P = .01). The disc height of the cranial adjacent segments in patients with repeat procedure was significantly lower than in patients without repeat procedure (P = .01).

CONCLUSION
The physiological aging of the cervical spine does not overcome ASD. The disc height and the SDI in adjacent segment are significantly worse compared to adjoining segments. Patients who underwent repeat procedure had even worse findings of disc height and SDI.
A functional drug re-purposing screening identifies carfilzomib as a drug preventing 17β-estradiol: ERα signaling and cell proliferation in breast cancer cells
Authors: Busonero Claudia , Leone Stefano , Klemm Cinzia , Acconcia Filippo 
Published: May 2017

AbstractMost cases of breast cancer (BC) are estrogen receptor α-positive (ERα+) at diagnosis. The presence of ERα drives the therapeutic approach for this disease, which often consists of endocrine therapy (ET). 4OH-Tamoxifen and faslodex (i.e.,fulvestrant - ICI182,780) are two ETs that render tumor cells insensitive to 17β-estradiol (E2)-dependent proliferative stimuli and prevent BC progression. However, ET has limitations and serious failures in different tissues and organs. Thus, there is an urgent need to identify novel drugs to fight BC in the clinic. Re-positioning of old drugs for new clinical purposes is an attractive alternative for drug discovery. For this analysis, we focused on the modulation of intracellular ERα levels in BC cells as target for the screening of about 900 Food and Drug Administration (FDA) approved compounds that would hinder E2:ERα signaling and inhibit BC cell proliferation. We found that carfilzomib induces ERα degradation and prevents E2 signaling and cell proliferation in two ERα+ BC cell lines. Remarkably, the analysis of carfilzomib effects on a cell model system with an acquired resistance to 4OH-tamoxifen revealed that this drug has an antiproliferative effect superior to faslodex in BC cells. Therefore, our results identify carfilzomib as a drug preventing E2:ERα signaling and cell proliferation in BC cells and suggest its possible re-position for the treatment of ERα+ BC as well as for those diseases that have acquired resistance to 4OH-tamoxifen.
Nanoscale Dynamics of Centromere Nucleosomes and the Critical Roles of CENP-A
Authors: Stumme-Diers Micah P. , Banerjee Siddhartha , Hashemi Mohtadin , Sun Zhiqiang , Lyubchenko Yuri L. 
Published: May 2017

ABSTRACTIn the absence of a functioning centromere, chromosome segregation becomes aberrant, leading to an increased rate of aneuploidy. The highly specific recognition of centromeres by kinetochores suggests that specific structural characteristics define this region, however, the structural details and mechanism underlying this recognition remains a matter of intense investigation. To address this, High speed atomic force microscopy was used for direct visualization of the spontaneous dynamics of CENP-A nucleosomes at the sub-second time scale. We report that CENP-A nucleosomes change conformation spontaneously and reversibly, utilizing two major pathways: unwrapping, and looping of the DNA; enabling core transfer between neighboring DNA substrates. Along with these nucleosome dynamics we observed that CENP-A stabilizes the histone core against dissociating to histone subunits, unique from H3 cores which are only capable of such plasticity in the presence of remodeling factors. These findings have implications for the dynamics and integrity of nucleosomes at the centromere.
COPI mediates recycling of an exocytic SNARE from endosomes by recognition of a ubiquitin sorting signal
Authors: Xu Peng , Hankins Hannah M. , Macdonald Chris , Erlinger Samuel J. , Frazier Meredith N. , Diab Nicholas S. , Piper Robert C. , Jackson Lauren P. , MacGurn Jason A. , Graham Todd R. 
Published: May 2017

ABSTRACTThe COPI coat forms transport vesicles from the Golgi complex and plays a poorly defined role in endocytic trafficking. Here we show that COPI mediates delivery of a budding yeast SNARE (Snc1) from early endosomes to the Golgi complex through recognition of a polyubiquitin sorting signal. Snc1 is a v-SNARE that drives fusion of exocytic vesicles with the plasma membrane, and then recycles through early endosomes back to the Golgi for reuse. Removal of ubiquitin from Snc1, or deletion of a β’-COP subunit propeller domain that binds K63-linked polyubiquitin, causes aberrant accumulation of Snc1 in early endosomes. Moreover, replacement of the β’-COP propeller domain with unrelated ubiquitin-binding domains restores Snc1 recycling. These results indicate that ubiquitination, a modification well known to target membrane proteins to the lysosome or vacuole for degradation, can also function as recycling signal to sort a SNARE into COPI vesicles at early endosomes for Golgi delivery.
Identification and Prioritisation of Variants in the Short Open-Reading Frame Regions of the Human Genome
Authors: Jackson Felix , Wayland Matthew , Prabakaran Sudhakaran 
Published: May 2017

AbstractAs whole-genome sequencing technologies improve and accurate maps of the entire genome are assembled, short open-reading frames (sORFs) are garnering interest as functionally important regions that were previously overlooked. However, there is a paucity of tools available to investigate variants in sORF regions of the genome. Here we investigate the performance of commonly used tools for variant calling and variant prioritisation in these regions, and present a framework for optimising these processes. First, the performance of four widely used germline variant calling algorithms is systematically compared. Haplotype Caller is found to perform best across the whole genome, but FreeBayes is shown to produce the most accurate variant set in sORF regions. An accurate set of variants is found by taking the intersection of called variants. The potential deleteriousness of each variant is then predicted using a pathogenicity scoring algorithm developed here, called sORF-c. This algorithm uses supervised machine-learning to predict the pathogenicity of each variant, based on a holistic range of functional, conservation-based and region-based scores defined for each variant. By training on a dataset of over 130,000 variants, sORF-c outperforms other comparable pathogenicity scoring algorithms on a test set of variants in sORF regions of the human genome.List of AbbreviationsAUPRCArea under the precision-recall curveBEDBrowser Extensible DataCADDCombined annotation-dependent depletionDANNDeleterious annotation of genetic variants using neural networksEPOEnredo, Pecan, Ortheus pipelineGATKGenome analysis toolkitGIABGenome in a bottleHGMDHuman gene mutation databaseIndelsInsertions and deletionsMSMass spectrometryORFOpen reading frameRFRandom ForestsROCReceiver Operating CharacteristicsSEPsORF encoded peptidesklearnScikit-learn packageSNVsSingle nucleotide variantssORFShort open-reading frameTFTranscription factorTSSTranscription start siteVCFVariant Call Format file
Regulation of Iron Homeostasis by SPAK-dependent Modulation of FBXL5 Stability
Authors: Powers David N. , Vashisht Ajay A. , Shenouda Monika , Yao Calvin , Wohlschlegel James A. 
Published: May 2017

ABSTRACTIntracellular iron homeostasis is regulated by a proteolytic switch whereby the E3 ubiquitin ligase FBXL5 targets iron regulatory proteins (IRPs) for ubiquitin-dependent degradation in iron-replete conditions while it is itself degraded during iron deficiency allowing IRPs to accumulate and regulate their downstream RNA targets. The cellular pathways that control FBXL5 degradation in low iron conditions are not well understood. Here, we report the identification of the STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) as a novel regulator of FBXL5 stability. We find that SPAK, a kinase previously implicated in osmotic stress regulation, regulates intracellular iron homeostasis through its physical association with FBXL5. This role is dependent on its kinase activity as overexpression of constitutively active SPAK increases FBXL5 poly-ubiquitination and degradation. Through this work, we have discovered a novel role for SPAK that extends beyond its well-established function in salt homeostasis and raises the possibility for signaling crosstalk between iron homeostatic and osmotic regulatory pathways.
The Envelope Proteome Changes Driven by RamA Overproduction inKlebsiella pneumoniaethat Enhance Acquired β-Lactam Resistance
Authors: Jiménez-Castellanos Juan-Carlos , Wan Nur Ismah Wan Ahmad Kamil , Takebayashi Yuiko , Findlay Jacqueline , Schneiders Thamarai , Heesom Kate J. , Avison Matthew B. 
Published: May 2017

AbstractOBJECTIVESInKlebsiella pneumoniae,overproduction of RamA results in reduced envelope permeability and reduced antimicrobial susceptibility but clinically relevant resistance is rarely observed. Here we have tested whether RamA over-production can enhance acquired β-lactam resistance mechanisms inK. pneumoniaeand have defined the envelope protein abundance changes seen upon RamA overproduction during growth in low and high osmolarity media.METHODSEnvelope permeability was estimated using a fluorescent dye accumulation assay. Antibiotic susceptibility was measured using disc testing. Total envelope protein production was quantified using LC-MS/MS proteomics and transcript levels quantified by Real Time RT-PCR.RESULTSRamA overproduction enhanced β-lactamase mediated β-lactam resistance, in some cases dramatically, without altering β-lactamase production. It increased production of efflux pumps and decreased OmpK35 porin production, thoughmicFover-expression showed that OmpK35 reduction has little impact on envelope permeability. A survey ofK. pneumoniaebloodstream isolates revealedramAhyperexpression in 3 out of 4 carbapenemase producers, 1/21 CTX-M producers and 2/19 strains not carrying CTX-M or carbapenemases.CONCLUSIONSWhilst RamA is not a key mediator of antibiotic resistance inK. pneumoniaeon its own, it is potentially important for enhancing the spectrum of acquired β-lactamase mediated β-lactam resistance. LC-MS/MS proteomics analysis has revealed that this enhancement is achieved predominantly through activation of efflux pump production.
Initial-state-dependent, robust, transient neural dynamics encode conscious visual perception
Authors: Baria Alexis T. , Maniscalco Brian , He Biyu J. 
Published: May 2017

ABSTRACTRecent research has identified late-latency, long-lasting neural activity as a robust correlate of conscious perception. Yet, the dynamical nature of this activity is poorly understood, and the mechanisms governing its presence or absence and the associated conscious perception remain elusive. We applied dynamic-pattern analysis to whole-brain slow cortical dynamics recorded by magnetoencephalography (MEG) in human subjects performing a threshold-level visual perception task. Up to 1 second before stimulus onset, brain activity pattern across widespread cortices significantly predicted whether a threshold-level visual stimulus was later consciously perceived. This initial state of brain activity interacts nonlinearly with stimulus input to shape the evolving cortical activity trajectory, with seen and unseen trials following well separated trajectories. Furthermore, cortical activity trajectories during conscious perception are fast evolving and robust to small variations in the initial state. These results suggest that brain dynamics underlying conscious visual perception belongs to the class of initial-state-dependent, robust, transient neural dynamics.AUTHOR SUMMARYWhat brain mechanisms underlie conscious perception? A commonly adopted paradigm for studying this question is to present human subjects with threshold-level stimuli. When shown repeatedly, the same stimulus is sometimes consciously perceived, sometimes not. Using magnetoencephalography, we shed light on the neural mechanisms governing whether the stimulus is consciously perceived in a given trial. We observed that depending on the initial brain state defined by widespread activity pattern in the slow cortical potential (<5 Hz) range, a physically identical, brief (30 - 60 ms) stimulus input triggers distinct sequences of activity pattern evolution over time that correspond to either consciously perceiving the stimulus or not. Such activity pattern evolution forms a “trajectory” in the state space and affords significant single-trial decoding of perceptual outcome from 1 sec before to 3 sec after stimulus onset. While previous theories on conscious perception have emphasized sustained, high-level activity, we found that brain dynamics underlying conscious perception exhibit fast-changing activity patterns. These results significantly further our understanding on the neural mechanisms governing conscious access of a stimulus and the dynamical nature of neural activity underlying conscious perception.
Identification and dynamics of the DHHC16-DHHC6 palmitoylation cascade
Authors: Abrami Laurence , Dallavilla Tiziano , Sandoz Patrick A. , Demir Mustafa , Kunz Béatrice , Savoglidis Georgios , Hatzimanikatis Vassily , van der Goot F. Gisou 
Published: May 2017

ABSTRACTS-Palmitoylation is the only reversible post-translational lipid modification. Knowledge about the DHHC family of palmitoyltransferases is very limited. Here we show that mammalian DHHC6, which modifies key proteins of the endoplasmic reticulum, is controlled by an upstream palmitoyltransferase, DHHC16, revealing the first palmitoylation cascade. Combination of site specific mutagenesis of the three DHHC6 palmitoylation sites, experimental determination of kinetic parameters and data-driven mathematical modelling allowed us to obtain detailed information on the 8 differentially palmitoylated DHHC6 species. We found that species rapidly interconvert through the action of DHHC16 and the Acyl Protein Thioesterase APT2, that each species varies in terms of turnover rate and activity, altogether allowing the cell to robustly tune its DHHC6 activity.
Gender in sustainable entrepreneurship: evidence from the UK
Authors: Outsios Georgios , Farooqi Seemab Ara 
Published: May 2017

Purpose
Existing research highlights gender as an important dimension for entrepreneurship theory and practice. This study aims to explore the differences between female and male sustainable entrepreneurs in the areas of previous professional experiences, their performance and growth, their use of financial resources and their overall attitude to risk.

Design/methodology/approach
Through a feminist perspective and on the basis of empirical evidence gathered through a series of 20 in-depth, semi-structured interviews with male and female sustainable entrepreneurs in the UK, thr authors analyse differences between male and female sustainable entrepreneurs.

Findings
The findings suggest that female role models play a significant role in the emergence of women sustainable entrepreneurs who start from the same experience levels as men, show strong feminist attitudes and are conscious of their contribution to global sustainability. Sustainable entrepreneurship offers women professional development and a limited flexibility to balance work and family commitments. Lack of funding appears to be a major constraint applying to both female and male participants, while the authors argue that business pragmatism in a difficult investment environment triggered women’s reluctance to take on debt. Nonetheless, female sustainable entrepreneurs were found to have developed and used their professional and social networks to a greater extent than their male counterparts.

Originality/value
This study offers a new gender perspective to the research of sustainable entrepreneurship and, at the same time, contributes with findings from research on sustainable entrepreneurs to the study of gender in management.
Democracy and international financial integration in Pakistan
Authors: Jawaid Syed Tehseen , Abbas Shujaat , Saleem Shaikh Muhammad 
Published: May 2017

PurposeThe purpose of the study is to investigate the relationship between international financial integration (IFI) index and democracy (DEM) in Pakistan by using long-time series data from 1975 to 2013.Design/methodology/approachThe IFI index is constructed by principal component analysis. IFI consists of foreign direct investment (FDI), remittances (REM) and external debt (ED), whereas the Polity IV index is used for DEM. Johansen and the autoregressive distributed lag method for cointegration methods are used to find a long run relationship. Dynamic ordinary least square (DOLS), fully modified ordinary least square (FMOLS) and canonical regression (CR) have been used to find the nature of the relationship. Rolling window analysis has been done to find the year wise coefficients.FindingsDOLS, FMOLS, canonical regression CR and cointegration results suggest a significant negative long-run relationship between IFI and DEM in Pakistan. Rolling windows analysis highlights that DEM has improved IFI in Pakistan from 2008 to 2013.Originality/valueThis study constructs an index for financial integration using principle component analysis on capital inflows, i.e. FDI, REM, ED, to explore the impact of DEM on IFI in Pakistan from 1975 to 2013. This study investigates for the first time ever the relationship between IFI index and DEM in Pakistan.