bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Binding Site on the Mechanical Unfolding Mechanism of Ubiquitin
Authors: Cao Penghui , Yoon Gwonchan , Tao Weiwei , Eom Kilho , Park Harold S. 
Published: March 2015

AbstractWe apply novel atomistic simulations based on potential energy surface exploration to investigate the constant force-induced unfolding of ubiquitin. At the experimentally-studied force clamping level of 100 pN, we find a new unfolding mechanism starting with the detachment between β5 and β3 involving the binding site of ubiquitin, the Ile44 residue. This new unfolding pathway leads to the discovery of new intermediate configurations, which correspond to the end-to-end extensions previously seen experimentally. More importantly, it demonstrates the novel finding that the binding site of ubiquitin can be responsible not only for its biological functions, but also its unfolding dynamics. We also report in contrast to previous single molecule constant force experiments that when the clamping force becomes smaller than about 300 pN, the number of intermediate configurations increases dramatically, where almost all unfolding events at 100 pN involve an intermediate configuration. By directly calculating the life times of the intermediate configurations from the height of the barriers that were crossed on the potential energy surface, we demonstrate that these intermediate states were likely not observed experimentally due to their lifetimes typically being about two orders of magnitude smaller than the experimental temporal resolution.
Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer
Authors: Faber Anthony C. , Farago Anna F. , Costa Carlotta , Dastur Anahita , Gomez-Caraballo Maria , Robbins Rebecca , Wagner Bethany L. , Rideout William M. , Jakubik Charles T. , Ham Jungoh , Edelman Elena J. , Ebi Hiromichi , Yeo Alan T. , Hata Aaron N. , Song Youngchul , Patel Neha U. , March Ryan J. , Tam Ah Ting , Milano Randy J. , Boisvert Jessica L. , Hicks Mark A. , Elmiligy Sarah , Malstrom Scott E. , Rivera Miguel N. , Harada Hisashi , Windle Brad E. , Ramaswamy Sridhar , Benes Cyril H. , Jacks Tyler , Engelman Jeffrey A. 
Published: March 2015

Significance
Small-cell lung cancer (SCLC) is an aggressive carcinoma with few effective treatment options beyond first-line chemotherapy. BH3 mimetics, such as ABT-263, promote apoptosis in SCLC cell lines, but early phase clinical trials demonstrated no significant clinical benefit. Here, we examine the sensitivity of a large panel of cancer cell lines, including SCLC, to ABT-263 and find that high Bcl2-interacting mediator of cell death (BIM) and low myeloid cell leukemia 1 (MCL-1) expression together predict sensitivity. SCLC cells relatively resistant to ABT-263 are sensitized by TORC1/2 inhibition via MCL-1 reduction. Combination of ABT-263 and TORC1/2 inhibition stabilizes or shrinks tumors in xenograft models, in autochthonous SCLC tumors in a genetically engineered mouse model, and in a patient-derived xenograft SCLC model. Collectively, these data support a compelling new therapeutic strategy for treating SCLC.
Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression
Authors: Turner Kristen M. , Sun Youting , Ji Ping , Granberg Kirsi J. , Bernard Brady , Hu Limei , Cogdell David E. , Zhou Xinhui , Yli-Harja Olli , Nykter Matti , Shmulevich Ilya , Yung W. K. Alfred , Fuller Gregory N. , Zhang Wei 
Published: March 2015

SignificanceGlioblastoma is the most common and aggressive type of glioma, with a median survival of 15 mo. A major obstacle to effective treatment is de novo or acquired resistance to standard-care therapies, including radiation and temozolomide. Enhanced DNA repair can allow damaged or mutated cells to survive, contributing to resistance and tumor recurrence. We have identified Akt3 as the dominant Akt isoform that robustly stimulates glioma progression. We also discovered key roles for Akt3 in activating DNA repair pathways, which led to enhanced survival of human glioblastoma cells following radiation or temozolomide treatment. Our work has potential broad application to multiple cancer types in which Akt3 is expressed. Blocking this pathway may help prevent or alleviate DNA repair-mediated therapeutic resistance.
Locating landmarks on high-dimensional free energy surfaces
Authors: Chen Ming , Yu Tang-Qing , Tuckerman Mark E. 
Published: March 2015

Significance
The problem of generating and navigating high-dimensional free energy surfaces is a significant challenge in the study of complex systems. The approach introduced represents an advance in this area, and its ability to generate and organize the key features of a high-dimensional free energy surface, i.e., its landmarks, with high efficiency impacts numerous problems in the materials and biomolecular sciences for which prediction of optimal structures is key. These include polypeptide and nucleic acid structure and crystal design and structure prediction. Moreover, as the algorithm targets the free energy surface, candidate structures can be ranked based on their relative free energies, which is not possible with algorithms that target only the bare potential energy surface.
Salient features of otoacoustic emissions are common across tetrapod groups and suggest shared properties of generation mechanisms
Authors: Bergevin Christopher , Manley Geoffrey A. , Köppl Christine 
Published: March 2015

Significance
Healthy ears not only detect sound but can emit it as well. These sounds can occur either spontaneously and continuously or in response to acoustic stimulation. Evoked emissions are increasingly used as clinical diagnostic tools. The mechanisms underlying their generation, however, are incompletely understood. In particular, otoacoustic emissions occur in a wide variety of species, from frogs to humans, suggesting basic, shared principles. Here, we analyzed both spontaneous and evoked otoacoustic emissions from a bird and a lizard. We relate these data to those from humans and suggest that otoacoustic emissions originate from similar biomechanical principles despite gross differences in the underlying anatomy of the ear.
Structure and dynamics of the MKK7–JNK signaling complex
Authors: Kragelj Jaka , Palencia Andrés , Nanao Max H. , Maurin Damien , Bouvignies Guillaume , Blackledge Martin , Jensen Malene Ringkjøbing 
Published: March 2015

Significance
In the mitogen-activated protein kinase (MAPK) pathways, N-terminal intrinsically disordered regulatory domains of the MAPK kinases (MKK) control signaling specificity by binding to their cognate MAPKs via docking sites carrying homologous recognition sequences. MKK7 activates the c-Jun N-terminal kinase (JNK) pathway and is the only MKK containing three motifs within its regulatory domain. Here we obtain a comprehensive picture of the structure, dynamics, affinity, stoichiometry, and kinetics of the MKK7–JNK signaling complex. Importantly, we show using a combination of X-ray crystallography and NMR exchange spectroscopy that the second docking site of MKK7 binds to JNK via two alternative binding modes, providing insight into the regulation of signaling specificity by short linear motifs.
Oncogenic fusion protein EWS-FLI1 is a network hub that regulates alternative splicing
Authors: Selvanathan Saravana P. , Graham Garrett T. , Erkizan Hayriye V. , Dirksen Uta , Natarajan Thanemozhi G. , Dakic Aleksandra , Yu Songtao , Liu Xuefeng , Paulsen Michelle T. , Ljungman Mats E. , Wu Cathy H. , Lawlor Elizabeth R. , Üren Aykut , Toretsky Jeffrey A. 
Published: March 2015

SignificanceAlternative splicing of RNA allows a limited number of coding regions in the human genome to produce proteins with diverse functionality. Alternative splicing has also been implicated as an oncogenic process. Identifying aspects of cancer cells that differentiate them from noncancer cells remains an ongoing challenge, and our research suggests that alternatively spliced mRNA and subsequent protein isoforms will provide new anticancer targets. We determined that the key oncoprotein of Ewing sarcoma (ES), EWS-FLI1, regulates alternative splicing in multiple cell line models. These experiments establish oncogenic aspects of splicing that are specific to cancer cells and thereby illuminate potentially oncogenic splicing shifts as well as provide a useful stratification mechanism for ES patients.
Disruption of hierarchical predictive coding during sleep
Authors: Strauss Melanie , Sitt Jacobo D. , King Jean-Remi , Elbaz Maxime , Azizi Leila , Buiatti Marco , Naccache Lionel , van Wassenhove Virginie , Dehaene Stanislas 
Published: March 2015

Significance
Sleeping disrupts the conscious awareness of external sounds. We investigated the stage of processing at which this disruption occurs. In the awake brain, when a regular sequence of sounds is presented, a hierarchy of brain areas uses the available regularities to predict forthcoming sounds and to respond with a series of “prediction error” signals when these predictions are violated. Using simultaneous recordings of electroencephalography and magnetoencephalography signals, we discovered that both short-term and long-term brain responses to auditory prediction errors are disrupted during non-rapid eye movement and rapid eye movement sleep; however, the brain still exhibits detectable auditory responses and a capacity to habituate to frequently repeated sounds. Thus, sleep appears to selectively affect the brain’s prediction and error detection systems.
Performance of Cage-Raised, Overwintered Hybrid Striped Bass Fed Fish Meal- or Soybean-Based Diets
Authors: Rossi Waldemar , Tomasso Joseph R , Gatlin Delbert M 
Published: March 2015

Abstract
We conducted a 26-week study to evaluate the performance of cage-raised hybrid Striped Bass (female White Bass Morone chrysops × male Striped Bass M. saxatilis) fed fish meal (FM) and soybean (SOY; soybean meal + soy protein concentrate) based diets. A FM reference diet was formulated to contain crude protein (CP) at 450 g/kg, lipid at 120 g/kg, and an estimated digestible energy level of 13 MJ/kg. Two test diets (SOY and SOY+GBA) were formulated to replace 70% of the CP in the reference diet with SBM in the absence or presence of GroBiotic-A (GBA), a yeast-based prebiotic, at 20 g/kg. The other 12% of dietary FM in the reference diet was replaced with SPC in the test diets, further reducing FM inclusion to 70 g/kg. Each diet was fed to quadruplicate groups of 40 advanced juvenile hybrid Striped Bass (initial weight ∼ 54 g/fish) stocked into each of twelve 1-m3 floating cages, which were equally divided into four 0.05-ha, rubber-lined ponds according to a randomized complete block design. Caged fish in each pond were fed one of the randomly assigned diets to apparent satiation once daily. After 26 weeks of feeding, results showed that (1) the overall growth performance, survival, and feed efficiency of the fish were unaffected by diet; (2) the intraperitoneal fat ratio was significantly lower in fish that received the SOY-based diets; and (3) plasma glucose and lysozyme activity were significantly lower in fish that were fed the SOY-based diets, whereas plasma osmolality, hematocrit, neutrophil oxidative radical production (nitroblue tetrazolium test), and extracellular superoxide anion production of head-kidney macrophages were unaffected by diet. We conclude that low-FM, SOY-based diets can support adequate performance and normal physiological responses of hybrid Striped Bass during overwintering.
Logical transformation of genome-scale metabolic models for gene level applications and analysis
Authors: Zhang Cheng , Ji Boyang , Mardinoglu Adil , Nielsen Jens , Hua Qiang 
Published: March 2015

Abstract
Motivation: In recent years, genome-scale metabolic models (GEMs) have played important roles in areas like systems biology and bioinformatics. However, because of the complexity of gene–reaction associations, GEMs often have limitations in gene level analysis and related applications. Hence, the existing methods were mainly focused on applications and analysis of reactions and metabolites.
Results: Here, we propose a framework named logic transformation of model (LTM) that is able to simplify the gene–reaction associations and enables integration with other developed methods for gene level applications. We show that the transformed GEMs have increased reaction and metabolite number as well as degree of freedom in flux balance analysis, but the gene–reaction associations and the main features of flux distributions remain constant. In addition, we develop two methods, OptGeneKnock and FastGeneSL by combining LTM with previously developed reaction-based methods. We show that the FastGeneSL outperforms exhaustive search. Finally, we demonstrate the use of the developed methods in two different case studies. We could design fast genetic intervention strategies for targeted overproduction of biochemicals and identify double and triple synthetic lethal gene sets for inhibition of hepatocellular carcinoma tumor growth through the use of OptGeneKnock and FastGeneSL, respectively.
Availability and implementation: Source code implemented in MATLAB, RAVEN toolbox and COBRA toolbox, is public available at https://sourceforge.net/projects/logictransformationofmodel.
Contact: nielsenj@chalmers.se or qhua@ecust.edu.cn
Supplementary information: Supplementary data are available at Bioinformatics Online.
Introduction
Authors: Cummings Brian , Simpson James 
Published: March 2015

Abstract
This book examines cultural history and cultural transformation in the period spanning the Middle Ages and Renaissance, and how such transition relates to modernity. Taking a dynamically diachronic approach, it offers a fresh perspective on the historiography of culture and literature, with emphasis on the idea of periodization and the tendency to divide cultural history into different eras. Many of the essays focus on themes spanning the fourteenth and seventeenth centuries, each linking pre- and post-Reformation cultures, including those related to religion, and highlight the creative and destructive anxieties as well as the legacy of the Reformation.
National Histories
Authors: Butterfield Ardis 
Published: March 2015

Abstract
Nation and vernacularity are naturally intertwined, as Adrian Hastings, Richard Helgerson, and Benedict Anderson would attest. Hastings, Helgerson, and Anderson all argue that the rise of nation coincides with a decisively new burgeoning of the vernacular, even as this moment occurs in a different century. This article explores three issues concerning nation that have particular relevance to cross-period “cultural reformations” and are radically affected by England’s long relationship with France: nation’s relation to modernity, to language, and to England and Englishness. It examines the entanglement between English and French in the context of nationhood and considers a bifurcated Anglo-French model for vernacularity that it argues is central to understanding of nation and crucially resistant to it at the same time.
Place
Authors: Simpson James 
Published: March 2015

Abstract
The question of the Church’s location became a central issue of the Protestant Reformation: was it the material, visible Church containing the saved and the damned (as yet unable to be distinguished), or the immaterial, invisible Church of the Elect? This little noticed but hugely significant issue preoccupied Reformation theorists, but already in the late fourteenth century writers were conscious of it. Pilgrimage narratives, particularly narratives in which the visible, located Church’s relics are exposed as disgusting, exploitative and fake, underline the fragilities of the “located” Church. This essay defines the theological issue of place, and then sees how it works in practice with two Canterbury pilgrimage texts, Chaucer’s Pardoner’s Tale and Desiderius Erasmus’s Pilgrimage of Pure Devotion.
Travel
Authors: Hadfield Andrew 
Published: March 2015

Abstract
Advances in technology had dramatically improved mapping and navigational possibilities that made travel within Europe easier, more comfortable, and more feasible. In the early seventeenth century, writers such as Fynes Moryson, Thomas Coryat, and William Lithgow began to provide accounts of their extensive travels. However, the ethnological models that were used by Europeans in the sixteenth century were hardly modern. While the discovery of the New World showed the scope and diversity of the known universe, it also encouraged a heightened xenophobia and racism. There are also other more practical considerations implying that change was not as rapid as might be expected. This article examines travel in the context of cultural history and how the Reformation became a key impediment to travel. It looks at travelers who were prepared to go beyond what was generally expected or even acceptable despite the obvious dangers and discomforts, focusing on the experiences of Margery Kempe and William Lithgow.
The Saints
Authors: Mueller Janel 
Published: March 2015

Abstract
In his authoritative New Testament formulations, St. Paul describes the saints of Christianity as the “beloved of God and the called of Jesus Christ” for their obedience to the faith in him...” Peter Brown, in his account of the Christian communities of the post-apostolic church and later antiquity, states that “the cult of the saints” emerges from beliefs and practices that differ from Paul’s normative definitions. St. Augustine’s transhistorical composition of his two cities in City of God retraces Paul’s serial tracking of the saints who are the true members of Christ’s Church. This article examines the depiction of Christian saints in medieval literature in Western Europe, particularly early Christian virgins martyred by pagan oppressors. It looks at the life of John Wyclif, an Oxford scholar and cleric, and his views about the character and validity of the Church and its saints. It also analyzes Michael Walzer’s The Revolution of the Saints and his arguments regarding the value of the model of Puritan sainthood in present-day circumstances.
Vernacular Theology
Authors: Betteridge Thomas 
Published: March 2015

Abstract
This article explores the problems arising from the asymmetrical status of mysticism across the period between medieval and Renaissance. It begins with James Nayler’s mysticism before proceeding with a discussion of vernacular theology in relation to social and cultural change during the period between Lollardy and the English Civil War. It then considers the failure of mysticism in the context of historiography, the connections between religious literature produced across the period between Lollardy and the English Civil War, and how confessionalization gave rise to Protestantism and Roman Catholicism. It also examines the religious writings of Julian of Norwich and George Herbert before concluding with an assessment of religious reform in Western Europe during the period.
Conscience
Authors: Strohm Paul 
Published: March 2015

Abstract
This article considers a Christian view of conscience starting with St. Augustine’s personal crisis in his Confessions. Augustine’s conscience sits at the margins of the self, balanced between interior and exterior. A new emphasis emerges in Protestant views of conscience, including Martin Luther’s emphasis on conscientia mea in his writings and his understanding of conscience. A Reformation view of personal conscience is illustrated in Henry VIII’s frequent references to “my conscience,” and other instances. The clash of personal and collective views of conscience underlies the views of sixteenth-century judge James Hales and Marian chancellor Stephen Gardiner. The evangelically leaning Hales sees conscience as a private matter, a personal secret, unknowable to any other person. In contrast, Gardiner, a Catholic, insists that conscience is a recognizable and unproblematic entity with evident properties that make it easily identifiable.
When English Became Latin
Authors: Machan Tim William 
Published: March 2015

Abstract
The English language, at all grammatical levels, underwent a profound, albeit gradual, change between 1377 and 1642. These phonological changes include the Great Vowel Shift and the change in inflectional morphology. This article examines the transition from Middle English to Modern English and how English became Latin. It considers the retention of what might be called England’s sociolinguistic infrastructure, alongside a wide-ranging reconfiguration of English’s grammar and social uses. It discusses three unfamiliar constancies that characterize the decisive shift in the English language between the medieval and early modern epochs: the first involved the object of grammatical inquiry in early modern England, the second concerned the character of England’s linguistic repertoire of which diglossia was the notable organizing principle, and the third relates to the cultural significance that English was understood to project as an emerging High Language.
Heresy and Treason
Authors: Loewenstein David 
Published: March 2015

Abstract
In the sixteenth and seventeenth centuries, an acute religious crisis occurred in England due to the troublesome specter of heresies proliferating at the time. During the 1520s and 1530s, Thomas More, Lord Chancellor, played a major role in the escalating polemical warfare against Lutheran and evangelical heresy. And in the 1640s and 1650s, the fragmentation of Protestantism provoked powerful new fears of unbridled heresies and the rise of anti-heretical writings. This article examines the cultural fears sparked by the hysterical religious imagination and how they generated enormous anxieties, savagery, and bitter religious contention and polarization. It also looks at the anti-heresy literature of the English Civil War and Interregnum in the context of new legislation enacted by Parliament to control the proliferation of religious error. In addition, it considers the remarkable continuities between the late Middle Ages and early modern period with regard to heresy, treason, fears, and the feverish religious imagination, along with what was distinctive about the imaginings of heretics and heresies during those unstable decades.
Naughty Printed Books
Authors: Kastan David Scott 
Published: March 2015

Abstract
The Index librorum prohibitorum, first issued in 1559, the Roman Catholic Church’s official effort to ban certain books, is often contrasted with John Milton’s Areopagitica, so often claimed the foundational text of a modern notion of freedom of expression. But the opposition is more a function of a modern desire than of historical fact. The two texts do not so much display this reassuring opposition as their unnerving similarity. This article examines and attempts to undo some of the oppositions that have structured most of the scholarly discussion on the subject of censorship: Catholic versus Protestant, state versus individual, repression versus freedom. All of these play their role in an undeniably appealing history of liberty and toleration, but it is not a history that has much purchase in early modern England, as may be shown by a consideration of the efforts of the Church and authorities in England to prevent the circulation of what they called “naughty printed books.”