bluuebunny/crossref_metadata_2025_split huggingface dataset:
Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months
Authors: Wasserstein Melissa P. , Diaz George A. , Lachmann Robin H. , Jouvin Marie‐Hélène , Nandy Indrani , Ji Allena J. , Puga Ana Cristina 
Published: January 2018

AbstractOlipudase alfa, a recombinant human acid sphingomyelinase (ASM), is an enzyme replacement therapy for the treatment of nonneurologic manifestations of acid sphingomyelinase deficiency (ASMD). This ongoing, open‐label, long‐term study (NCT02004704) assessed safety and efficacy of olipudase alfa following 30 months of treatment in five adult patients with ASMD. There were no deaths, serious or severe events, or discontinuations during 30 months of treatment. The majority of adverse events were mild and included headache, nausea, and abdominal pain. No patient developed anti‐drug antibodies and there were no clinically significant adverse changes in vital signs, hematology, or cardiac safety parameters. Statistically significant reductions in liver (31%) and spleen (39%) volumes were maintained through 30 months of treatment. There was a mean increase in lung diffusing capacity of 35%, and clinically relevant improvements in infiltrative lung disease parameters. Lipid profiles improved in all patients. Improvements in bone mineral density of the spine were observed in some patients. Chitotriosidase in serum and lyso‐sphingomyelin in dried blood spots decreased with olipudase alfa treatment, suggesting utility as biomarkers for monitoring treatment efficacy. Olipudase alfa is the first etiology‐specific treatment in development for ASMD. This study demonstrates that treatment with olipudase alfa for 30 months is well‐tolerated and associated with life‐transforming sustained improvements in relevant disease clinical measures.
Understanding change in violence‐related attitudes for adolescents in relationship education
Authors: Savasuk‐Luxton Rachel , Adler‐Baeder Francesca , Haselschwerdt Megan L. 
Published: January 2018

ABSTRACTRelationship education (RE) targets common correlates of adolescent dating violence (ADV), such as gender role beliefs (GRB) and DV acceptance (DVA), yet few studies have evaluated the influence of RE on GRB and DVA and none have considered participants' sociodemographic characteristics. Using a sample of adolescents from the United States (Mage = 15.66 years; 58% female), this study examined pre‐ and post‐test GRB and DVA scores of RE participants (n = 1645) compared to nonparticipants (n = 522) and explored the differential and combined effects of participants' sociodemographic characteristics on change. Black males held the most traditional GRB at pre‐test, but became more egalitarian after programming. RE participation also appeared to act as a buffer against an increase in DVA for females, but not males. Study findings provide a more complex picture of the role of RE in shifting beliefs and attitudes associated with ADV and provide implications for programming.
Richard of St Victor's Solutions to Problems of Architectural Representation in the Twelfth Century
Authors: Kinsella Karl 
Published: January 2018

AbstractThis article argues that Richard of St Victor's twelfth-century architectural drawings for his historical exegesis of Ezekiel's vision of the Temple of Jerusalem is more sophisticated than the historiography has suggested to date. In his commentary, Richard provided plans and elevations for a number of different buildings, including the Temple's gatehouse. When attempting to convey the dimensions of the gatehouse, he made a distinction between measurements taken as if along a flat plane and those that take the slope of the mountain into account, calling theseplanumandsuperficiesrespectively, words that indicate a strong correlation to contemporary practices in geometry. When he wished to illustrate the dimensions of a gatehouse's interior, he included a lateral section of the building, which is possibly the earliest in existence. The use of the termplanum(similar in meaning to the subsequent word ‘plan’) and the appearance of a section are unusually early, although there is still no evidence that Richard's work directly influenced later architectural drawings.
The Hammer-beam Roof of Westminster Hall and the Structural Rationale of Hugh Herland
Authors: Beech Robert 
Published: January 2018

AbstractThis paper examines the carpentry of the late medieval roof of Westminster Hall. The structure, a hammer-beam roof, is analysed from the perspective of the king's carpenter Hugh Herland. This analysis is based on drawings made in 1913 to facilitate the repair of the roof, and on the author's archaeological reconstruction of the carpentry based on those drawings. Herland's experience at Winchester in the early 1390s, immediately before beginning work at Westminster, is also considered. The paper also places the Westminster roof in the context of earlier hammer-beam roofs, particularly Pilgrims' Hall, Winchester. It concludes that the hammer-beam carpentry was crucial to the roof's structure, and that Herland intended the hall's ‘great arched ribs’ primarily as ornamental components.
Reviving Antiquity with Granite: Spolia and the Development of Roman Renaissance Architecture
Authors: Waters Michael J. 
Published: January 2018

AbstractAncient granite columns have been a pervasive element in the architecture of Rome since the Imperial era. However, in the fifteenth century, just as the effort to revive Antiquity intensified, these ubiquitous and durable ancient columns fell out of use. It was instead the stone travertine that became the columnar material of choice. Yet, just as quickly as this change occurred, within an exceptionally short period of thirty years, beginning with the construction of the Palazzo della Cancelleria courtyard, Rome saw a renascence in their application. While little has been made of this material shift, this article argues that the sudden extensive employment of spoliated granite columns was a crucial component in the recovery of a distinctly local Roman Antiquity. It was through the use and transformation of spolia that builders and patrons attempted to create an architecture that not only recalled Antiquity, but resubstantiated it, literally making it whole again.
‘Proceeding like Guy Faux’: the Antiquarian Investigation of St Stephen's Chapel Westminster, 1790–1837
Authors: Hill Rosemary 
Published: January 2018

AbstractSt Stephen's Chapel Westminster is one of Europe's great lost buildings. An elaborate palatine chapel, work on it began in 1292 and continued until at least 1363. After 1546 it became the House of Commons and was so obscured by successive alterations that the original building had passed out of living memory by the late eighteenth century. It was then that it attracted the interest of a number of antiquaries who recorded it in the years up to and after the fire of 1834. In 1837 it was demolished. The antiquaries’ accounts provide the only records of the chapel's appearance and construction and have been much used in studies of the medieval building. This article, however, considers them as a body of work in their own right, one that casts light not only on St Stephen's but on the changing attitudes of the Romantic age towards history and the medieval past in the years which saw the transformation of the Gothic Revival and the birth of the modern idea of conservation.
Edwin Lutyens in Spain: the Palace of El Guadalperal
Authors: Basarrate Íñigo 
Published: January 2018

ABSTRACTAlthough the work of Edwin Lutyens has received careful scholarly study since the 1980s, his projects in Spain remain very little known. Unfortunately, Lutyens was unable to complete his Spanish commissions, mostly because of the deterioration of country's economy and social order in the 1930s, and this has played a major role in keeping these projects in the dark. Furthermore the devastation caused by the Civil War obliterated most of the evidence once held in Spanish archives.This paper focuses on Lutyens's main commission in Spain, the palace of El Guadalperal, designed for the eighteenth Duke of Peñaranda as a country house on his estate in south west Spain. This decades-long commission, lasting from 1915 to 1934, represents a very significant and original work in Lutyens's output. The first version for the palace shows his capacity to adapt his architecture to the local climate and architectural traditions, while the second would have been, if built, his largest country house, approaching the grandeur and magnificence of the Viceroy's House in Delhi.
Theobalds, Hertfordshire: The Plan and Interiors of an Elizabethan Country House
Authors: Cole Emily 
Published: January 2018

AbstractThis article aims to reconstruct the plan of Theobalds, Hertfordshire, built between 1564 and 1585 by Sir William Cecil, Lord Burghley. Theobalds was perhaps the most significant English country house of the Elizabethan period and in 1607 was taken on as a royal palace. It was visited by all the major court and political figures of the age, while its fame also extended overseas. Theobalds was innovative in various respects, as the article makes clear, and it had a profound impact on the architecture of its generation. Its importance is all the more extraordinary given that Theobalds was so short-lived: the house was taken down shortly after 1650 and few traces of it survive today. The assumption has been that, because the house was demolished so long ago, it could not be well understood. This article contradicts that view by reconstructing in detail the plan of Theobalds, using evidence provided by primary documents.
Capillary hysteresis in sloshing dynamics: a weakly nonlinear analysis
Authors: Viola Francesco , Brun P.-T. , Gallaire François 
Published: January 2018

The sloshing of water waves in a vertical cylindrical tank is an archetypal damped oscillator in fluid mechanics. The wave frequency is traditionally derived in the potential flow limit (Lamb, Hydrodynamics, Cambridge University Press, 1932), and the damping rate results from the combined effects of the viscous dissipation at the wall, in the bulk and at the free surface (Case & Parkinson, J. Fluid Mech., vol. 2, 1957, pp. 172–184). Still, the classic theoretical prediction accounting for these effects significantly underestimates the damping rate when compared to careful laboratory experiments (Cocciaro et al., J. Fluid Mech., vol. 246, 1993, pp. 43–66). Specifically, theory provides a unique value for the damping rate, while experiments reveal that the damping increases as the sloshing amplitude decreases. Here, we investigate theoretically the effects of capillarity at the contact line on the decay time of capillary–gravity waves. To this end, we marry a model for the inviscid waves to a nonlinear empiric law for the contact line that incorporates contact angle hysteresis. The resulting system of equations is solved by means of a weakly nonlinear analysis using the method of multiple scales. Capillary effects have a dramatic influence on the calculated damping rate, especially when the sloshing amplitude gets small: this nonlinear interfacial term increases in the limit of zero wave amplitude. In contrast to viscous damping, where the wave motion decays exponentially, the contact angle hysteresis can act as Coulomb solid friction, thus yielding the arrest of the contact line in a finite time.
Erik M. Conway Receives 2017 Athelstan Spilhaus Award
Authors:   AGU
Published: January 2018

Erik M. Conway received the Athelstan Spilhaus Award at the 2017 American Geophysical Union Fall Meeting Honors Ceremony, held on 13 December 2017 in New Orleans, La. The award honors an individual “for the enhancement of the public engagement with Earth and space sciences.”
Hubert H. G. Savenije Receives 2017 International Award
Authors:   AGU
Published: January 2018

Hubert H. G. Savenije received the 2017 International Award at the American Geophysical Union Fall Meeting Honors Ceremony, held on 13 December 2017 in New Orleans, La. The award honors “an individual scientist, group, or a small team for making an outstanding contribution to furthering the Earth and space sciences and using science for the benefit of society in developing nations.”
Anti-Trop2 blockade enhances the therapeutic efficacy of ErbB3 inhibition in head and neck squamous cell carcinoma
Authors: Redlich Nathan , Robinson Anthony M. , Nickel Kwangok P. , Stein Andrew P. , Wheeler Deric L. , Adkins Douglas R. , Uppaluri Ravindra , Kimple Randall J. , Van Tine Brian A. , Michel Loren S. 
Published: January 2018

AbstractErbB3 has been widely implicated in treatment resistance, but its role as a primary treatment target is less clear. Canonically ErbB3 requires EGFR or ErbB2 for activation, whereas these two established treatment targets are thought to signal independently of ErbB3. In this study, we show that ErbB3 is essential for tumor growth of treatment-naive HNSCC patient-derived xenografts. This ErbB3 dependency occurs via ErbB3-mediated control of EGFR activation and HIF1α stabilization, which require ErbB3 and its ligand neuregulin-1. Here, we show that ErbB3 antibody treatment selects for a population of ErbB3-persister cells that express high levels of the transmembrane protein Trop2 that we previously identified as an inhibitor of ErbB3. Co-treatment with anti-ErbB3 and anti-Trop2 antibodies is synergistic and produces a greater anti-tumor response than either antibody alone. Collectively, these data both compel a revision of ErbB-family signaling and delineate a strategy for its effective inhibition in HNSCC.
Deregulated PP1α phosphatase activity towards MAPK activation is antagonized by a tumor suppressive failsafe mechanism
Authors: Chen Ming , Wan Lixin , Zhang Jiangwen , Zhang Jinfang , Mendez Lourdes , Clohessy John G. , Berry Kelsey , Victor Joshua , Yin Qing , Zhu Yuan , Wei Wenyi , Pandolfi Pier Paolo 
Published: January 2018

AbstractThe mitogen-activated protein kinase (MAPK) pathway is frequently aberrantly activated in advanced cancers, including metastatic prostate cancer (CaP). However, activating mutations or gene rearrangements among MAPK signaling components, such as Ras and Raf, are not always observed in cancers with hyperactivated MAPK. The mechanisms underlying MAPK activation in these cancers remain largely elusive. Here we discover that genomic amplification of the PPP1CA gene is highly enriched in metastatic human CaP. We further identify an S6K/PP1α/B-Raf signaling pathway leading to activation of MAPK signaling that is antagonized by the PML tumor suppressor. Mechanistically, we find that PP1α acts as a B-Raf activating phosphatase and that PML suppresses MAPK activation by sequestering PP1α into PML nuclear bodies, hence repressing S6K-dependent PP1α phosphorylation, 14-3-3 binding and cytoplasmic accumulation. Our findings therefore reveal a PP1α/PML molecular network that is genetically altered in human cancer towards aberrant MAPK activation, with important therapeutic implications.
MXene molecular sieving membranes for highly efficient gas separation
Authors: Ding Li , Wei Yanying , Li Libo , Zhang Tao , Wang Haihui , Xue Jian , Ding Liang-Xin , Wang Suqing , Caro Jürgen , Gogotsi Yury 
Published: January 2018

AbstractMolecular sieving membranes with sufficient and uniform nanochannels that break the permeability-selectivity trade-off are desirable for energy-efficient gas separation, and the arising two-dimensional (2D) materials provide new routes for membrane development. However, for 2D lamellar membranes, disordered interlayer nanochannels for mass transport are usually formed between randomly stacked neighboring nanosheets, which is obstructive for highly efficient separation. Therefore, manufacturing lamellar membranes with highly ordered nanochannel structures for fast and precise molecular sieving is still challenging. Here, we report on lamellar stacked MXene membranes with aligned and regular subnanometer channels, taking advantage of the abundant surface-terminating groups on the MXene nanosheets, which exhibit excellent gas separation performance with H2 permeability >2200 Barrer and H2/CO2 selectivity >160, superior to the state-of-the-art membranes. The results of molecular dynamics simulations quantitatively support the experiments, confirming the subnanometer interlayer spacing between the neighboring MXene nanosheets as molecular sieving channels for gas separation.
Curvy surface conformal ultra-thin transfer printed Si optoelectronic penetrating microprobe arrays
Authors: Sim Kyoseung , Rao Zhoulyu , Li Yanbin , Yang Dong , Yu Cunjiang 
Published: January 2018

AbstractPenetrating neural probe arrays are powerful bio-integrated devices for studying basic neuroscience and applied neurophysiology, underlying neurological disorders, and understanding and regulating animal and human behavior. This paper presents a penetrating microprobe array constructed in thin and flexible fashion, which can be seamlessly integrated with the soft curvy substances. The function of the microprobes is enabled by transfer printed ultra-thin Si optoelectronics. As a proof-of-concept device, microprobe array with Si photodetector arrays are demonstrated and their capability of mapping the photo intensity in space are illustrated. The design strategies of utilizing thin polyimide based microprobes and supporting substrate, and employing the heterogeneously integrated thin optoelectronics are keys to accomplish such a device. The experimental and theoretical investigations illustrate the materials, manufacturing, mechanical and optoelectronic aspects of the device. While this paper primarily focuses on the device platform development, the associated materials, manufacturing technologies, and device design strategy are applicable to more complex and multi-functionalities in penetrating probe array-based neural interfaces and can also find potential utilities in a wide range of bio-integrated systems.
Handling variability and incompleteness of biological data by flexible nets: a case study for Wilson disease
Authors: Júlvez Jorge , Dikicioglu Duygu , Oliver Stephen G. 
Published: January 2018

AbstractMathematical models that combine predictive accuracy with explanatory power are central to the progress of systems and synthetic biology, but the heterogeneity and incompleteness of biological data impede our ability to construct such models. Furthermore, the robustness displayed by many biological systems means that they have the flexibility to operate under a range of physiological conditions and this is difficult for many modeling formalisms to handle. Flexible nets (FNs) address these challenges and represent a paradigm shift in model-based analysis of biological systems. FNs can: (i) handle uncertainties, ranges and missing information in concentrations, stoichiometry, network topology, and transition rates without having to resort to statistical approaches; (ii) accommodate different types of data in a unified model that integrates various cellular mechanisms; and (iii) be employed for system optimization and model predictive control. We present FNs and illustrate their capabilities by modeling a well-established system, the dynamics of glucose consumption by a microbial population. We further demonstrate the ability of FNs to take control actions in response to genetic or metabolic perturbations. Having bench-marked the system, we then construct the first quantitative model for Wilson disease—a rare genetic disorder that impairs copper utilization in the liver. We used this model to investigate the feasibility of using vitamin E supplementation therapy for symptomatic improvement. Our results indicate that hepatocytic inflammation caused by copper accumulation was not aggravated by limitations on endogenous antioxidant supplies, which means that treating patients with antioxidants is unlikely to be effective.
The Endogenous GRP78 Interactome in Human Head and Neck Cancers: A Deterministic Role of Cell Surface GRP78 in Cancer Stemness
Authors: Chen Hsin-Ying , Chang Joseph Tung-Chieh , Chien Kun-Yi , Lee Yun-Shien , You Guo-Rung , Cheng Ann-Joy 
Published: January 2018

AbstractCell surface glucose regulated protein 78 (GRP78), an endoplasmic reticulum (ER) chaperone, was suggested to be a cancer stem cell marker, but the influence of this molecule on cancer stemness is poorly characterized. In this study, we developed a mass spectrometry platform to detect the endogenous interactome of GRP78 and investigated its role in cancer stemness. The interactome results showed that cell surface GRP78 associates with multiple molecules. The influence of cell population heterogeneity of head and neck cancer cell lines (OECM1, FaDu, and BM2) according to the cell surface expression levels of GRP78 and the GRP78 interactome protein, Progranulin, was investigated. The four sorted cell groups exhibited distinct cell cycle distributions, asymmetric/symmetric cell divisions, and different relative expression levels of stemness markers. Our results demonstrate that cell surface GRP78 promotes cancer stemness, whereas drives cells toward a non-stemlike phenotype when it chaperones Progranulin. We conclude that cell surface GRP78 is a chaperone exerting a deterministic influence on cancer stemness.
Evaluation of animal-to-human and human-to-human transmission of influenza A (H7N9) virus in China, 2013–15
Authors: Virlogeux Victor , Feng Luzhao , Tsang Tim K. , Jiang Hui , Fang Vicky J. , Qin Ying , Wu Peng , Wang Xiling , Zheng Jiandong , Lau Eric H. Y. , Peng Zhibin , Yang Juan , Cowling Benjamin J. , Yu Hongjie 
Published: January 2018

AbstractA novel avian-origin influenza A(H7N9) virus emerged in China in March 2013 and by 27 September 2017 a total of 1533 laboratory-confirmed cases have been reported. Occurrences of animal-to-human and human-to-human transmission have been previously identified, and the force of human-to-human transmission is an important component of risk assessment. In this study, we constructed an ecological model to evaluate the animal-to-human and human-to-human transmission of H7N9 during the first three epidemic waves in spring 2013, winter/spring 2013–2014 and winter/spring 2014–2015 in China based on 149 laboratory-confirmed urban cases. Our analysis of patterns in incidence in major cities allowed us to estimate a mean incubation period in humans of 2.6 days (95% credibility interval, CrI: 1.4–3.1) and an effective reproduction number Re of 0.23 (95% CrI: 0.05–0.47) for the first wave, 0.16 (95% CrI: 0.01–0.41) for the second wave, and 0.16 (95% CrI: 0.01–0.45) for the third wave without a significant difference between waves. There was a significant decrease in the incidence of H7N9 cases after live poultry market closures in various major cities. Our analytic framework can be used for continued assessment of the risk of human to human transmission of A(H7N9) virus as human infections continue to occur in China.