bluuebunny/crossref_metadata_2025 huggingface dataset:
Overcoming Peak Overlaps in Titanium- and Vanadium-Bearing Materials with Multiple Linear Least Squares Fitting
Authors: Mengason Michael , Ritchie Nicholas
Published: March 2017

The evolution of the energy dispersive spectrometer (EDS) from the lithium-drifted silicon detector [Si(Li)] to the silicon drift detector (SDD) has created new opportunities in the field of electron probe X-ray microanalysis. The SDD permits operation at significantly higher count rates than the Si(Li) and also provides a more stable energy scale. X-ray spectra captured by EDS can now be analyzed qualitatively or quantitatively under the same beam conditions as used for wavelength dispersive spectrometry (WDS). Standards-based quantitative EDS (SB-Quant-EDS) can thus provide analyses that are accurate and precise for an ever growing number of materials measurement problems. In this study, we analyze NIST research glasses with “known” nominal concentrations of titanium (Ti) and vanadium (V) to evaluate the external reproducibility of the SB-Quant-EDS technique in the presence of severe peak overlaps. We additionally analyze several naturally occurring oxide minerals by WDS and EDS simultaneously and evaluate the outputs of these two methods when quantifying the same analytical volume within the sample.
Does Safeguards Need Saving? Lessons from the Ukraine–Passenger Cars Dispute
Authors: GNUTZMANN-MKRTCHYAN AREVIK , LESTER SIMON
Published: March 2017

The Panel Report in Ukraine–Passenger Cars provides an opportunity to revisit an old debate over the role of safeguard measures in the WTO. With regard to the legal findings, the Panel followed the established jurisprudence in this area, and found a number of violations of the Safeguards Agreement. With regard to the economics, we delve more deeply into the economic and political background of the safeguards investigation. Ukraine was hit by the economic crisis shortly after its WTO accession that significantly liberalized import tariffs on passenger cars. Next, we offer a de novo look at the injury and causation issues in this case, and discuss the challenges of an industry reliant on offshored production that sees a safeguard as a mechanism to attract foreign direct investment (FDI) for production. We conclude with an assessment of the operation of the WTO's safeguards regime, along with some tentative suggestions for reform. Overall, our examination of the economic analysis by the investigating authority and the legal review by the WTO Panel raises questions about particular aspects of the domestic and WTO processes, but concludes that the system worked well in this case.
Trade and Agricultural Disease: Import Restrictions in the Wake of the India–Agricultural Products Dispute
Authors: SAGGI KAMAL , WU MARK
Published: March 2017

Trade in agricultural products raises sensitivities, particularly when imports originate from a trading partner experiencing an outbreak of some type of agricultural disease. In this article, we explain why despite the negative externalities associated with diseased imports, an importing country is generally not permitted to ban such imports outright under WTO law. Rather, it is allowed to do so only under specific circumstances. We also highlight how the recent India–Agricultural Products ruling contributes to the jurisprudence of two issues concerning the SPS Agreement: the interpretation of international standards, and the relationship between the risk assessment and scientific evidence requirements.
Ask for the Moon, Settle for the Stars: What is a Reasonable Period to Comply with WTO Awards?
Authors: MAVROIDIS PETROS C. , MEAGHER NIALL , PRUSA THOMAS J. , YANGUAS TATIANA
Published: March 2017

The World Trade Organization (WTO) dispute settlement process allows a defending Member a ‘reasonable period of time’ (RPT) to implement any findings that its contested measures are inconsistent with WTO law. If agreement on this RPT cannot be reached, Article 21.3(c) of the Understanding on Rules and Procedures Governing the Settlement of Disputes (DSU) provides for the possibility of arbitration on the length of the RPT. The DSU provides limited guidelines on the RPT, stating only that it should not normally exceed 15 months. In practice, Arbitrators have developed the standard that the RPT should reflect the shortest possible period under the domestic legal system of the defending Member to make the changes necessary to comply with the WTO rulings. Our research confirms that in practice Arbitrators have determined this period by ‘splitting the difference’ approximately between the periods suggested by the complaining and defending Member. In addition, the process appears to reward defending Members that request an RPT that exceeds the 15-month guideline in Article 21.3(c).
WTO Dispute Settlement in 2015: Going Strong after Two Decades
Authors: BOWN CHAD P. , MAVROIDIS PETROS C.
Published: March 2017

On 1 January 1995, the WTO and its new and sophisticated dispute settlement system entered into force. We have thus already entered the twenty-first year of its life. Although the number of disputes has dropped somewhat over the last decade, there is no sign of weakening. Indeed, during 2015, the year we discuss in this volume, the WTO adjudicating bodies issued 16 reports, including three reports discussing the extent of the reasonable period of time.
Tape: Or, Rewinding the Phonographic Regime
Authors: BOHLMAN ANDREA F. , McMURRAY PETER
Published: March 2017

Magnetic tape follows the contours of the twentieth century in striking ways, from the overtly sonic and musical to less obvious political and social transformations. This introductory article sets the tone for this special issue, an effort to connect discrete histories of tape through a focus on its materialities. We posit the existence of a phonographic regime that coheres around a loose set of assumptions that often appear in tandem with broad claims about what ‘sound recording’ or even ‘analogue media’ are. This regime dates back to the invention of phonography but persists through many contemporary histories of sound recording. We challenge the regime by thinking with and through tape recording. One of tape's critical media operations, ‘rewind’, serves as a central focus for our push-back against the regime. As a button-interface, it highlights the physical engagement of humans with materialities, including the corporal labours of using technology, with iconography that digital technologies still employ. As a mechanism of respooling, it points to the industrial histories of various spooling forerunners from textiles to film reels. As we explore its cultural techniques in musical practices, we consider rewind, above all, as a temporal gesture that offers new paths backward into history.
Relays: Audiotape, Material Affordances, and Cultural Practice
Authors: KANE BRIAN
Published: March 2017

This article considers the relationship between audiotape's material affordances and the audibility of cultural practices. Not all changes in the materiality of sound media are audible to listeners, and not all changes in the audibility of cultural practices require changes in their material support. Thus focus on the affordances of sound technologies – those possibilities of sound technologies that may or may not be engaged by its users, and the wide range of practices that such technologies support – can help to connect materiality and audibility. I address the affordances of audiotape by examining a number of small case studies where established sonic practices encounter a transition from phonography to audiotape: musique concrète and the tape loop, serialist composition, and Les Paul's use of overdubbing. Finally, I consider the nature of the audiotape archive and its mode of access in order to pose some general questions about the meaning and use of audiotape's affordances.
Making Tapes in Poland: The Compact Cassette at Home
Authors: BOHLMAN ANDREA F.
Published: March 2017

This article offers a history of the compact cassette in Poland from 1963 to 2015, focusing on its vibrant presence as the medium of choice for unofficial musical culture. I explore tapes’ capacity to reveal a history of everyday musical and technological fluencies: as a sonic archive they offer a window into networked epistemologies of sound under state socialism. Listening to homemade tapes – a process that builds on ethnographic encounters with their makers – I explore the work we can hear across the medium's noisy recordings and stress their position at the crossroads of musicology's methodologies. Tape's reusability, so carefully explained in historical anecdotes and technical manuals in the 1960s, facilitated democratic debate for the social movements of the 1980s. The format's fungibility and plurality made it not only a convenient conduit for discussion, but also a medium that – in form and substance – modelled the importance of dissent, revision, and return in political discourse.
Tape, Prince, and the Studio: Interview with Susan Rogers 23 May 2016, Cambridge, MA
Authors: HELMREICH STEFAN , McMURRAY PETER
Published: March 2017

Susan Rogers has lived many musical lives. As a faculty member at Berklee College of Music, she directs the Berklee Music Cognition and Cognition Laboratory, expanding her research in auditory memory, which she began during her doctoral studies with Daniel Levitin at McGill University. She also teaches analogue studio production, drawing on two decades of experience in recording studios. She is especially well known for her years working as Prince's staff engineer (1983–87), a period in which she not only encountered Prince's own unique uses of tape, but also created his now-infamous tape vault. In many ways, the immediate impetus for this interview was Prince's untimely passing on 21 April 2016. In previous interviews, Rogers had already emerged as a lucid commentator on Prince's work first-hand, but that context adds a certain emotional heft to this interview, conducted one month after the pop music star's death.
Tapes on Open Reels: Tia Blake at the Southern Folklife Collection
Authors: WEISS STEVEN
Published: March 2017

On 16 September 1976, in the neighbourhood of Cite du Havre in Montréal, Québec, a 24-year-old singer and songwriter named Christina ‘Tia’ Blake recorded a demo tape in Studio A of the Canadian Broadcasting Corporation (CBC). Tia had responded to a general request from CBC Radio looking for original songs written by local artists. She recorded three original songs that Thursday, including one song about her father and another written for an old boyfriend. She and the CBC producer listened to the playback together. The producer shook his head. There was nothing there he could use. He gave Tia the tape to keep.
Episodic Demands, Resources, and Engagement
Authors: Reina-Tamayo Andrea M. , Bakker Arnold B. , Derks Daantje
Published: March 2017

Abstract. This study contributes to the literature on work engagement and job demands-resources (JD-R) theory by exploring the momentary relations between episodic demands, resources, engagement, and performance during various activities (e.g., checking e-mails) within a day. Using experience-sampling methodology, 61 Dutch employees completed activity characteristics, engagement, and performance surveys at three different times during the day for one week. Results from 413 observations showed that 88% of the total variance in engagement fluctuates from activity to activity. Multilevel path analysis results confirmed that during activities, episodic engagement was positively related to performance, and mediated the positive associations of resources and negative associations of hindering demands with performance.
Finding Meaning in the Struggle of Work
Authors: Highhouse Scott , Nye Christopher D. , Matthews Russell A.
Published: March 2017

Abstract. It is suggested that work importance research has suffered from construct proliferation, and that the literature would benefit from returning to Dubin’s (1956) original notion of work importance as a general construct – representing the degree to which work plays a central role in one’s life space. Measures of three work importance constructs (i.e., work involvement, job involvement, work ethic endorsement) were administered to (n = 758) working adults from the USA to examine dimensionality using bifactor analysis. Results showed the bifactor model fit the data better than a one-factor or three-factor model. The bifactor model suggests that both general and domain-specific factors appear to exist, but that the general work importance factor predicts most work outcomes to a substantial degree.
Polar Interlopers in the Aurora
Authors: Crane Leah
Published: March 2017

A new study suggests that poleward boundary intensifications in the aurora are caused by fast flows of plasma from the poles into the auroral oval.
GOES-16 Satellite Lights Up Lightning Flashes in New Video
Authors: Wendel JoAnna
Published: March 2017

The satellite's lightning mapper instrument will help scientists forecast extreme weather.
Prognostic impact of bone marrow fibrosis in polycythemia vera: validation of the IWG-MRT study and additional observations
Authors: Barraco D , Cerquozzi S , Hanson C A , Ketterling R P , Pardanani A , Gangat N , Tefferi A
Published: March 2017

In 2012, the International Working Group for Myeloproliferative Neoplasms (MPN) Research and Treatment (IWG-MRT) reported an associations between mild bone marrow (BM) fibrosis (⩾grade 1) in polycythemia vera (PV) and a lower incidence of thrombosis during the clinical course and a higher risk of fibrotic progression. The objective in the current study of 262 patients with PV was to validate these observations and also identify other risk factors for myelofibrosis-free survival (MFFS). About 127 (48%) patients displayed ⩾grade 1 reticulin fibrosis at the time of diagnosis; presenting clinical and laboratory features were not significantly different between patients with or without BM fibrosis. In univariate analysis, BM fibrosis had no significant impact on overall, leukemia-free or thrombosis-free survival, whereas a significant association was noted for MFFS (P=0.009, hazard ratio 2.9; 95% confidence interval 1.32–6.78); other risk factors for MFFS included leukocytosis ⩾15 × 109/l, presence of palpable splenomegaly and abnormal karyotype. During multivariable analysis, leukocytosis ⩾15 × 109/l, palpable splenomegaly and ⩾grade 1 BM reticulin fibrosis remained significant. The current study validates the previously observed association between ⩾grade 1 BM reticulin fibrosis in PV and subsequent fibrotic progression, and identifies leukocytosis and palpable splenomegaly as additional risk factors for fibrotic progression; additional studies are required to clarify the impact of BM fibrosis on thrombosis and that of abnormal karyotype on MFFS.
Structure and assembly of scalable porous protein cages
Authors: Sasaki Eita , Böhringer Daniel , van de Waterbeemd Michiel , Leibundgut Marc , Zschoche Reinhard , Heck Albert J. R. , Ban Nenad , Hilvert Donald
Published: March 2017

Proteins that self-assemble into regular shell-like polyhedra are useful, both in nature and in the laboratory, as molecular containers. Here we describe cryo-electron microscopy (EM) structures of two versatile encapsulation systems that exploit engineered electrostatic interactions for cargo loading. We show that increasing the number of negative charges on the lumenal surface of lumazine synthase, a protein that naturally assembles into a ∼1-MDa dodecahedron composed of 12 pentamers, induces stepwise expansion of the native protein shell, giving rise to thermostable ∼3-MDa and ∼6-MDa assemblies containing 180 and 360 subunits, respectively. Remarkably, these expanded particles assume unprecedented tetrahedrally and icosahedrally symmetric structures constructed entirely from pentameric units. Large keyhole-shaped pores in the shell, not present in the wild-type capsid, enable diffusion-limited encapsulation of complementarily charged guests. The structures of these supercharged assemblies demonstrate how programmed electrostatic effects can be effectively harnessed to tailor the architecture and properties of protein cages.
Structural basis of homo- and heterotrimerization of collagen I
Authors: Sharma Urvashi , Carrique Loïc , Vadon-Le Goff Sandrine , Mariano Natacha , Georges Rainier-Numa , Delolme Frederic , Koivunen Peppi , Myllyharju Johanna , Moali Catherine , Aghajari Nushin , Hulmes David J. S.
Published: March 2017

Fibrillar collagen molecules are synthesized as precursors, procollagens, with large propeptide extensions. While a homotrimeric form (three α1 chains) has been reported in embryonic tissues as well as in diseases (cancer, fibrosis, genetic disorders), collagen type I usually occurs as a heterotrimer (two α1 chains and one α2 chain). Inside the cell, the role of the C-terminal propeptides is to gather together the correct combination of three α chains during molecular assembly, but how this occurs for different forms of the same collagen type is so far unknown. Here, by structural and mutagenic analysis, we identify key amino acid residues in the α1 and α2 C-propeptides that determine homo- and heterotrimerization. A naturally occurring mutation in one of these alters the homo/heterotrimer balance. These results show how the C-propeptide of the α2 chain has specifically evolved to permit the appearance of heterotrimeric collagen I, the major extracellular building block among the metazoa.
EGFR/ARF6 regulation of Hh signalling stimulates oncogenic Ras tumour overgrowth
Authors: Chabu Chiswili , Li Da-Ming , Xu Tian
Published: March 2017

Multiple signalling events interact in cancer cells. Oncogenic Ras cooperates with Egfr, which cannot be explained by the canonical signalling paradigm. In turn, Egfr cooperates with Hedgehog signalling. How oncogenic Ras elicits and integrates Egfr and Hedgehog signals to drive overgrowth remains unclear. Using a Drosophila tumour model, we show that Egfr cooperates with oncogenic Ras via Arf6, which functions as a novel regulator of Hh signalling. Oncogenic Ras induces the expression of Egfr ligands. Egfr then signals through Arf6, which regulates Hh transport to promote Hh signalling. Blocking any step of this signalling cascade inhibits Hh signalling and correspondingly suppresses the growth of both, fly and human cancer cells harbouring oncogenic Ras mutations. These findings highlight a non-canonical Egfr signalling mechanism, centered on Arf6 as a novel regulator of Hh signalling. This explains both, the puzzling requirement of Egfr in oncogenic Ras-mediated overgrowth and the cooperation between Egfr and Hedgehog.
Laser-mediated rupture of chlamydial inclusions triggers pathogen egress and host cell necrosis
Authors: Kerr Markus C. , Gomez Guillermo A. , Ferguson Charles , Tanzer Maria C. , Murphy James M. , Yap Alpha S. , Parton Robert G. , Huston Wilhelmina M. , Teasdale Rohan D
Published: March 2017

Remarkably little is known about how intracellular pathogens exit the host cell in order to infect new hosts. Pathogenic chlamydiae egress by first rupturing their replicative niche (the inclusion) before rapidly lysing the host cell. Here we apply a laser ablation strategy to specifically disrupt the chlamydial inclusion, thereby uncoupling inclusion rupture from the subsequent cell lysis and allowing us to dissect the molecular events involved in each step. Pharmacological inhibition of host cell calpains inhibits inclusion rupture, but not subsequent cell lysis. Further, we demonstrate that inclusion rupture triggers a rapid necrotic cell death pathway independent of BAK, BAX, RIP1 and caspases. Both processes work sequentially to efficiently liberate the pathogen from the host cytoplasm, promoting secondary infection. These results reconcile the pathogen's known capacity to promote host cell survival and induce cell death.
Moonshots and metastatic disease: the need for a multi-faceted approach when studying atypical responses
Authors: De La Torre Kristine , Cohen Elly , Loeser Anne , Hurlbert Marc ,   on behalf of the Metastatic Breast Cancer Alliance
Published: March 2017

Clinical research generally focuses on results involving a statistical mean with little attention in trial design to patients who respond considerably better or worse than average. Exploring the reasons underlying an “atypical response” will increase understanding of the mechanisms involved in cancer progression and treatment resistance, accelerate biomarker identification, and improve precision medicine by allowing clinicians to prospectively select optimal treatments. Based on our review, we suggest two ways to move this field forward. First, we suggest that clear categorization of “atypical responders” is needed. This encompasses three sub-categories of patients: “exceptional responders” (those with an unusually favorable treatment response), “rapid progressors” (patients demonstrating an unusually poor or no therapeutic response), and “exceptional survivors” (patients who have far outlived their initial prognosis). Such categorization may depend upon the clinical context and disease subtype. Second, we suggest that atypical responses may be due not only to somatic mutations in tumors, but also to inherited polymorphisms in non-tumor tissue, host and tumor environments, lifestyle factors, co-morbidities, use of complementary and integrative medicine, and the interaction among these components. Here, we summarize new research initiatives exploring atypical responses, the potential reasons for atypical responses, and a strategic call to action. Rigorous studies of normal and atypical responses to treatment will be needed to strengthen understanding of the role of non-tumor factors. Clinical trial design for targeted and other types of therapies should be enhanced to collect data in a standardized manner beyond tumor genetics, resulting in more thorough study of the whole patient.
Serum FABP5 concentration is a potential biomarker for residual risk of atherosclerosis in relation to cholesterol efflux from macrophages
Authors: Furuhashi Masato , Ogura Masatsune , Matsumoto Megumi , Yuda Satoshi , Muranaka Atsuko , Kawamukai Mina , Omori Akina , Tanaka Marenao , Moniwa Norihito , Ohnishi Hirofumi , Saitoh Shigeyuki , Harada-Shiba Mariko , Shimamoto Kazuaki , Miura Tetsuji
Published: March 2017

Cholesterol efflux capacity (CEC) from macrophages, the first step in the reverse cholesterol transport pathway, is inversely associated with residual risk for atherosclerotic cardiovascular disease. Fatty acid-binding protein 4 (FABP4) and FABP5 are expressed in both adipocytes and macrophages and play significant roles in the development of insulin resistance and atherosclerosis. Both FABP4 and FABP5 are secreted from cells, and their circulating levels are associated with insulin resistance and atherosclerosis. We investigated the association between CEC and levels of FABP4 and FABP5 in 250 subjects without any medications. CEC was positively correlated with HDL cholesterol level and negatively correlated with concentrations of high-sensitivity C-reactive protein (hsCRP) and FABP5, but not FABP4. Multiple regression analysis demonstrated that FABP5 concentration was an independent predictor of CEC after adjustment of age, gender and levels of HDL cholesterol and hsCRP. In 129 of the 250 subjects who underwent carotid ultrasonography, mean intima-media thickness was negatively correlated with CEC and was positively correlated with concentrations of FABP4 and FABP5. In conclusion, in contrast to FABP4, circulating FABP5 is associated with decreased CEC and carotid atherosclerosis, suggesting that FABP5 level is a regulatory factor of CEC and a potential biomarker for residual risk of atherosclerosis.
Importance of Zinc Transporter 8 Autoantibody in the Diagnosis of Type 1 Diabetes in Latin Americans
Authors: Gomes Karla Fabiana Brasil , Semzezem Cintia , Batista Rodolfo , Fukui Rosa Tsuneshiro , Santos Aritania Sousa , Correia Márcia Regina , Passos-Bueno Maria Rita , Silva Maria Elizabeth Rossi da
Published: March 2017

There is a scarcity of data of zinc transporter-8 autoantibody (ZnT8A) on mixed populations such as Brazilian. Therefore, we evaluated the relevance of ZnT8A for type 1 diabetes (T1D) diagnosis and the role of ZnT8 coding gene (SLC30A8) in T1D predisposition.Patients with T1D (n = 629; diabetes duration = 11 (6–16) years) and 651 controls were genotyped for SLC30A8 rs16889462 and rs2466295 variants (BeadXpress platform). ZnT8 triple antibody was measured by ELISA; glutamic acid decarboxylase (GAD65A) and protein tyrosine phosphatase (IA-2A) autoantibodies by radioimmunoassay. Results: Znt8A was detected in 68.7% of recent-onset T1D patients and 48.9% of the entire patient cohort, similar to GAD65A (68.3% and 47.2%) and IA-2A (64.8% and 42.4%) positivities respectively. ZnT8A was the only antibody in 8.4% of patients. Znt8A and IA2A frequencies and titers were independent of gender and ethnicity, whereas GAD65A titers were greater in females. The diabetes duration-dependent decline in ZnT8A frequency was similar to GAD65A and IA-2A. The SLC30A8 rs2466293 AG + GG genotypes were associated with T1D risk in non-European descents (56.2% × 42.9%; p = 0.018), and the GG genotype with higher ZnT8A titers in recent-onset T1D: 834.5 IU/mL (711.3–2190.0) × 281 IU/mL (10.7–726.8); p = 0.027. Conclusion ZnT8A detection increases T1D diagnosis rate even in mixed populations. SLC30A8 rs2466293 was associated with T1D predisposition in non-European descents.
Resveratrol sequentially induces replication and oxidative stresses to drive p53-CXCR2 mediated cellular senescence in cancer cells
Authors: Li Boxuan , Hou Dong , Guo Haiyang , Zhou Haibin , Zhang Shouji , Xu Xiuhua , Liu Qiao , Zhang Xiyu , Zou Yongxin , Gong Yaoqin , Shao Changshun
Published: March 2017

Resveratrol (RSV) acts either as an antioxidant or a pro-oxidant depending on contexts. RSV-treated cancer cells may experience replication stress that can lead to cellular senescence or apoptosis. While both oxidative and replication stresses may mediate the anti-proliferation effect of RSV, to what extent each contributes to the impaired proliferation in response to RSV remains uncharacterized. We here report the study of the roles of replication and oxidative stresses in mediating cellular senescence in cancer cells treated with RSV. RSV induced S-phase arrest and cellular senescence in a dose-dependent manner in U2OS and A549 cancer cells as well as in normal human fibroblasts. We observed that nucleosides significantly alleviated RSV-induced replication stress and DNA damage response, and consequently attenuating cellular senescence. While the elevation of reactive oxygen species (ROS) also mediated the pro-senescent effect of RSV, it occurred after S-phase arrest. However, the induction of ROS by RSV was independent of S-phase arrest and actually reinforced the latter. We also demonstrated a critical role of the p53-CXCR2 axis in mediating RSV-induced senescence. Interestingly, CXCR2 also functioned as a barrier to apoptosis. Together, our results provided more insights into the biology of RSV-induced stress and its cellular consequences.
A Biologically-validated HCV E1E2 Heterodimer Structural Model
Authors: Castelli Matteo , Clementi Nicola , Pfaff Jennifer , Sautto Giuseppe A. , Diotti Roberta A. , Burioni Roberto , Doranz Benjamin J. , Dal Peraro Matteo , Clementi Massimo , Mancini Nicasio
Published: March 2017

The design of vaccine strategies and the development of drugs targeting the early stages of Hepatitis C virus (HCV) infection are hampered by the lack of structural information about its surface glycoproteins E1 and E2, the two constituents of HCV entry machinery. Despite the recent crystal resolution of limited versions of both proteins in truncated form, a complete picture of the E1E2 complex is still missing. Here we combined deep computational analysis of E1E2 secondary, tertiary and quaternary structure with functional and immunological mutational analysis across E1E2 in order to propose an in silico model for the ectodomain of the E1E2 heterodimer. Our model describes E1-E2 ectodomain dimerization interfaces, provides a structural explanation of E1 and E2 immunogenicity and sheds light on the molecular processes and disulfide bridges isomerization underlying the conformational changes required for fusion. Comprehensive alanine mutational analysis across 553 residues of E1E2 also resulted in identifying the epitope maps of diverse mAbs and the disulfide connectivity underlying E1E2 native conformation. The predicted structure unveils E1 and E2 structures in complex, thus representing a step towards the rational design of immunogens and drugs inhibiting HCV entry.
Short-Course, High-Dose Rifampicin Achieves Wolbachia Depletion Predictive of Curative Outcomes in Preclinical Models of Lymphatic Filariasis and Onchocerciasis
Authors: Aljayyoussi Ghaith , Tyrer Hayley E. , Ford Louise , Sjoberg Hanna , Pionnier Nicolas , Waterhouse David , Davies Jill , Gamble Joanne , Metuge Haelly , Cook Darren A. N. , Steven Andrew , Sharma Raman , Guimaraes Ana F. , Clare Rachel H. , Cassidy Andrew , Johnston Kelly L. , Myhill Laura , Hayward Laura , Wanji Samuel , Turner Joseph D. , Taylor Mark J. , Ward Stephen A.
Published: March 2017

Lymphatic filariasis (LF) and onchocerciasis are priority neglected tropical diseases targeted for elimination. The only safe drug treatment with substantial curative activity against the filarial nematodes responsible for LF (Brugia malayi, Wuchereria bancrofti) or onchocerciasis (Onchocerca volvulus) is doxycycline. The target of doxycycline is the essential endosymbiont, Wolbachia. Four to six weeks doxycycline therapy achieves >90% depletion of Wolbachia in worm tissues leading to blockade of embryogenesis, adult sterility and premature death 18–24 months post-treatment. Long treatment length and contraindications in children and pregnancy are obstacles to implementing doxycycline as a public health strategy. Here we determine, via preclinical infection models of Brugia malayi or Onchocerca ochengi that elevated exposures of orally-administered rifampicin can lead to Wolbachia depletions from filariae more rapidly than those achieved by doxycycline. Dose escalation of rifampicin achieves >90% Wolbachia depletion in time periods of 7 days in B. malayi and 14 days in O. ochengi. Using pharmacokinetic-pharmacodynamic modelling and mouse-human bridging analysis, we conclude that clinically relevant dose elevations of rifampicin, which have recently been determined as safe in humans, could be administered as short courses to filariasis target populations with potential to reduce anti-Wolbachia curative therapy times to between one and two weeks.
Compensation effect of winter wheat grain yield reduction under straw mulching in wide-precision planting in the North China Plain
Authors: Liu Xinhui , Ren Yujie , Gao Chao , Yan Zhenxing , Li Quanqi
Published: March 2017

Climate change and the growing demand for food security force growers to identify ways both to improve food production and to reduce agricultural carbon emissions. Although straw mulching is known to decrease CO2 emissions, winter wheat grain yield in the North China Plain was declined under straw mulching. In an effort to determine the most effective way to increase winter wheat yield under straw mulching, a field experiment was conducted using two planting patterns (wide-precision planting and conventional-cultivation planting) and two straw mulching rates (0 and 0.6 kg/m2). The results showed the wide-precision planting/non-mulching treatment significantly increased the leaf area index more than the other three treatments at the early growth stage. This treatment improved aboveground dry matter accumulation and was conducive to increased spike weight in the late growth stage. By contrast, straw mulching significantly reduced winter wheat grain yields by lowering both spike number and 1000-grain weight at the mature plant stage. In the wide-precision planting/mulching treatment, a significantly increased spike number compensated for grain yield losses. The results support the idea that wide-precision planting combined with straw mulching has the potential to decrease the winter wheat grain yield reduction previously observed with straw mulching in the North China Plain.
ALK
G1269A mutation as a potential mechanism of acquired resistance to crizotinib in an ALK-rearranged inflammatory myofibroblastic tumor
Authors: Michels Sebastian Y. F. , Scheel Andreas H. , Wündisch Thomas , Heuckmann Johannes M. , Menon Roopika , Puesken Michael , Kobe Carsten , Pasternack Helen , Heydt Carina , Scheffler Matthias , Fischer Rieke , Schultheis Anne M. , Merkelbach-Bruse Sabine , Heukamp Lukas , Büttner Reinhard , Wolf Jürgen
Published: March 2017

Inflammatory myofibroblastic tumors are rare mesenchymal neoplasms frequently harboring oncogenic chromosomal rearrangements, most commonly, involving the ALK (anaplastic lymphoma kinase) gene. Treatment of this molecularly defined subgroup with the anaplastic lymphoma kinase inhibitor crizotinib has shown to be effective. However, comparable to lung adenocarcinoma, resistance inevitably develops. Second generation anaplastic lymphoma kinase inhibitors such as ceritinib are able to overcome acquired resistance to crizotinib. Here, we report the case of a patient with an inflammatory myofibroblastic tumors harboring a DCTN1-ALK fusion who developed resistance to crizotinib treatment. Next-generation sequencing of a rebiopsy sample revealed the acquisition of the ALK
G1269A
mutation as a mechanism of resistance. Therapy with ceritinib resulted in a short but profound clinical, metabolic and morphologic response. This case illustrates that (i) different tumor entities may share similar oncogenic driver mechanisms, rendering them vulnerable for the same therapeutic substances and (ii) likewise, the same mode of resistance may occur under targeted therapy among different tumor entities.
Mona Lisa is always happy – and only sometimes sad
Authors: Liaci Emanuela , Fischer Andreas , Heinrichs Markus , van Elst Ludger Tebartz , Kornmeier Jürgen
Published: March 2017

The worldwide fascination of da Vinci’s Mona Lisa has been dedicated to the emotional ambiguity of her face expression. In the present study we manipulated Mona Lisa’s mouth curvature as one potential source of ambiguity and studied how a range of happier and sadder face variants influences perception. In two experimental conditions we presented different stimulus ranges with different step sizes between stimuli along the happy-sad axis of emotional face expressions. Stimuli were presented in random order and participants indicated the perceived emotional face expression (first task) and the confidence of their response (second task). The probability of responding ‘happy’ to the original Mona Lisa was close to 100%. Furthermore, in both conditions the perceived happiness of Mona Lisa variants described sigmoidal functions of the mouth curvature. Participants’ confidence was weakest around the sigmoidal inflection points. Remarkably, the sigmoidal functions, as well as confidence values and reaction times, differed significantly between experimental conditions. Finally, participants responded generally faster to happy than to sad faces. Overall, the original Mona Lisa seems to be less ambiguous than expected. However, perception of and reaction to the emotional face content is relative and strongly depends on the used stimulus range.
Fabrication of Porous Ag/TiO2/Au Coatings with Excellent Multipactor Suppression
Authors: Wu Duoduo , Ma Jianzhong , Bao Yan , Cui Wanzhao , Hu Tiancun , Yang Jing , Bai Yuanrui
Published: March 2017

Porous Ag/TiO2/Au coatings with excellent multipactor suppression were prepared by fabrication of porous Ag surface through two-step wet chemical etching, synthesis of TiO2 coatings by electroless-plating-like solution deposition and deposition of Au coatings via electroless plating. Porous structure of Ag surface, TiO2 coatings on porous Ag surface and Au coatings on porous Ag/TiO2 surface were verified by field-emission scanning electron microscopy, the composition and crystal type of TiO2 coatings was characterized by X-ray photoelectron spectroscopy and X-ray diffraction. Secondary electron yield (SEY) measurement was used to monitor the SEY coefficient of the porous Ag coatings and Ag/TiO2/Au coatings. The as-obtained porous Ag coatings were proved exhibiting low SEY below 1.2, and the process was highly reproducible. In addition, the porous Ag/TiO2/Au coatings showed excellent multipactor suppression with the SEY 1.23 and good environmental stability. It is worth mentioning that the whole preparation process is simple and feasible, which would provide a promising application in RF devices.
Extreme Ultraviolet Fractional Orbital Angular Momentum Beams from High Harmonic Generation
Authors: Turpin Alex , Rego Laura , Picón Antonio , San Román Julio , Hernández-García Carlos
Published: March 2017

We investigate theoretically the generation of extreme-ultraviolet (EUV) beams carrying fractional orbital angular momentum. To this end, we drive high-order harmonic generation with infrared conical refraction (CR) beams. We show that the high-order harmonic beams emitted in the EUV/soft x-ray regime preserve the characteristic signatures of the driving beam, namely ringlike transverse intensity profile and CR-like polarization distribution. As a result, through orbital and spin angular momentum conservation, harmonic beams are emitted with fractional orbital angular momentum, and they can be synthesized into structured attosecond helical beams –or “structured attosecond light springs”– with rotating linear polarization along the azimuth. Our proposal overcomes the state of the art limitations for the generation of light beams far from the visible domain carrying non-integer orbital angular momentum and could be applied in fields such as diffraction imaging, EUV lithography, particle trapping, and super-resolution imaging.
Three electron beams from a laser-plasma wakefield accelerator and the energy apportioning question
Authors: Yang X. , Brunetti E. , Gil D. Reboredo , Welsh G. H. , Li F. Y. , Cipiccia S. , Ersfeld B. , Grant D. W. , Grant P. A. , Islam M. R. , Tooley M. P. , Vieux G. , Wiggins S. M. , Sheng Z. M. , Jaroszynski D. A.
Published: March 2017

Laser-wakefield accelerators are compact devices capable of delivering ultra-short electron bunches with pC-level charge and MeV-GeV energy by exploiting the ultra-high electric fields arising from the interaction of intense laser pulses with plasma. We show experimentally and through numerical simulations that a high-energy electron beam is produced simultaneously with two stable lower-energy beams that are ejected in oblique and counter-propagating directions, typically carrying off 5–10% of the initial laser energy. A MeV, 10s nC oblique beam is ejected in a 30°–60° hollow cone, which is filled with more energetic electrons determined by the injection dynamics. A nC-level, 100s keV backward-directed beam is mainly produced at the leading edge of the plasma column. We discuss the apportioning of absorbed laser energy amongst the three beams. Knowledge of the distribution of laser energy and electron beam charge, which determine the overall efficiency, is important for various applications of laser-wakefield accelerators, including the development of staged high-energy accelerators.
Association of SCN10A Polymorphisms with the Recurrence of Atrial Fibrillation after Catheter Ablation in a Chinese Han Population
Authors: Wu Haiqing , Xu Juan , Chen Songwen , Zhou Genqing , Qi Baozhen , Wei Yong , Hu En , Tang Dongdong , Chen Gang , Li Hongli , Zhao Liqun , Shi Yongyong , Liu Shaowen
Published: March 2017

The nonsynonymous SCN10A single nucleotide polymorphism (SNP) rs6795970 has been reported to associate with PR interval and atrial fibrillation (AF) and in strong linkage disequilibrium (LD) with the AF-associated SNP rs6800541. In this study, we investigated whether rs6795970 polymorphisms are associated with AF recurrence after catheter ablation. A total of 502 consecutive patients with AF who underwent catheter ablation were included. AF recurrence was defined as a documented episode of any atrial arrhythmias lasting ≥30 s after a blanking period of 3 months. AF recurrence was observed between 3 and 12 months after catheter ablation in 24.5% of the patients. There was a significant difference in the allele distribution (p = 7.86 × 10−5) and genotype distribution (p = 1.42 × 10−5) of rs6795970 between the AF recurrence and no recurrence groups. In a multivariate analysis, we identified the following independent predictors of AF recurrence: the rs6795970 genotypes in an additive model (OR 0.36, 95%CI 0.22~0.60, p = 7.04 × 10−5), a history of AF ≥36 months (OR 3.57, 95%CI 2.26~5.63, p = 4.33 × 10−8) and left atrial diameter (LAD) ≥40 mm (OR 1.85, 95%CI 1.08~3.19, p = 0.026). These data suggest that genetic variation in SCN10A may play an important role in predicting AF recurrence after catheter ablation in the Chinese Han population.
Assessing muscle spasticity with Myotonometric and passive stretch measurements: validity of the Myotonometer
Authors: Li Xiaoyan , Shin Henry , Li Sheng , Zhou Ping
Published: March 2017

Spasticity of the biceps brachii muscle was assessed using the modified Ashworth Scale (MAS), Myotonometry and repeated passive stretch techniques, respectively. Fourteen subjects with chronic hemiplegia participated in the study. Spasticity was quantified by muscle displacements and compliance from the Myotonometer measurements and resistive torques from the repeated passive stretch at velocities of 5 °/s and 100 °/s, respectively. Paired t-tests indicated a significant decrease of muscle displacement and compliance in the spastic muscles as compared to the contralateral side (muscle displacement: spastic: 4.84 ± 0.33 mm, contralateral: 6.02 ± 0.49 mm, p = 0.038; compliance: spastic: 1.79 ± 0.12 mm/N, contralateral: 2.21 ± 0.18 mm/kg, p = 0.048). In addition, passive stretch tests indicated a significant increase of total torque at the velocity of 100 °/s compared with that of 5 °/s (Tt5 = 2.82 ± 0.41 Nm, Tt100 = 6.28 ± 1.01 Nm, p < 0.001). Correlation analysis revealed significant negative relationships between the stretch test and the Myotonometer measurements (r < −0.5, p < 0.05). Findings of this study provided validation of the Myotonometry technique and its high sensitivity in examination of spasticity in stroke.
The Adhesion of Lactobacillus salivarius REN to a Human Intestinal Epithelial Cell Line Requires S-layer Proteins
Authors: Wang Ran , Jiang Lun , Zhang Ming , Zhao Liang , Hao Yanling , Guo Huiyuan , Sang Yue , Zhang Hao , Ren Fazheng
Published: March 2017

Lactobacillus salivarius REN, a novel probiotic isolated from Chinese centenarians, can adhere to intestinal epithelial cells and subsequently colonize the host. We show here that the surface-layer protein choline-binding protein A (CbpA) of L. salivarius REN was involved in adherence to the human colorectal adenocarcinoma cell line HT-29. Adhesion of a cbpA deletion mutant was significantly reduced compared with that of wild-type, suggesting that CbpA acts as an adhesin that mediates the interaction between the bacterium and its host. To identify the molecular mechanism of adhesion, we determined the crystal structure of a truncated form of CbpA that is likely involved in binding to its cell-surface receptor. The crystal structure identified CbpA as a peptidase of the M23 family whose members harbor a zinc-dependent catalytic site. Therefore, we propose that CbpA acts as a multifunctional surface protein that cleaves the host extracellular matrix and participates in adherence. Moreover, we identified enolase as the CbpA receptor on the surface of HT-29 cells. The present study reveals a new class of surface-layer proteins as well as the molecular mechanism that may contribute to the ability of L. salivarius REN to colonize the human gut.
Aluminum-induced dreierketten chain cross-links increase the mechanical properties of nanocrystalline calcium aluminosilicate hydrate
Authors: Geng Guoqing , Myers Rupert J. , Li Jiaqi , Maboudian Roya , Carraro Carlo , Shapiro David A. , Monteiro Paulo J. M.
Published: March 2017

The incorporation of Al and increased curing temperature promotes the crystallization and cross-linking of calcium (alumino)silicate hydrate (C-(A-)S-H), which is the primary binding phase in most contemporary concrete materials. However, the influence of Al-induced structural changes on the mechanical properties at atomistic scale is not well understood. Herein, synchrotron radiation-based high-pressure X-ray diffraction is used to quantify the influence of dreierketten chain cross-linking on the anisotropic mechanical behavior of C-(A-)S-H. We show that theab-planar stiffness is independent of dreierketten chain defects, e.g. vacancies in bridging tetrahedra sites and Al for Si substitution. Thec-axis of non-cross-linked C-(A-)S-H is more deformable due to the softer interlayer opening but stiffens with decreased spacing and/or increased zeolitic water and Ca2+of the interlayer. Dreierketten chain cross-links act as ‘columns’ to resist compression, thus increasing the bulk modulus of C-(A-)S-H. We provide the first experimental evidence on the influence of the Al-induced atomistic configurational change on the mechanical properties of C-(A-)S-H. Our work advances the fundamental knowledge of C-(A-)S-H on the lowest level of its hierarchical structure, and thus can impact the way that innovative C-(A-)S-H-based cementitious materials are developed using a ‘bottom-up’ approach.
Multiplex visibility graphs to investigate recurrent neural network dynamics
Authors: Bianchi Filippo Maria , Livi Lorenzo , Alippi Cesare , Jenssen Robert
Published: March 2017

A recurrent neural network (RNN) is a universal approximator of dynamical systems, whose performance often depends on sensitive hyperparameters. Tuning them properly may be difficult and, typically, based on a trial-and-error approach. In this work, we adopt a graph-based framework to interpret and characterize internal dynamics of a class of RNNs called echo state networks (ESNs). We design principled unsupervised methods to derive hyperparameters configurations yielding maximal ESN performance, expressed in terms of prediction error and memory capacity. In particular, we propose to model time series generated by each neuron activations with a horizontal visibility graph, whose topological properties have been shown to be related to the underlying system dynamics. Successively, horizontal visibility graphs associated with all neurons become layers of a larger structure called a multiplex. We show that topological properties of such a multiplex reflect important features of ESN dynamics that can be used to guide the tuning of its hyperparamers. Results obtained on several benchmarks and a real-world dataset of telephone call data records show the effectiveness of the proposed methods.