bluuebunny/crossref_metadata_2025 huggingface dataset:
Political Science and American Political Thought
Authors: Dyer Justin Buckley
Published: June 2017

Written as a short personal reflection, this article explores the development of political science as an organized professional discipline in the United States. At its inception, political science in the United States was principally concerned with political thought and constitutionalism, and it was taught with the public-spirited purpose of educating for citizenship in a constitutional democracy. Twentieth-century methodological trends at one time threatened to remove political thought and constitutionalism from the curriculum of political science, but recent disciplinary trends suggest that American political thought does have a place in twenty-first-century political science.
Presidential Greatness and Political Science: Assessing the 2014 APSA Presidents and Executive Politics Section Presidential Greatness Survey
Authors: Rottinghaus Brandon , Vaughn Justin S.
Published: June 2017

Debates about presidential greatness have been with us for decades, facilitated in part by numerous systematic surveys of scholars with expertise in American history and politics. Nevertheless, the voice of political scientists in this debate has been relatively muted when compared particularly with the role that historians have had in making these determinations. This article introduces and assesses results of a recent effort to capture the attitudes of political science presidency experts about presidential greatness. By surveying the membership of the APSA Presidents and Executive Politics section, we could identify and then compare specifically the attitudes of political scientists against the growing body of ratings and rankings of a phenomenon with long-standing interest and importance.
Merging Graphics and Text to Better Convey Experimental Results: Designing an “Enhanced Bar Graph”
Authors: Berry William D. , Hauenstein Matthew
Published: June 2017

We propose a format for presenting experimental results that combines a graph’s strength in facilitating general-pattern recognition with a table’s strength in displaying numerical results. The format supplements a conventional bar graph with additional text labels and graphics but also can be based on a dot plot. The resulting enhanced bar graph conveys general patterns about treatment effects; displays point estimates and confidence intervals for all key quantities of interest relevant to testing hypotheses (e.g., first differences in the mean of the dependent variable); and clarifies the interpretation of these quantities as treatment effects. Presenting information in a single figure avoids the need to devote scarce journal space to both a graph and a table. Moreover, an enhanced bar graph prevents readers from having to move back and forth between a graph and a table of numerical results—thereby reducing their cognitive load and facilitating their understanding of the findings.
1,003 reference genomes of bacterial and archaeal isolates expand coverage of the tree of life
Authors: Mukherjee Supratim , Seshadri Rekha , Varghese Neha J , Eloe-Fadrosh Emiley A , Meier-Kolthoff Jan P , Göker Markus , Coates R Cameron , Hadjithomas Michalis , Pavlopoulos Georgios A , Paez-Espino David , Yoshikuni Yasuo , Visel Axel , Whitman William B , Garrity George M , Eisen Jonathan A , Hugenholtz Philip , Pati Amrita , Ivanova Natalia N , Woyke Tanja , Klenk Hans-Peter , Kyrpides Nikos C
Published: June 2017

We present 1,003 reference genomes that were sequenced as part of the Genomic Encyclopedia of Bacteria and Archaea (GEBA) initiative, selected to maximize sequence coverage of phylogenetic space. These genomes double the number of existing type strains and expand their overall phylogenetic diversity by 25%. Comparative analyses with previously available finished and draft genomes reveal a 10.5% increase in novel protein families as a function of phylogenetic diversity. The GEBA genomes recruit 25 million previously unassigned metagenomic proteins from 4,650 samples, improving their phylogenetic and functional interpretation. We identify numerous biosynthetic clusters and experimentally validate a divergent phenazine cluster with potential new chemical structure and antimicrobial activity. This Resource is the largest single release of reference genomes to date. Bacterial and archaeal isolate sequence space is still far from saturated, and future endeavors in this direction will continue to be a valuable resource for scientific discovery.
Electrical resistance of individual defects at a topological insulator surface
Authors: Lüpke Felix , Eschbach Markus , Heider Tristan , Lanius Martin , Schüffelgen Peter , Rosenbach Daniel , von den Driesch Nils , Cherepanov Vasily , Mussler Gregor , Plucinski Lukasz , Grützmacher Detlev , Schneider Claus M. , Voigtländer Bert
Published: June 2017

Three-dimensional topological insulators host surface states with linear dispersion, which manifest as a Dirac cone. Nanoscale transport measurements provide direct access to the transport properties of the Dirac cone in real space and allow the detailed investigation of charge carrier scattering. Here we use scanning tunnelling potentiometry to analyse the resistance of different kinds of defects at the surface of a (Bi0.53Sb0.47)2Te3 topological insulator thin film. We find the largest localized voltage drop to be located at domain boundaries in the topological insulator film, with a resistivity about four times higher than that of a step edge. Furthermore, we resolve resistivity dipoles located around nanoscale voids in the sample surface. The influence of such defects on the resistance of the topological surface state is analysed by means of a resistor network model. The effect resulting from the voids is found to be small compared with the other defects.
A solid state source of photon triplets based on quantum dot molecules
Authors: Khoshnegar Milad , Huber Tobias , Predojević Ana , Dalacu Dan , Prilmüller Maximilian , Lapointe Jean , Wu Xiaohua , Tamarat Philippe , Lounis Brahim , Poole Philip , Weihs Gregor , Majedi Hamed
Published: June 2017

Producing advanced quantum states of light is a priority in quantum information technologies. In this context, experimental realizations of multipartite photon states would enable improved tests of the foundations of quantum mechanics as well as implementations of complex quantum optical networks and protocols. It is favourable to directly generate these states using solid state systems, for simpler handling and the promise of reversible transfer of quantum information between stationary and flying qubits. Here we use the ground states of two optically active coupled quantum dots to directly produce photon triplets. The formation of a triexciton in these ground states leads to a triple cascade recombination and sequential emission of three photons with strong correlations. We record 65.62 photon triplets per minute under continuous-wave pumping, surpassing rates of earlier reported sources. Our structure and data pave the way towards implementing multipartite photon entanglement and multi-qubit readout schemes in solid state devices.
Cryogenic strength improvement by utilizing room-temperature deformation twinning in a partially recrystallized VCrMnFeCoNi high-entropy alloy
Authors: Jo Y. H. , Jung S. , Choi W. M. , Sohn S. S. , Kim H. S. , Lee B. J. , Kim N. J. , Lee S.
Published: June 2017

The excellent cryogenic tensile properties of the CrMnFeCoNi alloy are generally caused by deformation twinning, which is difficult to achieve at room temperature because of insufficient stress for twinning. Here, we induced twinning at room temperature to improve the cryogenic tensile properties of the CrMnFeCoNi alloy. Considering grain size effects on the critical stress for twinning, twins were readily formed in the coarse microstructure by cold rolling without grain refinement by hot rolling. These twins were retained by partial recrystallization and played an important role in improving strength, allowing yield strengths approaching 1 GPa. The persistent elongation up to 46% as well as the tensile strength of 1.3 GPa are attributed to additional twinning in both recrystallized and non-recrystallization regions. Our results demonstrate that non-recrystallized grains, which are generally avoided in conventional alloys because of their deleterious effect on ductility, can be useful in achieving high-strength high-entropy alloys.
Autism-like behaviours and enhanced memory formation and synaptic plasticity in Lrfn2/SALM1-deficient mice
Authors: Morimura Naoko , Yasuda Hiroki , Yamaguchi Kazuhiko , Katayama Kei-ichi , Hatayama Minoru , Tomioka Naoko H. , Odagawa Maya , Kamiya Akiko , Iwayama Yoshimi , Maekawa Motoko , Nakamura Kazuhiko , Matsuzaki Hideo , Tsujii Masatsugu , Yamada Kazuyuki , Yoshikawa Takeo , Aruga Jun
Published: June 2017

Lrfn2/SALM1 is a PSD-95-interacting synapse adhesion molecule, and human LRFN2 is associated with learning disabilities. However its role in higher brain function and underlying mechanisms remain unknown. Here, we show that Lrfn2 knockout mice exhibit autism-like behavioural abnormalities, including social withdrawal, decreased vocal communications, increased stereotyped activities and prepulse inhibition deficits, together with enhanced learning and memory. In the hippocampus, the levels of synaptic PSD-95 and GluA1 are decreased. The synapses are structurally and functionally immature with spindle shaped spines, smaller postsynaptic densities, reduced AMPA/NMDA ratio, and enhanced LTP. In vitro experiments reveal that synaptic surface expression of AMPAR depends on the direct interaction between Lrfn2 and PSD-95. Furthermore, we detect functionally defective LRFN2 missense mutations in autism and schizophrenia patients. Together, these findings indicate that Lrfn2/LRFN2 serve as core components of excitatory synapse maturation and maintenance, and their dysfunction causes immature/silent synapses with pathophysiological state.
Optogenetic control of RhoA reveals zyxin-mediated elasticity of stress fibres
Authors: Oakes Patrick W. , Wagner Elizabeth , Brand Christoph A. , Probst Dimitri , Linke Marco , Schwarz Ulrich S. , Glotzer Michael , Gardel Margaret L.
Published: June 2017

Cytoskeletal mechanics regulates cell morphodynamics and many physiological processes. While contractility is known to be largely RhoA-dependent, the process by which localized biochemical signals are translated into cell-level responses is poorly understood. Here we combine optogenetic control of RhoA, live-cell imaging and traction force microscopy to investigate the dynamics of actomyosin-based force generation. Local activation of RhoA not only stimulates local recruitment of actin and myosin but also increased traction forces that rapidly propagate across the cell via stress fibres and drive increased actin flow. Surprisingly, this flow reverses direction when local RhoA activation stops. We identify zyxin as a regulator of stress fibre mechanics, as stress fibres are fluid-like without flow reversal in its absence. Using a physical model, we demonstrate that stress fibres behave elastic-like, even at timescales exceeding turnover of constituent proteins. Such molecular control of actin mechanics likely plays critical roles in regulating morphodynamic events.
Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase
Authors: Hutchinson Jonathan P. , Rowland Paul , Taylor Mark R. D. , Christodoulou Erica M. , Haslam Carl , Hobbs Clare I. , Holmes Duncan S. , Homes Paul , Liddle John , Mole Damian J. , Uings Iain , Walker Ann L. , Webster Scott P. , Mowat Christopher G. , Chung Chun-wa
Published: June 2017

Kynurenine-3-monooxygenase (KMO) is a key FAD-dependent enzyme of tryptophan metabolism. In animal models, KMO inhibition has shown benefit in neurodegenerative diseases such as Huntington’s and Alzheimer’s. Most recently it has been identified as a target for acute pancreatitis multiple organ dysfunction syndrome (AP-MODS); a devastating inflammatory condition with a mortality rate in excess of 20%. Here we report and dissect the molecular mechanism of action of three classes of KMO inhibitors with differentiated binding modes and kinetics. Two novel inhibitor classes trap the catalytic flavin in a previously unobserved tilting conformation. This correlates with picomolar affinities, increased residence times and an absence of the peroxide production seen with previous substrate site inhibitors. These structural and mechanistic insights culminated in GSK065(C1) and GSK366(C2), molecules suitable for preclinical evaluation. Moreover, revising the repertoire of flavin dynamics in this enzyme class offers exciting new opportunities for inhibitor design.
Differential processing of thalamic information via distinct striatal interneuron circuits
Authors: Assous Maxime , Kaminer Jaime , Shah Fulva , Garg Arpan , Koós Tibor , Tepper James M.
Published: June 2017

Recent discoveries of striatal GABAergic interneurons require a new conceptualization of the organization of intrastriatal circuitry and their cortical and thalamic inputs. We investigated thalamic inputs to the two populations of striatal neuropeptide Y (NPY) interneurons, plateau low threshold spike (PLTS) and NPY-neurogliaform (NGF) cells. Optogenetic activation of parafascicular inputs evokes suprathreshold monosynaptic glutamatergic excitation in NGF interneurons and a disynaptic, nicotinic excitation through cholinergic interneurons. In contrast, the predominant response of PLTS interneurons is a disynaptic inhibition dependent on thalamic activation of striatal tyrosine hydroxylase interneurons (THINs). In contrast, THINs do not innervate NGF or fast spiking interneurons, showing significant specificity in THINs outputs. Chemospecific ablation of THINs impairs prepulse inhibition of the acoustic startle response suggesting an important behavioural role of this disynaptic pathway. Our findings demonstrate that the impact of the parafascicular nucleus on striatal activity and some related behaviour critically depend on synaptic interactions within interneuronal circuits.
The deubiquitinating enzymes USP4 and USP17 target hyaluronan synthase 2 and differentially affect its function
Authors: Mehić M , de Sa V K , Hebestreit S , Heldin C-H , Heldin P
Published: June 2017

The levels of hyaluronan, a ubiquitous glycosaminoglycan prominent in the extracellular matrix, is balanced through the actions of hyaluronan-synthesizing enzymes (HAS1, 2 and 3) and degrading hyaluronidases (Hyal 1, 2, 3 and PH20). Hyaluronan accumulates in rapidly remodeling tissues, such as breast cancer, due to deregulated expression of the HAS2 gene and/or alterations of HAS2 activity. The activity of HAS2 is regulated by post-translational modifications, including ubiquitination. In order to identify deubiquitinating enzymes (DUBs) that are involved in de-ubiquitination of HAS2, a complementary (cDNA) library of 69 Flag-HA-tagged human DUBs cloned into retroviral vectors was screened in human embryonic kidney (HEK) 293T cells for their ability to de-ubiquitinate myc-tagged HAS2. Several DUBs were found to decrease the ubiquitination of 6myc-HAS2, among which, the most effective were USP17 and USP4. USP17 efficiently removed polyubiquitination, whereas USP4 preferentially removed monoubiquitination of 6myc-HAS2. Co-immunoprecipitation studies revealed interactions between HAS2 and USP17, as well as between HAS2 and USP4, in membrane preparations of HEK293T cells. USP17 significantly stabilized 6myc-HAS2 protein levels, whereas USP4 did not. The silencing of USP17 led to decreased hyaluronan production, whereas the suppression of USP4 increased hyaluronan synthesis. Importantly, high levels of USP17 and HAS2 were detected in a panel of cancer cell lines compared to normal cells, and immunohistochemical stainings revealed higher expression of USP17 and HAS2 in tissues of lung cancer patients compared to normal tissue. In conclusion, USP17 and USP4 differently affect HAS2 ubiquitination, and the stability and function of HAS2.
High-dimensional quantum key distribution based on multicore fiber using silicon photonic integrated circuits
Authors: Ding Yunhong , Bacco Davide , Dalgaard Kjeld , Cai Xinlun , Zhou Xiaoqi , Rottwitt Karsten , Oxenløwe Leif Katsuo
Published: June 2017

Quantum key distribution provides an efficient means to exchange information in an unconditionally secure way. Historically, quantum key distribution protocols have been based on binary signal formats, such as two polarization states, and the transmitted information efficiency of the quantum key is intrinsically limited to 1 bit/photon. Here we propose and experimentally demonstrate, for the first time, a high-dimensional quantum key distribution protocol based on space division multiplexing in multicore fiber using silicon photonic integrated lightwave circuits. We successfully realized three mutually unbiased bases in a four-dimensional Hilbert space, and achieved low and stable quantum bit error rate well below both the coherent attack and individual attack limits. Compared to previous demonstrations, the use of a multicore fiber in our protocol provides a much more efficient way to create high-dimensional quantum states, and enables breaking the information efficiency limit of traditional quantum key distribution protocols. In addition, the silicon photonic circuits used in our work integrate variable optical attenuators, highly efficient multicore fiber couplers, and Mach-Zehnder interferometers, enabling manipulating high-dimensional quantum states in a compact and stable manner. Our demonstration paves the way to utilize state-of-the-art multicore fibers for noise tolerance high-dimensional quantum key distribution, and boost silicon photonics for high information efficiency quantum communications.
Clinical Efficacy and Post-Treatment Seromarkers Associated with the Risk of Hepatocellular Carcinoma among Chronic Hepatitis C Patients
Authors: Lee Mei-Hsuan , Huang Chung-Feng , Lai Hsueh-Chou , Lin Chun-Yen , Dai Chia-Yen , Liu Chun-Jen , Wang Jing-Houng , Huang Jee-Fu , Su Wen-Pang , Yang Hung-Chih , Kee Kwong-Ming , Yeh Ming-Lun , Chuang Po-Heng , Hsu Shih-Jer , Huang Ching-I , Kao Jung-Ta , Chen Chieh-Chang , Chen Sheng-Hung , Jeng Wen-Juei , Yang Hwai-I , Yuan Yong , Lu Sheng-Nan , Sheen I-Shyan , Liu Chen-Hua , Peng Cheng-Yuan , Kao Jia-Horng , Yu Ming-Lung , Chuang Wan-Long , Chen Chien-Jen
Published: June 2017

This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004–2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22–0.63) for those without cirrhosis and 0.54 (0.31–0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased aspartate aminotransferase and α-fetoprotein levels were associated with HCC (p < 0.001). The treatment of chronic hepatitis C patients before they developed cirrhosis showed a higher efficacy than did the treatment of those who had already developed cirrhosis. Patients with SVR may still have a risk of HCC and need to be regularly monitored.
Endothelial Cell-derived Extracellular Vesicles Size-dependently Exert Procoagulant Activity Detected by Thromboelastometry
Authors: Holnthoner Wolfgang , Bonstingl Cornelia , Hromada Carina , Muehleder Severin , Zipperle Johannes , Stojkovic Stefan , Redl Heinz , Wojta Johann , Schöchl Herbert , Grillari Johannes , Weilner Sylvia , Schlimp Christoph J.
Published: June 2017

Endothelial cells (ECs) are major modulators of hemostasis by expressing and releasing pro- and anticoagulant mediators into the circulation. Previous studies showed that cultured ECs release procoagulant mediators into cell culture supernatants as evidenced by the reduction of viscoelastic clotting time. This effect was reversed with an anti-tissue factor antibody. Here, we aimed to investigate whether tissue factor (TF) was released by endothelial-derived extracellular vesicles (EVs) and which portion of the released vesicles displays the most prominent procoagulant properties. After stimulation of ECs with tumor-necrosis factor-α (TNF-α) the supernatants of EC cultures were subjected to differential centrifugation steps to collect larger and smaller EVs which were then characterised by nanoparticle tracking analysis (NTA) and flow cytometry. Mixed with fresh human blood and analysed by thromboelastometry EVs exerted a significant procoagulant stimulus, which could be partly reversed by addition of an anti-TF antibody. Moreover, TF activity was confirmed in the centrifuged fractions. In summary, our results provide evidence of the procoagulant potential of smaller and larger endothelial-derived EV fractions detected by thromboelastometry. The observed effect is most likely due to the release of TF-bearing EVs of different dimensions, which are released upon TNF-α stimulation of endothelial cell cultures.
Arabidopsis Transporter ABCG37/PDR9 contributes primarily highly oxygenated Coumarins to Root Exudation
Authors: Ziegler Jörg , Schmidt Stephan , Strehmel Nadine , Scheel Dierk , Abel Steffen
Published: June 2017

The chemical composition of root exudates strongly impacts the interactions of plants with microorganisms in the rhizosphere and the efficiency of nutrient acquisition. Exudation of metabolites is in part mediated by ATP-binding cassette (ABC) transporters. In order to assess the contribution of individual ABC transporters to root exudation, we performed an LC-MS based non-targeted metabolite profiling of semi-polar metabolites accumulating in root exudates of Arabidopsis thaliana plants and mutants deficient in the expression of ABCG36 (PDR8/PEN3), ABCG37 (PDR9) or both transporters. Comparison of the metabolite profiles indicated distinct roles for each ABC transporter in root exudation. Thymidine exudation could be attributed to ABCG36 function, whereas coumarin exudation was strongly reduced only in ABCG37 deficient plants. However, coumarin exudation was compromised in abcg37 mutants only with respect to certain metabolites of this substance class. The specificity of ABCG37 for individual coumarins was further verified by a targeted LC-MS based coumarin profiling method. The response to iron deficiency, which is known to strongly induce coumarin exudation, was also investigated. In either treatment, the distribution of individual coumarins between roots and exudates in the investigated genotypes suggested the involvement of ABCG37 in the exudation specifically of highly oxygenated rather than monohydroxylated coumarins.
Gag-protease coevolution analyses define novel structural surfaces in the HIV-1 matrix and capsid involved in resistance to Protease Inhibitors
Authors: Codoñer Francisco M , Peña Ruth , Blanch-Lombarte Oscar , Jimenez-Moyano Esther , Pino Maria , Vollbrecht Thomas , Clotet Bonaventura , Martinez-Picado Javier , Draenert Rika , Prado Julia G.
Published: June 2017

Despite the major role of Gag in establishing resistance of HIV-1 to protease inhibitors (PIs), very limited data are available on the total contribution of Gag residues to resistance to PIs. To identify in detail Gag residues and structural interfaces associated with the development of HIV-1 resistance to PIs, we traced viral evolution under the pressure of PIs using Gag-protease single genome sequencing and coevolution analysis of protein sequences in 4 patients treated with PIs over a 9-year period. We identified a total of 38 Gag residues correlated with the protease, 32 of which were outside Gag cleavage sites. These residues were distributed in 23 Gag-protease groups of coevolution, with the viral matrix and the capsid represented in 87% and 52% of the groups. In addition, we uncovered the distribution of Gag correlated residues in specific protein surfaces of the inner face of the viral matrix and at the Cyclophilin A binding loop of the capsid. In summary, our findings suggest a tight interdependency between Gag structural proteins and the protease during the development of resistance of HIV-1 to PIs.
Theory of Inverse Edelstein Effect of The Surface States of A Topological Insulator
Authors: Geng H. , Luo W. , Deng W. Y. , Sheng L. , Shen R. , Xing D. Y.
Published: June 2017

The surface states of three-dimensional topological insulators possess the unique property of spin-momentum interlocking. This property gives rise to the interesting inverse Edelstein effect (IEE), in which an applied spin bias μ is converted to a measurable charge voltage difference V. We develop a semiclassical theory for the IEE of the surface states of Bi2Se3 thin films, which is applicable from the ballistic regime to diffusive regime. We find that the efficiency of the spin-charge conversion, defined as γ = V/μ, exhibits a universal dependence on the ratio between sample size and electron mean free path. The efficiency increases from γ = π/4 in the ballistic limit to γ = π in the diffusive limit, suggesting that sufficient strength of impurity scattering is favorable for the IEE.
Tamm plasmon modes on semi-infinite metallodielectric superlattices
Authors: Isić Goran , Vuković Slobodan , Jakšić Zoran , Belić Milivoj
Published: June 2017

We analyze the fundamental properties of optical waves referred to as Tamm plasmon modes (TPMs) which are tied to the interface of a semi-infinite two-phase metallodielectric superlattice with an arbitrary homogeneous capping medium. Such modes offer new ways of achieving high electromagnetic field localization and spontaneous emission enhancement in the vicinity of the interface in conjunction with absorption loss management, which is crucial for future applications. The homointerface, formed when the capping medium has the same permittivity as one of the superlattice constituents, is found to support a TPM whose dispersion overlaps the single-interface surface plasmon polariton (SPP) dispersion but which has a cut off at the topological transition point. In contrast, a heterointerface formed for an arbitrary capping medium, is found to support multiple TPMs whose origin can be traced by considering the interaction between a single-interface SPP and the homointerface TPM burried under the top layer of the superlattice. By carrying out a systematic comparison between TPMs and single-interface SPPs, we find that the deviations are most pronounced in the vicinity of the transition frequency for superlattices in which dielectric layers are thicker than metallic ones.
ADAMTS-7 is associated with a high-risk plaque phenotype in human atherosclerosis
Authors: Bengtsson Eva , Hultman Karin , Dunér Pontus , Asciutto Giuseppe , Almgren Peter , Orho-Melander Marju , Melander Olle , Nilsson Jan , Hultgårdh-Nilsson Anna , Gonçalves Isabel
Published: June 2017

Several large-scale genome-wide association studies have identified single-nucleotide polymorphisms in the genomic region of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 repeats (ADAMTS)-7 and associations to coronary artery disease. Experimental studies have provided evidence for a functional role of ADAMTS-7 in both injury-induced vascular neointima formation and development of atherosclerotic lesions. However, whether ADAMTS-7 is associated with a specific plaque phenotype in humans has not been investigated. Carotid plaques (n = 206) from patients with and without cerebrovascular symptoms were analyzed for expression of ADAMTS-7 by immunohistochemistry and correlated to components associated with plaque vulnerability. Plaques from symptomatic patients showed increased levels of ADAMTS-7 compared with lesions from asymptomatic patients. High levels of ADAMTS-7 correlated with high levels of CD68-staining and lipid content, but with low smooth muscle cell and collagen content, which together are characteristics of a vulnerable plaque phenotype. ADAMTS-7 levels above median were associated with increased risk for postoperative cardiovascular events. Our data show that ADAMTS-7 is associated with a vulnerable plaque phenotype in human carotid lesions. These data support previous observations of a potential proatherogenic role of ADAMTS-7.
A Unified Framework for Complex Networks with Degree Trichotomy Based on Markov Chains
Authors: Hui David Shui Wing , Chen Yi-Chao , Zhang Gong , Wu Weijie , Chen Guanrong , Lui John C. S. , Li Yingtao
Published: June 2017

This paper establishes a Markov chain model as a unified framework for describing the evolution processes in complex networks. The unique feature of the proposed model is its capability in addressing the formation mechanism that can reflect the “trichotomy” observed in degree distributions, based on which closed-form solutions can be derived. Important special cases of the proposed unified framework are those classical models, including Poisson, Exponential, Power-law distributed networks. Both simulation and experimental results demonstrate a good match of the proposed model with real datasets, showing its superiority over the classical models. Implications of the model to various applications including citation analysis, online social networks, and vehicular networks design, are also discussed in the paper.
Chromatin organization regulates viral egress dynamics
Authors: Aho Vesa , Myllys Markko , Ruokolainen Visa , Hakanen Satu , Mäntylä Elina , Virtanen Jori , Hukkanen Veijo , Kühn Thomas , Timonen Jussi , Mattila Keijo , Larabell Carolyn A. , Vihinen-Ranta Maija
Published: June 2017

Various types of DNA viruses are known to elicit the formation of a large nuclear viral replication compartment and marginalization of the cell chromatin. We used three-dimensional soft x-ray tomography, confocal and electron microscopy, combined with numerical modelling of capsid diffusion to analyse the molecular organization of chromatin in herpes simplex virus 1 infection and its effect on the transport of progeny viral capsids to the nuclear envelope. Our data showed that the formation of the viral replication compartment at late infection resulted in the enrichment of heterochromatin in the nuclear periphery accompanied by the compaction of chromatin. Random walk modelling of herpes simplex virus 1–sized particles in a three-dimensional soft x-ray tomography reconstruction of an infected cell nucleus demonstrated that the peripheral, compacted chromatin restricts viral capsid diffusion, but due to interchromatin channels capsids are able to reach the nuclear envelope, the site of their nuclear egress.
Tomographic Particle Image Velocimetry using Smartphones and Colored Shadows
Authors: Aguirre-Pablo Andres A. , Alarfaj Meshal K. , Li Er Qiang , Hernández-Sánchez J. F. , Thoroddsen Sigurdur T.
Published: June 2017

We demonstrate the viability of using four low-cost smartphone cameras to perform Tomographic PIV. We use colored shadows to imprint two or three different time-steps on the same image. The back-lighting is accomplished with three sets of differently-colored pulsed LEDs. Each set of Red, Green & Blue LEDs is shone on a diffuser screen facing each of the cameras. We thereby record the RGB-colored shadows of opaque suspended particles, rather than the conventionally used scattered light. We subsequently separate the RGB color channels, to represent the separate times, with preprocessing to minimize noise and cross-talk. We use commercially available Tomo-PIV software for the calibration, 3-D particle reconstruction and particle-field correlations, to obtain all three velocity components in a volume. Acceleration estimations can be done thanks to the triple pulse illumination. Our test flow is a vortex ring produced by forcing flow through a circular orifice, using a flexible membrane, which is driven by a pressurized air pulse. Our system is compared to a commercial stereoscopic PIV system for error estimations. We believe this proof of concept experiment will make this technique available for education, industry and scientists for a fraction of the hardware cost needed for traditional Tomo-PIV.
Spatio-Temporal Steering for Testing Nonclassical Correlations in Quantum Networks
Authors: Chen Shin-Liang , Lambert Neill , Li Che-Ming , Chen Guang-Yin , Chen Yueh-Nan , Miranowicz Adam , Nori Franco
Published: June 2017

We introduce the concept of spatio-temporal steering (STS), which reduces, in special cases, to Einstein-Podolsky-Rosen steering and the recently-introduced temporal steering. We describe two measures of this effect referred to as the STS weight and robustness. We suggest that these STS measures enable a new way to assess nonclassical correlations in an open quantum network, such as quantum transport through nano-structures or excitation transfer in a complex biological system. As one of our examples, we apply STS to check nonclassical correlations among sites in a photosynthetic pigment-protein complex in the Fenna-Matthews-Olson model.
Structure of the human TRiC/CCT Subunit 5 associated with hereditary sensory neuropathy
Authors: Pereira Jose H. , McAndrew Ryan P. , Sergeeva Oksana A. , Ralston Corie Y. , King Jonathan A. , Adams Paul D.
Published: June 2017

The human chaperonin TRiC consists of eight non-identical subunits, and its protein-folding activity is critical for cellular health. Misfolded proteins are associated with many human diseases, such as amyloid diseases, cancer, and neuropathies, making TRiC a potential therapeutic target. A detailed structural understanding of its ATP-dependent folding mechanism and substrate recognition is therefore of great importance. Of particular health-related interest is the mutation Histidine 147 to Arginine (H147R) in human TRiC subunit 5 (CCT5), which has been associated with hereditary sensory neuropathy. In this paper, we describe the crystal structures of CCT5 and the CCT5-H147R mutant, which provide important structural information for this vital protein-folding machine in humans. This first X-ray crystallographic study of a single human CCT subunit in the context of a hexadecameric complex can be expanded in the future to the other 7 subunits that form the TRiC complex.
Dosage compensation in the process of inactivation/reactivation during both germ cell development and early embryogenesis in mouse
Authors: Li Xiaoyong , Hu Zhiqiang , Yu Xuelin , Zhang Chen , Ma Binbin , He Lin , Wei Chaochun , Wu Ji
Published: June 2017

Ohno proposed that dosage compensation in mammals evolved as a two-step mechanism involving X-inactivation and X-upregulation. While X-inactivation is well characterized, it remains to further analysis whether upregulation of the single activated X chromosome in mammals occurs. We obtained RNA-seq data, including single-cell RNA-seq data, from cells undergoing inactivation/reactivation in both germ cell development and early embryogenesis stages in mouse and calculated the X: A ratio from the gene expression. Our results showed that the X: A ratio is always 1, regardless of the number of X chromosomes being transcribed for expressed genes. Furthermore, the single-cell RNA-seq data across individual cells of mouse preimplantation embryos of mixed backgrounds indicated that strain-specific SNPs could be used to distinguish transcription from maternal and paternal chromosomes and further showed that when the paternal was inactivated, the average gene dosage of the active maternal X chromosome was increased to restore the balance between the X chromosome and autosomes. In conclusion, our analysis of RNA-seq data (particularly single-cell RNA-seq) from cells undergoing the process of inactivation/reactivation provides direct evidence that the average gene dosage of the single active X chromosome is upregulated to achieve a similar level to that of two active X chromosomes and autosomes present in two copies.
Sialic acid linkage differentiation of glycopeptides using capillary electrophoresis – electrospray ionization – mass spectrometry
Authors: Kammeijer Guinevere S. M. , Jansen Bas C. , Kohler Isabelle , Heemskerk Anthonius A. M. , Mayboroda Oleg A. , Hensbergen Paul J. , Schappler Julie , Wuhrer Manfred
Published: June 2017

Sialylation is a glycosylation feature that occurs in different linkages at the non-reducing end of a glycan moiety, the linkage isomers are often differentially associated with various biological processes. Due to very similar physico-chemical properties, the separation of isomeric sialylated glycopeptides remains challenging but of utmost importance in the biomedicine and biotechnology, including biomarker discovery, glyco-engineering and biopharmaceutical characterization. This study presents the implementation of a high-resolution separation platform based on capillary electrophoresis – mass spectrometry (CE–MS) allowing for the selective analysis of α2,3- and α2,6-sialylated glycopeptides. These differentially linked glycopeptides showed an identical fragmentation pattern (collision induced dissociation) but different electrophoretic mobilities, allowing for baseline separation of the different linkages without the need for an extensive sample preparation. The different migration behavior between the two moieties was found to correlate with differences in pKavalues. Using a novel methodology adapted from the so-called internal standard CE approach, a relative difference of 3.4·10−2in pKaunit was determined. This approach was applied for the analysis of tryptic glycopeptides of prostate specific antigen, which shows highly complex and heterogeneous glycosylation. The developed platform therefore appears attractive for the identification of differentially linked sialic acids that may be related to pathological conditions.
Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals
Authors: Miyama Takahiko , Kawase Takakazu , Kitaura Kazutaka , Chishaki Ren , Shibata Masashi , Oshima Kumi , Hamana Hiroshi , Kishi Hiroyuki , Muraguchi Atsushi , Kuzushima Kiyotaka , Saji Hiroh , Shin-I Tadasu , Suzuki Ryuji , Ichinohe Tatsuo
Published: June 2017

To expand our knowledge of the ontogeny of the T-cell receptor (TCR) repertoire of antigen-specific T-cell subsets, we combined next-generation deep sequencing and single-cell multiplex clonotype analysis to evaluate the diversity and frequency of paired TCRs, their functions and whether clonotypic TCRs are shared among different individuals. Using an HLA-A*02-restricted cytomegalovirus (CMV) pp65-derived immunogenic peptide, we found that the more dominant pp65-specific TCR clonotypes in the blood of healthy donors have higher binding affinities for the CMV peptide and arise from clonotypes that are highly shared among individuals. Interestingly, these highly shared HLA-A*02-restricted CMV-specific TCRs were detected in a CMV-seronegative individual as well as in HLA-A*02-negative donors albeit at lower frequency. More intriguingly, these shared TCR clonotypes were abundant in the stem memory T-cell subset, and TCR diversity of the stem memory T-cell repertoire was significantly lower than in the central memory and effector memory T-cell repertoires. These results suggest that the stem memory T-cell subset may serve as a reservoir of highly shared and highly functional memory T-cells.
Adiponectin regulates BMSC osteogenic differentiation and osteogenesis through the Wnt/β-catenin pathway
Authors: Wang Yiyao , Zhang Xiaohui , Shao Jun , Liu Hanghang , Liu Xian , Luo En
Published: June 2017

Recent studies have demonstrated the stimulatory effects of adiponectin on bone formation, but the mechanism underlying these effects remains unclear. The Wnt/β-catenin pathway, one of the most important pathways in osteogenesis, has rarely been associated with the osteogenic effects of adiponectin in previous studies. The present study was designed to investigate the effects of adiponectin on bone mesenchymal stem cell (BMSC) osteogenic differentiation and bone formation through the Wnt/β-catenin pathway. We detected adiponectin receptor expression in BMSCs, constructed a recombinant adenovirus containing the human adiponectin gene, and then used the adenovirus to transfect BMSCs in vitro or injected the adenovirus into bone defect areas in animal models. Wnt/β-catenin pathway and osteogenesis were detected by real-time PCR, western blotting, immunofluorescence, HE staining and micro-CT. In both our in vivo and in vitro experiments, we detected higher gene and protein expression levels of the Wnt/β-catenin pathway-related factors β-catenin and cyclinD1 in adiponectin transgenic BMSCs and rats. Similar results were noted regarding the gene and protein expression levels of osteogenesis-related genes. In addition, more new bone formation was observed in the adiponectin-treated groups. Our results indicate that adiponectin could facilitate BMSC osteogenic differentiation and osteogenesis, and the Wnt/β-catenin pathway was involved in the osteogenic effect of adiponectin.
An essential role of PI3K in the control of West Nile virus infection
Authors: Wang Leilei , Yang Long , Fikrig Erol , Wang Penghua
Published: June 2017

The phosphatidyl-inositol-3 kinases (PI3K) pathway regulates a variety of cellular processes, including cell proliferation, RNA processing, protein translation, autophagy, apoptosis and antiviral immunity. Many viruses depend on PI3K signaling for replication. However, its role in flaviviral infection has not been clearly defined. Here we report that PI3K signaling is critical for the control of West Nile virus (WNV) infection by regulating type I IFN (IFN-I) response. Inhibition of PI3K activity by 3-methyl adenine (3-MA), Wortmannin (WM) and LY294002 (LY) increased viral titers by 3–16 folds in primary mouse macrophages, embryonic fibroblasts and human cell lines. Both 3-MA and LY repressed IFN-I mRNA and protein expression significantly. Surprisingly, WM enhanced the mRNA expression of IFN-I and TNF-α, and TNF-α protein production modestly, while dramatically decreased the secreted IFN-I. Further studies showed that the catalytic subunit p110δ of class I PI3K played a role in induction of antiviral immune responses. Lastly translocation of interferon regulatory factor 7(IRF7) from the cytosol to the nuclei was effectively blocked in the presence of PI3K inhibitors. Our results clearly define an antiviral role of PI3K by modulating immune responses and demonstrate differential mode of action of three PI3K inhibitors on IFN-I.
Assessing Spatial and Temporal Patterns of Observed Ground-level Ozone in China
Authors: Wang Wan-Nan , Cheng Tian-Hai , Gu Xing-Fa , Chen Hao , Guo Hong , Wang Ying , Bao Fang-Wen , Shi Shuai-Yi , Xu Bin-Ren , Zuo Xin , Meng Can , Zhang Xiao-Chuan
Published: June 2017

Elevated ground-level ozone (O3), which is an important aspect of air quality related to public health, has been causing increasing concern. This study investigated the spatiotemporal distribution of ground-level O3 concentrations in China using a dataset from the Chinese national air quality monitoring network during 2013–2015. This research analyzed the diurnal, monthly and yearly variation of O3 concentrations in both sparsely and densely populated regions. In particular, 6 major Chinese cities were selected to allow a discussion of variations in O3 levels in detail, Beijing, Chengdu, Guangzhou, Lanzhou, Shanghai, and Urumchi, located on both sides of the Heihe-Tengchong line. Data showed that the nationwide 3-year MDA8 of ground-level O3 was 80.26 μg/m3. Ground-level O3 concentrations exhibited monthly variability peaking in summer and reaching the lowest levels in winter. The diurnal cycle reached a minimum in morning and peaked in the afternoon. Yearly average O3 MDA8 concentrations in Beijing, Chengdu, Lanzhou, and Shanghai in 2015 increased 12%, 25%, 34%, 22%, respectively, when compared with those in 2013. Compared with World Health Organization O3 guidelines, Beijing, Chengdu, Guangzhou, and Shanghai suffered O3 pollution in excess of the 8-hour O3 standard for more than 30% of the days in 2013 to 2015.
Integrated optical waveguide-based fluorescent immunosensor for fast and sensitive detection of microcystin-LR in lakes: Optimization and Analysis
Authors: Liu Lanhua , Zhou Xiaohong , Wilkinson James S. , Hua Ping , Song Baodong , Shi Hanchang
Published: June 2017

Nowadays, biosensor technologies which can detect various contaminants in water quickly and cost-effectively are in great demand. Herein, we report an integrated channel waveguide-based fluorescent immunosensor with the ability to detect a maximum of 32 contaminants rapidly and simultaneously. In particular, we use waveguide tapers to improve the efficiency of excitation and collection of fluorescent signals in the presence of fluorophore photobleaching in a solid surface bioassay. Under the optimized waveguide geometry, this is the first demonstration of using such a type of waveguide immunosensor for the detection of microcystin-LR (MC-LR) in lake water. The waveguide chip was activated by (3-Mercaptopropyl) trimethoxysilane/N-(4-maleimidobutyryloxy) succinimide (MTS/GMBS) for immobilization of BSA-MC-LR conjugate, which was confirmed to have uniform monolayer distribution by atomic force microscopy. All real lake samples, even those containing MC-LR in the sub-microgram per liter range (e.g. 0.5 μg/L), could be determined by the immunosensor with recovery rates between 84% and 108%, confirming its application potential in the measurement of MC-LR in real water samples.
No-scanning 3D measurement method using ultrafast dimensional conversion with a chirped optical frequency comb
Authors: Kato Takashi , Uchida Megumi , Minoshima Kaoru
Published: June 2017

A simultaneously high-precision, wide-range, and ultrafast time-resolution one-shot 3D shape measurement method is presented. Simultaneous times of flight from multiple positions to a target encoded in a chirped optical frequency comb can be obtained from spectral interferometry. We experimentally demonstrate a one-shot imaging profile measurement of a known step height of 480 µm with µm-level accuracy. We further demonstrate the extension of the dynamic range by measuring in one shot a large step height of 3 m while maintaining high accuracy using the accurate pulse-to-pulse separation of the optical frequency comb. The proposed method with its large dynamic range and measurement versatility can be applied to a broad range of applications, including microscopic structures, objects with large size or aspect ratio, and ultrafast time-resolved imaging. This study provides a powerful and versatile tool for 3D measurement, where various ranges of measurement performances can be tailored to demand.