bluuebunny/crossref_metadata_2025 huggingface dataset:
Serial Nostalgia: Rimini Protokoll's100% Cityand the Numbers We No Longer Are
Authors: EACHO DOUGLAS
Published: November 2018

Now a decade old, Rimini Protokoll's100% Citycontinues to stage civilians as statistical samples. Considering the project as a series, this paper proposes that ‘seriality’ governs not just the project's touring model, but also its creation of individuals, populations and a homogeneous group of ‘diverse’ metropolises. These serializations are a foundational part of the project of statistical reason. Surveying the nineteenth-century origins of these practices and their early public articulations, and contrasting these practices with the newly emerging regime of ‘big data’, this paper argues that this serial logic is in fact a nostalgic one.100% City’s celebration of statistics, however troubling, appears as a comforting articulation of a social model now dissolving in favour of algorithmic enumerations of peoples. The statistical project has long been tied to the theatre, while data analysis may articulate a limit to theatrical representation.
Atom Probe Compositional Analysis of Interphase Precipitated Nano-Sized Alloy Carbide in Multiple Microalloyed Low-Carbon Steels
Authors: Zhang Yongjie , Miyamoto Goro , Furuhara Tadashi
Published: November 2018

The composition of nano-sized alloy carbides formed by interphase precipitation in V–Nb and V–Ti multiple microalloyed low-carbon steels is analyzed by using three-dimensional atom probe. Carbide-forming alloying elements including V, Nb, and Ti, are simultaneously precipitated from the early stage of isothermal treatment, whose atoms are uniformly distributed in the carbide particles, even after prolonged holding. Cluster analysis by the maximum separation method, with parameters optimized using different methods, is carried out to extract alloy carbides from matrix. The composition of alloy carbides evaluated by site fraction of substitutional carbide-forming alloying elements indicates that at the early stage of their formation, Nb and Ti are more strongly enriched than V.
Statistical Study of Phase Relationship Between Magnetic and Plasma Pressures in the Near‐Earth Nightside Magnetosphere Using the THEMIS‐E Satellite
Authors: Nishi Katsuki , Shiokawa Kazuo , Glassmeier Karl‐Heinz , Mieth Johannes Z. D.
Published: November 2018

Distributions of plasma and magnetic pressures are the basic information to investigate macroscopic dynamics of the Earth's magnetosphere. Several studies have been made on magnetic and plasma pressures and macroscopic plasma instabilities in the magnetosphere. However, correlation between magnetic and plasma pressure variations has not been statistically investigated. In this paper, we analyze the statistical characteristics of the phase relationships between variations of magnetic and plasma pressures at frequencies of 4–15 mHz using 2 years of the THEMIS‐E satellite data in the nightside magnetosphere. Spectral peaks with coherence greater than 0.85 between magnetic and plasma pressures for 1‐hr time segments were selected. The average occurrence rates of the phase relationships are antiphase (within ±10∘ from 180°), 39.75%; in‐phase (within ±10∘ from 0°), 0.73%; and other phases (10–170°), 49.83%. For the other‐phase events, the phase differences are much closer to antiphase rather than to in‐phase. Thus, we conclude that the two pressure variations tend to be antiphase. The antiphase and in‐phase relationships are observed mainly at radial distances outside 8 RE and inside 8 RE, respectively. The high occurrence region of antiphase relationship is in the dawnside during magnetically quiet times and shifts to dusk side at active times defined as Dst <−10 nT. The occurrence rates of the phase relationships do not change significantly depending on the AE and Dst indices, plasma β, and IMF‐Bz. Based on these results, we discuss the correspondence between the phase relationships and the possible magnetohydrodynamic force balances that can produce these phase relationships.
Magnetosphere‐Ionosphere Connection of Storm‐Time Region‐2 Field‐Aligned Current and Ring Current: Arase and AMPERE Observations
Authors: Imajo S. , Nosé M. , Matsuoka A. , Kasahara S. , Yokota S. , Teramoto M. , Keika K. , Motoba T. , Anderson B. , Nomura R. , Fujimoto A. , Shinohara I. , Miyoshi Y.
Published: November 2018

Storm‐time region‐2 field‐aligned currents (R2 FACs) are believed to be connected between the ring current region and the ionosphere, but this connection has not been clarified by simultaneous in situ observations. We confirmed the connection of upward R2 FACs during 16 July and 18 June 2017 storm events using coordinated magnetic observations by the Arase satellite in medium‐Earth orbit and the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE). The upward FACs were determined by drastic changes in the azimuthal magnetic field at Arase in the off‐equatorial (3‐ to 4‐RE radial distance and 1–2 RE above the magnetic equator) postmidnight inner magnetosphere. The magnetic latitude of the FAC observed by Arase projected onto the ionosphere was consistent with that of the ionospheric FAC observed by the AMPERE. Using the conservation of the ratio between the current density and the total magnetic field along the field line, we showed that the current between Arase and AMPERE was almost conserved, meaning that a large portion of the R2 FAC was generated in the low‐latitude inner magnetosphere. We also calculated the plasma pressures of H+ and O+ ions and pressure‐driven currents to examine their relationship for the first event. The O+ pressure contributed significantly to the inner part of the total azimuthal current. The peaks of combined pressure of H+ and O+, and pressure‐driven currents were located inside and outside the FAC, respectively. A simple model calculation indicated that this spatial relationship is controlled by the day‐night asymmetry of magnetic field.
Pore‐Scale Modeling of Spontaneous Imbibition Behavior in a Complex Shale Porous Structure by Pseudopotential Lattice Boltzmann Method
Authors: Zheng Jiangtao , Ju Yang , Wang Moran
Published: November 2018

Spontaneous imbibition of fracturing fluid into shale matrix is one of the primary reasons for the low flowback rate in shale gas wells after the hydraulic fracturing. This leads to concerns of impacts on both environment and shale gas production. A direct pore‐scale simulation is crucial to gain a deep understanding of spontaneous imbibition behavior and its impacts. The porous structures in the shale matrix are characterized by not only a geometrical complexity but also a mixed wettability, which bring great challenges to simulation methods. An improved pseudo‐potential lattice Boltzmann method is proposed to simulate the spontaneous imbibition behavior in a reproduced three‐dimensional porous structure of shale. The results show that the nanoscale hydrophilic pores provide the driving force and a storage place for the residual treatment fluid. The pore size and wettability heterogeneity lead to the nonuniform menisci propagation and fracturing fluid distribution in the model. Specifically, the fracturing fluid imbibed quicker in the larger pores at the early stage and gradually migrated into the smaller pores during the process. With a limited volume of the fracturing fluid, a portion of the larger pores was finally reopened. The analysis of saturation and apparent gas permeability data during the spontaneous imbibition process showed a great recovery of the model permeability along with the reopened pores. These results provide direct evidence of the residual fracturing fluid migration pattern in the shale reservoir and its influence on shale gas production.
Observations of Air‐Sea Momentum Flux Variability Across the Inner Shelf
Authors: Ortiz‐Suslow David G. , Haus Brian K. , Williams Neil J. , Graber Hans C. , MacMahan Jamie H.
Published: November 2018

Over the open ocean, the aerodynamic drag coefficient is typically well predicted; however, the impact depth‐limited processes have on the drag remains underexplored. A case study is presented here where winds, waves, and currents were simultaneously observed from a mobile platform that repeatedly transected the inner shelf of Monterey Bay, CA. Eddy covariance‐derived drag coefficients were compared to several bulk parameterizations, including all of the roughness variations of COARE 3.5 and two explicitly depth‐limited models. The analysis demonstrated that the drag was underestimated by O(2–4) times and the variability with wind speed or cross‐shore distance was not well predicted. The drag based on a recent depth‐limited roughness length model performed substantially better than the rest of the bulk estimates, which were all within 15% of each other and effectively equivalent given typical operational uncertainties. The measured friction velocity was compared to a wave‐dependent parameterization and generalizing the model to arbitrary water depth significantly improved the mean observation‐model difference to within 30%. Latent variability in the observation‐model comparison was associated with stability, wind direction, and wave steepness. The wind stress angle variability was also analyzed. Stress veering was correlated with the alongshore surface current within 2 km from shore (r2= 0.7–0.95, p < 0.05); offshore of this margin, consistent wind stress veering was observed and may be attributable to a secondary, low‐frequency swell system. These results demonstrate that it remains a persistent challenge to accurately predict wind stress variability in the nearshore, especially at locations with complex wave and current fields.
Estimating Source Region Influences on Black Carbon Abundance, Microphysics, and Radiative Effect Observed Over South Korea
Authors: Lamb Kara D. , Perring Anne E. , Samset Bjørn , Peterson Dave , Davis Sean , Anderson Bruce E. , Beyersdorf Andreas , Blake Donald R. , Campuzano‐Jost Pedro , Corr Chelsea A. , Diskin Glenn S. , Kondo Yutaka , Moteki Nobuhiro , Nault Benjamin A. , Oh Jun , Park Minsu , Pusede Sally E. , Simpson Isobel J. , Thornhill Kenneth L. , Wisthaler Armin , Schwarz Joshua P.
Published: November 2018

East Asia is the strongest global source region for anthropogenic black carbon (BC), the most important light‐absorbing aerosol contributing to direct radiative climate forcing. To provide extended observational constraints on regional BC distributions and impacts, in situ measurements of BC were obtained with a single particle soot photometer during the May/June 2016 Korean‐United States Air Quality aircraft campaign (KORUS‐AQ) in South Korea. Unique chemical tracer relationships were associated with BC sourced from different regions. The extent and variability in vertical BC mass burden for 48 profiles over a single site near Seoul were investigated using back trajectory and chemical tracer analysis. Meteorologically driven changes in transport influenced the relative importance of different source regions, impacting observed BC loadings at all altitudes. Internal mixing and size distributions of BC further demonstrated dependence on source region: BC attributed to China had a larger mass median diameter (180 ± 13 nm) than BC attributed to South Korea (152 ± 25 nm), and BC associated with long‐range transport was less thickly coated (60 ± 4 nm) than that sourced from South Korea (75 ± 16 nm). The column BC direct radiative effect at the top of the atmosphere was estimated to be
 W/m2, with average values for different meteorological periods varying by a factor of 2 due to changes in the BC vertical profile. During the campaign, BC sourced from South Korea (≤ 31%), China (22%), and Russia (14%) were the most significant single‐region contributors to the column direct radiative effect.
Stress Field Evolution of the Southernmost Andean Cordillera From Paleostress Analysis (Argentine Tierra del Fuego)
Authors: Maestro A. , Ruano P. , Torres Carbonell P. , Bohoyo F. , Galindo‐Zaldívar J. , Pedrera A. , Ruiz‐Constán A. , González‐Castillo L. , Ibarra P. , López‐Martínez J.
Published: November 2018

The Argentine Tierra del Fuego comprises part of the roughly east‐west trending southern end of the Andean Cordillera intensely deformed since the Mesozoic. Mesostructures have been measured in Late Jurassic to Miocene rocks. Taking into account statistical criteria to provide a representative stress tensor from a fault population, this study defines 28 paleostress tensors pertaining to 22 sites. The orientation of σ1 shows two main modes trending E‐W to ESE‐WNW and NE‐SW. In addition, extensional sites reveal N‐S, NE‐SW, ESE‐WNW, and NW‐SE horizontal σ3 and vertical σ1. The stress fields obtained are congruous with a regional NE‐SW compressive stress direction active in the study zone since the Late Cretaceous. Shortening was coeval with a 30° counterclockwise rotation of the Patagonian orogenic curve and the indentation of the orogenic wedge against a basement high, the Río Chico Arch, up to the early Miocene. The indentation caused a modification in the orientation of the compressive stress trajectories, showing NE‐SW direction in Sorondo Range sector and NW‐SE in Mitre Peninsula area. Since the late Miocene, left‐lateral activity along the Magallanes‐Fagnano Fault System produced local deviations of the NE‐SW compressive stress toward an E‐W direction. The present‐day stress field is also characterized by NE‐SW subhorizontal P axis derived from earthquake focal mechanisms and geodetic studies.
The Spanish‐Portuguese Central System: An Example of Intense Intraplate Deformation and Strain Partitioning
Authors: de Vicente G. , Cunha P. P. , Muñoz‐Martín A. , Cloetingh S. A. P. L. , Olaiz A. , Vegas R.
Published: November 2018

The intraplate deformation of Iberia during the Cenozoic produced a series of ranges and deformation belts with a wide variety of structural trends. The Spanish‐Portuguese Central System is the most prominent feature crossing over the whole of central Iberia. It is a large thick‐skinned crustal pop‐up with NE‐SW to E‐W thrusts. However, the 500‐km‐long left‐lateral strike‐slip Messejana‐Plasencia fault, also NE‐SW oriented, bends these thrusts to produce NE‐SW local paleostresses close to the fault, which seems to be consistent with a common deformational arrangement. This is also supported by the similar sedimentary infilling characteristics found in the surrounding Cenozoic basins. The moment of the maximum intraplate deformation is registered at the same time in all these basins during the upper Priabonian‐lower Chattian. As there are two possible sources for the intraplate compressive stresses, the Pyrenean (N‐S shortening) orogen to the north and the Betic (NW‐SE shortening) orogen to the south, neither can simply explain both simultaneous movements (NE‐SW strike‐slip and NE‐SW thrusting). The deduced age of the main deformation indicates a Pyrenean origin. In contrast, the concept of strain partitioning between the two types of faults gives as a result an overall north trending compression. Existing data do not support crustal detachment from the Betics neither from the Pyrenees but are consistent with a crustal uplift related to lithospheric folding. The subsequent Betic‐related stress field only slightly reworked previously Pyrenean‐related structures, except for the Portuguese sector, where tectonic activity occurred mainly in the Upper Miocene.
Raindrop Size and Flow Depth Control Sediment Sorting in Shallow Flows on Steep Slopes
Authors: Wang L. , Fang N. F. , Yue Z. J. , Shi Z. H. , Hua L.
Published: November 2018

Raindrop size and flow depth interactions determine the energy available for erosion processes. A detailed laboratory study was conducted to investigate the influence of raindrop size on sediment sorting in shallow flows on steep slopes. Raindrops with sizes of 1.34, 2.45, and 4.04 mm were applied to three inflows (0.65, 1, and 2 L/min) with the same rainfall intensity (90 mm/hr). The De Brouckere mean diameter (D[4,3]) was enhanced with increases in the ratio between flow depth and raindrop size (h/d; p < 0.05), indicating that more raindrop energy dissipated in deeper flows. Moreover, a greater proportion of energy was dissipated from small raindrops than from large ones with an increasing flow depth. Particles >0.5 mm were slightly enriched by rolling under 1.34‐mm raindrop impact, whereas enrichment did not occur under 2.45‐ and 4.04‐mm raindrop impact, probably because the latter induced more severe aggregate disintegration, resulting in fewer coarse particles. The mean sediment concentrations under inflows of 0.65, 1, and 2 L/min were 101.65, 89.32, and 79.02 g/L, respectively. Shallow flows on steep slopes effectively carried detached particles; moreover, coarse particles could roll along the slopes, which was inconsistent with their behavior on gentle slopes. This study highlights the need to understand the influence of the interaction between raindrop size and flow depth on erosion processes associated with sediment size selectivity for better erosion modeling and water quality prediction.
Elevated allostatic load early in the course of schizophrenia
Authors: Savransky Anya , Chiappelli Joshua , Fisseha Feven , Wisner Krista M. , Xiaoming Du , Mirmomen S. Milad , Jones Aaron D. , Adhikari Bhim M. , Bruce Heather A. , Rowland Laura M. , Hong L. Elliot
Published: November 2018

Stress plays a significant role in schizophrenia from disease onset to exacerbation of psychotic symptoms. Allostatic load (AL) is a measure of cumulative stress to the organism. This study is an extension of our previous work on AL and its relationship to brain structures. Here, we further determined whether elevated AL is a function of illness chronicity, or if it is already present early in the course of schizophrenia. AL was compared in schizophrenia patients early in the illness (within 5 years of disease onset), patients with chronic schizophrenia (more than 5 years of illness), and two groups of healthy controls that were age-and sex-matched to the two patient groups. This work is presented with an expanded sample and includes about two-thirds of the participants who were previously reported. We found that patients with early psychosis had significantly elevated AL score compared with their age-matched controls (p = 0.005). Chronic course patients also had elevated AL compared with age-matched controls (p = 0.003). Immune and stress hormone AL subcomponents were nominally higher in early-stage patients compared with controls (p = 0.005 and 0.04, respectively). Greater AL was also associated with more severe positive psychotic symptoms in early-stage patients (r = 0.54, p = 0.01). Elevated levels of allostatic load are already present in the early years of the schizophrenia illness, particularly in patients with more severe psychotic symptoms. AL may be a useful evaluation for the need of early intervention on psychosomatic comorbidity.
Electron aspirator using electron–electron scattering in nanoscale silicon
Authors: Firdaus Himma , Watanabe Tokinobu , Hori Masahiro , Moraru Daniel , Takahashi Yasuo , Fujiwara Akira , Ono Yukinori
Published: November 2018

Current enhancement without increasing the input power is a critical issue to be pursued for electronic circuits. However, drivability of metal-oxide-semiconductor (MOS) transistors is limited by the source-injection current, and electrons that have passed through the source unavoidably waste their momentum to the phonon bath. Here, we propose the Si electron-aspirator, a nanometer-scaled MOS device with a T-shaped branch, to go beyond this limit. The device utilizes the hydrodynamic nature of electrons due to the electron–electron scattering, by which the injected hot electrons transfer their momentum to cold electrons before they relax with the phonon bath. This momentum transfer induces an electron flow from the grounded side terminal without additional power sources. The operation is demonstrated by observing the output-current enhancement by a factor of about 3 at 8 K, which reveals that the electron–electron scattering can govern the electron transport in nanometer-scaled MOS devices, and increase their effective drivability.
Mechanistic insights of enhanced spin polaron conduction in CuO through atomic doping
Authors: Smart Tyler J. , Cardiel Allison C. , Wu Feng , Choi Kyoung-Shin , Ping Yuan
Published: November 2018

The formation of a “spin polaron” stems from strong spin-charge-lattice interactions in magnetic oxides, which leads to a localization of carriers accompanied by local magnetic polarization and lattice distortion. For example, cupric oxide (CuO), which is a promising photocathode material and shares important similarities with high Tc superconductors, conducts holes through spin polaron hopping with flipped spins at Cu atoms where a spin polaron has formed. The formation of these spin polarons results in an activated hopping conduction process where the carriers must not only overcome strong electron−phonon coupling but also strong magnetic coupling. Collectively, these effects cause low carrier conduction in CuO and hinder its applications. To overcome this fundamental limitation, we demonstrate from first-principles calculations how doping can improve hopping conduction through simultaneous improvement of hole concentration and hopping mobility in magnetic oxides such as CuO. Specifically, using Li doping as an example, we show that Li has a low ionization energy that improves hole concentration, and lowers the hopping barrier through both the electron−phonon and magnetic couplings' reduction that improves hopping mobility. Finally, this improved conduction predicted by theory is validated through the synthesis of Li-doped CuO electrodes which show enhanced photocurrent compared to pristine CuO electrodes. We conclude that doping with nonmagnetic shallow impurities is an effective strategy to improve hopping conductivities in magnetic oxides.
Risk factors of levodopa-induced dyskinesia in Parkinson’s disease: results from the PPMI cohort
Authors: Eusebi Paolo , Romoli Michele , Paoletti Federico Paolini , Tambasco Nicola , Calabresi Paolo , Parnetti Lucilla
Published: November 2018

Levodopa-induced dyskinesias (LID) negatively impact on the quality of life of patients with Parkinson’s disease (PD). We assessed the risk factors for LID in a cohort of de-novo PD patients enrolled in the Parkinson’s Progression Markers Initiative (PPMI). This retrospective cohort study included all PD patients enrolled in the PPMI cohort. Main outcome was the incidence rate of dyskinesia, defined as the first time the patient reported a non-zero score in the item “Time spent with dyskinesia” of the MDS-UPDRS part IV. Predictive value for LID development was assessed for clinical and demographical features, dopamine transporter imaging (DaTscan) pattern, cerebrospinal fluid (CSF) biomarkers (Aβ42, total tau, phosphorylated tau, total α synuclein) and genetic risk score for PD. Overall, data from 423 PD patients were analyzed. The cumulative incidence rate of LID was 27.4% (95% CI = 23.2–32.0%), with a mean onset time of 5.81 years from PD diagnosis. Multivariate Cox regression analysis showed several factors predicting LID development, including female gender (HR = 1.61, 95% CI = 1.05–2.47), being not completely functional independent as measured by the modified Schwab & England ADL scale (HR = 1.81, 95% CI = 0.98–3.38), higher MDS-UPDRS part III score (HR = 1.03, 95% CI = 1.00–1.05), postural instability gait disturbances or intermediate phenotypes (HR = 1.95, 95% CI = 1.28–2.96), higher DaTscan caudate asymmetry index (HR = 1.02, 95% CI = 1.00–1.03), higher polygenic genetic risk score (HR = 1.39, 95% CI = 1.08–1.78), and an anxiety trait (HR = 1.02, 95% CI = 1.00–1.04). In PD patients, cumulative levodopa exposure, female gender, severity of motor and functional impairment, non-tremor dominant clinical phenotype, genetic risk score, anxiety, and marked caudate asymmetric pattern at DaTscan at baseline represent independent risk factors for developing LID.
A bound on the superconducting transition temperature
Authors: Esterlis I. , Kivelson S. A. , Scalapino D. J.
Published: November 2018

It is notoriously difficult to make quantitative theoretical predictions of the superconducting transition temperature, Tc, either from first-principles or even from a knowledge of normal state properties. Ultimately, this reflects the fact that the energy scales involved in the superconducting state are extremely small in natural units, and that Tc depends exponentially on a subtle interplay between different interactions so that small uncertainties in microscopic processes can lead to order one effects on Tc. However, in some circumstances, it may be possible to determine (approximate) bounds on Tc. Here we propose such a bound for the conventional phonon-mediated mechanism of pairing with strongly retarded interactions, i.e. in the case in which $$\hbar \bar \omega \ll E_F$$

ℏ

ω

¯

≪

E

F

, where $$\bar \omega$$

ω

¯

is an appropriate characteristic phonon frequency and EF is the Fermi energy. Specifically, drawing on both empirical results (shown in Fig. 2 below) and recent results1 of determinant quantum Monte Carlo (DQMC) studies of the paradigmatic Holstein model, we propose that $$k_BT_c \le A_{\max }\hbar \bar \omega$$

k

B

T

c

≤

A

max

ℏ

ω

¯

, where Amax is a dimensionless number of order one that we estimate to be Amax ≈ 1/10.
Floating photonic crystals utilizing magnetically aligned biogenic guanine platelets
Authors: Iwasaka Masakazu , Asada Hironori
Published: November 2018

Recently, structural colour formation and light control by accumulated guanine crystals were reported. However, the relationship between light interference by guanine platelets and light intensity in an individual platelet must be examined further. This study presents experimental evidence that the guanine crystal platelets of fishes aid in efficiently controlling the enhancement of light intensity based on light interference between platelets floating in a micro-space. In addition, a magnetic orientation technique enabled us to dynamically modulate the arrangement of platelets floating in water. A group orientation of the platelets under magnetic fields exhibited a distinct enhancement of the light interference between platelets present in the micro-space, and a two-fold enhancement of the reflected light intensity was achieved by comparing two arrangements of magnetically oriented platelets. The developed micro-optic light control method employing tiny platelets floating under aqueous liquid conditions is expected to facilitate the creation of tuneable optical micro-devices, e.g., a micro-‘search-light’ for individual cell analysis.
Controlled electron injection facilitated by nanoparticles for laser wakefield acceleration
Authors: Cho Myung Hoon , Pathak Vishwa Bandhu , Kim Hyung Taek , Nam Chang Hee
Published: November 2018

We propose a novel injection scheme for laser-driven wakefield acceleration in which controllable localized electron injection is obtained by inserting nanoparticles into a plasma medium. The nanoparticles provide a very confined electric field that triggers localized electron injection where nonlinear plasma waves are excited but not sufficient for background electrons self-injection. We present a theoretical model to describe the conditions and properties of the electron injection in the presence of nanoparticles. Multi-dimensional particle-in-cell (PIC) simulations demonstrate that the total charge of the injected electron beam can be controlled by the position, number, size, and density of the nanoparticles. The PIC simulation also indicates that a 5-GeV electron beam with an energy spread below 1% can be obtained with a 0.5-PW laser pulse by using the nanoparticle-assisted laser wakefield acceleration.
Expression profiling and in situ screening of circular RNAs in human tissues
Authors: Zaghlool Ammar , Ameur Adam , Wu Chenglin , Westholm Jakub Orzechowski , Niazi Adnan , Manivannan Manimozhi , Bramlett Kelli , Nilsson Mats , Feuk Lars
Published: November 2018

Circular RNAs (circRNAs) were recently discovered as a class of widely expressed noncoding RNA and have been implicated in regulation of gene expression. However, the function of the majority of circRNAs remains unknown. Studies of circRNAs have been hampered by a lack of essential approaches for detection, quantification and visualization. We therefore developed a target-enrichment sequencing method suitable for screening of circRNAs and their linear counterparts in large number of samples. We also applied padlock probes and in situ sequencing to visualize and determine circRNA localization in human brain tissue at subcellular levels. We measured circRNA abundance across different human samples and tissues. Our results highlight the potential of this RNA class to act as a specific diagnostic marker in blood and serum, by detection of circRNAs from genes exclusively expressed in the brain. The powerful and scalable tools we present will enable studies of circRNA function and facilitate screening of circRNA as diagnostic biomarkers.
Enhancing all-in-one bioreactors by combining interstitial perfusion, electrical stimulation, on-line monitoring and testing within a single chamber for cardiac constructs
Authors: Visone Roberta , Talò Giuseppe , Lopa Silvia , Rasponi Marco , Moretti Matteo
Published: November 2018

Tissue engineering strategies have been extensively exploited to generate functional cardiac patches. To maintain cardiac functionality in vitro, bioreactors have been designed to provide perfusion and electrical stimulation, alone or combined. However, due to several design limitations the integration of optical systems to assess cardiac maturation level is still missing within these platforms. Here we present a bioreactor culture chamber that provides 3D cardiac constructs with a bidirectional interstitial perfusion and biomimetic electrical stimulation, allowing direct cellular optical monitoring and contractility test. The chamber design was optimized through finite element models to house an innovative scaffold anchoring system to hold and to release it for the evaluation of tissue maturation and functionality by contractility tests. Neonatal rat cardiac fibroblasts subjected to a combined perfusion and electrical stimulation showed positive cell viability over time. Neonatal rat cardiomyocytes were successfully monitored for the entire culture period to assess their functionality. The combination of perfusion and electrical stimulation enhanced patch maturation, as evidenced by the higher contractility, the enhanced beating properties and the increased level of cardiac protein expression. This new multifunctional bioreactor provides a relevant biomimetic environment allowing for independently culturing, real-time monitoring and testing up to 18 separated patches.
Verbascoside: Identification, Quantification, and Potential Sensitization of Colorectal Cancer Cells to 5-FU by Targeting PI3K/AKT Pathway
Authors: Attia Yasmeen M. , El-Kersh Dina M. , Wagdy Hebatallah A. , Elmazar Mohamed M.
Published: November 2018

Colorectal cancer (CRC) is the third most common cancer mortality worldwide. Although, 5-Fluorouracil (5-FU)-based chemotherapeutic regimens remain the mainstay for treatment of CRC, intrinsic and acquired resistance to 5-FU is the main reason for treatment failure and relapse. Adjunct or add-on therapy, therefore, should be thought of to enhance responsiveness to 5-FU. Verbascoside (VER) is a phenylethanoid glycoside ingredient present in many Plantago species and was widely used in traditional medicine. VER showed antiproliferative effects in many cancer types including CRC. In the present study, VER in Plantago seeds was identified using UPLC-MS/MS and quantified using newly developed and validated UPLC-DAD followed by investigating its potential sensitization of CRC cells to 5-FU in vitro. The potential impact on PI3K/AKT pathway was also investigated. A synergistic cytotoxic interaction between 5-FU and VER besides G1 cell cycle arrest were detected. Enhanced apoptosis mainly by affecting Bax and Bcl-2 and to a lesser extent Bcl-xL and p53 was also observed. Additionally, 5-FU combined to VER was capable of significantly reducing PI3K and p-AKT/total AKT ratio. Overall, these results suggest a potential role of VER as an adjuvant treatment to decrease the resistance of CRC cells to 5-FU possibly by targeting the PI3K/AKT pathway.
Molecular basis of Mitomycin C enhanced corneal sensory nerve repair after debridement wounding
Authors: Stepp Mary Ann , Pal-Ghosh Sonali , Tadvalkar Gauri , Li Luowei , Brooks Stephen R. , Morasso Maria I.
Published: November 2018

The ocular surface is covered by stratified squamous corneal epithelial cells that are in cell:cell contact with the axonal membranes of a dense collection of sensory nerve fibers that act as sentinels to detect chemical and mechanical injuries which could lead to blindness. The sheerness of the cornea makes it susceptible to superficial abrasions and recurrent erosions which demand continuous regrowth of the axons throughout life. We showed previously that topical application of the antibiotic and anticancer drug Mitomycin C (MMC) enhances reinnervation of the corneal nerves and reduces recurrent erosions in mice via an unknown mechanism. Here we show using RNA-seq and confocal imaging that wounding the corneal epithelium by debridement upregulates proteases and protease inhibitors within the epithelium and leads to stromal nerve disruption. MMC attenuates these effects after debridement injury by increasing serpine1 gene and protein expression preserving L1CAM on axon surfaces of reinnervating sensory nerves. These data demonstrate at the molecular level that gene expression changes in the corneal epithelium and stroma modulate sensory axon integrity. By preserving the ability of axons to adhere to corneal epithelial cells, MMC enhances sensory nerve recovery after mechanical debridement injury.
Induction of N-Ras degradation by flunarizine-mediated autophagy
Authors: Zheng Ze-Yi , Li Jing , Li Fuhai , Zhu Yanqiao , Cui Kemi , Wong Stephen T. , Chang Eric C. , Liao Yi-Hua
Published: November 2018

Ras GTPases are powerful drivers for tumorigenesis, but directly targeting Ras for treating cancer remains challenging. The growth and transforming activity of the aggressive basal-like breast cancer (BLBC) are driven by N-Ras. To target N-Ras in BLBC, this study screened existing pharmacologically active compounds for the new ability to induce N-Ras degradation, which led to the identification of flunarizine (FLN), previously approved for treating migraine and epilepsy. The FLN-induced N-Ras degradation was not affected by a 26S-proteasome inhibitor. Rather, it was blocked by autophagy inhibitors. Furthermore, N-Ras can be seen co-localized with active autophagosomes upon FLN treatment, suggesting that FLN alters the autophagy pathway to degrade N-Ras. Importantly, FLN treatment recapitulated the effect of N-RAS silencing in vitro by selectively inhibiting the growth of BLBC cells, but not that of breast cancer cells of other subtypes. In addition, in vivo FLN inhibited tumor growth of a BLBC xenograft model. In conclusion, this proof-of-principle study presents evidence that the autophagy pathway can be coerced by small molecule inhibitors, such as FLN, to degrade Ras as a strategy to treat cancer. FLN has low toxicity and should be further investigated to enrich the toolbox of cancer therapeutics.
Gene-ecology of durum wheat HMW glutenin reflects their diffusion from the center of origin
Authors: Janni M. , Cadonici S. , Bonas U. , Grasso A. , Dahab A. A. D. , Visioli G. , Pignone D. , Ceriotti A. , Marmiroli N.
Published: November 2018

The production of many food items processed from wheat grain relies on the use of high gluten strength flours. As a result, about 80% of the allelic variability in the genes encoding the glutenin proteins has been lost in the shift from landraces to modern cultivars. Here, the allelic variability in the genes encoding the high molecular weight glutenin subunits (HMW-GSs) has been characterized in 152 durum wheat lines developed from a set of landraces. The allelic composition at the two Glu-1 loci (Glu-A1 and -B1) was obtained at both the protein and the DNA level. The former locus was represented by three alleles, of which the null allele Glu-A1c was the most common. The Glu-B1 locus was more variable, with fifteen alleles represented, of which Glu-B1b (HMW-GSs 7 + 8), -B1d (6 + 8) and -B1e (20 + 20) were the most frequently occurring. The composition of HMW-GSs has been used to make inferences regarding the diffusion and diversification of durum wheat. The relationships of these allelic frequencies with their geographical distribution within the Mediterranean basin is discussed in terms of gene-ecology.
Characteristics of the retinal microvasculature in association with cardiovascular risk markers in children with overweight, obesity and morbid obesity
Authors: Rijks Jesse , Vreugdenhil Anita , Dorenbos Elke , Karnebeek Kylie , Joris Peter , Berendschot Tos , Mensink Ronald , Plat Jogchum
Published: November 2018

To aim of this study was to evaluate characteristics of the retinal microvasculature, but particularly potential associations with classic and novel (endothelial function and low-grade inflammation)markers for cardiovascular risk, in a cohort of children with overweight and (morbid) obesity. Central retinal arteriolar equivalent(CRAE) and central retinal venular equivalent(CRVE) were assessed. CRAE was significantly lower and AVR significantly higher in children with morbid obesity than in children with overweight and normal weight(p < 0.01). CRVE did not differ significantly between the four weight categories. A multiple linear regression model with CRAE as dependent variable showed that only DBP z-score(β = −2.848,p = 0.029) and plasma glucose concentrations(β = 6.029,p = 0.019) contributed significantly to the variation in CRAE. Remarkably, despite a correlation between CRAE and circulating concentrations of the adhesion molecules VCAM-1 or ICAM-1, markers for inflammation and endothelial function did not contribute to the variation in CRAE. This is the first study showing in population of children with overweight and obesity that the retinal arteriolar microvasculature, but not venular diameter is aberrant, with increasing BMI z-score. CRAE was significantly associated with several cardiovascular risk markers, and multiple linear regression showed that a higher diastolic blood pressure z-score and lower fasting plasma glucose concentrations significantly contributed to the variance in CRAE.
Coordinated Turning Behaviour of Loitering Honeybees
Authors: Mahadeeswara Mandiyam Y. , Srinivasan Mandyam V.
Published: November 2018

Turning during flight is a complex behaviour that requires coordination to ensure that the resulting centrifugal force is never large enough to disrupt the intended turning trajectory. The centrifugal force during a turn increases with the curvature (sharpness) of the turn, as well as the speed of flight. Consequently, sharp turns would require lower flight speeds, in order to limit the centrifugal force to a manageable level and prevent unwanted sideslips. We have video-filmed honeybees flying near a hive entrance when the entrance is temporarily blocked. A 3D reconstruction and analysis of the flight trajectories executed during this loitering behaviour reveals that sharper turns are indeed executed at lower speeds. During a turn, the flight speed is matched to the curvature, moment to moment, in such a way as to maintain the centrifugal force at an approximately constant, low level of about 30% of the body weight, irrespective of the instantaneous speed or curvature of the turn. This ensures that turns are well coordinated, with few or no sideslips - as it is evident from analysis of other properties of the flight trajectories.
OCT3 promoter haplotype is associated with metformin pharmacokinetics in Koreans
Authors: Kwon Eun Young , Chung Jae-Yong , Park Hyo Jin , Kim Bo Min , Kim Minsuk , Choi Ji Ha
Published: November 2018

Organic cation transporter 3 (OCT3) is expressed in various organs in humans and plays an important role in the transport of organic cations and drugs including metformin. In this study, we identified genetic variations of the OCT3 promoter and functionally characterized each variant by in vitro assays. Next, the association between the functional haplotype of the OCT3 promoter and pharmacokinetics of metformin was evaluated. In our study population, 7 variations and 2 major haplotypes were identified, of which H2 haplotype yielded a significantly higher luciferase activity than did the wild type. Two variants of H2, c.-1603G > A and c.-1547T > G, yielded significantly lower luciferase activities, whereas the luciferase activity of another variant, c.-29G > A, was significantly higher. Two transcription factors, Sp1 and USF1, were involved in the regulation of OCT3 transcription. Analysis of clinical data revealed that 25 subjects, either homozygous or heterozygous for H2, showed increased AUCinf and Cmax by 17.2% and 15.9%, respectively [P = 0.016 and 0.031, GMR (90% CI) = 1.17 (1.06–1.29) and 1.17 (1.04–1.31), respectively], compared to the 20 subjects in the control group. Our study suggests that an OCT3 promoter haplotype affects the pharmacokinetics of metformin in Koreans as well as the OCT3 transcription rate.
Immunogenicity of anthrax recombinant peptides and killed spores in goats and protective efficacy of immune sera in A/J mouse model
Authors: Ndumnego Okechukwu C. , Koehler Susanne M. , Crafford Jannie E. , Beyer Wolfgang , van Heerden Henriette
Published: November 2018

Anthrax is primarily recognized as an affliction of herbivores with incubation period ranging from three to five days post-infection. Currently, the Sterne live-spore vaccine is the only vaccine approved for control of the disease in susceptible animals. While largely effective, the Sterne vaccine has several problems including adverse reactions in sensitive species, ineffectiveness in active outbreaks and incompatibility with antibiotics. These can be surmounted with the advent of recombinant peptides (non-living) next generation vaccines. The candidate vaccine antigens comprised of recombinant protective antigen (PA), spore-specific antigen (bacillus collagen-like protein of anthracis, BclA) and formaldehyde inactivated spores (FIS). Presently, little information exists on the protectivity of these novel vaccine candidates in susceptible ruminants. Thus, this study sought to assess the immunogenicity of these vaccine candidates in goats and evaluate their protectivity using an in vivo mouse model. Goats receiving a combination of PA, BclA and FIS yielded the highest antibody and toxin neutralizing titres compared to recombinant peptides alone. This was also reflected in the passive immunization experiment whereby mice receiving immune sera from goats vaccinated with the antigen combination had higher survival post-challenge. In conclusion, the current data indicate promising potential for further development of non-living anthrax vaccines in ruminants.
ADP-Ribosylation Factor-Like 2 (ARL2) regulates cilia stability and development of outer segments in rod photoreceptor neurons
Authors: Wright Zachary C. , Loskutov Yuriy , Murphy Daniel , Stoilov Peter , Pugacheva Elena , Goldberg Andrew F. X. , Ramamurthy Visvanathan
Published: November 2018

Photoreceptor cells are specialized neurons with a sensory cilium carrying an elaborate membrane structure, the outer segment (OS). Inherited mutations in genes involved in ciliogenesis frequently result in OS malformation and blindness. ADP-ribosylation factor-like 2 (ARL2) has recently been implicated in OS formation through its association with Binder of ARL2 (BART or ARL2BP), a protein linked to inherited blinding disease. To test the role of ARL2 in vision we created a transgenic mouse model expressing a tagged-dominant active form of human ARL2 (ARL2-Q70L) under a rod-specific promoter. Transgenic ARL2-Q70L animals exhibit reduced photoreceptor cell function as early as post-natal day 16 and progressive rod degeneration. We attribute loss of photoreceptor function to the defective OS morphogenesis in the ARL2-Q70L transgenic model. ARL2-Q70L expression results in shortened inner and outer segments, shortened and mislocalized axonemes and cytoplasmic accumulation of rhodopsin. In conclusion, we show that ARL2-Q70L is crucial for photoreceptor neuron sensory cilium development. Future research will expand upon our hypothesis that ARL2-Q70L mutant interferes with microtubule maintenance and tubulin regulation resulting in impaired growth of the axoneme and elaboration of the photoreceptor outer segment.
Light modulates oscillatory alpha activity in the occipital cortex of totally visually blind individuals with intact non-image-forming photoreception
Authors: Vandewalle Gilles , van Ackeren Markus J. , Daneault Véronique , Hull Joseph T. , Albouy Geneviève , Lepore Franco , Doyon Julien , Czeisler Charles A. , Dumont Marie , Carrier Julie , Lockley Steven W. , Collignon Olivier
Published: November 2018

The discovery of intrinsically photosensitive retinal ganglion cells (ipRGCs) marked a major shift in our understanding of how light information is processed by the mammalian brain. These ipRGCs influence multiple functions not directly related to image formation such as circadian resetting and entrainment, pupil constriction, enhancement of alertness, as well as the modulation of cognition. More recently, it was demonstrated that ipRGCs may also contribute to basic visual functions. The impact of ipRGCs on visual function, independently of image forming photoreceptors, remains difficult to isolate, however, particularly in humans. We previously showed that exposure to intense monochromatic blue light (465 nm) induced non-conscious light perception in a forced choice task in three rare totally visually blind individuals without detectable rod and cone function, but who retained non-image-forming responses to light, very likely via ipRGCs. The neural foundation of such light perception in the absence of conscious vision is unknown, however. In this study, we characterized the brain activity of these three participants using electroencephalography (EEG), and demonstrate that unconsciously perceived light triggers an early and reliable transient desynchronization (i.e. decreased power) of the alpha EEG rhythm (8–14 Hz) over the occipital cortex. These results provide compelling insight into how ipRGC may contribute to transient changes in ongoing brain activity. They suggest that occipital alpha rhythm synchrony, which is typically linked to the visual system, is modulated by ipRGCs photoreception; a process that may contribute to the non-conscious light perception in those blind individuals.
Wave nature and metastability of emergent crystals in chiral magnets
Authors: Hu Yangfan
Published: November 2018

Topological spin textures emerging in magnetic materials usually appear in crystalline states. A long-standing dilemma is whether we should understand these emergent crystals as gathering “particles” or coupling waves, the answer of which affects almost every aspect of our understanding on the subject. Here we prove that 2-D emergent crystals with long-range order in helimagnets, such as skyrmion crystals and dipole skyrmion crystals, have a wave nature. We systematically study their equilibrium properties, metastability, and phase transition path when unstable. We show that the robustness of a skyrmion crystal derives from its metastability, and that its phase transition dynamics at low (high) magnetic field is mediated by a soft mode which breaks (maintains) its hexagonal symmetry. Different from ordinary crystals which are formed by. and breaks into atoms, emergent crystals have a new formation (destruction) mechanism: they appear from (turn to) “single-Q” spin-density-wave states through nonlinear mode-mode interactions.