bluuebunny/crossref_metadata_2025 huggingface dataset:
Scopine Isolated in the Gas Phase
Authors: Écija Patricia , Vallejo‐López Montserrat , Uriarte Iciar , Basterretxea Francisco J. , Lesarri Alberto , Fernández José A. , Cocinero Emilio J.
Published: June 2016

The rotational spectrum of the tropane alkaloid scopine is detected by Fourier transform microwave spectroscopy in a pulsed supersonic jet. A nonconventional method for bringing the molecules intact into the gas phase is used in which scopine syrup is mixed with glycine powder and the solid mixture is vaporized with an ultrafast UV laser beam. Laser vaporization prevents the easy isomerization to scopoline previously observed with conventional heating methods. A single conformer is unambiguously observed in the supersonic jet and corresponds to the energetically most stable species according to quantum chemical calculations. Rotational and centrifugal distortion constants are accurately determined. The spectrum shows fine and hyperfine structure due to the hindered rotation of the methyl group and the presence of a quadrupolar nucleus (14N), respectively. This additional information allows the angle of N‐methyl inversion between the N−CH3 bond and the bicyclic C‐N‐C plane to be determined (131.8–137.8°), as well as the internal rotation barrier of the methyl group (6.235(1) kJ mol−1).
Ro‐vibrational Spectra of (para‐H2)N‐CH4 in He Droplets
Authors: Hoshina Hiromichi , Sliter Russell , Ravi Aakash , Kuma Susumu , Momose Takamasa , Vilesov Andrey F.
Published: June 2016

In this work, we report on the infrared spectroscopic study of clusters of CH4 molecules with up to N=80 para‐hydrogen molecules assembled inside He droplets. Upon increase of the number of the added para‐hydrogen molecules up to about N=12, both the rotational constant, B, and the origin frequency of the υ3 band of CH4 decrease gradually. In the range of 6 ≤N≤12, the spectra indicate some abrupt changes of B and υ3 with both values being approximately constant at N≥12. The origin of this effect is discussed. Comparison of the spectra of methane molecules in para‐hydrogen clusters to that in solid para‐hydrogen is also presented.
Controlled Movement of Cucurbiturils in Host–Guest Systems
Authors: Zhu Liangliang , Zhu Mingjie , Zhao Yanli
Published: June 2016

Controllable host–guest assemblies play a key role in developing supramolecular materials. This review highlights recent research progress for a type of host–guest systems based on cucurbiturils (CBs) and their derivatives, in which their structural states and related properties can be tuned in response to relative movements of CBs driven by a variety of external stimuli. By taking advantage of unique stimuli‐responsive features, these CB‐based host–guest systems have been grafted into applicable materials, such as biosystems, nanoarchitectures, and functional nanoparticles. In addition to discussing the preparation methodology and structural characterizations of several CB‐based host–guest materials, their charming functionalities, accompanied by variation in the in situ controlled manner and resulting property changes were highlighted. Future studies on the applications of CB‐based, smart, tunable materials are also predicted.
Carbon Dioxide‐Free Hydrogen Production with Integrated Hydrogen Separation and Storage
Authors: Dürr Stefan , Müller Michael , Jorschick Holger , Helmin Marta , Bösmann Andreas , Palkovits Regina , Wasserscheid Peter
Published: June 2016

An integration of CO2‐free hydrogen generation through methane decomposition coupled with hydrogen/methane separation and chemical hydrogen storage through liquid organic hydrogen carrier (LOHC) systems is demonstrated. A potential, very interesting application is the upgrading of stranded gas, for example, gas from a remote gas field or associated gas from off‐shore oil drilling. Stranded gas can be effectively converted in a catalytic process by methane decomposition into solid carbon and a hydrogen/methane mixture that can be directly fed to a hydrogenation unit to load a LOHC with hydrogen. This allows for a straight‐forward separation of hydrogen from CH4 and conversion of hydrogen to a hydrogen‐rich LOHC material. Both, the hydrogen‐rich LOHC material and the generated carbon on metal can easily be transported to destinations of further industrial use by established transport systems, like ships or trucks.
Understanding of Hysteresis Behaviors at the L‐H‐L Transitions in Tokamak Plasma Based on Bifurcation Concept
Authors: Chatthong B. , Onjun T.
Published: June 2016

The hysteresis behaviour at the L‐H‐L transitions in tokamak plasma is investigated based on bifurcation concept. The formation of an edge transport barrier (ETB) is modeled via thermal and particle transport equations with the flow shear suppression effect on anomalous transport included. The anomalous transport is modeled based on critical gradients threshold and the flow shear is calculated from the force balance equation, couples the two transport equations leading to a non‐linear behaviour. Analytical investigation reveals that the fluxes versus gradients space exhibits bifurcation behaviour with s ‐curve soft bifurcation type. Apparently, the backward H‐L transition occurs at lower values than that of the forward L‐H transition, illustrating hysteresis behaviour. The hysteresis properties, i.e. locations of threshold fluxes, gradients and their ratios are analyzed as a function of neoclassical and anomalous transport values and critical gradients. It is found that the minimum heat flux for maintaining H ‐mode depends on several plasma parameters including the strength of anomalous transport and neoclassical transport. In particular, the hysteresis depth becomes larger when neoclassical transport decreases or anomalous transport increases. (© 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Effects of Multi‐Species Ions on Sheath and Presheath in a Magnetic Field Decreasing toward a Wall
Authors: Fukano A. , Nishioka S. , Goto I. , Hatayama A.
Published: June 2016

In the divertor region, the plasma contains deuterium (D) ion and tritium (T) ion in an open magnetic field. The effect of D ion and T ion on the electric potential near the wall in plasma with magnetic field decreasing toward a wall is investigated analytically. The distribution of the electric potential is obtained by plasma‐sheath equation, where D ion and T ion are considered. The potential distribution depends on the parameters such as the profile of the magnetic field, the temperatures of D ion and T ion, and the amount rate of T ion to D ion. The particle distribution also is shown. (© 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Simulations of Tungsten Re‐deposition Using a Particle‐In‐Cell Code with Non‐uniform Super Particle Sizes
Authors: Ibano K. , Togo S. , Lang T. L. , Ogawa Y. , Lee H.T. , Ueda Y. , Takizuka T.
Published: June 2016

Tungsten (W), a promising candidate as divertor plasma facing material in magnetic fusion devices, is anticipated to promptly redeposit when sputtered or evaporated from surface due to its small ionization energy and long gyro radius. Using an artificial factor for the reaction cross sections, effects of ionization lengths to the re‐deposition rate was studied by a newly developed particle‐in‐cell code. Treating numbers of particles in a super particle, electric charge, and mass as particle variables in the code, a special scheme for ionization and recombination was developed and used for the calculation. Simulations on W test particles with imaginary properties (neglecting the electric force) revealed the effects of ejection angles. Simulations with secondary electrons from surface showed that the sheath potential is weakened and the re‐deposition rate becomes small. It was found that the multi‐ionization as well as the ionization mean‐free‐path influences the re‐deposition rate in both simulations. (© 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Simulation of Radiative Divertor Plasmas by Ar Seeding with the Full W‐Wall in JT‐60SA
Authors: Kawashima H. , Shimizu K. , Hoshino K. , Nakano T. , Asakura N.
Published: June 2016

Radiative divertor plasmas for JT‐60SA with a full tungsten (W) wall, which is one of options in future, have been simulated with a SOL/divertor integrated code, SONIC. A conventional modified‐coronal radiation (MCR) model with a finite confinement time is used for both Ar and W for the purpose of wide‐range parameter surveys for the divertor plasma to obtain the required conditions (qt ≤ 10 MW/m2, nSepe–mid = 3∼8×1019 m–3,Prad< ∼ 30 MW), saving the calculation time. At low W density ratio (nW /ni = 1×10–5), due to low radiative power from W ions, Ar density ratio (nAr/ni ≥ 1.0× 10–3) and a strong gas puff (Γp ≥ 3.0×1022 s–1) are inevitable to suppress the divertor heat flux down to 10 MW/m2. Increasing nW/ni to 1×10–3 in the divertor region, the divertor heat load becomes low and the operative regions are expanded. While, the W production shall be suppressed since the W radiation is increased with replacement of Ar radiation and the particle recycling decreased. A Monte‐Carlo module (IMPMC) implemented in SONIC for Ar seeding reveals that the spatial distribution of Ar ions is predominantly determined by shell structures of the Ar ions. The consistency between IMPMC and MCR calculations is demonstrated for the averaged n Ar/n i ratio, the electron density and temperature profiles on the divertor target and typical parameter such as the divertor heat load. It shows that the detailed analysis with IMPMC model can be speedily obtained, using a steady state solution obtained by MCR model as an initial state. (© 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ginzburg‐Landau Model in a Finite Shear‐Layer and Onset of Transport Barrier Nonlinear Oscillations: A Paradigm for TypeIII ELMs
Authors: Leconte M. , Jeon Y.M. , Yun G. S.
Published: June 2016

We study a Reaction‐Diffusion model describing the nonlinear oscillations of a transport barrier in a finite shear‐layer (width dE ≪ a), where a is the plasma minor radius, based on a 1D reduced model derived to explain nonlinear barrier oscillations in 3D turbulence simulations [P. Beyer, S. Benkadda, G. Fuhr‐Chaudier et al., Phys. Rev. Lett. 94, 105001 (2005)]. We show that this single nonlinear equation encompasses most of the physics of these barrier relaxations. The nonlinear oscillations have common characteristics with type‐III edge localized modes (ELMs), such as a repetition frequency which decreases with increasing power. In addition to the flow shear, the shear‐layer width is also shown to control the nature of the oscillations. (© 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Gyrokinetic Model beyond the Standard Ordering
Authors: Miyato N.
Published: June 2016

An energy‐conserving reduced kinetic model is formulated which is valid for perturbations with large amplitude and long wavelength beyond the standard gyrokinetic ordering. The standard gyrokinetic model is elegantly formulated by the two‐step phase space transformation consisting of the guiding‐center and gyro‐center transformations, but the amplitude of perturbations is assumed to be small in return for use of the two‐step transformation. Besides, the wavelength of perturbations is assumed to be short in deriving the gyrokinetic Poisson equation. Both limitations are relaxed by using the modified guiding‐center 1‐form for flowing plasmas [Miyato et al., J. Phys. Soc. Jpn. 78, 104501 (2009)]. (© 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Engage faculty to boost student success, completion
Authors: Hope Joan
Published: June 2016

CHICAGO — Administrators can set goals for student retention and completion rates, but they can't achieve them alone. “To move the dial, you have to have faculty become involved,” said Craig Foltin, executive vice president and provost at Cuyahoga Community College in Ohio.
Time‐course measurements of drug concentrations in hair and toenails after single administrations of pharmaceutical products
Authors: Kuwayama Kenji , Miyaguchi Hajime , Iwata Yuko T. , Kanamori Tatsuyuki , Tsujikawa Kenji , Yamamuro Tadashi , Segawa Hiroki , Inoue Hiroyuki
Published: June 2016

Hair and nails are often used to prove long‐term intake of drugs in forensic drug testing. The aim of this study was to evaluate the effectiveness of drug testing using hair and nails and the feasibility of determining when drugs were ingested by measuring the time‐courses of drug concentrations in hair and toenails after single administrations of various drugs. Healthy subjects ingested four pharmaceutical products containing eight active ingredients in single doses. Hair and toenails were collected at predetermined intervals, and drug concentrations in hair and nails were measured for 12 months. The administered drugs and their main metabolites were extracted using micropulverized extraction with a stainless steel bullet and were analyzed using liquid chromatography/tandem mass spectrometry. Acidic compounds such as ibuprofen and its metabolites were not detected in both specimens. Acetaminophen, a weakly acidic compound, was detected in nails more frequently than in hair. The maximum concentration of allyl isopropyl acetylurea, a neutral compound, in nails was significantly higher than in hair. Nails are an effective specimen to detect neutral and weakly acidic compounds. For fexofenadine, a zwitterionic compound, and for most basic compounds, the maximum concentrations in hair segments tended to be higher than those in nails. The hair segments showing the maximum concentrations varied between drugs, samples, and subjects. Drug concentrations in hair segments greatly depended on the selection of the hair. Careful interpretation of analytical results is required to predict the time of drug intake. Copyright © 2016 John Wiley & Sons, Ltd.
Xenon elimination kinetics following brief exposure
Authors: Schaefer Maximilian S. , Piper Thomas , Geyer Hans , Schneemann Julia , Neukirchen Martin , Thevis Mario , Kienbaum Peter
Published: June 2016

Xenon is a modern inhalative anaesthetic with a very low solubility in tissues providing rapid elimination and weaning from anaesthesia. Besides its anaesthetic properties, Xenon promotes the endogenous erythropoietin biosynthesis and thus has been enlisted as prohibited substance by the World Anti‐Doping Agency (WADA). For effective doping controls, knowledge about the elimination kinetics of Xenon and the duration of traceability are of particular importance. Seventy‐seven full blood samples were obtained from 7 normal weight patients undergoing routine Xenon‐based general anaesthesia with a targeted inspiratory concentration of 60% Xenon in oxygen. Samples were taken before and during Xenon inhalation as well as one, two, 4, 8, 16, 24, 32, 40, and 48 h after exposure. Xenon concentrations were assessed in full blood by gas chromatography and triple quadrupole tandem mass spectrometry with a detection limit of 0.25 µmol/L. The elimination of Xenon was characterized by linear regression of log‐transformed Xenon blood concentrations, as well as non‐linear regression. Xenon exposure yielded maximum concentrations in arterial blood of 1.3 [1.1; 1.6] mmol/L. Xenon was traceable for 24 to 48 h. The elimination profile was characterized by a biphasic pattern with a rapid alpha phase, followed by a slower beta phase showing a first order kinetics (c[Xe] = 69.1e‐0.26x, R2 = 0.83, t1/2 = 2.7 h). Time in hours after exposure could be estimated by 50*ln(1.39/c[Xe]0.077). Xenon's elimination kinetics is biphasic with a delayed beta phase following a first order kinetics. Xenon can reliably be detected for at least 24 h after brief exposure. Copyright © 2016 John Wiley & Sons, Ltd.
Can trait patterns along gradients predict plant community responses to climate change?
Authors: Guittar John , Goldberg Deborah , Klanderud Kari , Telford Richard J. , Vandvik Vigdis
Published: June 2016

Plant functional traits vary consistently along climate gradients and are therefore potential predictors of plant community response to climate change. We test this space‐for‐time assumption by combining a spatial gradient study with whole‐community turf transplantation along temperature and precipitation gradients in a network of 12 grassland sites in Southern Norway. Using data on eight traits for 169 species and annual vegetation censuses of 235 turfs over 5 yr, we quantify trait‐based responses to climate change by comparing observed community dynamics in transplanted turfs to field‐parameterized null model simulations. Three traits related to species architecture (maximum height, number of dormant meristems, and ramet‐ramet connection persistence) varied consistently along spatial temperature gradients and also correlated to changes in species abundances in turfs transplanted to warmer climates. Two traits associated with resource acquisition strategy (SLA, leaf area) increased along spatial temperature gradients but did not correlate to changes in species abundances following warming. No traits correlated consistently with precipitation. Our study supports the hypothesis that spatial associations between plant traits and broad‐scale climate variables can be predictive of community response to climate change, but it also suggests that not all traits with clear patterns along climate gradients will necessarily influence community response to an equal degree.
Recognize 6 signs it's time for a web redesign or redevelopment
Authors: Talarico Donna
Published: June 2016

A shiny, new, state‐of‐the‐art website stays that way for only so long. Rapidly changing technology and a constant evolution of how people interact with online content challenge us to keep up with our digital identity.
Production, purification, and characterization of carboxymethyl cellulase from novel strain Bacillus megaterium
Authors: Shahid Zeeshan Hussain , Irfan Muhammad , Nadeem Muhammad , Syed Quratulain , Qazi Javed Iqbal
Published: June 2016

In the present investigation a strain of Bacillus megaterium BM05 was evaluated for cellulase production in submerged fermentation using wheat straw as a substrate. Various nutritional and cultural parameters were optimized to obtain maximum production of carboxymethyl cellulase. The strain produced best titer of cellulase at initial medium pH of 5, inoculum size of 1% using 2% wheat straw with 0.8% NaCl in medium for 48 h of fermentation period. Further supplementation of CMC as an additional carbon source and yeast extract as nitrogen sources favored enzyme production. Organic acids found to be inhibitory effect on secretion of cellulase enzyme by B. megaterium BM05. The enzyme exhibited molecular weight of 53.55 kDa as revealed by SDS‐PAGE. The enzyme had optimum pH and temperature of 6.5°C and 50°C with stability range of 6.0–8.0 and 30°C–40°C for 140 min, respectively. The enzyme had half life of 38.9 min at 80°C. Metal profile of the enzyme indicated that K+ (125%) and Na+ (118%) were the activators while Pb+2 (15%) and Hg+2 (13%) were the inhibitors. The endoglucanase had Km and Vmax value of 1.73 and 0.95 U/mL using CMC‐Na as a substrate, respectively. Turnover number (Kcat) and catalytic efficiency (Kcat/Km) of purified enzyme was 1556.11 min and 1.3 × 106 M/s, respectively. © 2016 American Institute of Chemical Engineers Environ Prog, 35: 1741–1749, 2016
Effects of reduced oxygen environment on the reaction to fire of a poly(urethane‐isocyanurate) foam
Authors: Marquis Damien M. , Hermouet Fabien , Guillaume Éric
Published: June 2016

Thanks to their thermal insulation properties, rigid polyisocyanurate foams are commonly used in the modern built environment, as well as in transportation and industrial applications. However, the fire behaviour of this kind of foam remains one of the most limiting factors for their wider use as insulation material in some sectors. Indeed, this type of material is thermally and chemically reactive. The general scope of this study is to investigate the effects of a reduced oxygen atmosphere on the reaction to fire of flame‐retardant polyisocyanurate foam. This paper reports the results of an experimental campaign, which was performed using a controlled‐atmosphere cone calorimeter, coupled to a Fourier transform infrared spectrophotometer. The dependence of the results on both oxygen concentration and irradiance level is presented and discussed. The chemical compositions of the identified gaseous products were qualified and quantified during both the decomposition and the combustion processes. Copyright © 2016 John Wiley & Sons, Ltd.
Experimentelle Bestimmung der Nichtlinearität von Spannungsgrenzbedingungen im Bereich geringer Spannungen
Authors: Bergholz Katharina , Herle Ivo
Published: June 2016

Frühere Forschungen haben gezeigt, dass es sich bei den Scherparametern φ' und c' der Mohr‐Coulombschen Bruchbedingung nicht um Materialkonstanten, sondern um zustandsabhängige Kennwerte handelt. Folglich weist die Spannungsgrenzbedingung überkonsolidierter Böden eine Nichtlinearität auf, die sich im Bereich geringer Spannungen in einer mehr oder weniger starken Krümmung der Grenzumhüllenden zum Koordinatenursprung äußert. Mithilfe experimenteller Untersuchungen wurde die Entwicklung der effektiven Scherparameter als Funktion des mittleren Druckniveaus sowie der Vorbelastung analysiert. Dazu wurden Bodenproben eines schluffigen Tons auf unterschiedliche Überkonsolidierungsgrade und ‐spannungen vorbelastet und im Anschluss entlang verschiedener unkonventioneller Spannungspfade abgeschert, um auch in den Bereich sehr niedriger Spannungen vorzudringen, der mit konventionellen triaxialen Kompressionsversuchen schwer zu erkunden ist. Die Versuchsreihe hat belegt, dass insbesondere die vom Boden erfahrene Höchstspannung Einfluss auf den Grad der Nichtlinearität des Bruchkriteriums hat: je höher die Vorbelastung, desto ausgeprägter die Krümmung. Das Überkonsolidierungsverhältnis wirkt sich dahingegen deutlicher auf die Steifigkeit der Bodenreaktion aus, was indirekt für eine Abhängigkeit der volumetrischen Antwort vom Spannungspfad spricht.
Transplantation with autologous bone marrow‐derived mesenchymal stem cells for alcoholic cirrhosis: Phase 2 trial
Authors: Suk Ki Tae , Yoon Jung‐Hwan , Kim Moon Young , Kim Chang Wook , Kim Ja Kyung , Park Hana , Hwang Seong Gyu , Kim Dong Joon , Lee Byung Seok , Lee Sae Hwan , Kim Hong Soo , Jang Jae Young , Lee Chang‐Hyeong , Kim Byung Seok , Jang Yoon Ok , Cho Mee Yon , Jung Eun Sun , Kim Yong Man , Bae Si Hyun , Baik Soon Koo
Published: June 2016

Bone marrow‐derived mesenchymal stem cell (BM‐MSC) transplantation has been suggested as an effective therapy for liver cirrhosis. The efficacy and safety of autologous BM‐MSC transplantation in the treatment of alcoholic cirrhosis were investigated. Seventy‐two patients with baseline biopsy‐proven alcoholic cirrhosis who had been alcohol‐abstinent for more than 6 months underwent a multicenter, randomized, open‐label, phase 2 trial. Patients were randomly assigned to three groups: one control group and two autologous BM‐MSC groups that underwent either one‐time or two‐time hepatic arterial injections of 5 × 107 BM‐MSCs 30 days after BM aspiration. A follow‐up biopsy was performed 6 months after enrollment, and adverse events were monitored for 12 months. The primary endpoint was improvement in fibrosis quantification based on picrosirius red staining. The secondary endpoints included liver function tests, Child‐Pugh score, and Model for End‐stage Liver Disease score. Outcomes were analyzed by per‐protocol analysis. In terms of fibrosis quantification (before versus after), the one‐time and two‐time BM‐MSC groups were associated with 25% (19.5 ± 9.5% versus 14.5 ± 7.1%) and 37% (21.1 ± 8.9% versus 13.2 ± 6.7%) reductions in the proportion of collagen, respectively (P < 0.001). In the intergroup comparison, two‐time BM‐MSC transplantation in comparison with one‐time BM‐MSC transplantation was not associated with improved results in fibrosis quantification (P > 0.05). The Child‐Pugh scores of both BM‐MSC groups (one‐time 7.6 ± 1.0 versus 6.3 ± 1.3 and two‐time 7.8 ± 1.2 versus 6.8 ± 1.6) were also significantly improved following BM‐MSC transplantation (P < 0.05). The proportion of patients with adverse events did not differ among the three groups. Conclusion: Autologous BM‐MSC transplantation safely improved histologic fibrosis and liver function in patients with alcoholic cirrhosis. (Hepatology 2016;64:2185‐2197)
A new 3p25 locus is associated with liver fibrosis progression in human immunodeficiency virus/hepatitis C virus‐coinfected patients
Authors: Ulveling Damien , Le Clerc Sigrid , Cobat Aurélie , Labib Taoufik , Noirel Josselin , Laville Vincent , Coulonges Cédric , Carpentier Wassila , Nalpas Bertrand , Heim Markus H. , Poynard Thierry , Cerny Andreas , Pol Stanislas , Bochud Pierre‐Yves , Dabis François , Theodorou Ioannis , Lévy Yves , Salmon Dominique , Abel Laurent , Dominguez Stéphanie , Zagury Jean‐François ,   the HEPAVIH ANRS CO13 Cohort Study Group,   the Swiss Hepatitis C Cohort Study Group,   the French ANRS HC EP 26 Genoscan Study Group
Published: June 2016

There is growing evidence that human genetic variants contribute to liver fibrosis in subjects with hepatitis C virus (HCV) monoinfection, but this aspect has been little investigated in patients coinfected with HCV and human immunodeficiency virus (HIV). We performed the first genome‐wide association study of liver fibrosis progression in patients coinfected with HCV and HIV, using the well‐characterized French National Agency for Research on AIDS and Viral Hepatitis CO13 HEPAVIH cohort. Liver fibrosis was assessed by elastography (FibroScan), providing a quantitative fibrosis score. After quality control, a genome‐wide association study was conducted on 289 Caucasian patients, for a total of 8,426,597 genotyped (Illumina Omni2.5 BeadChip) or reliably imputed single‐nucleotide polymorphisms. Single‐nucleotide polymorphisms with P values <10−6 were investigated in two independent replication cohorts of European patients infected with HCV alone. Two signals of genome‐wide significance (P < 5 × 10−8) were obtained. The first, on chromosome 3p25 and corresponding to rs61183828 (P = 3.8 × 10−9), was replicated in the two independent cohorts of patients with HCV monoinfection. The cluster of single‐nucleotide polymorphisms in linkage disequilibrium with rs61183828 was located close to two genes involved in mechanisms affecting both cell signaling and cell structure (CAV3) or HCV replication (RAD18). The second signal, obtained with rs11790131 (P = 9.3 × 10−9) on chromosome region 9p22, was not replicated. Conclusion: This genome‐wide association study identified a new locus associated with liver fibrosis severity in patients with HIV/HCV coinfection, on chromosome 3p25, a finding that was replicated in patients with HCV monoinfection; these results provide new relevant hypotheses for the pathogenesis of liver fibrosis in patients with HIV/HCV coinfection that may help define new targets for drug development or new prognostic tests, to improve patient care. (Hepatology 2016;64:1462‐1472)
RNA helicase DEAD box protein 5 regulates Polycomb repressive complex 2/Hox transcript antisense intergenic RNA function in hepatitis B virus infection and hepatocarcinogenesis
Authors: Zhang Hao , Xing Zheng , Mani Saravana Kumar Kailasam , Bancel Brigitte , Durantel David , Zoulim Fabien , Tran Elizabeth J. , Merle Philippe , Andrisani Ourania
Published: June 2016

Chronic hepatitis B virus (HBV) infection is a major factor in hepatocellular carcinoma (HCC) pathogenesis by a mechanism not yet understood. Elucidating mechanisms of HBV‐mediated hepatocarcinogenesis is needed to gain insights into classification and treatment of HCC. In HBV replicating cells, including virus‐associated HCCs, suppressor of zeste 12 homolog (SUZ12), a core subunit of Polycomb repressive complex2 (PRC2), undergoes proteasomal degradation. This process requires the long noncoding RNA, Hox transcript antisense intergenic RNA (HOTAIR). Intriguingly, HOTAIR interacts with PRC2 and also binds RNA‐binding E3 ligases, serving as a ubiquitination scaffold. Herein, we identified the RNA helicase, DEAD box protein 5 (DDX5), as a regulator of SUZ12 stability and PRC2‐mediated gene repression, acting by regulating RNA‐protein complexes formed with HOTAIR. Specifically, knockdown of DDX5 and/or HOTAIR enabled reexpression of PRC2‐repressed genes epithelial cell adhesion molecule (EpCAM) and pluripotency genes. Also, knockdown of DDX5 enhanced transcription from the HBV minichromosome. The helicase activity of DDX5 stabilized SUZ12‐ and PRC2‐mediated gene silencing, by displacing the RNA‐binding E3 ligase, Mex‐3 RNA‐binding family member B (Mex3b), from HOTAIR. Conversely, ectopic expression of Mex3b ubiquitinated SUZ12, displaced DDX5 from HOTAIR, and induced SUZ12 down‐regulation. In G2 phase of cells expressing the HBV X protein (HBx), SUZ12 preferentially associated with Mex3b, but not DDX5, resulting in de‐repression of PRC2 targets, including EpCAM and pluripotency genes. Significantly, liver tumors from HBx/c‐myc bitransgenic mice and chronically HBV‐infected patients exhibited a strong negative correlation between DDX5 messenger RNA levels, pluripotency gene expression, and liver tumor differentiation. Notably, chronically infected HBV patients with HCC expressing reduced DDX5 exhibited poor prognosis after tumor resection, identifying DDX5 as an important player in poor prognosis HCC. Conclusion: The RNA helicase DDX5, and E3 ligase Mex3b, are important cellular targets for the design of novel, epigenetic therapies to combat HBV infection and poor prognosis HBV‐associated liver cancer. (Hepatology 2016;64:1033‐1048)
Noninvasive imaging methods to determine severity of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
Authors: Hannah William N. , Harrison Stephen A.
Published: June 2016

Nonalcoholic fatty liver disease (NAFLD) is now the most common form of liver disease in developed countries, with an estimated prevalence of 20%‐30% and increasing to as high as 90% in diabetics. As the rates of NAFLD continue to rise in parallel with those of the obesity pandemic, it is increasingly important to differentiate those patients with the highest risk of progression to fibrosis and cirrhosis. In fact, those patients with nonalcoholic steatohepatitis (NASH) and fibrosis are at the greatest risk of progression to advanced disease, cirrhosis, and hepatocellular cancer and are more likely to develop liver‐related mortality. Thus, it is critically important to distinguish between NASH and non‐NASH NAFLD. Whereas liver biopsy remains the gold standard for staging of disease, complications of this procedure and other well‐recognized limitations make it impractical for widespread use given the overall NAFLD disease burden. Noninvasive imaging modalities are increasingly being utilized to evaluate and stage NAFLD in patients with such a wide spectrum of disease. In this article, the role of these new and promising noninvasive imaging modalities to assess disease severity in NAFLD are reviewed. (Hepatology 2016;64:2234‐2243)
Linear viral load increase of a single HPV‐type in women with multiple HPV infections predicts progression to cervical cancer
Authors: Depuydt Christophe E. , Thys Sofie , Beert Johan , Jonckheere Jef , Salembier Geert , Bogers Johannes J.
Published: June 2016

Persistent high‐risk human papillomavirus (HPV) infection is strongly associated with development of high‐grade cervical intraepithelial neoplasia or cancer (CIN3+). In single type infections, serial type‐specific viral‐load measurements predict the natural history of the infection. In infections with multiple HPV‐types, the individual type‐specific viral‐load profile could distinguish progressing HPV‐infections from regressing infections. A case‐cohort natural history study was established using samples from untreated women with multiple HPV‐infections who developed CIN3+ (n = 57) or cleared infections (n = 88). Enriched cell pellet from liquid based cytology samples were subjected to a clinically validated real‐time qPCR‐assay (18 HPV‐types). Using serial type‐specific viral‐load measurements (≥3) we calculated HPV‐specific slopes and coefficient of determination (R2) by linear regression. For each woman slopes and R2 were used to calculate which HPV‐induced processes were ongoing (progression, regression, serial transient, transient). In transient infections with multiple HPV‐types, each single HPV‐type generated similar increasing (0.27copies/cell/day) and decreasing (−0.27copies/cell/day) viral‐load slopes. In CIN3+, at least one of the HPV‐types had a clonal progressive course (R2 ≥ 0.85; 0.0025copies/cell/day). In selected CIN3+ cases (n = 6), immunostaining detecting type‐specific HPV 16, 31, 33, 58 and 67 RNA showed an even staining in clonal populations (CIN3+), whereas in transient virion‐producing infections the RNA‐staining was less in the basal layer compared to the upper layer where cells were ready to desquamate and release newly‐formed virions. RNA‐hybridization patterns matched the calculated ongoing processes measured by R2 and slope in serial type‐specific viral‐load measurements preceding the biopsy. In women with multiple HPV‐types, serial type‐specific viral‐load measurements predict the natural history of the different HPV‐types and elucidates HPV‐genotype attribution.
Discoidin Receptor 2 Controls Bone Formation and Marrow Adipogenesis
Authors: Ge Chunxi , Wang Zhengyan , Zhao Guisheng , Li Binbin , Liao Jinhui , Sun Hanshi , Franceschi Renny T
Published: June 2016

Cell–extracellular matrix (ECM) interactions play major roles in controlling progenitor cell fate and differentiation. The receptor tyrosine kinase, discoidin domain receptor 2 (DDR2), is an important mediator of interactions between cells and fibrillar collagens. DDR2 signals through both ERK1/2 and p38 MAP kinase, which stimulate osteoblast differentiation and bone formation. Here we show that DDR2 is critical for skeletal development and differentiation of marrow progenitor cells to osteoblasts while suppressing marrow adipogenesis. Smallie mice (Ddr2slie/slie), which contain a nonfunctional Ddr2 allele, have multiple skeletal defects. A progressive decrease in tibial trabecular bone volume/total volume (BV/TV) was observed when wild-type (WT), Ddr2wt/slie, and Ddr2slie/slie mice were compared. These changes were associated with reduced trabecular number (Tb.N) and trabecular thickness (Tb.Th) and increased trabecular spacing (Tb.Sp) in both males and females, but reduced cortical thickness only in Ddr2slie/slie females. Bone changes were attributed to decreased bone formation rather than increased osteoclast activity. Significantly, marrow fat and adipocyte-specific mRNA expression were significantly elevated in Ddr2slie/slie animals. Additional skeletal defects include widened calvarial sutures and reduced vertebral trabecular bone. To examine the role of DDR2 signaling in cell differentiation, bone marrow stromal cells (BMSCs) were grown under osteogenic and adipogenic conditions. Ddr2slie/slie cells exhibited defective osteoblast differentiation and accelerated adipogenesis. Changes in differentiation were related to activity of runt-related transcription factor 2 (RUNX2) and PPARγ, transcription factors that are both controlled by MAPK-dependent phosphorylation. Specifically, the defective osteoblast differentiation in calvarial cells from Ddr2slie/slie mice was associated with reduced ERK/MAP kinase and RUNX2-S319 phosphorylation and could be rescued with a constitutively active phosphomimetic RUNX2 mutant. Also, DDR2 was shown to increase RUNX2-S319 phosphorylation and transcriptional activity while also increasing PPARγ-S112 phosphorylation, but reducing its activity. DDR2 is, therefore, important for maintenance of osteoblast activity and suppression of marrow adipogenesis in vivo and these actions are related to changes in MAPK-dependent RUNX2 and PPARγ phosphorylation. © 2016 American Society for Bone and Mineral Research.
Oxidized LDL‐Exposed Human Macrophages Display Increased MMP‐9 Expression and Secretion Mediated by Endoplasmic Reticulum Stress
Authors: Sanda Gabriela M. , Deleanu Mariana , Toma Laura , Stancu Camelia S. , Simionescu Maya , Sima Anca V.
Published: June 2016

Oxidatively modified low‐density lipoproteins (oxLDL) alter the proper function of the endoplasmic reticulum (ER), inducing ER stress (ERS), which consequently activates inflammatory pathways in macrophages. Matrix metalloproteinase‐9 (MMP‐9) is the main protease acting on the degradation of the extracellular matrix and the ensuing destabilization of the atherosclerotic plaque. We aimed to investigate whether ERS induced by oxLDL or tunicamycin (TM) in human macrophages is associated with the stimulation of MMP‐9 expression and secretion. The results showed that oxLDL induced in THP‐1 macrophages: (i) increase of MMP‐9 gene expression and its pro‐form secretion, (ii) intracellular accumulation of 7‐ketocholesterol, (iii) ERS activation (increased eIF2α phosphorylation, XBP1 and CHOP mRNA levels, and Grp78 protein expression), and (iv) oxidative stress (increased levels of reactive oxygen species and NADPH oxidase activity). Incubation of macrophages with ERS inducer, TM determined the secretion of both pro‐ and active‐form of MMP‐9 and oxidative stress. Treatment of oxLDL or TM‐incubated cells with ERS inhibitor, sodium phenylbutyrate decreased MMP‐9 gene expression, secretion, and activity. The inhibitor of NADPH oxidase, apocynin, decreased XBP‐1 and CHOP mRNA levels, and MMP‐9 gene expression and secretion in oxLDL‐exposed cells. In conclusion, oxLDL stimulate MMP‐9 expression and secretion in human macrophages by mechanisms involving ERS. J. Cell. Biochem. 118: 661–669, 2017. © 2016 Wiley Periodicals, Inc.
Synthesis, Antioxidant, and Anti‐Inflammatory Evaluation of Novel Thiophene‐Fused Quinoline Based β‐Diketones and Derivatives
Authors: Mahajan Pravin , Nikam Mukesh , Asrondkar Ashish , Bobade Anil , Gill Charansingh
Published: June 2016

Novel thieno[2,3‐b]quinoline‐2‐carboxylic acid derivatives including β‐diketone, pyrazole, and flavone were prepared under ultrasonication and evaluated for in vitro antioxidant and anti‐inflammatory activities. Antioxidant activity was determined by DPPH radical scavenging method and anti‐inflammatory activity by HRBC membrane stabilization method. Some of the Compounds showed good antioxidant activity, whereas, some of the compounds bearing pyrazole core showed good anti‐inflammatory activity. Further in silico physicochemical properties were also calculated for good oral drug bioavailability and drug likeness of synthesized compounds.
Pollen‐based reconstructions of Late Holocene climate on the southern slopes of the central Tianshan Mountains, Xinjiang,NWChina
Authors: Zhang Yun , Kong Zhaochen , Yang Zhenjing
Published: June 2016

To quantitatively describe the Late Holocene palaeoclimatic history of the southern slopes of the Tianshan Mountains in Xinjiang, China, we collected 74 surface pollen samples (from −154 to 4285 m), together with 81 fossil samples from Swan Lake. Based on modern pollen assemblage and redundancy analysis (RDA) of surface pollen data, five pollen zones were divided (alpine cushion vegetation, alpine meadow, subalpine meadow steppe, montane desert, and typical desert zones). Modern pollen–climate transfer functions were developed to quantitatively reconstruct palaeoclimate of the area using the weighted averaging partial least squares regression method. Reconstructed mean annual precipitation and mean annual temperature results suggest that a dry/warm or humid/cold climate pattern prevailed over the past 4200 aBP. Notably, three cold and humid stages were detected at 4200–4000 cal. aBP, 3700–2000 cal. aBP, and 1170–930 cal. aBP. Moreover, a humid ‘Medieval Warm Period’ (MWP) occurred not only on the northern slopes but also on the southern slopes of the Tianshan Mountains. However, based on palaeo‐environmental records and on archaeological documents, it would appear that a dryMWPoccurred in southern parts of south Xinjiang, with this being different from theMWPon the Tianshan Mountains. Interactions between monsoon and the westerly airflows might account for this difference. The data will improve understanding of past atmospheric circulation systems in the different parts of Xinjiang and will help to predict the future climate in the world.
Dissolved and colloidal phosphorus fluxes in forest ecosystems—an almost blind spot in ecosystem research
Authors: Bol Roland , Julich Dorit , Brödlin Dominik , Siemens Jan , Kaiser Klaus , Dippold Michaela Anna , Spielvogel Sandra , Zilla Thomas , Mewes Daniela , von Blanckenburg Friedhelm , Puhlmann Heike , Holzmann Stefan , Weiler Markus , Amelung Wulf , Lang Friederike , Kuzyakov Yakov , Feger Karl‐Heinz , Gottselig Nina , Klumpp Erwin , Missong Anna , Winkelmann Carola , Uhlig David , Sohrt Jakob , von Wilpert Klaus , Wu Bei , Hagedorn Frank
Published: June 2016

Understanding and quantification of phosphorus (P) fluxes are key requirements for predictions of future forest ecosystems changes as well as for transferring lessons learned from natural ecosystems to croplands and plantations. This review summarizes and evaluates the recent knowledge on mechanisms, magnitude, and relevance by which dissolved and colloidal inorganic and organic P forms can be translocated within or exported from forest ecosystems. Attention is paid to hydrological pathways of P losses at the soil profile and landscape scales, and the subsequent influence of P on aquatic ecosystems. New (unpublished) data from the German Priority Program 1685 “Ecosystem Nutrition: Forest Strategies for limited Phosphorus Resources” were added to provide up‐to‐date flux‐based information.

Nitrogen (N) additions increase the release of water‐transportable P forms. Most P found in percolates and pore waters belongs to the so‐called dissolved organic P (DOP) fractions, rich in orthophosphate‐monoesters and also containing some orthophosphate‐diesters. Total solution P concentrations range from ca. 1 to 400 µg P L−1, with large variations among forest stands. Recent sophisticated analyses revealed that large portions of the DOP in forest stream water can comprise natural nanoparticles and fine colloids which under extreme conditions may account for 40–100% of the P losses. Their translocation within preferential flow passes may be rapid, mediated by storm events. The potential total P loss through leaching into subsoils and with streams was found to be less than 50 mg P m−2 a−1, suggesting effects on ecosystems at centennial to millennium scale. All current data are based on selected snapshots only. Quantitative measurements of P fluxes in temperate forest systems are nearly absent in the literature, probably due to main research focus on the C and N cycles. Therefore, we lack complete ecosystem‐based assessments of dissolved and colloidal P fluxes within and from temperate forest systems.
Normothermic ex vivo liver perfusion using steen solution as perfusate for human liver transplantation: First North American results
Authors: Selzner Markus , Goldaracena Nicolas , Echeverri Juan , Kaths Johan M. , Linares Ivan , Selzner Nazia , Serrick Cyril , Marquez Max , Sapisochin Gonzalo , Renner Eberhard L. , Bhat Mamatha , McGilvray Ian D. , Lilly Leslie , Greig Paul D. , Tsien Cynthia , Cattral Mark S. , Ghanekar Anand , Grant David R.
Published: June 2016

The European trial investigating normothermic ex vivo liver perfusion (NEVLP) as a preservation technique for liver transplantation (LT) uses gelofusine, a non–US Food and Drug Administration–approved, bovine‐derived, gelatin‐based perfusion solution. We report a safety and feasibility clinical NEVLP trial with human albumin–based Steen solution. Transplant outcomes of 10 human liver grafts that were perfused on the Metra device at 37 °C with Steen solution, plus 3 units of erythrocytes were compared with a matched historical control group of 30 grafts using cold storage (CS) as the preservation technique. Ten liver grafts were perfused for 480 minutes (340‐580 minutes). All livers cleared lactate (final lactate 1.46 mmol/L; 0.56‐1.74 mmol/L) and produced bile (61 mL; 14‐146 mL) during perfusion. No technical problems occurred during perfusion, and all NEVLP‐preserved grafts functioned well after LT. NEVLP versus CS had lower aspartate aminotransferase and alanine aminotransferase values on postoperative days 1‐3 without reaching significance. No difference in postoperative graft function between NEVLP and CS grafts was detected as measured by day 7 international normalized ratio (1.1 [1‐1.56] versus 1.1 [1‐1.3]; P = 0.5) and bilirubin (1.5; 1‐7.7 mg/dL versus 2.78; 0.4‐15 mg/dL; P = 0.5). No difference was found in the duration of intensive care unit stay (median, 1 versus 2 days; range, 0‐8 versus 0‐23 days; P = 0.5) and posttransplant hospital stay (median, 11 versus 13 days; range, 8‐17 versus 7‐89 days; P = 0.23). Major complications (Dindo‐Clavien ≥ 3b) occurred in 1 patient in the NEVLP group (10%) compared with 7 (23%) patients in the CS group (P = 0.5). No graft loss or patient death was observed in either group. Liver preservation with normothermic ex vivo perfusion with the Metra device using Steen solution is safe and results in comparable outcomes to CS after LT. Using US Food and Drug Administration–approved Steen solution will avoid a potential regulatory barrier in North America. Liver Transplantation 22 1501–1508 2016 AASLD.
Patterning Surfaces on Azo‐Based Multilayer Films via Surface Wrinkling Combined with Visible Light Irradiation
Authors: Zong Chuanyong , Zhao Yan , Ji Haipeng , Xie Jixun , Han Xue , Wang Juanjuan , Cao Yanping , Lu Conghua , Li Hongfei , Jiang Shichun
Published: June 2016

Here, a simple combined strategy of surface wrinkling with visible light irradiation to fabricate well tunable hierarchical surface patterns on azo‐containing multilayer films is reported. The key to tailor surface patterns is to introduce a photosensitive poly(disperse orange 3) intermediate layer into the film/substrate wrinkling system, in which the modulus decrease is induced by the reversible photoisomerization. The existence of a photoinert top layer prevents the photoisomerization‐induced stress release in the intermediate layer to some extent. Consequently, the as‐formed wrinkling patterns can be modulated over a large area by light irradiation. Interestingly, in the case of selective exposure, the wrinkle wavelength in the exposed region decreases, while the wrinkles in the unexposed region are evolved into highly oriented wrinkles with the orientation perpendicular to the exposed/unexposed boundary. Compared with traditional single layer‐based film/substrate systems, the multilayer system consisting of the photosensitive intermediate layer offers unprecedented advantages in the patterning controllability/universality. As demonstrated here, this simple and versatile strategy can be conveniently extended to functional multilayer systems for the creation of prescribed hierarchical surface patterns with optically tailored microstructures.

image