bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Decision to Explore New Alternatives: The Coexistence of Under‐ and Over‐exploration
Authors: Teodorescu Kinneret , Erev Ido
Published: May 2013

The decision whether to explore new alternatives or to choose from familiar ones is implicit in many of our daily activities. How is this decision made? When will deviation from optimal exploration be observed? The current paper examines exploration decisions in the context of a multi‐alternative “decisions from experience” task. In each trial, participants could choose a familiar option (the status quo) or a new alternative (risky exploration). The observed exploration rates were more sensitive to the frequent outcome from choosing new alternatives than to the average outcome. That is, the implicit decision whether to explore a new alternative reflects underweighting of rare events: Over‐exploration was documented in “Rare Disasters” environments, and insufficient exploration was evident in “Rare Treasures” environments. In addition, the results reveal a decrease in exploration of new alternatives over time even when it is always optimal and some exploration even when it is never reinforcing. These results can be captured with models that share a distinction between “data collection” and “outcome‐driven” decision modes. Under the data collection mode, the decision maker collects information about the environment, to be used in future choices. Under the outcome‐driven mode, the decision maker relies on small samples of previous experiences with familiar versus unfamiliar alternatives, before the selection of a specific alternative. The predictive value of a two‐parameter “explorative sampler” quantification of these assumptions is demonstrated. Copyright © 2013 John Wiley & Sons, Ltd.
Chemiluminescence determination of moxifloxacin in pharmaceutical and biological samples based on its enhancing effect of the luminol–ferricyanide system using a microfluidic chip
Authors: Suh Yeoun Suk , Kamruzzaman Mohammad , Alam Al‐Mahmnur , Lee Sang Hak , Kim Young Ho , Kim Gyu‐Man , Dang Trung Dung
Published: May 2013

A sensitive determination of a synthetic fluoroquinolone antibacterial agent, moxifloxacin (MOX), by an enhanced chemiluminescence (CL) method using a microfluidic chip is described. The microfluidic chip was fabricated by a soft‐lithographic procedure using polydimethyl siloxane (PDMS). The fabricated PDMS microfluidic chip had three‐inlet microchannels for introducing the sample, chemiluminescent reagent and oxidant, and a 500 µm wide, 250 µm deep and 82 mm long microchannel. An enhanced CL system, luminol–ferricyanide, was adopted to analyze the MOX concentration in a sample solution. CL light was emitted continuously after mixing luminol and ferricyanide in the presence of MOX on the PDMS microfluidic chip. The amount of MOX in the luminol–ferricyanide system influenced the intensity of the CL light. The linear range of MOX concentration was 0.14–55.0 ng/mL with a correlation coefficient of 0.9992. The limit of detection (LOD) and limit of quantification (LOQ) were 0.06 and 0.2 ng/mL respectively. The presented method afforded good reproducibility, with a relative standard deviation (RSD) of 1.05% for 10 ng/mL of MOX, and has been successfully applied for the determination of MOX in pharmaceutical and biological samples. Copyright © 2013 John Wiley & Sons, Ltd.
Energy hyperspace for stacking interaction in AU/AU dinucleotide step: Dispersion‐corrected density functional theory study
Authors: Mukherjee Sanchita , Kailasam Senthilkumar , Bansal Manju , Bhattacharyya Dhananjay
Published: May 2013

Double helical structures of DNA and RNA are mostly determined by base pair stacking interactions, which give them the base sequence‐directed features, such as small roll values for the purine–pyrimidine steps. Earlier attempts to characterize stacking interactions were mostly restricted to calculations on fiber diffraction geometries or optimized structure using ab initio calculations lacking variation in geometry to comment on rather unusual large roll values observed in AU/AU base pair step in crystal structures of RNA double helices. We have generated stacking energy hyperspace by modeling geometries with variations along the important degrees of freedom, roll, and slide, which were chosen via statistical analysis as maximally sequence dependent. Corresponding energy contours were constructed by several quantum chemical methods including dispersion corrections. This analysis established the most suitable methods for stacked base pair systems despite the limitation imparted by number of atom in a base pair step to employ very high level of theory. All the methods predict negative roll value and near‐zero slide to be most favorable for the purine–pyrimidine steps, in agreement with Calladine's steric clash based rule. Successive base pairs in RNA are always linked by sugar–phosphate backbone with C3′‐endo sugars and this demands C1′–C1′ distance of about 5.4 Å along the chains. Consideration of an energy penalty term for deviation of C1′–C1′ distance from the mean value, to the recent DFT‐D functionals, specifically ωB97X‐D appears to predict reliable energy contour for AU/AU step. Such distance‐based penalty improves energy contours for the other purine–pyrimidine sequences also. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 107–120, 2014.
Unusual cause of myocardial infarction and congestive heart failure in a patient with prosthetic valve endocarditis
Authors: Bloechlinger Stefan , Nebiker Mathias , Windecker Stephan
Published: May 2013

In a patient with staphylococcus lugdunensis prosthetic aortic valve endocarditis and coronary septic embolism accompanied by antero‐lateral myocardial infarction, embolic material was successfully aspirated from the bifurcation of the left anterior descending coronary artery and the first diagonal branch. A good angiographic result was documented six months thereafter when the patient presented with a second complication, pulsatile compression of the left main coronary artery by an abscess cavity originating between the aortic and mitral annulus, leading to congestive heart failure. The patient underwent successful surgical replacement of the aortic valve prosthesis with concomitant patch reconstruction of the annulus as well as tricuspid annuloplasty. © 2013 Wiley Periodicals, Inc.
Photoinduced Charge‐Transfer Interactions on a Graphene/Block Copolymer Electrostatically Bound to Tetracationic Porphyrin in Aqueous Media
Authors: Skaltsas Theodosis , Pispas Stergios , Tagmatarchis Nikos
Published: May 2013

Stable dispersions of exfoliated graphene in aqueous media with the aid of the amphiphilic block copolymer poly(isoprene‐b‐acrylic acid) (PI‐b‐PAA), in the form of its anion, were used to electrostatically bind cationic 5,10,15,20‐tetrakis(1‐methyl‐4‐pyridinio)porphine tetra(p‐toluenesulfonate) (H2P4+). A new graphene/PI‐b‐PAA−–H2P4+ ensemble was formed and examined by dynamic light scattering, UV/Vis and fluorescence emission spectroscopy. The efficient fluorescence quenching of H2P4+ in the graphene/PI‐b‐PAA−–H2P4+ ensemble was probed by using steady‐state and time‐resolved photoluminescence, suggesting that electron/energy‐transfer phenomena occur within the nanoensemble. Blank experiments validated the concept of electrostatic interactions that govern the formation of graphene/PI‐b‐PAA−–H2P4+ ensemble, which signified the importance of graphene as an electron acceptor toward the preparation of some new donor–acceptor systems. Finally, kinetic analysis of the lifetime profiles of the fluorescence emission gave information regarding the quenching rate constant and quantum yield of the singlet excited state of H2P4+ in the graphene/PI‐b‐PAA−–H2P4+ ensemble.
Enantiocontrolled Total Synthesis of (−)‐Mersicarpine
Authors: Iwama Yusuke , Okano Kentaro , Sugimoto Kenji , Tokuyama Hidetoshi
Published: May 2013

A racemic synthesis of mersicarpine (1) was achieved by the Mizoroki–Heck reaction and a DIBALH‐mediated reductive ring‐expansion reaction. Based on a first‐generation synthesis, a second‐generation enantiocontrolled total synthesis of (−)‐mersicarpine (1) was achieved by an 8‐pot/11‐step sequence in 21 % overall yield from commercially available 2‐ethylcyclohexanone. Subjection of a ketoester, which was prepared by an asymmetric Michael addition (according to the protocol by d’Angelo and Desmaële), and phenylhydrazine to modified Fischer indole conditions provided a six‐membered tricyclic indole. Benzylic oxidation and subsequent oxime formation provided a ketoxime, which was treated with diisobutylaluminum hydride (DIBALH) to construct the characteristic azepinoindole skeleton in good yield. In the DIBALH‐mediated reductive ring‐expansion reaction, gradually increasing the reaction temperature and in situ‐protection of the nitrogen in an oxygen‐sensitive azepinoindole with a benzyloxycarbonyl (Cbz) group were crucial for the high‐yielding process. With these methodologies, the short‐step and efficient synthesis of (−)‐mersicarpine was accomplished. Several synthetic efforts are also described.
Untersuchungen zur Zitronenbatterie
Authors: Peper‐Bienzeisler Renate , Bröll Leena , Pöhls Christin , Jansen Walter
Published: May 2013

Die Zitronenbatterie ist ein wohlbekannter Versuch aus vielen Versuchsanleitungen für Kinder. Er wird aber auch oft eingesetzt, um älteren Schülern und Studenten Grundzüge der Elektrochemie aufzuzeigen. Ein Zinkblech und ein Kupferblech werden dabei in eine Zitrone gesteckt. Die Metalle werden über einen Draht und ein Voltmeter miteinander verbunden, um die Spannung (etwa 0,9 V) zu messen. Doch gewöhnlich ist der Strom zu gering, um eine Leuchtdiode oder einen anderen Verbraucher zu betreiben. Die meisten Lehrbücher und Lehrkräfte präsentieren die folgende Erklärung: Zinkatome werden als positiv geladene Zink‐Ionen gelöst, die Elektronen wandern durch den Draht zum Kupfer. Hier werden Wasserstoff‐Ionen aus der Zitronensäure durch die Elektronen zu Wasserstoff reduziert. Aber ist das wirklich richtig? Dieser Beitrag zeigt, dass die Hauptreaktion an der Kupferelektrode die Reduktion des Sauerstoffs ist. Daher ist die Zitronenbatterie eine Art von Zink/Luft‐Batterie.

The lemon battery is a well‐known experiment in many science textbooks for children but also often used for older pupils und students to illustrate electrochemical principles. A piece of zinc and a piece of copper are inserted into a lemon. The metals are connected by a wire and a multimeter to measure the voltage (about 0.9 V). But usually the current is too low to power an LED or another device. Most of the textbooks and most of the teachers present the following explanation: Zinc atoms are dissolved as positive charged zinc ions. The electrons are moving through the wire to the copper. Here hydrogen ions from the citric acid are reduced by the electrons to form hydrogen. But is it really true? We now show here that the main reaction at the copper electrode is the reduction of oxygen. Therefore the lemon battery is a type of a zinc air battery.
An Interpretation of the “Anomalous” Changes in the Low‐Wavenumber Range of the Raman Spectra of L‐Alanine Crystals
Authors: Kolesov Boris A. , Boldyreva Elena V.
Published: May 2013

“Anomalous changes” in the temperature‐ and pressure‐ dependences of the intensities and wavenumbers of the two low‐wavenumber modes in Raman spectra of single‐crystals of L‐alanine have been interpreted in terms of a change in relative contributions of stretching and deformational components into the intermolecular vibrational bands. The relative contributions of the two components into a lattice vibration result from a change of relative orientations of molecules linked by hydrogen bonds in a three‐dimensional network on variations of temperature or pressure.
Individual heterogeneity in reproductive rates and cost of reproduction in a long‐lived vertebrate
Authors: Chambert Thierry , Rotella Jay J. , Higgs Megan D. , Garrott Robert A.
Published: May 2013

Individual variation in reproductive success is a key feature of evolution, but also has important implications for predicting population responses to variable environments. Although such individual variation in reproductive outcomes has been reported in numerous studies, most analyses to date have not considered whether these realized differences were due to latent individual heterogeneity in reproduction or merely random chance causing different outcomes among like individuals. Furthermore, latent heterogeneity in fitness components might be expressed differently in contrasted environmental conditions, an issue that has only rarely been investigated. Here, we assessed (i) the potential existence of latent individual heterogeneity and (ii) the nature of its expression (fixed vs. variable) in a population of female Weddell seals (Leptonychotes weddellii), using a hierarchical modeling approach on a 30‐year mark–recapture data set consisting of 954 individual encounter histories. We found strong support for the existence of latent individual heterogeneity in the population, with “robust” individuals expected to produce twice as many pups as “frail” individuals. Moreover, the expression of individual heterogeneity appeared consistent, with only mild evidence that it might be amplified when environmental conditions are severe. Finally, the explicit modeling of individual heterogeneity allowed us to detect a substantial cost of reproduction that was not evidenced when the heterogeneity was ignored.
Benzo[c]thiophene Chromophores Linked to Cationic Fe and Ru Derivatives for NLO Materials: Synthesis Characterization and Quadratic Hyperpolarizabilities
Authors: Silva Tiago J. L. , Mendes Paulo J. , Garcia M. Helena , Robalo M. Paula , Prates Ramalho J. P. , Palace Carvalho A. J. , Büchert Marina , Wittenburg Christian , Heck Jürgen
Published: May 2013

η5‐Monocyclopentadienyliron(II)/ruthenium(II) complexes of the general formula [M(η5‐C5H5)(PP)(L1)][PF6] {M = Fe, PP = dppe; M = Ru, PP = dppe or 2PPh3; L1 = 5‐[3‐(thiophen‐2‐yl)benzo[c]thiophenyl]thiophene‐2‐carbonitrile} have been synthesized and studied to evaluate their molecular quadratic hyperpolarizabilities. The compounds were fully characterized by NMR, FTIR and UV/Vis spectroscopy and their electrochemical behaviour studied by cyclic voltammetry. Quadratic hyperpolarizabilities (β) were determined by hyper‐Rayleigh scattering measurements at a fundamental wavelength of 1500 nm. Density functional theory calculations were employed to rationalize the second‐order non‐linear optical properties of these complexes.
Optical and Electrical Properties of Hierarchical Nanostructured Al‐Doped ZnO Powders Prepared through a Mild Solution Route
Authors: Chen Ruiqiang , Zhu Pengli , Zhao Tao , Fu Xianzhu , Zhou Fengrui , Sun Rong
Published: May 2013

Hierarchical nanostructured Al‐doped ZnO (AZO) powders were successfully prepared through a mild solution route. The crystal structure and morphology of AZO were determined by X‐ray diffraction, scanning electron microscopy, and transmission electron microscopy. The morphology of the samples changed from random flower‐like nanostructures to uniform flower‐like hierarchical nanostructures with different Al doping contents. The optical and electrical properties of AZO were studied by UV/Vis spectroscopy and four‐point probe. The optical band gap of AZO increased initially but then decreased as the Al content was increased owing to the Burstein–Mass effect and the many‐body effect. Conversely, the electrical resistivity of the AZO powders first decreased and then increased with the Al doping content increasing because of changes in the electron and dopant concentrations. AZO exhibited the smallest electrical resistivity with an Al doping content of 1.0 at‐%, which is two orders of magnitude smaller than the electrical resistivity of ZnO.
Synthesis of [Cp′Fe(η3‐BH4)] and Its Conversion to [Cp′FeBH2]3
Authors: Maekawa Miyuki , Daniliuc Constantin G. , Jones Peter G. , Hohenberger Johannes , Sutter Jörg , Meyer Karsten , Walter Marc D.
Published: May 2013

Salt metathesis of [Cp′FeI]2[1, Cp′ = η5‐1,2,4‐(Me3C)3C5H2] and NaBH4(2 equiv.) in tetrahydrofuran yields the low‐spin iron complex [Cp′Fe(η3‐BH4)] (2), which is thermally unstable and degrades slowly to the trimeric complex [Cp′FeBH2]3(3) and H2. Both molecules have been fully characterized by various spectroscopic techniques. An X‐ray structure analysis of3confirms its nature and reveals rather long B–B distances of 1.883(9) Å. DFT methods in combination with three complementary approaches [Wiberg bond indices (WBI), atoms in molecules (AIM) and compliance constants] have been used to explain the bonding in these iron(II) complexes. All methods predict a weak bonding interaction between the boron atoms in3.
CO Activation by (Diphosphane)platinum(0): Carbonate and Acetone Formation – Experimental and Mechanistic Study
Authors: Nicolas Emmanuel , Nocton Grégory , Mézailles Nicolas
Published: May 2013

The platinum(II) complex [(dcpp)Pt(C7H7)H] (1) [dcpp = 1,3‐bis(dicyclohexylphosphanyl)propane] reacts under 1 atm of CO to form the bis(carbonyl) complex of Pt0, [(dcpp)Pt(CO)2] (2). Complex2slowly crystallizes in toluene solution to form crystals of the Pt0dimer [(dcpp)(η1‐CO)Pt{μ‐C(O)}Pt(dcpp)] (3) in which one Pt atom is only three‐coordinated with the diphosphane dcpp and one μ‐C(O), while the other is coordinated in a tetrahedral arrangement with one μ‐C(O) and one η1‐CO. Complexes2and3were characterized in solution by31P NMR spectroscopy, and complex3readily reacts with O2to form the carbonate complex, [(dcpp)Pt(CO3)] (4). The reaction of the dimeric complex3with MeI allows the insertion of a methyl group into the carbonyl group to form the PtIIcomplex [(dcpp)Pt(C(O)Me)I] (5). Reaction of another equivalent of MeI with complex5leads to the formation and elimination of acetone and the bis(iodide) complex [(dcpp)PtI2] (6). X‐ray crystal structures of complexes3and4are reported along with DFT calculations and mechanistic studies of the formation of3,4,5, and6.
Periodate as an Oxidant for Catalytic Water Oxidation: Oxidation via Electron Transfer or O‐Atom Transfer?
Authors: Hetterscheid Dennis G. H. , Reek Joost N. H.
Published: May 2013

Treatment of Ir(OH)2 with sodium periodate in aqueous solution results in formation of dioxygen following the rate law v = kobs[Ir]0.65[IO4]0.5, with kobs = 1.5 × 10–3 {Ir(OH)2 = [IrCp*(Me2NHC)(OH)2], where Me2NHC = N‐dimethylimidazolin‐2‐ylidene and Cp* = cyclopentadienyl}. In situ ESI‐MS experiments in combination with DFT calculations show that [IrIII(IO3)]+ and [IrV(=O)(IO3)]+ species are present in the reaction mixture. On the basis of the presence of these species, a mechanistic pathway was calculated illustrating that water is not necessarily the source of the oxygen. A low‐lying pathway exists wherein O2 production proceeds via two consecutive O‐atom‐transfer reactions from periodate to the catalyst. The resulting iodite ligand is further oxidized to close the catalytic cycle. The rate‐determining step in this process is formation of the O–O bond. For this transition a 21.8 kcal/mol barrier was found. This value fits very well with the observed turnover frequency of 0.27 s–1. Although it is difficult to prove that this is the dominant pathway, these data clearly illustrate that one has to be very careful with interpretation of catalytic results in periodate‐driven water oxidation reactions.
A Strictly Dinuclear MnIII–GdIII Complex: Synthesis and Magnetic Properties
Authors: Costes Jean‐Pierre , Tuchagues Jean‐Pierre , Vendier Laure , Garcia‐Tojal Javier
Published: May 2013

A strictly heterodinuclear MnIII–Gd complex was prepared from a tripodal ligand and characterized by positive fast‐atom bombardment mass spectrometry, which evidenced replacement of a nitrato counterion by a monoethylcarbonato anion. Variable‐temperature direct current and alternating current studies confirm that the MnIII–Gd magnetic interaction is antiferromagnetic. Fitting of the magnetic susceptibility data yields an extremely weak interaction parameter JMnGd equal to –0.04 cm–1, along with a weak axial zero‐field splitting parameter DMn = 0.1 cm–1. This result confirms that a change in the manganese oxidation state, from MnII to MnIII, corresponds to a radical transformation of the magnetic behavior of Mn–Gd, from a ferromagnetic to an antiferromagnetic interaction. In accordance with the magnetic behavior of CoII–Gd complexes previously studied (high‐spin and low‐spin CoII ions), the observed magnetic behavior change may be explained by the difference in the electronic occupancy of the Mn 3d orbital, which is singly occupied for MnII and vacant for MnIII.
Fourth order finite volume solution to shallow water equations and applications
Authors: Erduran K. S.
Published: May 2013

This study presents the fourth order accurate finite volume solution to shallow water equations. Fourth order accuracy in space was provided by using the Monotone Upstream‐centered Schemes for Conservation Laws–Total Variation Diminishing scheme, whereas fourth order accurate solution in time was achieved by using the third order predictor scheme of Adams–Basforth followed by the fourth order corrector scheme of Adams–Moulton. The applicability and accuracy of the solution algorithm were explored on complex flow conditions. These flow conditions cover a theoretical well‐known partial two‐dimensional dam break problems and an experimental flow in a compound channel with or without a bridge. The applicability limits of the solution algorithm were discussed. The overall performance of the solution was found to be reasonably good. Copyright © 2013 John Wiley & Sons, Ltd.
Vertical structuring of gigantic jets
Authors: da Silva Caitano L. , Pasko Victor P.
Published: May 2013

Gigantic Jets (GJs) are initiated deep inside the thundercloud as intracloud discharges whose upward‐directed leaders manage to escape through the thundercloud top and propagate up to the ionosphere. The speed at which leaders propagate is limited by the air heating of every newly formed leader section, rate of which is slower at upper altitudes in the Earth's atmosphere. Despite the expected deceleration of an upward‐directed leader, GJs are observed to accelerate as they approach the ionosphere. In this letter, we discuss the dependence of the leader speed on current density in the leader stem, and we propose a simple time‐dynamic model for GJ propagation that includes the effects of the expansion of the streamer zone adjacent to the leader head. We propose that the GJ acceleration is a consequence of its vertical structuring and, therefore, can be used to trace the transition altitude between the leader and streamer zone sections of GJs.
Influence of El Niño‐Southern Oscillation in the mesosphere
Authors: Li Tao , Calvo Natalia , Yue Jia , Dou Xiankang , Russell J. M. , Mlynczak M. G. , She Chiao‐Yao , Xue Xianghui
Published: May 2013

Using the middle atmosphere temperature data set observed by the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) satellite experiment between 2002 and 2012, and temperatures simulated by the Whole Atmospheric Community Climate Model version 3.5 (WACCM3.5) between 1953 and 2005, we studied the influence of El Niño‐Southern Oscillation (ENSO) on middle atmosphere temperature during the Northern Hemisphere (NH) wintertime. For the first time, a significant winter temperature response to ENSO in the middle mesosphere has been observed, with an anomalous warming of ~1.0 K/MEI (Multivariate ENSO Index) in the tropics and an anomalous cooling of ~ −2.0 K/MEI in the NH middle latitudes. The observed temperature responses to ENSO in the mesosphere are opposite to those in the stratosphere, in agreement with previous modeling studies. Temperature responses to ENSO observed by SABER show similar patterns to those simulated by the WACCM3.5 model. Analysis of the WACCM3.5 residual mean meridional circulation response to ENSO reveals a significant downwelling in the tropical mesosphere and upwelling in the NH middle and high latitudes during warm ENSO events, which is mostly driven by anomalous eastward gravity wave forcing in the NH mesosphere.
A numerical investigation of surface crevasse propagation in glaciers using nonlocal continuum damage mechanics
Authors: Duddu R. , Bassis J. N. , Waisman H.
Published: May 2013

We use a nonlocal viscoelastic damage model to investigate the conditions that enable water‐free surface crevasse propagation in grounded marine‐terminating glaciers. Our simulations, on idealized rectangular ice slabs in contact with the ocean, show that crevasses propagate faster in thicker ice slabs. We find that: (1) the fraction of ice slab thickness penetrated by surface crevasses decreases with increasing seawater depth near the terminus; (2) a no‐slip (fixed) basal boundary condition retards crevasse growth; and (3) crevasses form closer to the terminus when the seawater depth is larger or when the glacier base is fixed to the bedrock, which could lead to calving of smaller icebergs. However, water‐free surface crevasses can penetrate (nearly) the entire ice thickness only in thicker ice slabs terminating in shallow seawater depths. This leads us to the conclusion that surface crevasses alone are not responsible for calving events in marine‐terminating and thin glaciers.
Noble gas composition in rainwater and associated weather patterns
Authors: Warrier Rohit B. , Clara Castro M. , Hall Chris M. , Lohmann Kyger C.
Published: May 2013

This work represents the first comprehensive noble gas study in rainwater. It was carried out in southeast Michigan. Results show that all rainwater samples are in disequilibrium with surface conditions. Two noble gas patterns are identified. The first one, associated with low‐pressure systems, presence of fog and light rainfall, displays a relative Ar enrichment together with Ne, Kr, and Xe depletion. The second one, associated with the passage of frontal systems, displays a mass‐dependent depletion pattern. Precipitation is characterized by thunderstorms, heavy rainfall, and high cloud ceiling heights. A diffusion mass‐transfer model suggests that noble gas patterns originate from ice. Complete re‐equilibration with surface conditions should occur within hours. For the first time, this study establishes a direct correlation between the noble gas composition in rainwater and weather patterns and highlights their potential to identify timing and location of recharge in shallow aquifer systems where infiltration is rapid.
Neutralization resistance of hepatitis C virus can be overcome by recombinant human monoclonal antibodies
Authors: Pedersen Jannie , Carlsen Thomas H.R. , Prentoe Jannick , Ramirez Santseharay , Jensen Tanja B. , Forns Xavier , Alter Harvey , Foung Steven K.H. , Law Mansun , Gottwein Judith , Weis Nina , Bukh Jens
Published: May 2013

Immunotherapy and vaccine development for hepatitis C virus (HCV) will depend on broadly reactive neutralizing antibodies (NAbs). However, studies in infectious strain JFH1-based culture systems expressing patient-derived Core-NS2 proteins have suggested neutralization resistance for specific HCV strains, in particular, of genotype 2. To further examine this phenomenon, we developed a panel of HCV genotype 2 recombinants for testing of sensitivity to neutralization by chronic-phase patient sera and lead human monoclonal antibodies (HMAbs). The novel Core-NS2 recombinants, with patient-derived genotype 2a (strain T9), 2b (strains DH8 and DH10), and 2c (strain S83) consensus sequences, were viable in Huh7.5 hepatoma cells without requirement for adaptive mutations, reaching HCV infectivity titers of 3.9-4.5 log10 focus-forming units per milliliter. In

in vitro

neutralization assays, we demonstrated that the novel genotype 2 viruses as well as prototype strains J6/JFH1(2a) and J8/JFH1(2b), all with authentic envelope proteins, were resistant to neutralization by genotype 2a, 2b, 2c, 2j, 2i, and 2q patient sera. However, these patient sera had high titers of HCV-specific NAbs, because they efficiently reduced the infectivity of J6(2a) and J8(2b) with deleted hypervariable region 1. The genotype 2a, 2b, and 2c viruses, found resistant to polyclonal patient sera neutralization, were efficiently neutralized by two lead HMAbs (AR4A and HC84.26).

Conclusion:

Using novel 2a, 2b, and 2c cell-culture systems, expressing authentic envelope proteins, we demonstrated resistance of HCV to patient-derived polyclonal high-titer NAbs. However, the same genotype 2 culture viruses were all sensitive to HMAbs recognizing conformational epitopes, indicating that neutralization resistance of HCV can be overcome by applying recombinant antibodies. These findings have important implications for HCV immunotherapy and vaccine development. (Hepatology 2013;58:1587–1597)
CD73 (ecto-5′-nucleotidase) hepatocyte levels differ across mouse strains and contribute to mallory-denk body formation
Authors: Snider Natasha T. , Griggs Nicholas W. , Singla Amika , Moons David S. , Weerasinghe Sujith V.W. , Lok Anna S. , Ruan Chunhai , Burant Charles F. , Conjeevaram Hari S. , Omary Bishr M.
Published: May 2013

Formation of hepatocyte Mallory-Denk bodies (MDBs), which are aggregates of keratins 8 and 18 (K8/K18), ubiquitin, and the ubiquitin-binding protein, p62, has a genetic predisposition component in humans and mice. We tested the hypothesis that metabolomic profiling of MDB-susceptible C57BL and MDB-resistant C3H mouse strains can illuminate MDB-associated pathways. Using both targeted and unbiased metabolomic analyses, we demonstrated significant differences in intermediates of purine metabolism. Further analysis revealed that C3H and C57BL livers differ significantly in messenger RNA (mRNA) level, protein expression, and enzymatic activity of the adenosine-generating enzyme, ecto-5′-nucleotidase (CD73), which was significantly lower in C57BL livers. CD73 mRNA levels were also dramatically decreased in human liver biopsies from hepatitis C and nonalcoholic fatty liver disease patients. Feeding mice with a diet containing the MDB-inducing agent, 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), significantly decreased CD73 protein and activity in C57BL livers and resulted in loss of plasma membrane CD73 expression and activity in isolated mouse hepatocytes. To further examine the role of CD73 in MDB formation

in vivo

, we fed wild-type (WT) and CD73−/− mice a DDC-containing diet. Liver enlargement, p62 induction, and disappearance of the K8/K18 cytoskeleton were attenuated in CD73−/−, compared to WT livers. MDB formation, as assessed by biochemical and immunofluorescence detection of keratin and ubiquitin complexes, was nearly absent in CD73−/− mice.

Conclusion:

Purine metabolism and CD73 expression are linked to susceptibility to MDB formation in livers of different mouse strains. Expression of the adenosine-generating enzyme, CD73, contributes to experimental MDB induction and is highly regulated in MDB-associated liver injury in mice and in chronic human liver disease. (Hepatology 2013;58:1790–1800)
Posttranscriptional destabilization of the liver-specific long noncoding RNA HULC by the IGF2 mRNA-binding protein 1 (IGF2BP1)
Authors: Hämmerle Monika , Gutschner Tony , Uckelmann Hannah , Ozgur Sevim , Fiskin Evgenij , Gross Matthias , Skawran Britta , Geffers Robert , Longerich Thomas , Breuhahn Kai , Schirmacher Peter , Stoecklin Georg , Diederichs Sven
Published: May 2013

Selected long noncoding RNAs (lncRNAs) have been shown to play important roles in carcinogenesis. Although the cellular functions of these transcripts can be diverse, many lncRNAs regulate gene expression. In contrast, factors that control the expression of lncRNAs remain largely unknown. Here we investigated the impact of RNA binding proteins on the expression of the liver cancer-associated lncRNA

HULC

(highly up-regulated in liver cancer). First, we validated the strong up-regulation of

HULC

in human hepatocellular carcinoma. To elucidate posttranscriptional regulatory mechanisms governing

HULC

expression, we applied an RNA affinity purification approach to identify specific protein interaction partners and potential regulators. This method identified the family of IGF2BPs (IGF2 mRNA-binding proteins) as specific binding partners of

HULC

. Depletion of IGF2BP1, also known as IMP1, but not of IGF2BP2 or IGF2BP3, led to an increased

HULC

half-life and higher steady-state expression levels, indicating a posttranscriptional regulatory mechanism. Importantly,

HULC

represents the first IGF2BP substrate that is destabilized. To elucidate the mechanism by which IGF2BP1 destabilizes

HULC,

the CNOT1 protein was identified as a novel interaction partner of IGF2BP1. CNOT1 is the scaffold of the human CCR4-NOT deadenylase complex, a major component of the cytoplasmic RNA decay machinery. Indeed, depletion of CNOT1 increased

HULC

half-life and expression. Thus, IGF2BP1 acts as an adaptor protein that recruits the CCR4-NOT complex and thereby initiates the degradation of the lncRNA

HULC

.

Conclusion:

Our findings provide important insights into the regulation of lncRNA expression and identify a novel function for IGF2BP1 in RNA metabolism. (Hepatology 2013;58:1703–1712)
Loss of caspase-8 in hepatocytes accelerates the onset of liver regeneration in mice through premature nuclear factor kappa B activation
Authors: Freimuth Julia , Bangen Jörg-Martin , Lambertz Daniela , Hu Wei , Nevzorova Yulia Alexandrowna , Sonntag Roland , Gassler Nikolaus , Riethmacher Dieter , Trautwein Christian , Liedtke Christian
Published: May 2013

The cytokine tumor necrosis factor alpha (TNF-α; TNF) plays a critical role early in liver regeneration following partial hepatectomy (PH). TNF stimulates at least three different pathways leading to nuclear factor kappa B (NF-κB) activation, apoptosis signaling by way of caspase-8 (Casp8), and activation of cJun N-terminal kinases (JNK). The present study aimed to better define the role of Casp8 during liver regeneration. We performed PH in mice lacking Casp8 specifically in hepatocytes (Casp8Δhepa) and determined their liver regeneration capacity by measuring liver mass restoration and kinetics of cell cycle progression. Casp8Δhepa mice showed an accelerated onset of DNA synthesis after PH, delayed hepatocyte mitosis, but overall normal liver mass restoration. Analysis of immediate TNF-dependent signaling pathways revealed that loss of Casp8 prevents proteolytic cleavage of the receptor-interacting protein 1 (RIP1) in hepatocytes and subsequently triggers premature activation of NF-κB and JNK/cJun related signals. In order to define the role of NF-κB in this setting we blocked NF-κB activation in Casp8Δhepa mice by concomitant inactivation of the NF-κB essential modulator (NEMO) in hepatocytes. Lack of NEMO largely reverted aberrant DNA synthesis in Casp8Δhepa mice but resulted in incomplete termination of the regeneration process and hepatomegaly.

Conclusion:

Casp8 comprises a nonapoptotic function during liver regeneration by balancing RIP1, NF-κB, and JNK activation. While loss of Casp8 triggers NF-κB activation and thus improves liver regeneration, combined loss of Casp8 and NEMO impairs a controlled regenerative response and drives hepatomegaly. (Hepatology 2013;58:1779–1789)
Identification of driver genes in hepatocellular carcinoma by exome sequencing
Authors: Cleary Sean P. , Jeck William R. , Zhao Xiaobei , Chen Kui , Selitsky Sara R. , Savich Gleb L. , Tan Ting-Xu , Wu Michael C. , Getz Gad , Lawrence Michael S. , Parker Joel S. , Li Jinyu , Powers Scott , Kim Hyeja , Fischer Sandra , Guindi Maha , Ghanekar Anand , Chiang Derek Y.
Published: May 2013

Genetic alterations in specific driver genes lead to disruption of cellular pathways and are critical events in the instigation and progression of hepatocellular carcinoma (HCC). As a prerequisite for individualized cancer treatment, we sought to characterize the landscape of recurrent somatic mutations in HCC. We performed whole-exome sequencing on 87 HCCs and matched normal adjacent tissues to an average coverage of 59×. The overall mutation rate was roughly two mutations per Mb, with a median of 45 nonsynonymous mutations that altered the amino acid sequence (range, 2-381). We found recurrent mutations in several genes with high transcript levels:

TP53

(18%);

CTNNB1

(10%);

KEAP1

(8%);

C16orf62

(8%);

MLL4

(7%); and

RAC2

(5%). Significantly affected gene families include the nucleotide-binding domain and leucine-rich repeat-containing family, calcium channel subunits, and histone methyltransferases. In particular, the

MLL

family of methyltransferases for histone H3 lysine 4 were mutated in 20% of tumors.

Conclusion:

The

NFE2L2
-
KEAP1

and

MLL

pathways are recurrently mutated in multiple cohorts of HCC. (Hepatology 2013;58:1693–1702)
The Chemistry of PCR Primers: Concept and Application
Authors: Takei Fumie , Nakatani Kazuhiko
Published: May 2013

DNA is a typical organic compound with marked differences from other chemicals and biopolymers because DNA can be amplified by the enzyme polymerase. DNA can be, in principle, amplified from a single copy by the polymerase chain reaction (PCR). In this review, we focus our attention on the chemistry of PCR primers. Because PCR is basic technology in biology research fields, we sometimes use chemically labeled primers without any awareness of the chemistry they leave behind. We would like to emphasize that chemically labeled primers contain a lot of potential for different chemistry ideas and much study is still necessary to advance PCR for single‐nucleotide polymorphism (SNP) typing, genetic diagnosis, and other fields. Two categories of primers, affinity‐capture primers and signaling primers, are discussed from the viewpoints of their chemical concepts and applications. Affinity‐capture primers are used for purification, isolation, and manipulation of PCR products by high specificity and affinity to the cognate molecules by moleculemolecule interactions, whereas signaling primers report the hybridization and/or progress of PCR amplification by a signal change, in most cases by a fluorescence change. The content of this review may be useful for a better understanding of the chemistry of PCR primers and, more importantly, for the invention of novel PCR chemistry.
IMPROVED EFFICIENCY OF IRRIGATION WATER USE: A SOUTH AFRICAN FRAMEWORK
Authors: Reinders Felix B , van der Stoep Isobel , Backeberg Gerhard R
Published: May 2013

Irrigated agriculture plays a major role in the livelihoods of nations all over the world and in South Africa it is not different. With the agricultural water use sector being the largest of all water use sectors in South Africa, there have been increased expectations that the sector should increase efficiency and reduce consumption in order to increase the amount of water available for other uses.

In a recent study on irrigation efficiency, the approach is that irrigation efficiency should be assessed by applying a water balance to a specific situation rather than by calculating various performance indicators such as conveyance efficiency or application efficiency. Unfortunately the concept of irrigation efficiency is frequently misunderstood leading to the widespread belief that water just disappears with low irrigation efficiencies and re‐appears with improvements. The purpose of an irrigation system is to apply the desired amount of water, at the correct application rate and uniformly to the whole field, at the right time, with the least amount of non‐beneficial water consumption (losses), and as economically as possible. The fraction of the water abstracted from the source that can be utilised by the plant, can be called the beneficial water use component and optimised irrigation water supply is therefore aimed at maximising this component. It implies that water must be delivered from the source to the field both efficiently (with the least volume for production along the supply system) and effectively (at the right time, in the right quantity and at the right quality). Optimising water use at farm level requires careful consideration of the implications of decisions made during both development (planning and design), and management (operation and maintenance), taking into account technical, economic and environmental issues.

The South African framework covers four levels of water management infrastructure: ‐the water source, bulk conveyance system, the irrigation scheme and the irrigation farm. The water balance approach can be applied at any level, within defined boundaries, or across all levels to assess performance within the whole Water Management Area. Copyright © 2013 John Wiley & Sons, Ltd.
Unravelling ionization and fragmentation pathways of carotenoids using orbitrap technology: a first step towards identification of unknowns
Authors: Bijttebier Sebastiaan K. A. , D'Hondt Els , Hermans Nina , Apers Sandra , Voorspoels Stefan
Published: May 2013

Vegetables are a major source of carotenoids and carotenoids are identified as potentially important natural antioxidants that may aid in the prevention of several human chronic degenerative diseases. Characterization of carotenoids in organic biological matrices is a crucial step in any research valorization trajectory. This study reports for the first time the use of high mass resolution and exact mass orbitrap technology for the elucidation of carotenoid fragmentation pathways. This contributes to the generation of new tools for identifying unknown carotenoids based on fragmentation patterns. Two different chromatographic methods making use of different mobile phases resulted in the generation of different ion species because of the large influence of the mobile phase solvent composition on ionization. It was shown that depending on the molecular ion species that are generated (protonated ions or radical molecular ions), different fragments are formed when applying higher energy collisional dissociation. Fragmentation and the abundance of fragments provide valuable structural information on the type of functional groups, the polyene backbone and the location of double bonds in ring structures of carotenoids. Furthermore, coherence between specific substructures in the molecules and characteristic fragmentation patterns was observed allowing the assignment of fragmentation patterns for carotenoid substructures that can theoretically be extrapolated to carotenoids with similar (sub)structures. Differentiation between isomeric carotenoids by compound specific fragments could however not be made for all the isomeric groups under study. As a wide variety of isomeric forms of carotenoids exist in nature, the combination of good chromatographic separation with high resolution mass spectrometry and other complementary qualitative structure elucidation techniques such as a photo diode array detector and/or nuclear magnetic resonance spectroscopy are indispensable for unambiguous identification of unknown carotenoids. Copyright © 2013 John Wiley & Sons, Ltd.
Phosphorus characterization of manure composts and combined organic fertilizers by a sequential‐fractionation method
Authors: Takahashi Shigeru
Published: May 2013

Characterization of the forms of phosphorus (P) in organic soil amendments was conducted by sequential P fractionation. More than 60% of total P was inorganic P (Pi). The major Pi forms in the cattle‐manure composts were NaHCO3‐ and HCl‐extractable P fractions. HCl‐extractable Pi was the predominant P form and a considerable proportion of the total P was present in the HCl‐extractable organic P fraction in the poultry manure composts and combined organic fertilizers.
Climate‐strategic agriculture and the water‐soil‐waste nexus
Authors: Lal Rattan
Published: May 2013

Adoption of input‐responsive varieties enhanced food production during the second half of the 20th century. However, even bigger challenges lie ahead because of the growing societal demands. For example, the global population of 7.2 billion in 2013 is projected to reach 9.2 billion by 2050 and stabilize at 10 billion by 2100. The growing and increasingly affluent population, with preference towards more and more meat‐based diet, is likely to jeopardize the finite, fragile, and dwindling soil and water resources which are already under great stress in densely populated countries in Asia and elsewhere. Economic growth and increase in gross domestic product also lead to generation of waste or by‐products, along with contamination and eutrophication of water resources. International trade in food/feed products also involves transfer of virtual water, which is a serious issue when water‐scarce countries export virtual water to water‐endowed countries. The problem is confounded by the present and future climate change driven by the growing energy demands of the carbon civilization. Thus, adaptation to climate change represents both a threat and an opportunity for sustainable development. Adaptive strategies must be sustainable socially and environmentally and advance the Millennium Development Goals, while buffering agroecosystems against extreme climate events (e.g., pedologic, agronomic, and ecologic drought). Thus, recognizing and addressing the water‐soil‐waste nexus is important to achieving climate‐strategic agriculture. Sustainable intensification of agroecosystems, producing more per unit consumption of essential resources, must consider judicious management of hydrological and biogeochemical cycles (C, N, P, S). The soil C pool must be managed and enhanced to offset anthropogenic emissions, and mitigate/adapt to the climate change. The pace of adoption of recommended land use and soil‐/plant‐/animal‐management practices can be kept at par with advances in scientific knowledge through continuous dialogue between scientists on the one hand and policy makers / land managers on the other to translate research data into policy and action plans.
Does Corporate Social Responsibility Hit the Mark? A Stakeholder Oriented Methodology for CSR Assessment
Authors: Calabrese Armando , Costa Roberta , Menichini Tamara , Rosati Francesco
Published: May 2013

Is corporate social responsibility (CSR) commitment effectively disclosed through a company's sustainably report? Moreover, in what measure is a company's CSR commitment really acknowledged by its stakeholders? Because it has been observed that stakeholders' recognition of a company's social and environmental conduct highly impacts the business returns of CSR initiatives, it is therefore not surprising that measurement of the stakeholder perception is a key issue for CSR assessment.

In this paper, we propose a method enabling companies to evaluate the effectiveness of their CSR policies both in terms of disclosure and capacity to fulfill both stakeholder social and environmental expectations. The method we propose compares, through a gap analysis, three measures as follows: the company commitment disclosed through its sustainability report, the company CSR commitment perceived by its stakeholders, and the CSR commitment that stakeholders require to the company. The outcome of the proposed methodology provides managerial insights for evaluating the effectiveness of ongoing CSR practices and for formulating CSR strategies. An application illustrates the use of the methodology in practice. Copyright © 2013 John Wiley & Sons, Ltd.