bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear categorization of the energetic-beam-driven instability with drag and diffusion
Authors: Lesur M. , Idomura Y.
Published: September 2012

The Berk–Breizman (BB) extension of the bump-on-tail instability includes a finite, fixed wave damping (γ
d), and a collision operator with drag (ν
f) and diffusion (ν
d). The BB model is applied to a one-dimensional plasma, to investigate the kinetic nonlinearities, which arise from the resonance of a single electrostatic wave with an energetic-particle beam. For a fixed value of the linear drive normalized to the linear frequency, γ
L0/ω
0 = 0.1, the long-time nonlinear evolution is systematically categorized as damped, steady-state, periodic, chaotic and chirping. The chirping regime is sub-categorized as periodic, chaotic, bursty and intermittent. Up–down asymmetry and hooked chirping branches are also categorized. For large drag, holes with quasi-constant velocity are observed, in which case the solution is categorized into steady, wavering and oscillating holes. Two complementary parameter spaces are considered: (1) the (γ
d, ν
d) space for fixed ν
d/ν
f ratios; (2) the (ν
f, ν
d) space for fixed γ
d/γ
L0 ratios, close to and far from marginal stability. The presence of drag and diffusion (instead of a Krook model) qualitatively modifies the nonlinear bifurcations. The bifurcations between steady-state, periodic and steady-hole solutions agree with analytic theory. Moreover, the boundary between steady and periodic solutions agrees with analytic theory. Nonlinear instabilities are found in both subcritical and barely unstable regimes. Quasi-periodic chirping is shown to be a special case of bursty chirping, limited to a region relatively far from marginal stability.
Initial measurements of the DIII-D off-axis neutral beams
Authors: Heidbrink W.W. , Zeeland M.A. Van , Grierson B.A. , Muscatello C.M. , Park J.M. , Petty C.C. , Prater R. , Zhu Y.B.
Published: September 2012

Two of the eight neutral-beam sources on the DIII-D tokamak were modified to allow injection below the midplane. To validate off-axis beam performance, the various beams are injected sequentially into low-power plasmas that are optimized for accurate neutron, neutral–particle, fast-ion D-alpha and fast-ion pressure measurements. As expected, the fast-ion profile is broader with off-axis injection than with on-axis injection. The driven toroidal rotation also broadens with off-axis injection and the central fast-ion density is several times smaller. The number of trapped ions in the core depends sensitively on the pitch of the magnetic field lines. Comparisons with classical predictions agree with the measurements for some diagnostics but are discrepant for others.
Plasma isotopic effect on the damping rate of toroidal Alfvén eigenmodes with intermediate toroidal mode numbers*
Authors: Testa D. , Panis T. , Blanchard P. , Fasoli A.
Published: September 2012

This paper reports on the results of recent experiments performed on the JET tokamak on toroidal Alfvén eigenmodes (TAEs) with toroidal mode number (n) in the range up to |n| = 7. The stability properties of these medium-n TAEs are investigated experimentally using a set of compact in-vessel antennas, providing a direct and real-time measurement of the frequency, damping rate and amplitude for each individual toroidal mode number. The measurements, reported here, of the damping rate (γ/ω) for these medium-n modes were obtained during a deuterium to helium to hydrogen changeover experimental campaign, and are used to infer the effect of the plasma effective isotopic composition (A
EFF) on the stability properties of these medium-n TAEs. We find that the damping rate of n = 1 TAEs decreases approximately as γ/ω ∼ 1/A
EFF as reported previously, but only for modes whose frequency is close to the centre of the n = 1 toroidal gap and for density and current profiles giving an open gap structure. Conversely, for n ⩾ 3 TAEs we find that their damping rate approximately increases as γ/ω ∼ A
EFF.
Effects of rippled fields due to ferritic inserts and ELM mitigation coils on energetic ion losses in a 15 MA inductive scenario in ITER
Authors: Shinohara K. , Tani K. , Oikawa T. , Putvinski S. , Schaffer M. , Loarte A.
Published: September 2012

The energetic ion loss has been assessed using the F3D-OFMC code for a 15 MA inductive scenario with Q = 10 and the latest information on the first wall geometry, the implementation of ferritic inserts (FI) and the ELM mitigation/control coils. Alpha particles and NB ions generated by the neutral beam injectors with the injection energy of 1 MeV are well confined and the heat load on the first wall is negligibly small and allowable for the magnetic background by the toroidal field coils and FI. However, an increase in the loss of these energetic ions is observed when the magnetic field by the ELM coils is applied. The increase in the loss fraction is larger for NB ions than for alpha particles under the ELM coil field. The origin of the expelled NB ions is dominantly trapped ions generated in the peripheral region due to a high-density plasma of the 15 MA scenario.
Electron fishbones in FTU and Tore Supra tokamaks
Authors: Guimarães-Filho Z.O. , Benkadda S. , Elbeze D. , Botrugno A. , Buratti P. , Calabrò G. , Decker J. , Dubuit N. , Garbet X. , Maget P. , Merle A. , Pucella G. , Sabot R. , Tuccillo A.A. , Zonca F.
Published: September 2012

This work presents a comparative study of the experimental observation of MHD instabilities identified as electron fishbone-like modes that appear in plasmas with lower hybrid current drive in FTU and Tore Supra tokamaks. Initially, the mode-induced electronic temperature oscillations measured by electron cyclotron emission were used to study the evolutions of the frequency and position of these modes. In FTU, where fishbones with and without bursting behaviour are observed, it was found that the evolutions of the mode position and frequency follow opposite trend in the two regimes. In Tore Supra, where abrupt changes between modes with different mode structures are often observed, it was found that the mode position evolves continuously and the wavenumbers follow an inverse cascade starting from an m/n = 4/4 mode and finishing in an 1/1 mode. In a second step, the energy of resonant electrons was estimated from the resonant condition of the precession drift frequency. It was found that in Tore Supra the resonant condition does not change during the frequency jumps. The relevance of the correction due to the pitch angle of the resonant electrons and the possible role of the energetic passing particles in the drive of these modes are discussed from the results obtained in both machines.
Orbit-following fusion alpha wall load simulation for ITER scenario 4 including full orbit effects
Authors: Snicker A. , Sipilä S. , Kurki-Suonio T.
Published: September 2012

A large population of fusion-born alphas present in ITER scenario 4 is a potential risk to the first wall elements. In this study, the ITER scenario 4 alpha wall loads are estimated using the Monte Carlo orbit-following code ASCOT. To ensure realistic wall load profiles, we have adopted three different methods to record the wall collision points: (i) pure guiding centre tracking, (ii) guiding centre tracking away from the wall and gyro-orbit following close to it and (iii) pure gyro-orbit following. It is found that pure gyro-orbit simulation produces an averaged wall load roughly three times as large as the pure guiding centre wall load while the peak power loads differ roughly by a factor of five.
Study of ICRH scenarios for thermal ion heating in JET D–T plasmas
Authors: Kazakov Ye.O. , Kiptily V.G. , Sharapov S.E. , Van Eester D.
Published: September 2012

Various ion cyclotron resonance heating (ICRH) scenarios relevant for the D–T phase of the JET tokamak are studied. Recent ICRH experiments in JET (3He)–D and (3He)–H plasmas confirmed the possibility of electron heating enhancement in the mode conversion (MC) regime due to the constructive interference of the reflected fast waves. Such a heating enhancement in D–T plasma is investigated first for JET-like conditions for both dipole and +π/2 ICRH antenna phasing, and for T concentration varied from 0% to 100%. It is shown that most of the MC scenarios at comparable concentrations of D and T species suffer from a parasitic absorption by fusion-born alpha-particles and NBI-produced fast ions whereas the impact of such fast ions in the minority heating (MH) ICRH schemes is substantially smaller. A possibility of ion heating enhancement due to the interference effect is shown for the MH scenarios. It is found that thermal ion heating becomes dominant in tritium-rich plasmas with T concentration ∼80%. The efficiency of ion heating in such a scenario is compared with the alternative 3He minority ICRH scenario in D : T = 50 : 50 plasmas.
Magnetic configuration effects on TAE-induced losses and a comparison with the orbit-following model in the Large Helical Device
Authors: Ogawa Kunihiro , Isobe Mitsutaka , Toi Kazuo , Spong Donald A. , Osakabe Masaki
Published: September 2012

Fast-ion losses from Large Helical Device (LHD) plasmas due to toroidal Alfvén eigenmodes (TAEs) were measured by a scintillator-based lost fast-ion probe (SLIP) to understand the loss processes. TAE-induced losses measured by the SLIP appeared in energy E ranges of around 50–180 keV with pitch angles χ between 35°–45°, and increased with the increase in TAE amplitudes. Position shifts of the magnetic axis due to a finite plasma pressure led not only to an increase in TAE-induced losses but also to a stronger scaling of fast-ion losses on TAE amplitudes. Characteristics of the observed fast-ion losses were compared with a numerical simulation based on orbit-following models in which the TAE fluctuations are taken into account. The calculation indicated that the number of lost fast ions reaching the SLIP increased with the increase in the TAE amplitude at the TAE gap. Moreover, the calculated dependence of fast-ion loss fluxes on the fluctuation amplitude became stronger in the case of large magnetic axis shifts, compared with the case of smaller shifts, as was observed in the experiments. The simulation results agreed qualitatively with the experimental observations in the LHD.
Observation of fast ion behaviour with a neutron emission profile monitor in MAST
Authors: Cecconello M. , Sangaroon S. , Turnyanskiy M. , Conroy S. , Wodniak I. , Akers R.J. , Ericsson G.
Published: September 2012

Preliminary measurements of neutron emissivity at the Mega Amp Spherical Tokamak (MAST) along collimated lines-of-sight show a clear correlation between the neutron emissivity temporal and spatial evolution and the evolution of different MHD instabilities. In particular, the variations in neutron emissivity during sawtooth oscillations are compared with changes in the classical fast ion slowing-down time, while fast ion losses are observed in bursts during fishbones or as a continuous process during long-lived modes.
Assessment of turbulent beam ion redistribution in tokamaks through velocity space-dependent gyrokinetic analyses
Authors: Albergante M. , Fasoli A. , Graves J.P. , Brunner S. , Cooper W.A.
Published: September 2012

We present the interface between a gyrokinetic code and a guiding centre code dedicated to the study of fast ion turbulent transport. A set of velocity space-dependent (kinetic) transport quantities, representing the link between the two codes, is presented. The code suite is applied to DEMO and TCV plasmas. While negligible alpha particle transport is observed for both tokamaks, important beam ion redistribution is obtained for simulations of DEMO. Results for the TCV tokamak demonstrate that the influence of turbulent fields on fast ion transport strongly depends on the plasma scenario.
Saturation of a toroidal Alfvén eigenmode due to enhanced damping of nonlinear sidebands
Authors: Todo Y. , Berk H.L. , Breizman B.N.
Published: September 2012

This paper examines nonlinear magneto-hydrodynamic effects on the energetic particle driven toroidal Alfvén eigenmode (TAE) for lower dissipation coefficients and with higher numerical resolution than in the previous simulations (Todo et al 2010 Nucl. Fusion
50 084016). The investigation is focused on a TAE mode with toroidal mode number n = 4. It is demonstrated that the mechanism of mode saturation involves generation of zonal (n = 0) and higher-n (n ⩾ 8) sidebands, and that the sidebands effectively increase the mode damping rate via continuum damping. The n = 0 sideband includes the zonal flow peaks at the TAE gap locations. It is also found that the n = 0 poloidal flow represents a balance between the nonlinear driving force from the n = 4 components and the equilibrium plasma response to the n = 0 fluctuations. The spatial profile of the n = 8 sideband peaks at the n = 8 Alfvén continuum, indicating enhanced dissipation due to continuum damping.
Experimental measurements of ion cyclotron range of frequency minority-heated fast-ion distributions on Alcator C-Mod
Authors: Bader A. , Granetz R.S. , Parker R.R. , Bonoli P.T. , Hutchinson I.H. , Sears J. , Wukitch S.J.
Published: September 2012

Ion cyclotron resonance heating is the primary auxiliary heating on the Alcator C-Mod tokamak and is commonly used on other devices, and is planned for use on ITER. The RF-power density on C-Mod is above 5 MW m−3 providing for a unique opportunity to study wave–particle effects in the high RF power per particle regime. Minority heating produces a highly energetic tail in the minority distribution function which is measured using a compact neutral particle analyser. In this paper, we present the measurements of the fast-ion spectrum between 200 and 2 MeV, compiled over an entire experimental campaign. We also estimate the effective tail temperatures for the fast-ion distribution. We find that the fast-ion distribution is less energetic and less dense with increasing electron density; is more energetic with increasing plasma current; and is more dense but has no measurable change in energy with increasing RF power. Some possible explanations for these findings are discussed.
Adiabatic description of long range frequency sweeping
Authors: Nyqvist R.M. , Lilley M.K. , Breizman B.N.
Published: September 2012

A theoretical framework is developed to describe long range frequency sweeping events in the 1D electrostatic bump-on-tail model with fast particle sources and collisions. The model includes three collision operators (Krook, drag (dynamical friction) and velocity space diffusion), and allows for a general shape of the fast particle distribution function. The behaviour of phase space holes and clumps is analysed in the absence of diffusion, and the effect of particle trapping due to separatrix expansion is discussed. With a fast particle distribution function whose slope decays above the resonant phase velocity, hooked frequency sweeping is found for holes in the presence of drag collisions alone.
Gamma-ray spectroscopy measurements of confined fast ions on ASDEX Upgrade
Authors: Nocente M. , Garcia-Munoz M. , Gorini G. , Tardocchi M. , Weller A. , Akaslompolo S. , Bilato R. , Bobkov V. , Cazzaniga C. , Geiger B. , Grosso G. , Herrmann A. , Kiptily V. , Maraschek M. , McDermott R. , Noterdaeme J.M. , Podoba Y. , Tardini G.
Published: September 2012

Evidence of γ-ray emission from fast ions in ASDEX Upgrade (AUG) is presented. The plasma scenarios developed for the experiments involve deuteron or proton acceleration. The observed γ-ray emission level induced by energetic protons is used to determine the effective tail temperature of the proton distribution function that can be compared with neutral particle analyser measurements. More generally the measured emission rate is used to assess the confinement of protons with energies <400 keV in discharges affected by toroidal Alfvén eigenmode instabilities. The derived information on confined ions is combined with observations made with the AUG fast ion loss detector.
Alfvén eigenmode stability and fast ion loss in DIII-D and ITER reversed magnetic shear plasmas
Authors: Van Zeeland M.A. , Gorelenkov N.N. , Heidbrink W.W. , Kramer G.J. , Spong D.A. , Austin M.E. , Fisher R.K. , García Muñoz M. , Gorelenkova M. , Luhmann N. , Murakami M. , Nazikian R. , Pace D.C. , Park J.M. , Tobias B.J. , White R.B.
Published: September 2012

Neutral beam injection into reversed-magnetic shear DIII-D plasmas produces a variety of Alfvénic activity including toroidicity-induced Alfvén eigenmodes (TAEs) and reversed shear Alfvén eigenmodes (RSAEs). With measured equilibrium profiles as inputs, the ideal MHD code NOVA is used to calculate eigenmodes of these plasmas. The postprocessor code NOVA-K is then used to perturbatively calculate the actual stability of the modes, including finite orbit width and finite Larmor radius effects, and reasonable agreement with the spectrum of observed modes is found. Using experimentally measured mode amplitudes, fast ion orbit following simulations have been carried out in the presence of the NOVA calculated eigenmodes and are found to reproduce the dominant energy, pitch and temporal evolution of the losses measured using a large bandwidth scintillator diagnostic. The same analysis techniques applied to a DT 8 MA ITER steady-state plasma scenario with reversed-magnetic shear and both beam ion and alpha populations show Alfvén eigenmode instability. Both RSAEs and TAEs are found to be unstable with maximum growth rates occurring for toroidal mode number n = 6 and the majority of the drive coming from fast ions injected by the 1 MeV negative ion beams. AE instability due to beam ion drive is confirmed by the non-perturbative code TAEFL. Initial fast ion orbit following simulations using the unstable modes with a range of amplitudes (δ
B/B = 10−5–10−3) have been carried out and show negligible fast ion loss. The lack of fast ion loss is a result of loss boundaries being limited to large radii and significantly removed from the actual modes themselves.
Controlling and exploiting phases in multi-spin systems using electron spin resonance and nuclear magnetic resonance
Authors: Simmons Stephanie , Wu Hua , Morton John J. L.
Published: September 2012

The phase of a superposition state is a quintessential characteristic that differentiates a quantum bit of information from a classical one. This phase can be manipulated dynamically or geometrically, and can be exploited to sensitively estimate Hamiltonian parameters, perform faithful quantum state tomography and encode quantum information into multiple modes of an ensemble. Here we discuss the methods that we have employed to manipulate and exploit the phase information of single-, two-, multi-qubit and multi-mode spin systems.
Robust dynamical decoupling
Authors: Souza Alexandre M. , Álvarez Gonzalo A. , Suter Dieter
Published: September 2012

Quantum computers, which process information encoded in quantum mechanical systems, hold the potential to solve some of the hardest computational problems. A substantial obstacle for the further development of quantum computers is the fact that the lifetime of quantum information is usually too short to allow practical computation. A promising method for increasing the lifetime, known as dynamical decoupling (DD), consists of applying a periodic series of inversion pulses to the quantum bits. In the present review, we give an overview of this technique and compare different pulse sequences proposed earlier. We show that pulse imperfections, which are always present in experimental implementations, limit the performance of DD. The loss of coherence due to the accumulation of pulse errors can even exceed the perturbation from the environment. This effect can be largely eliminated by a judicious design of pulses and sequences. The corresponding sequences are largely immune to pulse imperfections and provide an increase of the coherence time of the system by several orders of magnitude.
On the quantumness of correlations in nuclear magnetic resonance
Authors: Soares-Pinto D. O. , Auccaise R. , Maziero J. , Gavini-Viana A. , Serra R. M. , Céleri L. C.
Published: September 2012

Nuclear magnetic resonance (NMR) was successfully employed to test several protocols and ideas in quantum information science. In most of these implementations, the existence of entanglement was ruled out. This fact introduced concerns and questions about the quantum nature of such bench tests. In this paper, we address some issues related to the non-classical aspects of NMR systems. We discuss some experiments where the quantum aspects of this system are supported by quantum correlations of separable states. Such quantumness, beyond the entanglement–separability paradigm, is revealed via a departure between the quantum and the classical versions of information theory. In this scenario, the concept of quantum discord seems to play an important role. We also present an experimental implementation of an analogue of the single-photon Mach–Zehnder interferometer employing two nuclear spins to encode the interferometric paths. This experiment illustrates how non-classical correlations of separable states may be used to simulate quantum dynamics. The results obtained are completely equivalent to the optical scenario, where entanglement (between two field modes) may be present.
Quantum information processing by nuclear magnetic resonance on quadrupolar nuclei
Authors: Teles João , DeAzevedo Eduardo R. , Freitas Jair C. C. , Sarthour Roberto S. , Oliveira Ivan S. , Bonagamba Tito J.
Published: September 2012

Nuclear magnetic resonance is viewed as an important technique for the implementation of many quantum information algorithms and protocols. Although the most straightforward approach is to use the two-level system composed of spin

nuclei as qubits, quadrupolar nuclei, which possess a spin greater than

, are being used as an alternative. In this study, we show some unique features of quadrupolar systems for quantum information processing, with an emphasis on the ability to execute efficient quantum state tomography (QST) using only global rotations of the spin system, whose performance is shown in detail. By preparing suitable states and implementing logical operations by numerically optimized pulses together with the QST method, we follow the stepwise execution of Grover's algorithm. We also review some work in the literature concerning the relaxation of pseudo-pure states in spin

systems as well as its modelling in both the Redfield and Kraus formalisms. These data are used to discuss differences in the behaviour of the quantum correlations observed for two-qubit systems implemented by spin

and quadrupolar spin

systems, also presented in the literature. The possibilities and advantages of using nuclear quadrupole resonance experiments for quantum information processing are also discussed.
Solid-state multiple quantum NMR in quantum information processing: exactly solvable models
Authors: Fel'dman E. B. , Pyrkov A. N. , Zenchuk A. I.
Published: September 2012

Multiple quantum (MQ) NMR is an effective tool for the generation of a large cluster of correlated particles, which, in turn, represent a basis for quantum information processing devices. Studying the available exactly solvable models clarifies many aspects of the quantum information. In this study, we consider two exactly solvable models in the MQ NMR experiment: (i) the isolated system of two spin-

particles (dimers) and (ii) the large system of equivalent spin-

particles in a nanopore. The former model is used to describe the quantum correlations and their relations with the MQ NMR coherences, whereas the latter helps one to model the creation and decay of large clusters of correlated particles.
Nuclear magnetic resonance quantum information processing
Authors: Serra R. M. , Oliveira I. S.
Published: September 2012

For the past decade, nuclear magnetic resonance (NMR) has been established as a main experimental technique for testing quantum protocols in small systems. This Theme Issue presents recent advances and major challenges of NMR quantum information possessing (QIP), including contributions by researchers from 10 different countries. In this introduction, after a short comment on NMR-QIP basics, we briefly anticipate the contents of this issue.
Helical self-assembly of 2-(1,4,7,10-tetraazacyclododecan-1-yl)cyclohexan-1-ol (cycyclen)
Authors: Sousa Alvaro S. de , Sannasy Denzel , Fernandes Manuel A. , Marques Helder M.
Published: September 2012

The title macrocyclic amino alcohol compound, C14H30N4O, is investigated as a solid-state synthon for the design of a self-assembled tubular structure. It crystallizes in a helical column constructed by stereospecific O—H...N and N—H...N interactions. The hydrogen-bonding interactions, dependent upon macrocyclic ring helicity and molecular conformation, linkR,RandS,Senantiomers in a head-to-tail fashion, forming a continuous hydrophilic inner core.
An integrated approach for service quality and effectiveness improvement with a case study in the recycling pavilion service process of Isfahan municipality
Authors: Shahin Arash , Attafar Ali , Samea Monireh
Published: September 2012

Purpose

The purpose of this research is to propose a systematic and integrative approach for evaluating, assessing, analysing, and improving service quality and effectiveness.

Design/methodology/approach

A new approach is proposed, in which SERVQUAL and overall administration effectiveness (OAE) are integrated. The recycling pavilion service process of Isfahan municipality is examined. By distributing 120 questionnaires containing the 22 questions of the SERVQUAL instrument developed by Parasuraman et al. in four pavilions of four different regions of the city of Isfahan, the services quality gap was measured and the OAE indicator performance was calculated. In OAE, the quality ratio was measured based on the quality gap, and performance and availability ratios were measured based on the characteristics of the recycling pavilion services.

Findings

The empirical findings imply that the application of the proposed approach has resulted in a reduction of 0.59 of the gap average and a 36 per cent improvement of the OAE indicator.

Research limitations/implications

While a general approach is proposed for service application, the results of the case study may not be generalisable.

Originality/value

The proposed approach of this study presents a method for simultaneous analysis of service quality and effectiveness.
Human leukocyte antigens (HLA) associated drug hypersensitivity: consequences of drug binding to HLA
Authors: Yun J. , Adam J. , Yerly D. , Pichler W. J.
Published: September 2012

Recent publications have shown that certain human leukocyte antigen (HLA) alleles are strongly associated with hypersensitivity to particular drugs. As HLA molecules are a critical element in T‐cell stimulation, it is no surprise that particular HLA alleles have a direct functional role in the pathogenesis of drug hypersensitivity. In this context, a direct interaction of the relevant drug with HLA molecules as described by the p‐i concept appears to be more relevant than presentation of hapten‐modified peptides. In some HLA‐associated drug hypersensitivity reactions, the presence of a risk allele is a necessary but incomplete factor for disease development. In carbamazepine and HLA‐B*15:02, certain T‐cell receptor (TCR) repertoires are required for immune activation. This additional requirement may be one of the ‘missing links’ in explaining why most individuals carrying this allele can tolerate the drug. In contrast, abacavir generates polyclonal T‐cell response by interacting specifically with HLA‐B*57:01 molecules. T cell stimulation may be due to presentation of abacavir or of altered peptides. While the presence of HLA‐B*58:01 allele substantially increases the risk of allopurinol hypersensitivity, it is not an absolute requirement, suggesting that other factors also play an important role. In summary, drug hypersensitivity is the end result of a drug interaction with certain HLA molecules and TCRs, the sum of which determines whether the ensuing immune response is going to be harmful or not.
Synthesis, Evaluation and Molecular Docking of Thiazolopyrimidine Derivatives as Dipeptidyl Peptidase IV Inhibitors
Authors: Sharma Mani , Gupta Monica , Singh Divya , Kumar Manoj , Kaur Punit
Published: September 2012

A series of thiazolopyrimidine derivatives was designed, synthesized and screened for in‐vitro inhibition of Dipeptidyl Peptidase IV (DPP IV). The SAR study indicated the influence of substituted chemical modifications on thiazolopyrimidine scaffold. Compound 9 (IC50 = 0.489 μm) and 10 (IC50 = 0.329 μm) having heterocyclic‐substituted piperazine with acetamide linker resulted as most potent DPP IV inhibitors among all the compounds screened. Single dose (10 mg/kg) of both the compounds 9 and 10 significantly reduced glucose excursion during oral glucose tolerance test in streptozotocin induced diabetic rat model. Molecular docking studies illustrated the probable binding mode and interactions of thiazolopyrimidine nucleus and its derivatives at binding site of receptor. The binding site for DPP IV is composed of active site region (catalytic triad of Ser630, Asp708 and His740) including S1 and S2 sub‐pocket. The aryl moiety of compounds 9, 10 and 11 were observed to occupy S2 binding pocket and interacted with aromatic ring of Tyr662 and Tyr666 acquired through π‐π interaction. Thus, it is indicated that occupancy of the highly hydrophobic S2 pocket is more important for DPP IV inhibitory activity. The present study on substituted thiazolopyrimidine derivatives shows good to moderate inhibitory potential of DPP IV enzyme.
Biological Effects of AL622, a Molecule Rationally Designed to Release an EGFR and a c‐Src Kinase Inhibitor
Authors: Larroque‐Lombard Anne‐Laure , Ning Na , Rao Suman , Lauwagie Sylvia , Halaoui Ruba , Coudray Laëtitia , Huang Ying , Jean‐Claude Bertrand J.
Published: September 2012

In breast cancer cells expressing c‐Src and EGFR, a control of one of the two oncogenes over proliferation and invasion is observed, whereas in others, the synergistic interaction between them is required for tumor progression. With the purpose of developing molecules with the highest probability for blocking the adverse effects of these two oncogenes, we designed AL622, which contains a quinazoline head targeted to EGFR and a linker that bridges it to the PP2‐like structure for targeting c‐Src. In case the entire molecule would not be capable of blocking c‐Src, we designed AL622 to hydrolyze to an intact c‐Src‐targeting PP2 molecule. After confirming its binary c‐Src‐EGFR targeting potency of AL622, we analyzed its potency in isogenic NIH3T3 cells transfected with EGFR and HER2 and human breast cancer cells known to be dominated by c‐Src function. The results showed that in EGFR/HER‐2‐driven cells, it was more potent than PP2 and its activity was in the same range as the latter in more c‐Src‐driven cells. Its ability to block motility and invasion was comparable with that of PP2 and corresponding combinations, indicating that AL622 could be a better antitumor agent in cells where c‐Src and/or EGFR play a role.
Aberrant expression of myogenin in inclusion body myositis: Immunohistochemical studies of transcription factors regulating myogenesis in inflammatory myopathies
Authors: Kubota Akatsuki , Shimizu Jun , Iwata Atsushi , Tsuji Shoji
Published: September 2012

Objectives

We aimed to assess the immunohistochemistry of transcription factors that regulate myogenesis (Pax7, MyoD1, and myogenin) in inflammatory myopathies in relation to histopathological severity, and to determine whether there are some differences in immunohistochemical findings between idiopathic inflammatory myopathy (IIM) and inclusion body myositis (IBM).

Methods

We assessed 49 biopsied muscle specimens: 32 from IIM patients, 13 from IBM patients, and four from control subjects. Each specimen was classified into one of four grades of histopathological severity. The numbers of regenerative myofibers and nuclei positive for Pax7, MyoD1, or myogenin were counted.

Results

Pax7, MyoD1, and myogenin showed specific nuclear staining patterns. Moreover, myogenin‐positive plaque‐shaped signals were observed within degenerative myofibers in IBM patients, and double immunofluorescence staining showed aggregation of myogenin within Aβ42‐positive inclusion bodies. The number of nuclei positive for Pax7, MyoD1, or myogenin correlated with histopathological severity. In the specimens with moderate to severe histopathological changes, specimens from IBM patients showed less regenerative myofibers (IIM, mean ± SD, 45.0 ± 22.9 per 100 myofibers; IBM, 17.7 ± 7.8 per 100 myofibers; P = 0.0007) and less myogenin‐positive nuclei (IIM, mean ± SD, 7.28 ± 3.70 per 100 myofibers; IBM, 4.70 ± 1.40 per 100 myofibers; P = 0.0352) than those from IIM patients.

Conclusion

Aberrant localization of myogenin within degenerative myofibers in IBM may be related to the reduced numbers of regenerative fibers and myogenin‐positive nuclei in IBM. Further study is necessary to determine whether the expression of myogenin might be impaired in IBM.
Implants of 6 mm vs. 11 mm lengths in the posterior maxilla and mandible: a 1‐year multicenter randomized controlled trial
Authors: Guljé Felix , Abrahamsson Ingemar , Chen Stephen , Stanford Clark , Zadeh Homayoun , Palmer Richard
Published: September 2012

Background and aim

In cases with limited bone height, short implants could be a good alternative to augmentation procedures. The aim of this randomized controlled trial was to compare the clinical performance of implants of 6 mm or 11 mm in length in the posterior region.

Materials and methods

In this multicenter trial (six study sites), 95 subjects were included. Subjects were randomly allocated to receiving implants with lengths of either 6 or 11 mm both with a diameter of 4 mm (OsseoSpeed™ 4.0 S; Astra Tech AB; Mölndal, Sweden). In all cases, there had to be sufficient bone height to allow placement of an implant of at least 11 mm in length. Two or three implants were placed per subject using one‐stage surgery with a 42–48 days' healing period before loading. They were restored with a screw‐retained splinted fixed prosthesis. Clinical and radiographic examinations were performed preoperatively, postsurgery, at loading, and 6 and 12 months after prosthesis placement.

Results

A total of 208 implants were inserted in 49 subjects receiving 6‐mm implants (test) and in 46 subjects receiving 11 mm implants (control). Two 6‐mm implants failed before loading and one 6 and 11 mm implants failed before 1‐year evaluation. From loading to the 12 months' follow‐up, a mean marginal bone gain of 0.06 mm in the 6 mm group and 0.02 mm in the 11 mm group was found (P = 0.478). Soft tissue behavior was equal in both groups (Bleeding and plaque [P = 1.0] probing depth [P = 0.91]).

Conclusion

One‐year data indicate that treatment with the 6 mm implants is as reliable as treatment with the 11 mm implants. This provides a good treatment option in situations with limited bone height in the premolar and molar regions. Whether or not short implants provide a predictable treatment alternative to bone augmentation procedures remains to be investigated in the future randomized controlled clinical trials.
Chronic renal outcome after living donor liver transplantation
Authors: Nishi Hiroshi , Shibagaki Yugo , Kido Ryo , Tamura Sumihito , Nangaku Masaomi , Sugawara Yasuhiko , Fujita Toshiro
Published: September 2012

Chronic kidney disease (CKD) is one of the common complications after deceased donor liver transplantation. Although the worldwide pressing shortage in deceased donors has directed attention to living donor liver transplantation (LDLT), LDLT cohort data focusing on chronic renal dysfunction is limited. A total of 280 adult LDLT recipients (median 49 yr, 156 men) at the University of Tokyo hospital between 1996 and 2006 were reviewed. A total of 224 pre‐transplant liver failure patients (80.0%) showed an estimated glomerular filtration rate (eGFR) of more than 60 mL/min/1.73 m2. However, during follow‐up at a mean of 1222 d after transplantation, eGFR declined to 60 mL/min/1.73 m2 and 30 mL/min/1.73 m2 in 150 (53.2%) and 21 (7.5%), respectively, and four patients (1.4%) required maintenance renal replacement therapy. Multivariate Cox proportional hazard model regression analysis revealed that recipient age (HR, 3.42 per 10‐yr increment; p < 0.001) and pre‐transplant eGFR (HR, 0.85 per 10‐mL/min/1.73 m2 increment; p = 0.04) were associated independently with a post‐transplant decrease in eGFR to less than 30 mL/min/1.73 m2. We conclude that higher age and lower pre‐transplant eGFR of an LDLT recipient indicate a high likelihood of subsequent development of advanced CKD. Preventive or therapeutic intervention should be optimized for these high‐risk patients.
Scratching as a Window into the Emotional Responses of Wild Tufted Capuchin Monkeys
Authors: Polizzi di Sorrentino Eugenia , Schino Gabriele , Tiddi Barbara , Aureli Filippo
Published: September 2012

Emotional responses to social interactions and the associated behavioural measures (e.g., self‐directed behaviours,SDBs) have been little studied in New World monkeys, especially in wild settings. In this study, we investigated the factors affecting anxiety in a wild group of tufted capuchin monkeys (Cebus apella nigritus) using self‐scratching (hereafter scratching) as its measure. Scratching was more strongly affected by the social context than by individual characteristics. Indeed, inter‐individual variability was not explained by the age, sex and dominance rank of the monkeys. The monkeys scratched themselves more often when being distant from other group members than when in close proximity with them, suggesting that even short‐distance separation from group members may be an important factor affecting capuchins emotional response. The risk of receiving aggression seemed also to elicit anxiety, as scratching was higher when in proximity to more dominant individuals and females, which were the categories of group members that were more aggressive. By contrast, scratching was lower when in proximity to more secure partners, like kin. Finally, scratching rates following the receipt of aggression were higher than at baseline, indicating a post‐conflict increase in anxiety. Overall, our results contribute to the understanding of the factors affecting emotional responses in capuchin monkeys, confirming and expanding previous findings in other animal species.
Individual and Sex Differences in Habituation and Neophobia in House Sparrows (Passer domesticus)
Authors: Ensminger Amanda L. , Westneat David F.
Published: September 2012

Heterogeneity in the environment favours foragers that are flexible (phenotypically plastic). However, consistent individual differences in behaviour (personality), such as in risk‐taking, might affect an individual's ability to find food, avoid predators and adjust to new conditions. It is now well known that personalities exist in many taxa, but much less is known about individual variation in plasticity. We measured the tendency to begin foraging across different levels of risk in house sparrows (Passer domesticus), using a behavioural reaction norm framework to simultaneously assess personality and plasticity. We asked whether individuals were consistently different across risk levels, and whether they differed in habituation and neophobia, both of which were treated as cases of plasticity. We found that males habituated more than females by beginning to feed sooner after repeated instances of a human disturbance in the presence of an initially unfamiliar object. Individuals of both sexes also exhibited consistent differences across trials, but did not differ in the rate of habituation beyond the difference between the sexes. When a novel object was placed in the foraging area, both sexes exhibited similar degrees of neophobia by delaying feeding. The magnitude of this change varied among birds, indicating individual differences in neophobia. Our results indicate that both personality and individual variation in plasticity exist but should be treated as independent phenomena. The presence of variation in plasticity implies that the raw material necessary for selection on neophobia exists, and that if heritable, plasticity in risk‐taking across contexts could evolve.
Biosecurity interceptions of an invasive lizard: origin of stowaways and human‐assisted spread within New Zealand
Authors: Chapple David G. , Whitaker Anthony H. , Chapple Stephanie N. J. , Miller Kimberly A. , Thompson Michael B.
Published: September 2012

Globalization, and the resultant movement of animals beyond their native range, creates challenges for biosecurity agencies. Limited records of unintentional introductions inhibit our understanding of the trade pathways, transport vectors and mechanisms through which hitchhiker organisms are spread as stowaways. Here, we adopt a phylogeographic approach to determine the source and human‐mediated dispersal pathways of New Zealand's only invasive lizard, the delicate skink (Lampropholis delicata), intercepted by biosecurity agencies in New Zealand. Biosecurity agencies correctly predicted the source region of 77% of stowaways, which were usually solitary adults, arriving via air or sea pathways during the cooler months, evading initial border checks and alive when detected. New arrivals from Australia comprised 16% of detections originating from the region between Brisbane and Sydney. Our analyses indicate human‐mediated dispersal has driven the post‐border spread of L. delicata within New Zealand. Propagule pressure was substantially greater for L. delicata compared with the noninvasive, congeneric Lampropholis guichenoti. Our results highlight the transport pathways, spread mechanisms, and stowaway characteristics of Lampropholis lizards entering New Zealand, which could enhance current biosecurity protocols and prevent the establishment of additional lizard species.
Unintended consequences and trade‐offs of fish passage
Authors: McLaughlin Robert L , Smyth Eric R B , Castro‐Santos Theodore , Jones Michael L , Koops Marten A , Pratt Thomas C , Vélez‐Espino Luis‐Antonio
Published: September 2012

We synthesized evidence for unintended consequences and trade‐offs associated with the passage of fishes. Provisioning of fish passageways at dams and dam removals are being carried out increasingly as resource managers seek ways to reduce fragmentation of migratory fish populations and restore biodiversity and nature‐like ecosystem services in tributaries altered by dams. The benefits of provisioning upstream passage are highlighted widely. Possible unwanted consequences and trade‐offs of upstream passage are coming to light, but remain poorly examined and underappreciated. Unintended consequences arise when passage of native and desirable introduced fishes is delayed, undone (fallback), results in patterns of movement and habitat use that reduce Darwinian fitness (e.g. ecological traps), or is highly selective taxonomically and numerically. Trade‐offs arise when passage decisions intended to benefit native species interfere with management decisions intended to control the unwanted spread of non‐native fishes and aquatic invertebrates, or genes, diseases and contaminants carried by hatchery and wild fishes. These consequences and trade‐offs will vary in importance from system to system and can result in large economic and environmental costs. For some river systems, decisions about how to manage fish passage involve substantial risks and could benefit from use of a formal, structured process that allows transparent, objective and, where possible, quantitative evaluation of these risks. Such a process can also facilitate the design of an adaptive framework that provides valuable insights into future decisions.
Tumour suppressor p16INK4a – anoikis‐favouring decrease in N/O‐glycan/cell surface sialylation by down‐regulation of enzymes in sialic acid biosynthesis in tandem in a pancreatic carcinoma model
Authors: Amano Maho , Eriksson Hanna , Manning Joachim C. , Detjen Katharina M. , André Sabine , Nishimura Shin‐Ichiro , Lehtiö Janne , Gabius Hans‐Joachim
Published: September 2012

Tumour suppressor p16INK4a is known to exert cell‐cycle control via cyclin‐dependent kinases. An emerging aspect of its functionality is the orchestrated modulation of N/O‐glycosylation and galectin expression to induce anoikis in human Capan‐1 pancreatic carcinoma cells. Using chemoselective N/O‐glycan enrichment technology (glycoblotting) and product characterization, we first verified a substantial decrease in sialylation. Tests combining genetic (i.e. transfection with α2,6‐sialyltransferase‐specific cDNA) or metabolic (i.e. medium supplementation with N‐acetylmannosamine to track down a bottleneck in sialic acid biosynthesis) engineering with cytofluorometric analysis of lectin binding indicated a role of limited substrate availability, especially for α2,6‐sialylation, which switches off reactivity for anoikis‐triggering homodimeric galectin‐1. Quantitative MS analysis of protein level changes confirmed an enhanced galectin‐1 presence along with an influence on glycosyltransferases (β1,4‐galactosyltransferase‐IV, α2,3‐sialyltransferase‐I) and detected p16INK4a‐dependent down‐regulation of two enzymes in the biosynthesis pathway for sialic acid [i.e. the bifunctional UDP‐N‐acetylglucosamine 2‐epimerase/N‐acetylmannosamine kinase (GNE) and N‐acetylneuraminic acid 9‐phosphate synthase] (P < 0.001). By contrast, quantitative assessment for the presence of nuclear CMP‐N‐acetylneuraminic acid synthase (which is responsible for providing the donor for enzymatic sialylation that also acts as feedback inhibitor of the epimerase activity of GNE) revealed a trend for an increase. Partial restoration of sialylation in GNE‐transfected cells supports the implied role of sialic acid availability for the glycophenotype. Fittingly, the extent of anoikis was reduced in double‐transfected (p16INK4a/GNE) cells. Thus, a second means of modulating cell reactivity to the growth effector galectin‐1 is established in addition to the common route of altering α2,6‐sialyltransferase expression: regulating enzymes of the pathway for sialic acid biosynthesis.
Satellite data identify decadal trends in the quality of Pygoscelis penguin chick‐rearing habitat
Authors: Cimino Megan A. , Fraser William R. , Irwin Andrew J. , Oliver Matthew J.
Published: September 2012

Pygoscelis penguins are experiencing general population declines in their northernmost range whereas there are reported increases in their southernmost range. These changes are coincident with decadal‐scale trends in remote sensed observations of sea ice concentrations (SIC) and sea surface temperatures (SST) during the chick‐rearing season (austral summer). Using SIC, SST, and bathymetry, we identified separate chick‐rearing niche spaces for the three Pygoscelis penguin species and used a maximum entropy approach (MaxEnt) to spatially and temporally model suitable chick‐rearing habitats in the Southern Ocean. For all Pygoscelis penguin species, the MaxEnt models predict significant changes in the locations of suitable chick‐rearing habitats over the period of 1982–2010. In general, chick‐rearing habitat suitability at specific colony locations agreed with the corresponding increases or decreases in documented population trends over the same time period. These changes were the most pronounced along the West Antarctic Peninsula where there has been a rapid warming event during at least the last 50 years.