bluuebunny/crossref_metadata_2025 huggingface dataset:
Trigger Simulations for GRB Detection with the Swift Burst Alert Telescope
Authors: Lien Amy , Sakamoto Takanori , Gehrels Neil , Palmer David , Graziani Carlo
Published: September 2012

Understanding the intrinsic cosmic long gamma-ray burst (GRB) rate is essential in many aspects of astrophysics and cosmology, such as revealing the connection between GRBs, supernovae (SNe), and stellar evolution. Swift, a multi-wavelength space telescope, is quickly expanding the GRB category by observing hundreds of GRBs and their redshifts. However, it remains difficult to determine the intrinsic GRB rate due to the complex trigger algorithm adopted by Swift. Current studies of the GRB rate usually approximate the Swift trigger algorithm by a single detection threshold. Nevertheless, unlike the previously flown GRB instruments, Swift has over 500 trigger criteria based on count rates and additional thresholds for localization. To investigate possible systematic biases and further explore the intrinsic GRB rate as a function of redshift and the GRB luminosity function, we adopt a Monte Carlo approach by simulating all trigger criteria used by Swift. A precise estimation of the intrinsic GRB rate is important to reveal the GRB origins and their relation to the black-hole forming SNe. Additionally, the GRB rate at high redshifts provides a strong probe of the star formation history in the early universe, which is hard to measure directly through other methods.
GRB host galaxies: theoretical investigation
Authors: Mao Jirong
Published: September 2012

Long gamma-ray bursts (GRBs) can be linked to the massive stars and their host galaxies are assumed to be the star-forming galaxies within small dark matter halos. We apply a galaxy evolution model, in which the star formation process inside the virialized dark matter halo at a given redshift is achieved. The star formation rates (SFRs) in the GRB host galaxies at different redshifts can be derived from our model. The related stellar masses, luminosities, and metalicities of these GRB host galaxies are estimated. We also calculate the X-ray and optical absorption of GRB afterglow emission. At higher redshift, the SFR of host galaxy is stronger, and the absorption in the X-ray and optical bands of GRB afterglow is stronger, when the dust and metal components are locally released, surrounding the GRB environment. These model predictions are compared with some observational data as well.
Carnegie Supernova Project: Spectroscopic Observations of Core Collapse Supernovae
Authors: Morrell Nidia I.
Published: September 2012

The Carnegie Supernova Project (CSP) has performed, during the period 2004-2009, the optical and NIR follow up of 253 supernovae (SNe) of all types. Among those, 124 were core collapse events, comprising 93 SNe of type II and 31 of types Ib/Ic/IIb. Our follow up consisted of photometric observations suitable to build detailed light curves and a considerable amount of optical spectroscopy.

The bulk of our observations is carried out at Las Campanas Observatory, while access to other facilities is also provided thanks to our strong collaboration with the Millennium Center for Supernova Studies (MCSS).

Our spectroscopic observations were primarily aimed at typing possible new SNe, and follow-up the evolution of CSP targets. One of the goals of the follow-up of type II SNe is the application of independent distance indicators such as the Standard Candle (SCM) and the Expanding Photosphere (EPM) methods. Moreover, through the study of the spectroscopic evolution of these objects, from as early as possible after explosion to the nebular phases, we hope to contribute to their further understanding. Specific analysis of particular objects is underway by members of the CSP and an extended collaboration.
Numerical code of the neutrino-transfer in three dimensions for core-collapse supernovae
Authors: Sumiyoshi Kohsuke , Yamada Shoichi
Published: September 2012

We develop a new numerical code of the multi-energy and multi-angle neutrino-radiation transfer in three dimensions (3D) for core-collapse supernovae. Our 3D code to solve the Boltzmann equations is based on the discretized-ordinate (SN) method with a fully implicit differencing for time advance. A basic set of neutrino reactions is implemented in the collision terms together with a realistic equation of state. By following the time evolution of neutrino distributions in six dimensions (3 spatial and 3 momentum-space) by the 3D Boltzmann solver, we study the 3D feature of neutrino transfer for given background models of supernova cores in order to understand the explosion mechanism through neutrino heating in multi dimensions.
Magnetic Energy Release in Relativistic Plasma
Authors: Takahashi Hiroyuki R. , Ohsuga Ken
Published: September 2012

The efficiency of the energy conversion rate in the relativistic magnetic reconnection is investigated by means of Relativistic Resistive Magnetohydrodynamic (R2MHD) simulations. We confirmed that the simple Sweet-Parker type magnetic reconnection is a slow process for the energy conversion as theoretically predicted by Lyubarsky (2005). After the Sweet-Parker regime, we found a growth of the secondary tearing instability in the elongated current sheet. Then the energy conversion rate and the outflow velocity of reconnection jet increase rapidly. Such a rapid energy conversion would explain the time variations observed in many astrophysical flaring events.

To construct a more realistic model of relativistic reconnection, we extend our R2MHD code to R3MHD code by including the radiation effects (Relativistic Resistive Radiation Magnetohydrodynamics R3MHD). The radiation field is described by the 0th and 1st moments of the radiation intensity (Farris et al. 2008, Shibata et al. 2011). The code has already passed some one-dimensional and multi-dimensional numerical problems. We demonstrate the first results of magnetic reconnection in the radiation dominated current sheet.
Shock Breakout of Type II Plateau Supernova
Authors: Tominaga Nozomu , Morokuma Tomoki , Blinnikov Sergei I.
Published: September 2012

Type II-plateau supernovae (SNe II-P) are fainter than Type Ia SNe and thus have so far been observed only at z < 1. We introduce shock breakout and propose a distant SN II-P survey at z > 1 with shock breakout. The first observation of shock breakout from the rising phase is reported in 2008. We first construct a theoretical model reproducing the UV-optical light curves (LCs) of the first example and demonstrate that the peak apparent g-band magnitude of the shock breakout would be mg ~ 26.4 mag if an identical SN occurs at a redshift z = 1, which can be reached by 8m-class telescopes. Furthermore, we present LCs of shock breakout of SN explosions with various main-sequence masses, metallicities, and explosion energies and derive the observable SN rate and reachable redshift as functions of filter and limiting magnitude by taking into account an initial mass function, cosmic star formation history, intergalactic absorption, and host galaxy extinction. The g-band observable SN rate with limiting magnitude 27.5 mag is 3.3 SNe deg−2 day−1 and half of them are located at z > 1.2.
Fate of most massive stars
Authors: Yusof Norhasliza , Hirschi Raphael , Kassim Hasan Abu
Published: September 2012

The first generations of stars are thought to have been more massive than Pop I stars and therefore some of these are thought to have produced pair creation supernovae (PCSNe) at the end of their life. However, the chemical signature of PCSNe is not observed in extremely metal poor stars (e.g. Umeda and Nomoto 2002) and it raises the following questions: Were stars born less (or more massive) than the mass range expected to lead to the PCSNe? Or was mass loss too strong during the evolution of these stars and prevented them from retaining enough mass to produce PCSNe? The discovery of very massive stars (VMS, M > 100 M⊙) in the Milky Way and LMC (Crowther et al. 2010) shows that VMS can form and exist. The observations of PCSN candidates (2006gy & 2007bi) also seems to indicate that such SNe may occur. Mass loss plays a crucial role in the life of VMS since the star will only die as a PCSN if the star retains a high mass throughout its life. In this paper, we shall describe the dependence of VMS evolution on metallicity and present stellar evolution models at various metallicities, including the effects of mass loss and rotation. Based on our models, we will give our predictions concerning the fate of these VMS, either a PCSN or SNIc (possibly GRBs in some cases) as a function of metallicity.
East Pacific ocean eddies and their relationship to subseasonal variability in Central American wind jets
Authors: Chang Chueh‐Hsin , Xie Shang‐Ping , Schneider Niklas , Qiu Bo , Small Justin , Zhuang Wei , Taguchi Bunmei , Sasaki Hideharu , Lin Xiaopei
Published: September 2012

Subseasonal variability in sea surface height (SSH) over the East Pacific warm pool off Central America is investigated using satellite observations and an eddy‐resolving ocean general circulation model. SSH variability is organized into two southwest‐tilted bands on the northwest flank of the Tehuantepec and Papagayo wind jets and collocated with the thermocline troughs. Eddy‐like features of wavelength ∼600 km propagate southwestward along the high‐variance bands at a speed of 9–13 cm/s. Wind fluctuations are important for eddy formation in the Gulf of Tehuantepec, with a recurring interval of 40–90 days. When forced by satellite wind observations, the model reproduces the two high‐variance bands and the phase propagation of the Tehuantepec eddies. Our observational analysis and model simulation suggest the following evolution of the Tehuantepec eddies. On the subseasonal timescale, in response to the gap wind intensification, a coastal anticyclonic eddy forms on the northwest flank of the wind jet and strengthens as it propagates offshore in the following two to three weeks. An energetics analysis based on the model simulation indicates that besides wind work, barotropic and baroclinic instabilities of the mean flow are important for the eddy growth. Both observational and model results suggest a re‐intensification of the anticyclonic eddy in response to the subsequent wind jet event. Off Papagayo, ocean eddy formation is not well correlated with local wind jet variability. In both the Gulfs of Tehuantepec and Papagayo, subseasonal SSH variability is preferentially excited on the northwest flank of the wind jet. Factors for this asymmetry about the wind jet axis as well as the origins of wind jet variability are discussed.
A novel particle tracking scheme for modeling contaminant transport in a dual‐continua fractured medium
Authors: Cadini F. , Bertoli I. , De Sanctis J. , Zio E.
Published: September 2012

The estimation of the extent and timing of solute migration in a fractured medium is a fundamental task for verifying the level of protection against contaminant releases (e.g., toxic chemicals or radionuclides) offered by the engineered and natural barriers of a waste repository. In this paper we present a novel approach for modeling solute transport in a fractured medium, based on an extension of the Kolmogorov‐Dmitriev theory of stochastic branching processes. The model equations for the expected values of the solute concentration take a form similar to that of classical dual‐continua models. On the other hand, the stochastic nature of the modeling approach lends itself to a new particle tracking scheme of resolution, which allows accounting for realistic features of the transport process. The proposed stochastic modeling framework and simulation solution approach are illustrated with reference to the experimental results from a case study of literature. Some of the model parameters are optimally identified by means of a genetic algorithm search aimed at best fitting the experimental data.
Variation of Ti‐in‐quartz in gneiss domes exposing the world's youngest ultrahigh‐pressure rocks, D'Entrecasteaux Islands, Papua New Guinea
Authors: Korchinski Megan , Little Timothy A. , Smith Euan , Millet Marc‐Alban
Published: September 2012

The D'Entrecasteaux Island gneiss domes, Papua New Guinea, expose the world's youngest ultrahigh‐pressure rocks (5–8 Ma), which were exhumed nearly isothermally to the mid‐crust at rates of cm yr−1. Because quartz grains are internally distorted by deformation bands and have strongly interlobate grain boundary microstructures indicative of rapid grain‐boundary migration, we infer that Ti content in the quartz was frozen in by dynamic recrystallization that accompanied the continued deformation of the gneisses as they were exhumed through the crust toward the surface. We infer that average Ti content of an assemblage of quartz grains in a sample depends on the ratio of cooling rate to dynamic recrystallization rate. An increase in the former preserves and captures a larger fraction of relatively high‐Ti, high‐temperature grains, whereas an increase in the latter removes such relict grains and replaces them with a newer set of lower‐Ti, low‐temperature recrystallized grains. Based on this concept, we use Ti‐in‐quartz as a tool to infer domains of differing relative cooling rate across four D'Entrecasteaux Island domes. Ti concentrations in quartz grains from 89 samples of quartzofeldspathic gneiss and eclogite increase inwardly away from the dome margins (2.5–20 ppm) toward the center of the domes (20–>100 ppm). From this, we infer that the most rapidly cooled rocks were exhumed near the center of the domes. Our data reinforces structurally based arguments that the symmetric domes were emplaced vertically into the crust as diapirs, rather than laterally exhumed as a result of large‐magnitude slip on dome‐bounding detachment faults.
Ionospheric flows relating to transpolar arc formation
Authors: Fear R. C. , Milan S. E.
Published: September 2012

Transpolar arcs are large‐scale auroral features which are observed within the polar cap when the IMF has a northward component. One leading candidate formation mechanism proposes that they are formed by reconnection in the magnetotail some time after a period of dayside reconnection with a non‐zero IMF BY component which introduces a twist into the magnetotail. As a result of the twist, the mechanism predicts that the return flows of the newly closed magnetic field lines are asymmetric about midnight; their direction should depend upon the IMF BY component in the hours beforehand and should be opposite in the northern and southern hemispheres. In this paper, we use data from the SuperDARN network of high‐latitude ionospheric radars to examine whether such ionospheric flows are present before the formation of 33 transpolar arcs. We find that the flows are present and in a manner that is consistent with the reconnection mechanism for 76% of the events; in the remaining few, the discrepancy can be attributed either to an uncertainty in the formation time determined for the arc (due to previous polar cap activity in the same local time sector) or due to the geometry of the radars which observe the backscatter.
Regulation of the V-type ATPase by redox modulation
Authors: Seidel Thorsten , Scholl Stefan , Krebs Melanie , Rienmüller Florian , Marten Irene , Hedrich Rainer , Hanitzsch Miriam , Janetzki Patricia , Dietz Karl-Josef , Schumacher Karin
Published: September 2012

ATP-hydrolysis and proton pumping by the V-ATPase (vacuolar proton-translocating ATPase) are subject to redox regulation in mammals, yeast and plants. Oxidative inhibition of the V-ATPase is ascribed to disulfide-bond formation between conserved cysteine residues at the catalytic site of subunit A. Subunits containing amino acid substitutions of one of three conserved cysteine residues of VHA-A were expressed in a vha-A null mutant background in Arabidopsis. In vitro activity measurements revealed a complete absence of oxidative inhibition in the transgenic line expressing VHA-A C256S, confirming that Cys256 is necessary for redox regulation. In contrast, oxidative inhibition was unaffected in plants expressing VHA-A C279S and VHA-A C535S, indicating that disulfide bridges involving these cysteine residues are not essential for oxidative inhibition. In vivo data suggest that oxidative inhibition might not represent a general regulatory mechanism in plants.
Residual compressive stress induced infrared-absorption frequency shift of hexagonal boron nitride in cubic boron nitride films prepared by plasma-enhanced chemical vapor deposition
Authors: Liu Yong , Jin Panpan , Chen Aili , Yang Hangsheng , Xu Yabo
Published: September 2012

The effects of compressive stress on the TO phonon frequencies of hexagonal boron nitride (hBN) in cubic BN (cBN) films were investigated using infrared absorption spectroscopy, showing that the B–N stretching vibration of hBN at 1380 cm−1 shifted to high wavenumbers under biaxial compressive stress with the rate 2.65 cm−1 per GPa, while the B–N–B bending vibration near 780 cm−1 shifted to low wavenumbers with the rate −3.45 cm−1/GPa. The density functional perturbation theoretical calculation was carried out to check the above phonon frequencies under stress for two typical orientations of hBN crystallite. The results are shown to be in fair agreement with the experimental data. Our results suggest that the residual compressive stress accumulated in cBN films can be evaluated from the IR peak position near 780 cm−1.
Velocity map photoelectron-photoion coincidence imaging on a single detector
Authors: Lehmann C. Stefan , Ram N. Bhargava , Janssen Maurice H. M.
Published: September 2012

Here we report on a new simplified setup for velocity map photoelectron-photoion coincidence imaging using only a single particle detector. We show that both photoelectrons and photoions can be extracted toward the same micro-channel-plate delay line detector by fast switching of the high voltages on the ion optics. This single detector setup retains essentially all the features of a standard two-detector coincidence imaging setup, viz., the high spatial resolution for electron and ion imaging, while only slightly decreasing the ion time-of-flight mass resolution. The new setup paves the way to a significant cost reduction in building a coincidence imaging setup for experiments aiming to obtain the complete correlated three-dimensional momentum distribution of electrons and ions.
Half-metallicity and magnetism of GeTe doped with transition metals V, Cr, and Mn: A theoretical study from the viewpoint of application in spintronics
Authors: Liu Y. , Bose S. K. , Kudrnovský J.
Published: September 2012

This work presents results for the magnetic properties of the compound GeTe doped with 3d transition metals V, Cr, and Mn from the viewpoint of potential application in spintronics. We report a systematic density-functional study of the electronic structure, magnetic and cohesive properties of these ternary compounds in both rock salt and zinc blende structures. In both cases, it is the Ge sublattice that is doped with the three transition metals. Some of these compounds are found to be half-metallic at their optimized cell volumes. For these particular cases, we calculate both exchange interactions and the Curie temperatures in order to provide some theoretical guidance to experimentalists trying to fabricate materials suitable for spintronic devices. Discussions relating our results to the existing experimental studies are provided whenever applicable and appropriate. Apparent discrepancy between experimental observations and our theoretical result for the case of Mn-doping is discussed in detail, pointing out various physical reasons and possible resolutions of the apparent discrepancy.
Optically transparent glass micro-actuator fabricated by femtosecond laser exposure and chemical etching
Authors: Lenssen Bo , Bellouard Yves
Published: September 2012

Femtosecond laser manufacturing combined with chemical etching has recently emerged as a flexible platform for fabricating three-dimensional devices and integrated optical elements in glass substrates. Here, we demonstrate an optically transparent micro-actuator fabricated out of a single piece of fused silica. This work paves the road for further functional integration in glass substrate and optically transparent microsystems.
AU-rich element-binding protein negatively regulates CCAAT enhancer-binding protein mRNA stability during long-term synaptic plasticity in
Aplysia
Authors: Lee Yong-Seok , Choi Sun-Lim , Jun Heejung , Yim Se-Jeong , Lee Jin-A , Kim Hyoung F. , Lee Seung-Hee , Shim Jaehoon , Lee Kyungmin , Jang Deok-Jin , Kaang Bong-Kiun
Published: September 2012

The consolidation of long-term memory for sensitization and synaptic facilitation in
Aplysia
requires synthesis of new mRNA including the immediate early gene
Aplysia
CCAAT enhancer-binding protein (
ApC/EBP
). After the rapid induction of
ApC/EBP
expression in response to repeated treatments of 5-hydroxytryptamine (5-HT),
ApC/EBP
mRNA is temporarily expressed in sensory neurons of sensory-to-motor synapses. However, the molecular mechanism underlying the rapid degradation of
ApC/EBP
transcript is not known. Here, we cloned an AU-rich element (ARE)-binding protein, ApAUF1, which functions as a destabilizing factor for
ApC/EBP
mRNA. ApAUF1 was found to bind to the 3′ UTR of
ApC/EBP
mRNA that contains AREs and subsequently reduces the expression of
ApC/EBP
3′ UTR-containing reporter genes. Moreover, overexpression of ApAUF1 inhibited the induction of
ApC/EBP
mRNA in sensory neurons and also impaired long-term facilitation of sensory-to-motor synapses by repetitive 5-HT treatments. These results provide evidence for a critical role of the posttranscriptional modification of
ApC/EBP
mRNA during the consolidation of synaptic plasticity.
Rescue of Notch signaling in cells incapable of GDP-
l
-fucose synthesis by gap junction transfer of GDP-
l
-fucose in
Drosophila
Authors: Ayukawa Tomonori , Matsumoto Kenjiroo , Ishikawa Hiroyuki O. , Ishio Akira , Yamakawa Tomoko , Aoyama Naoki , Suzuki Takuya , Matsuno Kenji
Published: September 2012

Notch (N) is a transmembrane receptor that mediates cell–cell interactions to determine many cell-fate decisions. N contains EGF-like repeats, many of which have an
O
-fucose glycan modification that regulates N-ligand binding. This modification requires GDP-
l
-fucose as a donor of fucose. The GDP-
l
-fucose biosynthetic pathways are well understood, including the de novo pathway, which depends on GDP-mannose 4,6 dehydratase (Gmd) and GDP-4-keto-6-deoxy-
d
-mannose 3,5-epimerase/4-reductase (Gmer). However, the potential for intercellularly supplied GDP-
l
-fucose and the molecular basis of such transportation have not been explored in depth. To address these points, we studied the genetic effects of mutating
Gmd
and
Gmer
on fucose modifications in
Drosophila
. We found that these mutants functioned cell-nonautonomously, and that GDP-
l
-fucose was supplied intercellularly through gap junctions composed of Innexin-2. GDP-
l
-fucose was not supplied through body fluids from different isolated organs, indicating that the intercellular distribution of GDP-
l
-fucose is restricted within a given organ. Moreover, the gap junction-mediated supply of GDP-
l
-fucose was sufficient to support the fucosylation of N-glycans and the O-fucosylation of the N EGF-like repeats. Our results indicate that intercellular delivery is a metabolic pathway for nucleotide sugars in live animals under certain circumstances.
Targeting blood-brain barrier sphingolipid signaling reduces basal P-glycoprotein activity and improves drug delivery to the brain
Authors: Cannon Ronald E. , Peart John C. , Hawkins Brian T. , Campos Christopher R. , Miller David S.
Published: September 2012

P-glycoprotein, an ATP-driven drug efflux pump, is a major obstacle to the delivery of small-molecule drugs across the blood-brain barrier and into the CNS. Here we test a unique signaling-based strategy to overcome this obstacle. We used a confocal microscopy-based assay with isolated rat brain capillaries to map a signaling pathway that within minutes abolishes P-glycoprotein transport activity without altering transporter protein expression or tight junction permeability. This pathway encompasses elements of proinflammatory- (TNF-α) and sphingolipid-based signaling. Critical to this pathway was signaling through sphingosine-1-phosphate receptor 1 (S1PR1). In brain capillaries, S1P acted through S1PR1 to rapidly and reversibly reduce P-glycoprotein transport activity. Sphingosine reduced transport by a sphingosine kinase-dependent mechanism. Importantly, fingolimod (FTY720), a S1P analog recently approved for treatment of multiple sclerosis, also rapidly reduced P-glycoprotein activity; similar effects were found with the active, phosphorylated metabolite (FTY720P). We validated these findings in vivo using in situ brain perfusion in rats. Administration of S1P, FTY720, or FTY729P increased brain uptake of three radiolabeled P-glycoprotein substrates,
3
H-verapamil (threefold increase),
3
H-loperamide (fivefold increase), and
3
H-paclitaxel (fivefold increase); blocking S1PR1 abolished this effect. Tight junctional permeability, measured as brain
14
C-sucrose accumulation, was not altered. Therefore, targeting signaling through S1PR1 at the blood-brain barrier with the sphingolipid-based drugs, FTY720 or FTY720P, can rapidly and reversibly reduce basal P-glycoprotein activity and thus improve delivery of small-molecule therapeutics to the brain.
Nitric oxide and glucocorticoids synergize in inducing apoptosis of CD4+8+ thymocytes: implications for ‘Death by Neglect’ and T-cell function
Authors: Cohen Orly , Ish-Shalom Eliran , Kfir-Erenfeld Shlomit , Herr Ingrid , Yefenof Eitan
Published: September 2012

Thymic epithelial cells (TECs) play a central role in T-cell development by presenting self-antigens on MHC proteins. Double-positive (DP) thymocytes that fail to interact with TEC via their TCR die by ‘Death by Neglect’. We demonstrated a role for TEC-derived glucocorticoids (GCs) in this process. In a previous study, we used an in vitro system recapitulating Death by Neglect, to demonstrate the involvement of nitric oxide (NO) and inducible NO synthase (iNOS) in this process. In this study, we show that NO synergizes with GCs to induce apoptosis of DP thymocytes in a fetal thymic organ culture. Also, DP thymocytes from iNOS−/− mice are less sensitive to GC-induced apoptosis. Furthermore, the number of DP thymocytes in iNOS−/− mice is higher than in wild-type mice, suggesting a role for NO in Death by Neglect. This phenomenon effects T-cell function profoundly: iNOS−/− T cells do not respond to TCR-mediated activation signals, measured by up-regulation of CD69, IL-2R and IFNγ secretion. This failure to activate is a result of TCR incompetence because iNOS−/− T cells respond to TCR-independent stimuli (phorbol myristate acetate and calcium ionophore). This study suggests that NO and GCs synergize to execute TEC-induced death of DP thymocytes.
Differences in Alcohol‐Soluble Protein from Genetically Altered Wheat Using Capillary Zone Electrophoresis, One‐ and Two‐Dimensional Electrophoresis, and a Novel Gluten Matrix Association Factor Analysis
Authors: Robertson George H. , Hurkman William , Anderson Olin D. , Tanaka Charlene K. , Cao Trung K. , Orts William J.
Published: September 2012

Wheat protein composition and organization play interrelated roles in determining physical properties for technological purposes. In prior research, a number of isogenic wheat lines of Bobwhite that have high levels of expression of the native Dx5 and/or Dy10 high‐molecular‐weight glutenin subunits (HMW‐GS) were examined vis‐à‐vis physical properties related to separation. In particular, these altered lines were characterized by poor mixing properties, the formation of mixtures in water that could not be separated by conventional mechanical methods, reduced water absorption, unique milling properties, and severely limited development of microscopic fibrils. These attributes suggested inherent organizational differences at submicroscopic and molecular levels among the various lines. Therefore, proteins were fractionated from whole meals using 70% ethanol to elucidate solubility characteristics and compositions and to infer structural properties. Capillary zone electrophoresis and one‐ and two‐dimensional SDS‐PAGE (2DE) revealed striking differences in the protein composition and solubility among these new lines and the Bobwhite from which they were derived. Generally, Bobwhite yielded soluble protein that included not only what would be considered as classical gliadins but also some of each of the HMW‐GS as monomers or polymers with low degrees of polymerization, whereas the genetically altered lines produced far less total soluble protein and very limited amounts of HMW‐GS. In the extreme, high levels of expression of Dx5 subunit not only led to reduced solubility of the HMW‐GS but also limited the solubility of the many other proteins that are normally soluble. In addition, a matrix association factor similar to the classical separation factor of analytical chemistry and chemical engineering was introduced and applied to 2DE data for insoluble and soluble protein to summarize and index relative involvement of specifically enhanced proteins in the insoluble gluten matrix after equilibration with ethanol. The highest relative association was determined for the HMW‐GS lines enriched in Dx5 or Dy10 protein and the lowest for Bobwhite. Greater association was indicated for Dx5 than for Dy10 protein in these lines. The value of the association factor was likely influenced by differences in glutamine‐to‐cysteine ratios and differences in altered glutenin chain configurations stemming from high levels of expression of a single or limited number of HMW‐GS.
Soil Suppressiveness to Fusarium Disease: Shifts in Root Microbiome Associated with Reduction of Pathogen Root Colonization
Authors: Klein Eyal , Ofek Maya , Katan Jaacov , Minz Dror , Gamliel Abraham
Published: September 2012

Soil suppressiveness to Fusarium disease was induced by incubating sandy soil with debris of wild rocket (WR; Diplotaxis tenuifolia) under field conditions. We studied microbial dynamics in the roots of cucumber seedlings following transplantation into WR-amended or nonamended soil, as influenced by inoculation with Fusarium oxysporum f. sp. radicis-cucumerinum. Disease symptoms initiated in nonamended soil 6 days after inoculation, compared with 14 days in WR-amended soil. Root infection by F. oxysporum f. sp. radicis-cucumerinum was quantified using real-time polymerase chain reaction (PCR). Target numbers were similar 3 days after inoculation for both WR-amended and nonamended soils, and were significantly lower (66%) 6 days after inoculation and transplanting into the suppressive (WR-amended) soil. This decrease in root colonization was correlated with a reduction in disease (60%) 21 days after inoculation and transplanting into the suppressive soil. Fungal community composition on cucumber roots was assessed using mass sequencing of fungal internal transcribed spacer gene fragments. Sequences related to F. oxysporum, Fusarium sp. 14005, Chaetomium sp. 15003, and an unclassified Ascomycota composed 96% of the total fungal sequences in all samples. The relative abundances of these major groups were highly affected by root inoculation with F. oxysporum f. sp. radicis-cucumerinum, with a 10-fold increase in F. oxysporum sequences, but were not affected by the WR amendment. Quantitative analysis and mass-sequencing methods indicated a qualitative shift in the root's bacterial community composition in suppressive soil, rather than a change in bacterial numbers. A sharp reduction in the size and root dominance of the Massilia population in suppressive soil was accompanied by a significant increase in the relative abundance of specific populations; namely, Rhizobium, Bacillus, Paenibacillus, and Streptomyces spp. Composition of the Streptomyces community shifted significantly, as determined by PCR denaturing gradient gel electrophoresis, resulting in an increase in the dominance of a specific population in suppressive soils after only 3 days. This shift was related mainly to the increase in Streptomyces humidus, a group previously described as antagonistic to phytopathogenic fungi. Thus, suitable soil amendment resulted in a shift in the root's bacterial communities, and infection by a virulent pathogen was contained by the root microbiome, leading to a reduced disease rate.
Balanced prescribing – principles and challenges
Authors: Aronson Jeffrey K.
Published: September 2012

Balanced prescribing is a process that recommends a medicine appropriate to the patient's condition and, within the limits created by the uncertainty that attends therapeutic decisions, a dosage regimen that optimizes the balance of benefit to harm. The essential steps in achieving this are (a) careful attention to the history, examination, and investigation of the patient's condition and drug therapy, (b) accurate diagnosis, (c) detailed attention to prescribing the dosage regimen in the light of the therapeutic goal, (d) careful writing of the prescription and (e) regular monitoring of therapy, including attention to beneficial outcomes, adverse reactions, and patient adherence. The two major requirements in determining the dosage regimen are (1) understanding the pathophysiology of a health problem and matching it to the mechanisms of action of the relevant medicines and (2) assessing the benefit to harm balance of the therapy, although the difficulties in doing this in the individual are great. Major challenges in prescribing include provision of adequate education for all prescribers early in their undergraduate training and maintaining their expertise after graduation, obtaining evidence to inform appropriate monitoring of therapy, reducing the incidence of medication errors, and providing high quality information that will at the same time guide prescribing decisions and be sufficiently flexible to allow prescribers to tailor therapy to the needs of the individual patient. Careful attention to all facets of prescribing can improve the chances of benefit, reduce the risks of adverse reactions and interactions, and enhance adherence to therapy.
Oral bioavailability of dabigatran etexilate (Pradaxa®) after co‐medication with verapamil in healthy subjects
Authors: Härtter Sebastian , Sennewald Regina , Nehmiz Gerhard , Reilly Paul
Published: September 2012

Aim

To investigate the effect of the P‐glycoprotein inhibitor verapamil on the pharmacokinetics and pharmacodynamics of dabigatran etexilate (DE).

Method

In this two part multiple crossover trial in 40 healthy subjects, DE 150 mg was given alone or with verapamil at different doses, duration of treatment (single vs. multiple dosing), formulations, and timings (before, concurrently or after DE). Primary pharmacokinetic endpoints were determined from concentrations of total dabigatran (unconjugated plus conjugated). Pharmacodynamic endpoints were determined from clotting time.

Results

The greatest effect was observed with single dose verapamil 120 mg immediate release given 1 h before single dose DE. Geometric mean area under the plasma concentration curve [AUC(0,∞)] and maximum analyte concentration in the plasma (Cmax) were increased by 143% [90% confidence interval (CI) 91, 208] and 179% (90% CI 115, 262), respectively. The effect was reduced to a 71% and 91% increase in AUC and Cmax, respectively, when DE was administered with verapamil 240 mg extended release. After multiple verapamil dosing, DE AUC(0,∞) and Cmax increases were 54% and 63%, respectively. However, DE given 2 h before verapamil increased DE AUC(0,∞) and Cmax by <20%. With regard to clotting prolongation, the dabigatran plasma concentration–effect relationship was generally not affected by the co‐administration of verapamil. Concomitant administration of DE and verapamil did not reveal any unexpected safety findings.

Conclusion

Verapamil increased DE bioavailability, likely due to inhibition of P‐glycoprotein. Our results suggest that an interaction between verapamil and DE can be minimized if DE is administered 2 h prior to verapamil.
Thiopurine metabolite measurement leads to changes in management of inflammatory bowel disease
Authors: Kennedy N. A. , Asser T. L. , Mountifield R. E. , Doogue M. P. , Andrews J. M. , Bampton P. A.
Published: September 2012

Background

The thiopurines azathioprine and 6‐mercaptopurine are recommended for maintenance of remission in inflammatory bowel disease (IBD). Measurement of concentrations of the metabolites 6‐thioguanine nucleotide and 6‐methylmercaptopurine helps delineate interindividual variation in metabolism that may underlie variability in efficacy and toxicity.

Aims

We aimed to perform a retrospective observational study to determine the utility of thiopurine metabolite testing following its introduction into South Australia.

Methods

All patients having thiopurine metabolite tests done at Flinders Medical Centre between November 2008 and January 2010 were identified. Case notes of patients with testing done in the context of treatment for IBD were interrogated to determine the reason for testing, clinical context and outcome.

Results

One hundred and fifty‐one patients were identified with thiopurine metabolite testing for IBD with 157 testing episodes. Eighty (51.0%) had testing done for flare or inefficacy, 18 (11.5%) for adverse effects, 5 (3.2%) for a combination of inefficacy and adverse effects, and 54 (34.4%) for routine or other reasons. Testing was followed by improved outcomes of increased efficacy, reduced toxicity or change to alternative therapy in 55.0% of the inefficacy/flare group, 27.8% of the suspected adverse reaction group, 60.0% of the combination group, and 13.0% of the routine/other group. Allopurinol was used as cotherapy in 16 patients and led to marked improvements in metabolite concentrations.

Conclusions

Thiopurine metabolite testing has quickly become established in South Australia. When used for inefficacy or adverse effects, it often leads to improved outcomes. Prospective studies are needed to determine whether routine testing to guide dosing is of benefit.
The role of chelants in controlling Cu(II)‐induced radical chemistry in oxidative hair colouring products
Authors: Naqvi K. R. , Marsh J. M. , Godfrey S. , Davis M. G. , Flagler M. J. , Hao J. , Chechik V.
Published: September 2012

Synopsis

The catalytic formation of hydroxyl radicals in oxidative hair colourant systems in the presence of added copper ions was measured and quantified using a colorimetric probe N,N′‐(5‐nitro‐1,3‐phenylene)bisglutaramide. Also monitored in the same experiments was the decomposition of hydrogen peroxide.

The first set of experiments was performed using aqueous model solutions containing the key oxidant actives in a hair colourant, ammonium hydroxide and hydrogen peroxide at pH 10, with added copper and calcium ions. The second set of experiments was performed in the presence of hair containing different levels of copper in conditions very close to those found during hair colouring. Both sets of experiments demonstrate the ability of copper ions to trigger the formation of hydroxyl radicals and catalyse the decomposition of hydrogen peroxide.

The ability of chelants ethylenediamine tetraacetic acid (EDTA) and N,N′‐ethylenediamine disuccinic acid (EDDS) to moderate the flux of hydroxyl radicals formed in solution systems was demonstrated in the presence of copper ions alone. However, only EDDS was successful in the presence of both calcium and copper ions. This was confirmed in the hair experiments where again only EDDS was successful at preventing hydroxyl radical formation where hair is added as the source of copper and calcium ions. These results are explained using metal speciation modelling and demonstrate the importance of the chelant to be able to specifically bind and prevent the one‐electron redox chemistry of copper in the presence of high levels of calcium ions as found in hair. The formation of hydroxyl radicals during the colouring process was shown to lead to hair structure damage as measured by protein loss. EDDS was demonstrated to significantly reduce cuticle damage by suppressing the formation of the hydroxyl radicals in systems with realistic concentrations of calcium and copper.
Struggles for value: value practices, injustice, judgment, affect and the idea of class
Authors: Skeggs Beverley , Loveday Vik
Published: September 2012

This paper is about the struggle for value by those who live intensified devaluation in the new conditions of legitimation and self‐formation, by which the self is required to repeatedly reveal its value through its accrual and investment in economic, symbolic, social and cultural capitals. It explores how this value struggle is experienced: felt affectively, known and spoken through discourses of injustice. Drawing on a small research project, which uses the British New Labour government's Respect Agenda as an evocative device to provoke discussion, the paper details how those positioned as already marginal to the dominant symbolic, presented as ‘useless’ subjects rather than ‘subjects of value’ of the nation, generate alternative ways for making value. It examines how the experience of injustice generates affective responses expressed as ‘ugly‐feelings’. The conversion of these ‘ugly feelings’ into articulations of ‘just‐talk’ reveals how different understandings of value, of what matters and what counts, come into effect and circulate alongside the dominant symbolic. The issue that most angered working‐class respondents is how they are positioned, judged, blamed and held responsible for an inheritance over which they have no control, ‘an accident of birth’. They were acutely aware of how they were constantly judged and de‐legitimated and how practices such as selfishness and greed were legitimate for others. Showing how they refuse to authorize those they consider lacking in value but with authority and in a position to judge, the paper demonstrates how class relations are lived through a struggle, not only against economic limitation but a struggle against unjustifiable judgment and authority and for dignified relationality. The paper reveals a struggle at the very core of ontology, demonstrating how the denigrated defend and make their lives liveable; an issue at the heart of current austerity politics which may have increased significance for the future.
Devalued, deskilled and diversified: explaining the proliferation of the strip industry in the UK
Authors: Sanders Teela , Hardy Kate
Published: September 2012

This paper looks beyond the debates that focus on the objectification of the female body to examine the question as to why strip clubs have proliferated and found a permanent place in the night‐time economy in the UK. Using empirical qualitative and quantitative data from the largest study into the strip industry in the UK to date, we challenge the common assumption that ‘demand’ is responsible for the rise in erotic dance. Instead, we argue that the proliferation of strip clubs is largely due to the internal economic structures of the industry which have developed partly in response to the financial crisis beginning in 2008. First, we argue that clubs profit from individual dancers through an exploitative system of fees and fines, rendering a strip club business a low cost investment with high returns and little risk to club owners. Second, we note that the last decade has seen diversification of the industry accompanied by deskilling and devaluing of dancing and dancers’ labour. Third, we demonstrate that despite the negative effects of these changes on workers, there has been an expansion of the industry as the ability to make profit, even during a financial crisis was ensured through the transferral of risk to workers. Overall, we suggest that far from proliferating as a response to demand, the industry has maintained its market presence due to its ability to establish highly financially exploitation employment relationships with dancers at a time of economic fragility.
Assessment in early childhood education: threats and challenges to effective assessment of immigrant children
Authors: Ntuli Esther , Nyarambi Arnold , Traore Moussa
Published: September 2012

Research indicates that early childhood professionals gather assessment information to monitor child development and learning, to guide curriculum planning and decision making, to identify children who may have special needs, to report and communicate with others, and to evaluate programmes. A review of literature indicates that immigrant children have low achievement assessment scores as compared with mainstream American children, also immigrant children enter kindergarten already behind their mainstream American peers. The current study explored early childhood teachers' perceptions of assessment measures used with immigrant children and the challenges faced when assessing immigrant children. Findings of the study reveal that there are several factors that make early childhood teachers fail to gather effective assessment information from immigrant children. Unless the factors are addressed, planning for effective curriculum for immigrant children using assessment data will continue to be a challenge for early childhood teachers. Factors that continue to affect gathering effective assessment data from immigrant children include language barriers, cultural clashes, socio‐economic factors, and culturally and linguistically biased assessment measures.
Translational neuropharmacology: the use of human isolated gastrointestinal tissues
Authors: Sanger GJ , Broad J , Kung V , Knowles CH
Published: September 2012

Translational sciences increasingly emphasize the measurement of functions in native human tissues. However, such studies must confront variations in patient age, gender, genetic background and disease. Here, these are discussed with reference to neuromuscular and neurosecretory functions of the human gastrointestinal (GI) tract. Tissues are obtained after informed consent, in collaboration with surgeons (surgical techniques help minimize variables) and pathologists. Given the difficulties of directly recording from human myenteric neurones (embedded between muscle layers), enteric motor nerve functions are studied by measuring muscle contractions/relaxations evoked by electrical stimulation of intrinsic nerves; responses are regionally dependent, often involving cholinergic and nitrergic phenotypes. Enteric sensory functions can be studied by evoking the peristaltic reflex, involving enteric sensory and motor nerves, but this has rarely been achieved. As submucosal neurones are more accessible (after removing the mucosa), direct neuronal recordings are possible. Neurosecretory functions are studied by measuring changes in short‐circuit current across the mucosa. For all experiments, basic questions must be addressed. Because tissues are from patients, what are the controls and the influence of disease? How long does it take before function fully recovers? What is the impact of age‐ and gender‐related differences? What is the optimal sample size? Addressing these and other questions minimizes variability and raises the scientific credibility of human tissue research. Such studies also reduce animal use. Further, the many differences between animal and human GI functions also means that human tissue research must question the ethical validity of using strains of animals with unproved translational significance.

Linked Article

BJP published a themed issue on Translational Neuropharmacology in 2011. To view the articles in this themed issue visit http://dx.doi.org/10.1111/bph.2011.164.issue‐4