bluuebunny/crossref_metadata_2025 huggingface dataset:
The glyoxalase pathway: the first hundred years… and beyond
Authors: Sousa Silva Marta , Gomes Ricardo A. , Ferreira Antonio E. N. , Ponces Freire Ana , Cordeiro Carlos
Published: June 2013

The discovery of the enzymatic formation of lactic acid from methylglyoxal dates back to 1913 and was believed to be associated with one enzyme termed ketonaldehydemutase or glyoxalase, the latter designation prevailed. However, in 1951 it was shown that two enzymes were needed and that glutathione was the required catalytic co-factor. The concept of a metabolic pathway defined by two enzymes emerged at this time. Its association to detoxification and anti-glycation defence are its presently accepted roles, since methylglyoxal exerts irreversible effects on protein structure and function, associated with misfolding. This functional defence role has been the rationale behind the possible use of the glyoxalase pathway as a therapeutic target, since its inhibition might lead to an increased methylglyoxal concentration and cellular damage. However, metabolic pathway analysis showed that glyoxalase effects on methylglyoxal concentration are likely to be negligible and several organisms, from mammals to yeast and protozoan parasites, show no phenotype in the absence of one or both glyoxalase enzymes. The aim of the present review is to show the evolution of thought regarding the glyoxalase pathway since its discovery 100 years ago, the current knowledge on the glyoxalase enzymes and their recognized role in the control of glycation processes.
Ras palmitoylation is necessary for N-Ras activation and signal propagation in growth factor signalling
Authors: Song Shu-Ping , Hennig Anne , Schubert Katja , Markwart Robby , Schmidt Philipp , Prior Ian A. , Böhmer Frank-Dietmar , Rubio Ignacio
Published: June 2013

Ras GTPases undergo post-translational modifications that govern their subcellular trafficking and localization. In particular, palmitoylation of the Golgi tags N-Ras and H-Ras for exocytotic transport and residency at the PM (plasma membrane). Following depalmitoylation, PM-Ras redistributes to all subcellular membranes causing an accumulation of palmitate-free Ras at endomembranes, including the Golgi and endoplasmic reticulum. Palmitoylation is unanimously regarded as a critical modification at the crossroads of Ras activity and trafficking control, but its precise relevance to native wild-type Ras function in growth factor signalling is unknown. We show in the present study by use of palmitoylation-deficient N-Ras mutants and via the analysis of palmitate content of agonist-activated GTP-loaded N-Ras that only palmitoylated N-Ras becomes activated by agonists. In line with an essential role of palmitoylation in Ras activation, dominant-negative RasS17N loses its blocking potency if rendered devoid of palmitoylation. Live-cell Ras–GTP imaging shows that N-Ras activation proceeds only at the PM, consistent with activated N-Ras–GTP being palmitoylated. Finally, palmitoylation-deficient N-Ras does not sustain EGF (epidermal growth factor) or serum-elicited mitogenic signalling, confirming that palmitoylation is essential for signal transduction by N-Ras. These findings document that N-Ras activation proceeds at the PM and suggest that depalmitoylation, by removing Ras from the PM, may contribute to the shutdown of Ras signalling.
Structure-guided optimization of protein kinase inhibitors reverses aminoglycoside antibiotic resistance
Authors: Stogios Peter J. , Spanogiannopoulos Peter , Evdokimova Elena , Egorova Olga , Shakya Tushar , Todorovic Nick , Capretta Alfredo , Wright Gerard D. , Savchenko Alexei
Published: June 2013

Activity of the aminoglycoside phosphotransferase APH(3′)-Ia leads to resistance to aminoglycoside antibiotics in pathogenic Gram-negative bacteria, and contributes to the clinical obsolescence of this class of antibiotics. One strategy to rescue compromised antibiotics such as aminoglycosides is targeting the enzymes that confer resistance with small molecules. We demonstrated previously that ePK (eukaryotic protein kinase) inhibitors could inhibit APH enzymes, owing to the structural similarity between these two enzyme families. However, limited structural information of enzyme–inhibitor complexes hindered interpretation of the results. In addition, cross-reactivity of compounds between APHs and ePKs represents an obstacle to their use as aminoglycoside adjuvants to rescue aminoglycoside antibiotic activity. In the present study, we structurally and functionally characterize inhibition of APH(3′)-Ia by three diverse chemical scaffolds, anthrapyrazolone, 4-anilinoquinazoline and PP (pyrazolopyrimidine), and reveal distinctions in the binding mode of anthrapyrazolone and PP compounds to APH(3′)-Ia compared with ePKs. Using this observation, we identify PP derivatives that select against ePKs, attenuate APH(3′)-Ia activity and rescue aminoglycoside antibiotic activity against a resistant Escherichia coli strain. The structures described in the present paper and the inhibition studies provide an important opportunity for structure-based design of compounds to target aminoglycoside phosphotransferases for inhibition, potentially overcoming this form of antibiotic resistance.
Realisation of semiconductor ternary quantum dot cellular automata
Authors: Das Kunal , De Debashis , De Mallika
Published: June 2013

Quantum dot cellular automata (QCA) have become a strong alternative for nanoscale computing. After a decade of exhaustive research on binary QCA, the newly introduced ternary QCA (tQCA) for implementing ternary logic needs further research to actually fabricate the tQCA cell. In this Letter, a quantum mechanical approach is presented for calculating the diverse parameters required for the fabrication of the tQCA. The effect of quantum dot size, the size of tQCA cell as well as the effect of temperature on polarisation for the tQCA cell are examined. The significant result for fabrication of the tQCA cell is tunnelling resistance, which must be greater than the quantum Hall resistance, that is, Rt ≫ 25.813 kΩ. The tQCA needs a quantum dot size which is < 6.36 nm to operate at room temperature and the distance of separation between two dots must be 5 nm. The steady‐state behaviour of the tQCA cell using the Hubbard model and the Schrödinger time‐independent equation is also explored.
Synthesis and magnetic properties of nickel three‐dimensional superlattice structure
Authors: Duan Hongyan , Li Fagen , Wu Wei , Wang Jun
Published: June 2013

High monodisperse nickel nanoparticles of 13 nm were successfully synthesised based on reduction of common nickel salts. Further annealing process prompted the formation of magnetic superlattices. The morphological features characterised by field emission scanning electron microscopy showed that the Ni nanoparticles self‐assembled periodically and formed close‐packed arrays. The results of magnetic hysteresis loops showed that the sample exhibited improved magnetic properties compared with those of other bigger nanoparticles. The Curie temperature of the sample was about 596 K, lower than that of the bulk material, which is discussed in terms of the finite‐size effects.
Fabrication and characterisation of Magneli phase Ti4O7 nanoparticles
Authors: Zhang Xiaoyan , Liu Ying , Ye Jinwen , Zhu Ruijie
Published: June 2013

Pure Magneli phase Ti4O7 nanoparticles with diameters of 200–500 nm were successfully synthesised under hydrogen atmospheres. In this reported work, the influences of reduction of temperature and time on the reduced phases were investigated, and it is shown that pure Ti4O7 can be obtained by heating at 850°C for 5 h. The as‐prepared materials are characterised by X‐ray diffraction (XRD), scanning electron microscopy, transmission electron microscopy, and the corresponding selected area electron diffraction indicates the single‐crystal structure, which is also consistent with the XRD results. N2 absorption (Brunauer‐Emmett‐Teller surface area) was also conducted on this material, the surface area being 8.351 m2/g. UV–vis diffuse reflectance spectra of the nanoparticles exhibited absorption beyond 325 nm, meanwhile, there is an absorption band that covers the visible‐light wavelengths and extends into the near‐infrared region.
DC‐contact radio‐frequency microelectromechanical system symmetric toggle switch on a borofloat substrate
Authors: Li Ling , Hou Zhihao , Zhao Chenxu , Liu Zewen
Published: June 2013

Presented is a DC‐contact radio‐frequency (RF) microelectromechanical system symmetric toggle switch for broadband power applications. Based on the lever principle, the proposed switching structure can be toggled upwards with extra restoring force using push electrodes. This push mechanism greatly improves the isolation and efficiently avoids the down‐state stiction of the contacts which leads to enhancement of the power‐handling capability. The measured actuated voltage is 33.4 V and the contact resistance of the switch can be further decreased to 0.18 Ω under a pull in voltage of 60 V, which results in the improvement of insertion loss. The switch can be properly restored with a voltage of 30 V applied to the push electrode. In addition, the substrate loss is reduced by using a Boroloat™ glass substrate. The RF measurement results show that the switch can handle a minimum 1 W incident RF signal power with isolation and an insertion loss of better than −30 and −0.24 dB from DC to the X‐band.
Large‐scale synthesis of hierarchical broccoli‐like zinc oxide under mild conditions and their catalytic properties
Authors: Guo Xiaodan , Yuan Yanqiu , Wang Aixiu , Huang Yuanwei , Chen Fangqiang , Hu Yilin , Wang Xinfeng , Yin Jingzhou
Published: June 2013

Large‐scale uniform hierarchical broccoli‐like zinc oxide (ZnO) superstructures assembled by nanorods were successfully synthesised via a facile solution method under mild conditions by using sodium carboxymethyl cellulose (NaCMC) as crystal growth modifiers. The morphology of the final products was simply tuned by adding different amounts of ammonia in the presence of NaCMC. In addition, the catalytic properties of as‐prepared products were investigated. It was found that these ZnO superstructures have good abilities to promote the thermal decomposition of ammonium perchlorate.
Ethylene glycol‐mediated direct synthesis of nanostructured nickel oxide–carbon composite material on nickel foam and its electrochemical property
Authors: Lv Sa , Wang Chao , Yang Xiaotian
Published: June 2013

A convenient ethylene glycol (EG)‐mediated one‐pot solvothermal route was designed for direct synthesis of nanostructured nickel oxide–carbon composite material on nickel foam. EG was employed as solvent, complex agent and carbon source. Furthermore, cyclic voltammetry and constant current charge–discharge measurements confirmed that the composite material electrode displayed good electrochemical activity with a maximum specific capacitance of 539 F g− 1 at a current density of 0.25 A g− 1.
Structural and dynamic properties of calcium aluminosilicate melts: A molecular dynamics study
Authors: Bouhadja M. , Jakse N. , Pasturel A.
Published: June 2013

The structural and dynamic properties of calcium aluminosilicate (CaO–Al2O3)1−x(SiO2)x melts with low silica content, namely, along the concentration ratio R = 1 are studied by classical molecular dynamics. An empirical potential has been developed here on the basis of our previous ab initio molecular dynamics. The new potential gives a description of the structural as well as the dynamics with a good accuracy. The self-intermediate scattering function and associated α-relaxation times are analyzed within the mode-coupling theory. Our results indicate a decrease of the fragility whose structural origin is a reduction of the number of fivefold coordinated Al atoms and non-bridging oxygen.
Impact of tensile strain on the oxygen vacancy migration in SrTiO3: Density functional theory calculations
Authors: AL-Hamadany Raied , Goss J. P. , Briddon P. R. , Mojarad Shahin A. , O'Neill A. G. , Rayson M. J.
Published: June 2013

Strontium titanate is a promising dielectric material for device applications including capacitors and gate dielectrics. However, oxygen vacancies, which are inevitable donor defects mobile under bias at room temperature, lead to undesirable leakage current in SrTiO3 thin films. Epitaxially grown SrTiO3 on lattice mismatched substrates leads to strained SrTiO3, inducing structural phase transitions from a cubosymmetric non-ferroelectric geometry to tetragonal and orthorhombic structures, depending upon the sign of the strain. In this study, density functional calculations have been performed to determine the impact of isotropic biaxial tensile strain in a (001) plane upon the phase of SrTiO3 and the activation energy for the migration of oxygen vacancies in such strained SrTiO3. The phase transition of the host material yields anisotropy in oxygen vacancy diffusion for diffusion within and between planes parallel to the strain. We found a general reduction in the barrier for diffusion within and normal to the plane of tensile strain. The inter-plane diffusion barrier reduces up to 25% at high values of strain. The variation in the barrier corresponding to in-plane diffusion is smaller in comparison to inter-plane diffusion. Finally, we reflect upon how the interplay between lattice strain with native defects plays a crucial role in the conduction mechanism of thin film, strained SrTiO3.
DNA damage in oral cancer cells induced by nitrogen atmospheric pressure plasma jets
Authors: Han Xu , Klas Matej , Liu Yueying , Sharon Stack M. , Ptasinska Sylwia
Published: June 2013

The nitrogen atmospheric pressure plasma jet (APPJ) was applied to induce DNA damage of SCC-25 oral cancer cells. Optical emission spectra were taken to characterize the reactive species produced in APPJ. In order to explore the spatial distribution of plasma effects, cells were placed onto photo-etched grid slides and the antibody H2A.X was used to locate double strand breaks of DNA inside nuclei using an immunofluorescence assay. The number of cells with double strand breaks in DNA was observed to be varied due to the distance from the irradiation center and duration of plasma treatment.
Spin exchange optical pumping based polarized 3He filling station for the Hybrid Spectrometer at the Spallation Neutron Source
Authors: Jiang C. Y. , Tong X. , Brown D. R. , Culbertson H. , Graves-Brook M. K. , Hagen M. E. , Kadron B. , Lee W. T. , Robertson J. L. , Winn B.
Published: June 2013

The Hybrid Spectrometer (HYSPEC) is a new direct geometry spectrometer at the Spallation Neutron Source at the Oak Ridge National Laboratory. This instrument is equipped with polarization analysis capability with 60° horizontal and 15° vertical detector coverages. In order to provide wide angle polarization analysis for this instrument, we have designed and built a novel polarized 3He filling station based on the spin exchange optical pumping method. It is designed to supply polarized 3He gas to HYSPEC as a neutron polarization analyzer. In addition, the station can optimize the 3He pressure with respect to the scattered neutron energies. The depolarized 3He gas in the analyzer can be transferred back to the station to be repolarized. We have constructed the prototype filling station. Preliminary tests have been carried out demonstrating the feasibility of the filling station. Here, we report on the design, construction, and the preliminary results of the prototype filling station.
The structures of thin layer formed by microphase separation of grafted Y-shaped block copolymers in solutions
Authors: Gao Hui-Min , Liu Hong , Lu Zhong-Yuan , Sun Zhao-Yan , An Li-Jia
Published: June 2013

We study the structure formation of grafted Y-shaped block copolymers in solutions via dissipative particle dynamics simulations. We systematically examine how the solvent quality, the grafting density, and the incompatibility between polymer blocks affect the morphology of the grafted layer. The layer thickness and the lateral domain size and inhomogeneity of the layer structures are analyzed. A power law, hlayer ∼ σn, is found between the layer thickness (hlayer) and the grafting density (σ), which shows three regimes, i.e., the brushes regime, the crossover regime, and the mushrooms regime. In the brushes regime, we also find that the exponent n is dependent on the grafting densities and solvent conditions, regardless of the incompatibility between the polymer blocks. In the mushrooms and the crossover regime, a variety of surface structures can be observed, such as mixed micelles, internally segregated micelles, hamburger micelles, segmented wormlike micelles, and dumbbell micelles. The stripe-like structure formed in the brushes regime is investigated in detail. The simulation results are in good agreement with theoretical predictions and experimental observations, and can be helpful for the surface structure design of functional materials.
Study of spin and orbital magnetization in Dy- and Gd-doped Co ferrite using magnetic Compton scattering
Authors: Mund H. S. , Sahariya Jagrati , Choudhary R. J. , Phase D. M. , Dashora Alpa , Itou M. , Sakurai Y. , Ahuja B. L.
Published: June 2013

Temperature dependent experimental magnetic Compton profiles (MCPs) of inverse spinel CoFe2−xRExO4 (x = 0.05; RE = Dy, Gd) have been decomposed into constituent profiles to determine site-specific spin moments. A comparison of MCPs of doped and undoped CoFe2O4 shows a decrease in spin moment on 5% doping of Dy and Gd. Reduction in spin moment is explained on the basis of migration of Co2+ ions from octahedral to tetrahedral sites, which is also supported by photoelectron spectroscopy measurements. The orbital moments deduced from combination of spin momentum density and magnetization data are found to be almost similar in doped ferrites.
Interband cascade lasers with room temperature threshold current densities below 100 A/cm2
Authors: Weih Robert , Kamp Martin , Höfling Sven
Published: June 2013

Interband Cascade Lasers (ICLs) with threshold current densities below 100 A/cm2 in pulsed operation at room temperature are presented. The laser structure comprises 10 active stages of 41 nm length, each stage containing a W-quantum well active region for emission in the spectral region around 3.6 μm. A comparison of devices with 6 and 10 stages shows that the latter have a reduced threshold due to an increased optical confinement factor, very competitive threshold power densities of 428 W cm−2 despite an increased threshold voltage and large differential slope efficiencies of 1390 mW/A. For a narrow ridge device, continuous wave operation is observed up to 65 °C.
Magnetic reconnection in a weakly ionized plasma
Authors: Leake James E. , Lukin Vyacheslav S. , Linton Mark G.
Published: June 2013

Magnetic reconnection in partially ionized plasmas is a ubiquitous phenomenon spanning the range from laboratory to intergalactic scales, yet it remains poorly understood and relatively little studied. Here, we present results from a self-consistent multi-fluid simulation of magnetic reconnection in a weakly ionized reacting plasma with a particular focus on the parameter regime of the solar chromosphere. The numerical model includes collisional transport, interaction and reactions between the species, and optically thin radiative losses. This model improves upon our previous work in Leake et al. [“Multi-fluid simulations of chromospheric magnetic reconnection in a weakly ionized reacting plasma,” Astrophys. J. 760, 109 (2012)] by considering realistic chromospheric transport coefficients, and by solving a generalized Ohm's law that accounts for finite ion-inertia and electron-neutral drag. We find that during the two dimensional reconnection of a Harris current sheet with an initial width larger than the neutral-ion collisional coupling scale, the current sheet thins until its width becomes less than this coupling scale, and the neutral and ion fluids decouple upstream from the reconnection site. During this process of decoupling, we observe reconnection faster than the single-fluid Sweet-Parker prediction, with recombination and plasma outflow both playing a role in determining the reconnection rate. As the current sheet thins further and elongates, it becomes unstable to the secondary tearing instability, and plasmoids are seen. The reconnection rate, outflows, and plasmoids observed in this simulation provide evidence that magnetic reconnection in the chromosphere could be responsible for jet-like transient phenomena such as spicules and chromospheric jets.
Exchange bias in La0.7Sr0.3MnO3/NiO and LaMnO3/NiO interfaces
Authors: Ning X. K. , Wang Z. J. , Zhao X. G. , Shih C. W. , Zhang Z. D.
Published: June 2013

Bilayers of La0.7Sr0.3MnO3/NiO and LaMnO3/NiO were prepared and magnetic exchange coupling investigated in these bilayers, where the Curie temperature of the ferromagnetic (FM) layer is lower than the Néel temperature of the antiferromagnetic layer. After small-field cooling, the LSMO/NiO bilayer exhibits an exchange bias with field HEB = 60 Oe, whereas the LMO/NiO sample shows weak magnetic interaction (∼22 Oe). The unconventional exchange bias in LSMO/NiO bilayer vanishes as temperature rises above 50 K. The weak magnetic interaction at the LMO/NiO interface is due to a larger Hubbard parameter value and smaller transfer integral value in the Mott insulator LMO compared with that for the FM conductor LSMO. The valence states of Mn and Ni ions across the interfaces for LSMO/NiO and LMO/NiO have been studied using X-ray photoelectron spectroscopy. We speculate that the FM interaction between Ni2+ and Mn4+ gives rise to magnetic regions that pin the ferromagnetic LSMO layer.
Amorphous/crystalline silicon interface defects induced by hydrogen plasma treatments
Authors: Geissbühler Jonas , De Wolf Stefaan , Demaurex Bénédicte , Seif Johannes P. , Alexander Duncan T. L. , Barraud Loris , Ballif Christophe
Published: June 2013

Excellent amorphous/crystalline silicon interface passivation is of extreme importance for high-efficiency silicon heterojunction solar cells. This can be obtained by inserting hydrogen-plasma treatments during deposition of the amorphous silicon passivation layers. Prolonged hydrogen-plasmas lead to film etching. We report on the defect creation induced by such treatments: A severe drop in interface-passivation quality is observed when films are etched to a thickness of less than 8 nm. Detailed characterization shows that this decay is due to persistent defects created at the crystalline silicon surface. Pristine interfaces are preserved when the post-etching film thickness exceeds 8 nm, yielding high quality interface passivation.
Water-impermeable fruits of the parasitic angiosperm Cassytha filiformis (Lauraceae): confirmation of physical dormancy in Magnoliidae and evolutionary considerations
Authors: Mahadevan Niranjan , Jayasuriya K. M. G. Gehan
Published: June 2013

Physical dormancy (PY) in seeds or fruits has been reported in 17 angiosperm families but not in basal angiosperms, magnoliids or gymnosperms. Here, we report PY in fruits (germination unit) of Cassytha filiformis, a parasitic species in the magnoliid clade. Moisture content of fruits ranged from 10% to 16%, and the seeds are orthodox (desiccation tolerant). Manually scarified fruits increased in mass >80% during imbibition, whereas untreated fruits increased <16%, via only a few fruits imbibing. Thus, the fruits are water impermeable. Dye did not penetrate the lignified palisade layer in the endocarp. Dye tracking of innately non-dormant fruits suggested that the carpellary micropyle is the water gap in C. filiformis fruits. Manual scarification broke dormancy of most, but not all, C. filiformis fruits. Thus, a high percentage of the germination units have PY and a low percentage PY + physiological dormancy. This is the first verified report of PY in the magnoliids; PY is now known to occur in four of the five major angiosperm clades. The evolutionary aspects of PY in Cassytha, an isolated genus in Lauraceae, are discussed.
On the Bonding in Bis-pyridine Iodonium Cations
Authors: Georgiou Dayne C. , Butler Phillip , Browne Elisse C. , Wilson David J. D. , Dutton Jason L.
Published: June 2013

A study on the bonding in bis-pyridine halonium cations has been carried out using both theoretical and synthetic techniques. The primary thrust for the study is to highlight the opportunities potentially afforded by considering iodine as a Lewis acid in a classic coordination sense. Our results suggest that the iodine dipyridine complex ([pyr-I-pyr]+) can be considered as a coordination complex of [I]+. The lighter bromine and chlorine analogues are more towards the covalent rather than the dative side of bonding, while [pyr-F-pyr]+ is best described as an ion-molecule complex with one strong covalent F-pyr bond and one weak F-pyr dispersion interaction. Finally, theoretical and synthetic studies suggest that the commercially available [pyr-F]+ cation cannot be considered as a coordination complex of ‘F+’, despite its use as a source of electrophilic fluorine.
Out of the tropics, but how? Fossils, bridge species, and thermal ranges in the dynamics of the marine latitudinal diversity gradient
Authors: Jablonski David , Belanger Christina L. , Berke Sarah K. , Huang Shan , Krug Andrew Z. , Roy Kaustuv , Tomasovych Adam , Valentine James W.
Published: June 2013

Latitudinal diversity gradients are underlain by complex combinations of origination, extinction, and shifts in geographic distribution and therefore are best analyzed by integrating paleontological and neontological data. The fossil record of marine bivalves shows, in three successive late Cenozoic time slices, that most clades (operationally here, genera) tend to originate in the tropics and then expand out of the tropics (OTT) to higher latitudes while retaining their tropical presence. This OTT pattern is robust both to assumptions on the preservation potential of taxa and to taxonomic revisions of extant and fossil species. Range expansion of clades may occur via “bridge species,” which violate climate-niche conservatism to bridge the tropical-temperate boundary in most OTT genera. Substantial time lags (∼5 Myr) between the origins of tropical clades and their entry into the temperate zone suggest that OTT events are rare on a per-clade basis. Clades with higher diversification rates within the tropics are the most likely to expand OTT and the most likely to produce multiple bridge species, suggesting that high speciation rates promote the OTT dynamic. Although expansion of thermal tolerances is key to the OTT dynamic, most latitudinally widespread species instead achieve their broad ranges by tracking widespread, spatially-uniform temperatures within the tropics (yielding, via the nonlinear relation between temperature and latitude, a pattern opposite to Rapoport’s rule). This decoupling of range size and temperature tolerance may also explain the differing roles of species and clade ranges in buffering species from background and mass extinctions.
Shiga toxin–binding site for host cell receptor GPP130 reveals unexpected divergence in toxin-trafficking mechanisms
Authors: Mukhopadhyay Somshuvra , Redler Brendan , Linstedt Adam D.
Published: June 2013

Shiga toxicosis is caused by retrograde trafficking of one of three types of Shiga toxin (STx), STx, STx1, or STx2. Trafficking depends on the toxin B subunits, which for STx and STx1 are identical and bind GPP130, a manganese (Mn)-sensitive intracellular trafficking receptor. Elevated Mn down-regulates GPP130, rendering STx/STx1 harmless. Its effectiveness against STx2, however, which is a serious concern in the developed world, is not known. Here we show that Mn-induced GPP130 down-regulation fails to block STx2 trafficking. To shed light on this result, we tested the purified B subunit of STx2 for binding to GPP130 and found that it failed to interact. We then mapped residues at the interface of the GPP130-STx/STx1 complex. In GPP130, binding mapped to a seven-residue stretch in its lumenal stem domain next to the transmembrane domain. This stretch was required for STx/STx1 transport. In STx/STx1, binding mapped to a histidine–asparagine pair on a surface-exposed loop of the toxin B subunit. Significantly, these residues are not conserved in STx2, explaining the lack of effectiveness of Mn against STx2. Together our results imply that STx2 uses an evolutionarily distinct trafficking mechanism and that Mn as a potential therapy should be focused on STx/STx1 outbreaks, which account for the vast majority of cases worldwide.
CHOP induces activating transcription factor 5 (ATF5) to trigger apoptosis in response to perturbations in protein homeostasis
Authors: Teske Brian F. , Fusakio Michael E. , Zhou Donghui , Shan Jixiu , McClintick Jeanette N. , Kilberg Michael S. , Wek Ronald C.
Published: June 2013

Environmental stresses that disrupt protein homeostasis induce phosphorylation of eIF2, triggering repression of global protein synthesis coincident with preferential translation of ATF4, a transcriptional activator of the integrated stress response (ISR). Depending on the extent of protein disruption, ATF4 may not be able to restore proteostatic control and instead switches to a terminal outcome that features elevated expression of the transcription factor CHOP (GADD153/DDIT3). The focus of this study is to define the mechanisms by which CHOP directs gene regulatory networks that determine cell fate. We find that in response to proteasome inhibition, CHOP enhances the expression of a collection of genes encoding transcription regulators, including ATF5, which is preferentially translated during eIF2 phosphorylation. Transcriptional expression of ATF5 is directly induced by both CHOP and ATF4. Knockdown of ATF5 increases cell survival in response to proteasome inhibition, supporting the idea that both ATF5 and CHOP have proapoptotic functions. Transcriptome analysis of ATF5-dependent genes reveals targets involved in apoptosis, including NOXA, which is important for inducing cell death during proteasome inhibition. This study suggests that the ISR features a feedforward loop of stress-induced transcriptional regulators, each subject to transcriptional and translational control, which can switch cell fate toward apoptosis.
Computed tomography coronary imaging as a gatekeeper for invasive coronary angiography in patients with newly diagnosed heart failure of unknown aetiology
Authors: ten Kate Gert‐Jan R. , Caliskan Kadir , Dedic Admir , Meijboom W. Bob , Neefjes Lisan A. , Manintveld Olivier C. , Krenning Boudewijn J. , Ouhlous Mohammed , Nieman Koen , Krestin Gabriel P. , de Feyter Pim J.
Published: June 2013

Aims

To evaluate the accuracy of cardiac computed tomography (CT) in distinguishing CAD and non‐CAD heart failure (HF) and its effectiveness as a gatekeeper for invasive coronary angiography (ICA).

Methods and results

We prospectively included 93 symptomatic patients with newly diagnosed HF of unknown aetiology (59 men; mean age 53 ± 13) and EF <45%, and/or fractional shortening <25%, and/or end‐diastolic LV diameter >60 mm (men) or >55 mm (women). In all patients, the CT calcium score (CTCS) was determined. CTCS = 0 excluded CAD HF. Additional CT coronary angiography (CTCA) was performed if CTCS >0. ICA was used as the gold standard for distinguishing between CAD and non‐CAD HF in patients with >20% luminal diameter narrowing on CTCA. CAD HF was defined as >50% luminal diameter narrowing in either (i) the left main coronary artery or proximal left anterior descending coronary artery or (ii) in multiple coronary arteries. Diagnostic accuracy and follow‐up data (20 ± 16 months) were collected for all patients. CTCS = 0 ruled out CAD HF in 43 patients (46%). The CT algorithm had 100% sensitivity, 95% specificity, 67% positive predictive value, and 100% negative predictive value for detecting CAD HF. Patients with CTCS = 0 or non‐CAD HF on CTCA had no coronary events during follow‐up, and ICA could have been safely avoided in 76 out of 93 patients (82%).

Conclusion

In patients with HF of unknown aetiology, cardiac CT combining CTCS and CTCA has high accuracy for detecting CAD HF and can be used effectively as a gatekeeper for ICA.
Lenient vs. strict rate control in patients with atrial fibrillation and heart failure: a post‐hoc analysis of the RACE II study
Authors: Mulder Bart A. , Van Veldhuisen Dirk J. , Crijns Harry J.G.M. , Tijssen Jan G.P. , Hillege Hans L. , Alings Marco , Rienstra Michiel , Groenveld Hessel F. , Van den Berg Maarten P. , Van Gelder Isabelle C. ,   for the RACE II investigators
Published: June 2013

Aims

It is unknown whether lenient rate control is an acceptable strategy in patients with AF and heart failure. We evaluated differences in outcome in patients with AF and heart failure treated with lenient or strict rate control.

Methods and results

This post‐hoc analysis of the RACE II trial included patients with an LVEF ≤ 40% at baseline or a previous hospitalization for heart failure or signs and symptoms of heart failure. Primary outcome was a composite of cardiovascular morbidity and mortality. Secondary endpoints were AF‐related symptoms and quality of life. Two hundred and eighty‐seven (46.7%) of the 614 patients had heart failure. Patients with heart failure had significantly higher NT‐proBNP plasma levels, a lower LVEF, and more often used ACE inhibitors, ARBs, and diuretics. At 3 years follow‐up, the primary outcome occurred more frequently in patients with heart failure (16.7% vs. 11.5%, P = 0.04). In heart failure patients, the estimated cumulative incidence of the primary outcome was 15.0% (n = 20) in the lenient and 18.2% (n = 26) in the strict group (P = 0.53). No differences were found in any of the primary outcome components, in either heart failure hospitalizations [8 (6.1%) vs. 9 (6.8%) patients in the lenient vs. strict group, respectively], symptoms, or quality of life.

Conclusion

In patients with AF and heart failure with a predominantly preserved EF, the stringency of rate control seems to have no effect on cardiovascular morbidity and mortality, symptoms, and quality of life.
Xenon treatment attenuates early renal allograft injury associated with prolonged hypothermic storage in rats
Authors: Zhao Hailin , Yoshida Akira , Xiao Wei , Ologunde Rele , O'Dea Kieran P. , Takata Masao , Tralau‐Stewart Catherine , George Andrew J. T. , Ma Daqing
Published: June 2013

Prolonged hypothermic storage elicits severe ischemia‐reperfusion injury (IRI) to renal grafts, contributing to delayed graft function (DGF) and episodes of acute immune rejection and shortened graft survival. Organoprotective strategies are therefore needed for improving long‐term transplant outcome. The aim of this study is to investigate the renoprotective effect of xenon on early allograft injury associated with prolonged hypothermic storage. Xenon exposure enhanced the expression of heat‐shock protein 70 (HSP‐70) and heme oxygenase 1 (HO‐1) and promoted cell survival after hypothermia‐hypoxia insult in human proximal tubular (HK‐2) cells, which was abolished by HSP‐70 or HO‐1 siRNA. In the brown Norway to Lewis rat renal transplantation, xenon administered to donor or recipient decreased the renal tubular cell death, inflammation, and MHC II expression, while delayed graft function (DGF) was therefore reduced. Pathological changes associated with acute rejection, including T‐cell, macrophage, and fibroblast infiltration, were also decreased with xenon treatment. Donors or recipients treated with xenon in combination with cyclosporin A had prolonged renal allograft survival. Xenon protects allografts against delayed graft function, attenuates acute immune rejection, and enhances graft survival after prolonged hypothermic storage. Furthermore, xenon works additively with cyclosporin A to preserve post‐transplant renal function.— Zhao, H., Yoshida, A., Xiao, W., Ologunde, R., O'Dea, K. P., Takata, M., Tralau‐Stewart, C., George, A. J. T., Ma, D., Xenon treatment attenuates early renal allograft injury associated with prolonged hypothermic storage in rats. FASEB J. 27, 4076–4088 (2013). www.fasebj.org
The TGFβ-induced phosphorylation and activation of p38 mitogen-activated protein kinase is mediated by MAP3K4 and MAP3K10 but not TAK1
Authors: Sapkota Gopal P.
Published: June 2013

The signalling pathways downstream of the transforming growth factor beta (TGFβ) family of cytokines play critical roles in all aspects of cellular homeostasis. The phosphorylation and activation of p38 mitogen-activated protein kinase (MAPK) has been implicated in TGFβ-induced epithelial-to-mesenchymal transition and apoptosis. The precise molecular mechanisms by which TGFβ cytokines induce the phosphorylation and activation of p38 MAPK are unclear. In this study, I demonstrate that TGFβ-activated kinase 1 (TAK1/MAP3K7) does not play a role in the TGFβ-induced phosphorylation and activation of p38 MAPK in MEFs and HaCaT keratinocytes. Instead,RNAi-mediated depletion of MAP3K4 and MAP3K10 results in the inhibition of the TGFβ-induced p38 MAPK phosphorylation. Furthermore, the depletion of MAP3K10 from cells homozygously knocked-in with a catalytically inactive mutant of MAP3K4 completely abolishes the TGFβ-induced phosphorylation of p38 MAPK, implying that among MAP3Ks, MAP3K4 and MAP3K10 are sufficient for mediating the TGFβ-induced activation of p38 MAPK.
Vaccinia virus protein N2 is a nuclear IRF3 inhibitor that promotes virulence
Authors: Ferguson Brian J. , Benfield Camilla T. O. , Ren Hongwei , Lee Vivian H. , Frazer Gordon L. , Strnadova Pavla , Sumner Rebecca P. , Smith Geoffrey L.
Published: June 2013

Vaccinia virus (VACV) expresses many proteins that are non-essential for virus replication but promote virulence by inhibiting components of the host immune response to infection. These immunomodulators include a family of proteins that have, or are predicted to have, a structure related to the B-cell lymphoma (Bcl)-2 protein. Five members of the VACV Bcl-2 family (N1, B14, A52, F1 and K7) have had their crystal structure solved, others have been characterized and a function assigned (C6, A46), and others are predicted to be Bcl-2 proteins but are uncharacterized hitherto (N2, B22, C1). Data presented here show that N2 is a nuclear protein that is expressed early during infection and inhibits the activation of interferon regulatory factor (IRF)3. Consistent with its nuclear localization, N2 inhibits IRF3 downstream of the TANK-binding kinase (TBK)-1 and after IRF3 translocation into the nucleus. A mutant VACV strain Western Reserve lacking the N2L gene (vΔN2) showed normal replication and spread in cultured cells compared to wild-type parental (vN2) and revertant (vN2-rev) viruses, but was attenuated in two murine models of infection. After intranasal infection, the vΔN2 mutant induced lower weight loss and signs of illness, and virus was cleared more rapidly from the infected tissue. In the intradermal model of infection, vΔN2 induced smaller lesions that were resolved more rapidly. In summary, the N2 protein is an intracellular virulence factor that inhibits IRF3 activity in the nucleus.
cis-Dichlorido(3,6,9-trithiabicyclo[9.3.1]pentadecane-κ2S3,S6)palladium(II) acetonitrile 0.8-solvate
Authors: Dawe Louise Nicole , Penney Lisa , Black Daniel A. , Miller David O. , Lucas C. Robert
Published: June 2013

In the title complex, [PdCl2(C12H22S3)]·0.8CH3CN, a potentially tridentate thioether ligand coordinates in acis-bidentate manner to yield a square-planar environment for the PdIIcation [mean deviation of the Pd from the Cl2S2plane = 0.0406 (7) Å]. Each square-planar entity packs in an inverse face-to-face manner, giving pairs with plane-to-plane separations of 3.6225 (12) Å off-set by 1.1263 (19) Å, with a Pd...Pd separation of 3.8551 (8) Å. A partial acetonitrile solvent molecule is present. The occupancy of this molecule was allowed to refine, and converged to 0.794 (10). The synthesis of the previously unreported 3,6,9-trithiabicyclo[9.3.1]pentadecane ligand is also outlined.
Br...O contacts and π–π stacking dominate the packing in methyl 4-bromo-3,5-dimethoxybenzoate
Authors: Saeed Aamer , Qasim Muhammad , Simpson Jim
Published: June 2013

The title compound, C10H11BrO4, a useful precursor to pharmaceutically active isocoumarin and isochroman derivatives, crystallizes with two unique molecules in the asymmetric unit. A π–π stacking interaction links the planar molecules in the asymmetric unit. Additional π–π contacts stack pairs of molecules along thecaxis. A feature of the crystal packing is the presence of a number of short Br...O contacts. A particularly unusual arrangement involves the formation of dimers, with pairs of Br...O contacts imposing a close Br...Br interaction and generating five-membered rings within an eight-membered ring formed by two Br...O contacts. Only two comparable arrangements have been reported previously. The Br...O contacts combine with weak C—H...O hydrogen bonds to form corrugated sheets of molecules approximately parallel to (001). These sheets are stacked along thecaxis by π–π interactions to generate a three-dimensional network.
Staffing trends in college and university libraries
Authors: Gremmels Gillian S.
Published: June 2013

Purpose

The paper aims to discern, document, and analyze current staffing trends in college and university libraries.

Design/methodology/approach

The author gathered information from the literatures of library and information science and higher education.

Findings

The paper details six trends across public and technical services affecting librarians, non‐MLS professionals, and paraprofessionals. The presentation of trends is followed by a discussion of three concerns the author has about these trends.

Research limitations/implications

The paper covers trends in college and university libraries but does not specifically address community college libraries. Community colleges may have similar issues, as well as unique trends; further research is encouraged.

Practical implications

Library managers will be able to compare developments in their libraries to the profession‐wide trends. They will also be able to link to a large body of literature on the topic.

Originality/value

This kind of comprehensive look at academic library staffing does not seem to have been published recently.
Evaluating reference data accuracy: a mixed methods study
Authors: Graber Alison , Alexander Stephanie , Bresnahan Megan , Gerke Jennie
Published: June 2013

Purpose

Reference data collection tools facilitate the collection of in‐depth data about reference interactions. Since this information may influence decisions, library managers should examine how these tools are used and assess how these data entry behaviors may impact the accuracy of the data. This paper aims to analyze reference staff perceptions and data entry behaviors using a reference data collection tool.

Design/methodology/approach

The two‐year mixed method study analyses reference staff perceptions and data entry behaviors related to the reference data collection tool used at the University of Colorado Boulder Libraries. The authors identified six distinct data entry behaviors for analysis in this study.

Findings

The survey results indicate that staff consider the tool to be both easy to use and useful. These findings, under the technology acceptance model, indicate technology acceptance, which influences adoption and use of the tool. Though rates of adoption and use of the tool are high, the authors' analysis of behaviors indicate that not all users record reference interactions in the same way, and this inconsistency may impact the accuracy of collected data.

Practical implications

Inconsistency in data entry behaviors should inform the design of staff training sessions, best practice guidelines, and the tool's interface.

Social implications

If data are used to justify changes to services and collections, decision makers need to be confident that data accurately reflect activity at library service points.

Originality/value

Previous studies related to reference data collection mention the importance of consistent data entry practices, but no studies have explicitly evaluated how inconsistencies in use may impact the accuracy of data.
Financial flexibility and the performance during the recent financial crisis
Authors: Meier Iwan , Bozec Yves , Laurin Claude
Published: June 2013

Purpose

The objective of this study is to test whether financial flexibility has value. Using the current financial crisis, the authors investigate whether firms that built up financial flexibility over the years preceding the crisis yield superior performance during the financial crisis.

Design/methodology/approach

Financial flexibility is measured along the following dimensions: cash and cash equivalents, debt (short‐term and total) and net debt. These proxies are measured as an average over the five years prior to the crisis, from September 2002 to August 2007. Firms are then sorted into ten portfolios and monthly stock returns for each portfolio are evaluated over the crisis period from September 2007 to March 2010.

Findings

The authors' results show that high pre‐crisis levels of cash do not seem to have a positive impact on firm value during the crisis. However, the results provide evidence that high pre‐crisis levels of debt had a negative impact on firm value during the latest financial crisis, supporting the hypothesis that financial flexibility has value.

Originality/value

The originality of the authors' approach is to evaluate the value of financial flexibility during a financial crisis. The recent financial crisis offers an ideal test case to evaluate whether financial flexibility has indeed value for the firm.
Exciting electrode optimization of a piezoceramic plate type ultrasonic motor by combining artificial immune algorithm and finite element analysis
Authors: Li Cun‐Cen , Yang Ming , Pang Ya‐Fei , Li Shi‐Yang
Published: June 2013

Purpose

The purpose of this paper is to propose an optimization method by combining artificial immune algorithm and finite element analysis to find the optimal exciting electrode of a piezoceramic plate type ultrasonic motor vibrator.

Design/methodology/approach

The artificial immune algorithm is selected as optimizer for its merit of fast convergence to global optimal solution. The finite element analysis is used to calculate the motion trajectory of contact point. The objective function is the work that the vibrator does to rotor. The design variables are the boundaries of exciting electrode on piezoceramic plate vibrator surface.

Findings

The calculated results and the experimental results show that using this method, both the position and the size of optimal exciting electrode of this ultrasonic motor can be quickly and accurately determined.

Originality/value

In order to successfully design an ultrasonic motor, both the position and the size of the exciting electrode must be investigated, so as to change more electric energy into mechanical energy. In this paper, an optimization method by combining artificial immune algorithm and finite element analysis is proposed for the exciting location optimization of a piezoceramic plate type ultrasonic motor to obtain large power output.