bluuebunny/crossref_metadata_2025 huggingface dataset:
Local magnetic moment formation at Sn119 Mössbauer impurity in RCo2 (R=Gd,Tb,Dy,Ho,Er) Laves phase compounds
Authors: de Oliveira A. L. , de Oliveira N. A. , Troper A.
Published: February 2008

In this work, we theoretically study the local magnetic moment formation and the systematics of the magnetic hyperfine fields at a Mösbauer Sn119 impurity diluted at the R site (R=Gd,Tb,Dy,Ho,Er) of the cubic Laves phase intermetallic compounds RCo2. One considers that the magnetic hyperfine fields have two contributions, (i) the contribution from R ions, calculated via an extended Daniel-Friedel [J. Phys. Chem. Solids 24, 1601 (1963)] model, and (ii) the contribution from the induced magnetic moments arising from the Co neighboring sites. Our calculated self-consistent total magnetic hyperfine fields are in a good agreement with recent experimental data.
Model and magnetic configuration effect on shock layer enhancement by an applied magnetic field
Authors: Matsuda Atsushi , Otsu Hirotaka , Kawamura Masaaki , Konigorski Detlev , Takizawa Yuji , Sato Shunichi , Abe Takashi
Published: February 2008

The combined effect of the model configuration and the magnetic field configuration on shock layer enhancement phenomena attributable to the applied magnetic field was investigated experimentally. For this study, two test models were used. One was a flat-faced model with a cylindrical permanent magnet. The other was a spherical blunt model with a spherical permanent magnet. The translational temperature distributions ahead of the two test models (i.e., the shock layer region) were measured using laser absorption spectroscopy. Comparison of the results obtained using the two test model cases showed that the shock layer enhancement caused by the applied magnetic field was greater for the spherical blunt model than for the flat-faced model. That experimental result qualitatively agrees with the computational fluid dynamics results, which suggest that the combined effect of the magnetic configuration and stream line (i.e., the model configuration) play key roles in shock layer enhancement phenomena.
High frequency EPR on dilute solutions of the single molecule magnet Ni4
Authors: de Loubens G. , Kent A. D. , Krymov V. , Gerfen G. J. , Beedle C. C. , Hendrickson D. N.
Published: February 2008

Dilute frozen solutions of the single molecule magnet Ni4 (S=4) have been studied using 130GHz electron paramagnetic resonance (EPR). Despite the random orientation of the molecules, well defined EPR absorption peaks are observed due to the strong variation of the splittings between the different spin states on magnetic field. Temperature dependent studies above 4K and comparison with simulations enable identification of the spin transitions and determination of the Hamiltonian parameters. The latter are found to be close to those of Ni4 single crystals. No echo was detected from Ni4 in pulsed experiments, which sets an upper bound of about 50ns on the spin coherence time.
Development of a second generation torsion balance based on a spherical superconducting suspension
Authors: Hammond Giles D. , Speake Clive C. , Matthews Anthony J. , Rocco Emanuele , Peña-Arellano Fabian
Published: February 2008

This paper describes the development of a second generation superconducting torsion balance to be used for a precision measurement of the Casimir force and a short range test of the inverse square law of gravity at 4.2K. The instrument utilizes niobium (Nb) as the superconducting element and employs passive damping of the parasitic modes of oscillation. Any contact potential difference between the torsion balance and its surroundings is nulled to within ≈50mV by applying known DC biases and fitting the resulting parabolic relationship between the measured torque and the applied voltage. A digital proportional-integral-derivative servo system has been developed and characterized in order to control the azimuthal position of the instrument. The angular acceleration and displacement noise are currently limited by the capacitive sensor at the level 3×10−8rads−2∕Hz and 30nm∕Hz at 100mHz. The possibility of lossy dielectric coatings on the surface of the torsion balance test masses is also investigated. Our measurements show that the loss angles δ are (1.5±2.3)×10−4 and (2.0±2.2)×10−4 at frequencies of 5 and 10mHz, respectively. These values of loss are not significant sources of error for measurements of the Casimir force using this experimental setup.
A portable energy-sensitive cosmic neutron detection instrument
Authors: Monk S. D. , Joyce M. J. , Jarrah Z. , King D. , Oppenheim M.
Published: February 2008

The construction and testing of a portable energy-sensitive neutron instrument are described. This instrument has been designed and constructed for the primary purpose of characterizing cosmic-ray neutron fields in the upper atmosphere and in cosmic reference field facilities. The instrument comprises a helium-3 proportional counter surrounded by 15mm of lead and 140mm of polyethylene creating a spherical structure with a diameter of 34cm. The instrument also incorporates 12 boron-coated diodes, six on the outside of the polyethylene layer with six placed within the structure. The dimensions, materials, and arrangement of these in the instrument have previously been optimized with the MCNPX Monte Carlo simulation software to provide a compromise between the requirements of portability and spectral response. Testing took place at several locations and experimental data from the instrument’s operation at the high-altitude Jungfraujoch laboratory in the Swiss alps are presented.
Spectral features of the geodesic acoustic mode and its interaction with turbulence in a tokamak plasma
Authors: Lan T. , Liu A. D. , Yu C. X. , Yan L. W. , Hong W. Y. , Zhao K. J. , Dong J. Q. , Qian J. , Cheng J. , Yu D. L. , Yang Q. W.
Published: February 2008

The three-dimensional wavenumber and frequency spectrum for the geodesic acoustic mode (GAM) has been measured in the HuanLiuqi-2A tokamak for the first time. The spectrum provides definite evidence for the GAM, which is characterized by kθ=kϕ=0 and krρi≈0.04−0.09 with the full width at half-maximum Δkrρi≈0.03−0.07. The localized GAM packet is observed to propagate outward in the radial direction with nearly the same phase and group velocity. The envelopes of the radial electric field and density fluctuations are observed to be modulated by the GAM. By comparing the experimental result with that of the envelope analysis using model signals, the mechanism of the envelope modulation has been identified. The results strongly suggest that the envelope modulation of the Ẽr fluctuations is dominantly caused by the direct regulation of the GAM during the GAM generation in the energy-conserving triad interaction, and the envelope modulation of the density fluctuations is induced by the GAM shearing effect, which transfers the fluctuation energy from low to high frequencies. In addition, the cross- and auto-bicoherences for interactions between the GAM and turbulent fluctuations show a similar peaked feature that may reflect the resonant property in the nonlinear coupling between the GAM and turbulent fluctuations.
Neutral modes of a two-dimensional vortex and their link to persistent cat’s eyes
Authors: Turner M. R. , Gilbert Andrew D. , Bassom Andrew P.
Published: February 2008

This paper considers the relaxation of a smooth two-dimensional vortex to axisymmetry after the application of an instantaneous, weak external strain field. In this limit the disturbance decays exponentially in time at a rate that is linked to a pole of the associated linear inviscid problem (known as a Landau pole). As a model of a typical vortex distribution that can give rise to cat’s eyes, here distributions are examined that have a basic Gaussian shape but whose profiles have been artificially flattened about some radius rc. A numerical study of the Landau poles for this family of vortices shows that as rc is varied so the decay rate of the disturbance moves smoothly between poles as the decay rates of two Landau poles cross. Cat’s eyes that occur in the nonlinear evolution of a vortex lead to an axisymmetric azimuthally averaged profile with an annulus of approximately uniform vorticity, rather like the artificially flattened profiles investigated. Based on the stability of such profiles it is found that finite thickness cat’s eyes can persist (i.e., the mean profile has a neutral mode) at two distinct radii, and in the limit of a thin flattened region the result that vanishingly thin cat’s eyes only persist at a single radius is recovered. The decay of nonaxisymmetric perturbations to these flattened profiles for larger times is investigated and a comparison made with the result for a Gaussian profile.
Field-induced phases of an orientable charged particle in a dilute background of point charges
Authors: Lancellotti Carlo , Sundaram Bala
Published: February 2008

We report numerical simulations of a two-dimensional dynamical model comprised of a rodlike particle surrounded by a cloud of smaller particles of the same charge, in the presence of an alternating electric field inside a box. We show that this system displays a remarkable dynamical effect; at low forcing frequencies the rod tends to align perpendicularly to the external field, whereas for higher field frequencies the standard orientation (parallel to the field) prevails. Interestingly, the transition between orientations is abrupt enough to resemble a phase transition. The fact that the “anomalous” orientation (perpendicular to the field) takes place is also interesting in the light of some recent laboratory experiments on colloidal solutions, where anomalous orientation at low frequencies was observed. Our toy model suggests that future physically realistic simulations of these systems should explore whether the anomalous orientation may be due to the collective dynamics of the colloidal particles, without necessarily involving more sophisticated electro-osmotic effects.
Electron/ion energy loss to discharge walls revised: A case study in low-temperature, thermally nonequilibrium plasmas
Authors: Ren Y. P. , Ostrikov K. , Xu S.
Published: February 2008

Reliable calculations of the electron/ion energy losses in low-pressure thermally nonequilibrium low-temperature plasmas are indispensable for predictive modeling related to numerous applications of such discharges. The commonly used simplified approaches to calculation of electron/ion energy losses to the chamber walls use a number of simplifying assumptions that often do not account for the details of the prevailing electron energy distribution function (EEDF) and overestimate the contributions of the electron losses to the walls. By direct measurements of the EEDF and careful calculation of contributions of the plasma electrons in low-pressure inductively coupled plasmas, it is shown that the actual losses of kinetic energy of the electrons and ions strongly depend on the EEDF. It is revealed that the overestimates of the total electron/ion energy losses to the walls caused by improper assumptions about the prevailing EEDF and about the ability of the electrons to pass through the repulsive potential of the wall may lead to significant overestimates that are typically in the range between 9 and 32%. These results are particularly important for the development of power-saving strategies for operation of low-temperature, low-pressure gas discharges in diverse applications that require reasonably low power densities.
Ferromagnetic resonance linewidth reduction in Fe∕Au multilayers using ion beams
Authors: Bilzer C. , Devolder T. , Chappert C. , Plantevin O. , Suszka A. K. , Hickey B. J. , Lamperti A. , Tanner B. K. , Mahrov B. , Demokritov S. O.
Published: February 2008

In order to optimize their magnetic properties, Fe∕Au multilayers were treated by pregrowth and postgrowth ion-beam bombardments. The ferromagnetic resonance linewidth was used as our main figure of merit. The pregrowth treatment of the MgO substrate using a 60eV atomic oxygen beam resulted in a reduction of the inhomogeneous linewidth broadening in comparison with a sample grown on an untreated substrate. This homogeneity increase is linked to the removal of substrate carbon contamination by the chemically active oxygen. It correlates with the reduced interface roughness. The postgrowth sample irradiation using 30keV He+ ions also reduces the inhomogeneous broadening in the linewidth. Fe and Au have a miscibility gap, but the demixing is kinetically quenched at room temperature. Ion collisions locally minimize the interface energy by providing the energy necessary for localized demixing, resulting in a smoothing effect. Combined, the pregrowth and the postgrowth irradiations lead to the lowest observed linewidth.
Time-of-arrival probabilities and quantum measurements. III. Decay of unstable states
Authors: Anastopoulos Charis
Published: February 2008

We study the decay of unstable states by formulating quantum tunneling as a time-of-arrival problem: we determine the detection probability for particles at a detector located a distance L from the tunneling region. For this purpose, we use a positive-operator-valued measure (POVM) for the time-of-arrival determined by Anastopoulos and Savvidou [J. Math. Phys. 47, 122106 (2006)]. This only depends on the initial state, the Hamiltonian, and the location of the detector. The POVM above provides a well-defined probability density and an unambiguous interpretation of all quantities involved. We demonstrate that the exponential decay only arises if three specific mathematical conditions are met. Their physical content is the following: (i) the decay time is much larger than any microscopic timescale, so that the fine details of the initial state can be ignored, (ii) there is no quantum coherence between the different “attempts” of the particle to traverse the barrier, and (iii) the transmission probability varies little within the momentum spread of the initial state. We also determine the long time limits of the decay probability and we identify regimes, in which the decays have no exponential phase.
Large volume Bridgman seal cell for neutron scattering experiments at ultralow temperatures
Authors: Done Robert , Chowdhury Mohammad , Goodway Chris , Adams Mark , Kirichek Oleg
Published: February 2008

A pressure cell (maximum working pressure of 100bars) has been developed for neutron scattering experiments at ultralow temperatures (T<100mK) which makes use of a Bridgman seal design more usually seen in higher temperature experiments in the kilobar range. The large volume of the cell (∼18cm3) and its construction from a high-strength aluminum alloy make it suitable for inelastic neutron scattering experiments. The cell has been proof tested in operando in search for the supersolid state of helium-4.
In situ 3ω techniques for measuring thermal conductivity of phase-change materials
Authors: Risk W. P. , Rettner C. T. , Raoux S.
Published: February 2008

Knowledge of the thermal conductivity of phase-change materials is essential for accurate modeling of nonvolatile memory devices that incorporate them. The “3ω method” is a well-established and sensitive technique for measuring this property. We report two new extensions of the 3ω technique that feature in situ monitoring of the phase-change material as it transitions from the as-deposited amorphous phase to the crystalline phase. One technique crystallizes the entire sample in a vacuum oven, while using the 3ω voltage to monitor the phase transition. The other technique uses the 3ω heater to crystallize only the material in the region of measurement.
Magneto-optical setup for in situ strain and transport measurements on superconductors
Authors: Villaume A. , Antonevici A. , Bourgault D. , Leggeri J. P. , Porcar L. , Villard C.
Published: February 2008

A recently developed magneto-optical (MO) imaging setup for investigations on superconductors is reported. The main originality of our setup is its ability to combine both strain and transport measurements in the temperature range of 6–300K with magneto-optical observations. We give here some theoretical considerations on the cryostat conception, which is a key point of our setup. In particular, the thermal and mechanical aspects are discussed. A detailed description of the MO setup and of the associated strain apparatus is given. Additionally, an example of MO strain and transport study on DyBCO coated conductors is given. Evidence of Luders Bands formation under strain in the Hastelloy® is revealed by the field penetration inside cracks in the DyBCO and MgO layers. A correlation between the damaging morphology and the critical current at 70K versus strain has been established.
A test of the chromosomal theory of ecotypic speciation inAnopheles gambiae
Authors: Manoukis Nicholas C. , Powell Jeffrey R. , Touré Mahamoudou B. , Sacko Adama , Edillo Frances E. , Coulibaly Mamadou B. , Traoré Sekou F. , Taylor Charles E. , Besansky Nora J.
Published: February 2008

The role of chromosomal inversions in speciation has long been of interest to evolutionists. Recent quantitative modeling has stimulated reconsideration of previous conceptual models for chromosomal speciation.Anopheles gambiae, the most important vector of human malaria, carries abundant chromosomal inversion polymorphism nonrandomly associated with ecotypes that mate assortatively. Here, we consider the potential role of paracentric inversions in promoting speciation inA. gambiaevia “ecotypification,” a term that refers to differentiation arising from local adaptation. In particular, we focus on the Bamako form, an ecotype characterized by low inversion polymorphism and fixation of an inversion, 2Rj, that is very rare or absent in all other forms ofA. gambiae. The Bamako form has a restricted distribution by the upper Niger River and its tributaries that is associated with a distinctive type of larval habitat, laterite rock pools, hypothesized to be its optimal breeding site. We first present computer simulations to investigate whether the population dynamics ofA. gambiaeare consistent with chromosomal speciation by ecotypification. The models are parameterized using field observations on the various forms ofA. gambiaethat exist in Mali, West Africa. We then report on the distribution of larvae of this species collected from rock pools and more characteristic breeding sites nearby. Both the simulations and field observations support the thesis that speciation by ecotypification is occurring, or has occurred, prompting consideration of Bamako as an independent species.
Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis
Authors: Perumal Shiamalee , Antipova Olga , Orgel Joseph P. R. O.
Published: February 2008

We describe the molecular structure of the collagen fibril and how it affects collagen proteolysis or “collagenolysis.” The fibril-forming collagens are major components of all mammalian connective tissues, providing the structural and organizational framework for skin, blood vessels, bone, tendon, and other tissues. The triple helix of the collagen molecule is resistant to most proteinases, and the matrix metalloproteinases that do proteolyze collagen are affected by the architecture of collagen fibrils, which are notably more resistant to collagenolysis than lone collagen monomers. Until now, there has been no molecular explanation for this. Full or limited proteolysis of the collagen fibril is known to be a key process in normal growth, development, repair, and cell differentiation, and in cancerous tumor progression and heart disease. Peptide fragments generated by collagenolysis, and the conformation of exposed sites on the fibril as a result of limited proteolysis, regulate these processes and that of cellular attachment, but it is not known how or why. Using computational and molecular visualization methods, we found that the arrangement of collagen monomers in the fibril (its architecture) protects areas vulnerable to collagenolysis and strictly governs the process. This in turn affects the accessibility of a cell interaction site located near the cleavage region. Our observations suggest that the C-terminal telopeptide must be proteolyzed before collagenase can gain access to the cleavage site. Collagenase then binds to the substrate's “interaction domain,” which facilitates the triple-helix unwinding/dissociation function of the enzyme before collagenolysis.
Amino acid polymorphisms in
Arabidopsis
phytochrome B cause differential responses to light
Authors: Filiault Daniele L. , Wessinger Carolyn A. , Dinneny Jose R. , Lutes Jason , Borevitz Justin O. , Weigel Detlef , Chory Joanne , Maloof Julin N.
Published: February 2008

Plants have a sophisticated system for sensing and responding to their light environment. The light responses of populations and species native to different habitats show adaptive variation; understanding the mechanisms underlying photomorphogenic variation is therefore of significant interest. In
Arabidopsis thaliana
, phytochrome B (PHYB) is the dominant photoreceptor for red light and plays a major role in white light. Because
PHYB
has been proposed as a candidate gene for several quantitative trait loci (QTLs) affecting light response, we have investigated sequence and functional variation in
Arabidopsis PHYB
. We examined
PHYB
sequences in 33
A. thaliana
individuals and in the close relative
Arabidopsis lyrata
. From 14 nonsynonymous polymorphisms, we chose 5 for further study based on previous QTL studies. In a larger collection of
A. thaliana
accessions, one of these five polymorphisms, I143L, was associated with variation in red light response. We used transgenic analysis to test this association and confirmed experimentally that natural
PHYB
polymorphisms cause differential plant responses to light. Furthermore, our results show that allelic variation of
PHYB
activity is due to amino acid rather than regulatory changes. Together with earlier studies linking variation in light sensitivity to photoreceptor genes, our work suggests that photoreceptors may be a common target of natural selection.
WAVE1 controls neuronal activity-induced mitochondrial distribution in dendritic spines
Authors: Sung Jee Young , Engmann Olivia , Teylan Merilee A. , Nairn Angus C. , Greengard Paul , Kim Yong
Published: February 2008

Mitochondrial fission and trafficking to dendritic protrusions have been implicated in dendritic spine development. Here, we show that Wiskott–Aldrich syndrome protein (WASP)-family verprolin homologous protein 1 (WAVE1) controls depolarization-induced mitochondrial movement into dendritic spines and filopodia and regulates spine morphogenesis. Depolarization-induced degradation of the p35 regulatory subunit of cyclin-dependent kinase 5 (Cdk5), with the resultant decreased inhibitory phosphorylation on WAVE1, depend on NMDA receptor activation. Thus, WAVE1 dephosphorylation and activation are likely associated with mitochondrial redistribution and spine morphogenesis.
Unfolded protein response and cell death after depletion of brefeldin A-inhibited guanine nucleotide-exchange protein GBF1
Authors: Citterio Carmen , Vichi Alessandro , Pacheco-Rodriguez Gustavo , Aponte Angel M. , Moss Joel , Vaughan Martha
Published: February 2008

Guanine nucleotide-exchange factors (GEFs) activate ADP-ribosylation factor (ARF) GTPases that recruit coat proteins to membranes to initiate transport vesicle formation. Three mammalian GEFs are inhibited by brefeldin A (BFA). GBF1, predominantly associated with
cis
-Golgi membranes, functions early in the secretory pathway, whereas BIG1 and BIG2 act in
trans
-Golgi or later sites. Perturbation of endoplasmic reticulum (ER) functions can result in accumulation of unfolded or misfolded proteins that causes ER stress and unfolded protein response (UPR), with accumulation of ER stress response element (ERSE) gene products. BFA treatment of cells causes accumulation of proteins in the ER, ER stress, and ultimately apoptosis. To assess involvement of BFA-sensitive GEFs in the damage resulting from prolonged BFA treatment, HepG2 cells were selectively depleted of BIG1, BIG2, or GBF1 by using specific siRNA. Only GBF1 siRNA dramatically slowed cell growth, led to cell-cycle arrest in G
0
/G
1
phase, and caused dispersion of Golgi markers β-COP and GM130, whereas ER structure appeared intact. GBF1 depletion also significantly increased levels of ER proteins calreticulin and protein disulfide isomerase (PDI). Proteomic analysis identified ER chaperones involved in the UPR that were significantly increased in amounts in GBF1-depleted cells. Upon ER stress, transcription factor ATF6 translocates from the ER to Golgi, where it is sequentially cleaved by site 1 and site 2 proteases, S1P and S2P, to a 50-kDa form that activates transcription of ERSE genes. Depletion of GBF1, but not BIG1 or BIG2, induced relocation of S2P from Golgi to ER with proteolysis of ATF6 followed by up-regulation of ER chaperones, mimicking a UPR response.
Requirement of protein kinase D1 for pathological cardiac remodeling
Authors: Fielitz Jens , Kim Mi-Sung , Shelton John M. , Qi Xiaoxia , Hill Joseph A. , Richardson James A. , Bassel-Duby Rhonda , Olson Eric N.
Published: February 2008

The adult heart responds to biomechanical stress and neurohormonal signaling by hypertrophic growth, accompanied by fibrosis, diminished pump function, and activation of a fetal gene program. Class II histone deacetylases (HDACs) suppress stress-dependent remodeling of the heart via their association with the MEF2 transcription factor, an activator of heart disease. Protein kinase D (PKD) is a stress-responsive kinase that phosphorylates class II HDACs, resulting in their dissociation from MEF2 with consequent activation of MEF2 target genes. To test whether PKD1 is required for pathological cardiac remodeling
in vivo
, we generated mice with a conditional PKD1-null allele. Mice with cardiac-specific deletion of PKD1 were viable and showed diminished hypertrophy, fibrosis, and fetal gene activation as well as improved cardiac function in response to pressure overload or chronic adrenergic and angiotensin II signaling. We conclude that PKD1 functions as a key transducer of stress stimuli involved in pathological cardiac remodeling
in vivo
.
The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors
Authors: Lin David Yin-wei , Tanaka Yoshimasa , Iwasaki Masashi , Gittis Apostolos G. , Su Hua-Poo , Mikami Bunzo , Okazaki Taku , Honjo Tasuku , Minato Nagahiro , Garboczi David N.
Published: February 2008

Signaling through the programmed death 1 (PD-1) inhibitory receptor upon binding its ligand, PD-L1, suppresses immune responses against autoantigens and tumors and plays an important role in the maintenance of peripheral immune tolerance. Release from PD-1 inhibitory signaling revives “exhausted” virus-specific T cells in chronic viral infections. Here we present the crystal structure of murine PD-1 in complex with human PD-L1. PD-1 and PD-L1 interact through the conserved front and side of their Ig variable (IgV) domains, as do the IgV domains of antibodies and T cell receptors. This places the loops at the ends of the IgV domains on the same side of the PD-1/PD-L1 complex, forming a surface that is similar to the antigen-binding surface of antibodies and T cell receptors. Mapping conserved residues allowed the identification of residues that are important in forming the PD-1/PD-L1 interface. Based on the structure, we show that some reported loss-of-binding mutations involve the PD-1/PD-L1 interaction but that others compromise protein folding. The PD-1/PD-L1 interaction described here may be blocked by antibodies or by designed small-molecule drugs to lower inhibitory signaling that results in a stronger immune response. The immune receptor-like loops offer a new surface for further study and potentially the design of molecules that would affect PD-1/PD-L1 complex formation and thereby modulate the immune response.
Economic Analysis of Reprocessing Single-Use Medical Devices: A Systematic Literature Review
Authors: Jacobs Philip , Polisena Julie , Hailey David , Lafferty Susan
Published: February 2008

Background.

Although an increasing number of medical devices are labeled “for single use only,” cleaning and reuse of single-use medical devices continues, because of the economic incentive. We conducted a survey of the economic literature to obtain the current evidence available and to assess the costs and benefits of reusing single-use medical devices.

Methods.

A comprehensive literature search was carried out to identify articles that compared single use and reuse of single-use medical devices and that met specific scientific criteria, including evaluation of economic outcomes. Each selected article was independently reviewed by 2 reviewers to extract cost and clinical outcome data and to assess the quality of the study.

Results.

Nine published articles met the selection criteria. The savings were about 49% of the direct cost. These savings would be offset by adverse-event costs, but none were detected. However, quality of the studies was generally poor.

Conclusions.

There is little available evidence of quality in the published literature to assess the practice of reuse of single-use medical devices. Moreover, data on clinical outcomes are missing and, where available, cannot be attributed specifically to the reuse of single-use medical devices.
Nanos2 suppresses meiosis and promotes male germ cell differentiation
Authors: Suzuki Atsushi , Saga Yumiko
Published: February 2008

In mouse fetal gonads, retinoic acid (RA) induces meiosis in the female germ cells, whereas the male germ cells never enter meiosis due to Cyp26b1-mediated RA metabolism. We show here that Nanos2 plays critical roles in the differentiation of male germ cells. We find that Nanos2 maintains the suppression of meiosis by preventing Stra8 expression, which is required for premeiotic DNA replication, after Cyp26b1 is decreased. We also demonstrate that Nanos2 activates a male-specific genetic program, which is supported by the inhibition of meiosis and the induction of male-type differentiation in female germ cells following the forced expression of Nanos2.
Sumoylation regulates multiple aspects of mammalian poly(A) polymerase function
Authors: Vethantham Vasupradha , Rao Nishta , Manley James L.
Published: February 2008

The addition of the poly(A) tail to the ends of eukaryotic mRNAs is catalyzed by poly(A) polymerase (PAP). PAP activity is known to be highly regulated, for example, by alternative splicing and phosphorylation. In this study we show that the small ubiquitin-like modifier (SUMO) plays multiple roles in regulating PAP function. Our discovery of SUMO-conjugated PAP began with the observation of a striking pattern of abundant higher-molecular-weight forms of PAP in certain mouse tissues and cell lines. PAP constitutes an unusual SUMO substrate in that, despite the absence of any consensus sumoylation sites, PAP interacts very strongly with the SUMO E2 enzyme ubc9 and can be extensively sumoylated both in vitro and in vivo. Six sites of sumoylation in PAP were identified, with two overlapping one of two nuclear localization signals (NLS). Strikingly, mutation of the two lysines at the NLS to arginines, or coexpression of a SUMO protease with wild-type PAP, caused PAP to be localized to the cytoplasm, demonstrating that sumoylation is required to facilitate PAP nuclear localization. Sumoylation also contributes to PAP stability, as down-regulation of sumoylation led to decreases in PAP levels. Finally, the activity of purified PAP was shown to be inhibited by in vitro sumoylation. Our study thus shows that SUMO regulates PAP in numerous distinct ways and is integral to normal PAP function.
Prohibitins control cell proliferation and apoptosis by regulating OPA1-dependent cristae morphogenesis in mitochondria
Authors: Merkwirth Carsten , Dargazanli Sascha , Tatsuta Takashi , Geimer Stefan , Löwer Beatrix , Wunderlich F. Thomas , von Kleist-Retzow Jürgen-Christoph , Waisman Ari , Westermann Benedikt , Langer Thomas
Published: February 2008

Prohibitins comprise an evolutionarily conserved and ubiquitously expressed family of membrane proteins with poorly described functions. Large assemblies of PHB1 and PHB2 subunits are localized in the inner membrane of mitochondria, but various roles in other cellular compartments have also been proposed for both proteins. Here, we used conditional gene targeting of murine Phb2 to define cellular activities of prohibitins. Our experiments restrict the function of prohibitins to mitochondria and identify the processing of the dynamin-like GTPase OPA1, an essential component of the mitochondrial fusion machinery, as the central cellular process controlled by prohibitins. Deletion of Phb2 leads to the selective loss of long isoforms of OPA1. This results in an aberrant cristae morphogenesis and an impaired cellular proliferation and resistance toward apoptosis. Expression of a long OPA1 isoform in PHB2-deficient cells suppresses these defects, identifying impaired OPA1 processing as the primary cellular defect in the absence of prohibitins. Our results therefore assign an essential function for the formation of mitochondrial cristae to prohibitins and suggest a coupling of cell proliferation to mitochondrial morphogenesis.
Trabid, a new positive regulator of Wnt-induced transcription with preference for binding and cleaving K63-linked ubiquitin chains
Authors: Tran Hoanh , Hamada Fumihiko , Schwarz-Romond Thomas , Bienz Mariann
Published: February 2008

A key effector of the canonical Wnt pathway is β-catenin, which binds to TCF/LEF factors to promote the transcription of Wnt target genes. In the absence of Wnt stimulation, β-catenin is phosphorylated constitutively, and modified with K48-linked ubiquitin for subsequent proteasomal degradation. Here, we identify Trabid as a new positive regulator of Wnt signaling in mammalian and Drosophila cells. Trabid show a remarkable preference for binding to K63-linked ubiquitin chains with its three tandem NZF fingers (Npl4 zinc finger), and it cleaves these chains with its OTU (ovarian tumor) domain. These activities of Trabid are required for efficient TCF-mediated transcription in cells with high Wnt pathway activity, including colorectal cancer cell lines. We further show that Trabid can bind to and deubiquitylate the APC tumor suppressor protein, a negative regulator of Wnt-mediated transcription. Epistasis experiments indicate that Trabid acts below the stabilization of β-catenin, and that it may affect the association or activity of the TCF–β-catenin transcription complex. Our results indicate a role of K63-linked ubiquitin chains during Wnt-induced transcription.
Epidural lidocaine‐bicarbonate‐adrenaline vs levobupivacaine for emergency Caesarean section: a randomised controlled trial*
Authors: Allam J. , Malhotra S. , Hemingway C. , Yentis S. M.
Published: February 2008

Epidural mixtures containing lidocaine with or without additives are commonly used to convert epidural analgesia in labour to anaesthesia for emergency Caesarean section, but direct comparisons with alternative, single agents in this situation are few. In a prospective double‐blinded trial, we compared a freshly prepared lidocaine‐bicarbonate‐adrenaline mixture (final concentrations 1.8%, 0.76% and 1 : 200,000, respectively) with our standard agent, levobupivacaine 0.5%, for extending epidural blockade for emergency Caesarean section. Using a sequential analysis technique, with data analysed in blocks of 40, women receiving epidural analgesia in labour who required top‐up for Caesarean section were randomly assigned to receive 20 ml of epidural solution over 3 min. The first analysis (n = 40) indicated that the study should be stopped, as significant differences were found in our primary outcome data. Median (IQR [range]) times to reach a block to touch to T5 and cold to T4 were, respectively, 7 (6–9 [5–17]) min and 7 (5–8 [4–17]) min for lidocaine‐bicarbonate‐adrenaline, and 14 (10 −17 [9–31]) min and 11 (9–14 [6–30]) min for levobupivacaine (p = 0.00004 and 0.001, respectively). Pre‐ and intra‐operative supplementation/pain, maternal side‐effects and neonatal outcomes (excluding five women who underwent instrumental delivery) were similar between the groups. Intra‐operative maternal sedation (scored by the mother on a 10‐point scale) was greater with lidocaine‐bicarbonate‐adrenaline (4.5 (3–8 [1–9])) than with levobupivacaine (3 (1–4 [1–7])), but not significantly so (p = 0.07). We conclude that epidural lidocaine‐bicarbonate‐adrenaline halves the onset time when extending epidural analgesia for Caesarean section although there is a possibility of increased maternal sedation.
Coagulation and biochemical effects of balanced salt‐based high molecular weight vs saline‐based low molecular weight hydroxyethyl starch solutions during the anhepatic period of liver transplantation
Authors: Ahn H. J. , Yang M. , Gwak M. S. , Koo M. S. , Bang S. R. , Kim G. S. , Lee S. K.
Published: February 2008

The anhepatic period of liver transplantation is generally marked by a decrease in preload, and the infusion of hydroxyethyl starch (HES) solution is often an effective way to restore volume deficits in non‐anaemic patients. However, the infusion of even limited amounts of HES solution during the anhepatic period may result in a worsening coagulopathy. Moreover, lactate‐containing HES solution may cause some degree of biochemical derangements in compromised recipients. Therefore, we compared two different types of HES solutions: a balanced salt‐based high molecular weight HES solution (670/0.75; high MW group) and a saline‐based low molecular weight HES solution (130/0.4; low MW group) with respect to coagulation and biochemical profiles. First, in an in vitro study (n = 48), thromboelastography was performed to determine the effects of two HES solutions on coagulation after diluting (11%) the recipient's blood sample with each HES solution. Second, in an in vivo study, 500 ml of one of the two 6% HES solution was administered to 74 recipients (n = 37, each group) for 30 min after starting the anhepatic period. The coagulation profiles, including thromboelastography, and biochemical profiles were measured before and 30 min after the end of infusion. Less impairment in the thromboelastography profiles and aPTT was observed in the high MW group. A higher calcium concentration and less reduction in platelet count were noted in the high MW group, but lactate accumulation was greater. In conclusion, a balanced salt‐based high molecular weight HES solution is a more effective volume replacement during the anhepatic period of liver transplantation with respect to coagulation than a saline‐based low molecular weight HES solution, although lactate accumulation is a possible concern.
Apnoea in pregnancy: an investigation using physiological modelling
Authors: McClelland S. H. , Bogod D. G. , Hardman J. G.
Published: February 2008

Oxygen desaturation during apnoea following anaesthetic induction in obstetrics is hazardous for mother and baby. This study investigated apnoea during pregnancy using computer simulation. The Nottingham Physiology Simulator was configured to replicate normal pregnant physiology. Three pregnant and three non‐pregnant subjects were created, representing population variation according to published physiological values. They each commenced apnoea from four levels of pre‐oxygenation from none to 99% complete denitrogenation. During apnoea, the physiological changes of rapid sequence induction were simulated. We found reduced apnoea tolerance in pregnancy, the median [range] time taken to fall to Sao2 < 90% after 99% complete denitrogenation being 4 min 52 s [3:43–6:17] in the pregnant subjects, vs 7 min 25 s [5:49–9:42] in the non‐pregnant subjects. The time taken to fall from Sao2 90% to 40% was 35 s [32–45] in the pregnant vs 45 s [38–56] in the non‐pregnant subjects. Two minutes of pre‐oxygenation by tidal breathing provides approximately 3.5–6 min before desaturation to < 90%.
Tracheal pressures during open suctioning*
Authors: Vanner R. , Bick E.
Published: February 2008

The purpose of this bench‐top study was to determine the subatmospheric tracheal pressures that could be generated by different sizes of suction catheters when placed into the different sizes of tracheal tubes encountered in adult anaesthetic practice. Five sizes of suction catheter were studied from 8 to 16 Fr and five sizes of tracheal tubes from 5 to 9 mm internal diameter. We found that the larger suction catheters generated potentially dangerous levels of subatmospheric pressure. If the size of suction catheter was limited so that the ratio of the outside diameter of the suction catheter to the inside diameter of the tracheal tubes was 0.5 or less, tracheal pressures were not more than 2 mmHg subatmospheric. We were able to recommend sizes of suction catheter to use for each size of tracheal tube.
Population pharmacokinetic modelling for enterohepatic circulation of mycophenolic acid in healthy Chinese and the influence of polymorphisms in UGT1A9
Authors: Jiao Zheng , Ding Jun‐jie , Shen Jie , Liang Hui‐qi , Zhong Long‐jin , Wang Yi , Zhong Ming‐kang , Lu Wei‐yue
Published: February 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Mycophenolic acid (MPA) undergoes enterohepatic circulation (EHC) in the body and several population models have been proposed to describe this process using sparse data.

• Recent studies in Whites have found that polymorphism in UGT1A9 could partly explain the large interindividual variability associated with the pharmacokinetics of MPA.

WHAT THIS STUDY ADDS

• A new population pharmacokinetic model for EHC combining MPA and its main glucuronide metabolite (MPAG) simultaneously was established based on physiological aspects of biliary excretion using intensive sampling data.

• Pharmacokinetic profiles of MPA and MPAG with the UGT1A9 polymorphism in healthy Chinese were characterized.

AIMS

To establish a population pharmacokinetic model that describes enterohepatic circulation (EHC) of mycophenolic acid (MPA) based on physiological considerations and to investigate the influence of polymorphisms of UGT1A9 on the pharmacokinetics of MPA.

METHODS

Pharmacokinetic data were obtained from two comparative bioavailability studies of oral mycophenolic mofetil formulations. Nonlinear mixed effects modelling was employed to develop an EHC model including both MPA and its main glucuronide metabolite (MPAG) simultaneously. Demographic characteristics and UGT1A9 polymorphisms were screened as covariates.

RESULTS

In total, 590 MPA and 589 MPAG concentration–time points from 42 healthy male volunteers were employed in this study. The chain compartment model included an intestinal compartment, a gallbladder compartment, a central and a peripheral compartment for MPA and a central compartment for MPAG. The typical population clearance (CL/F) estimates with its relative standard error for MPA and MPAG were 10.2 l h−1 (5.7%) and 1.38 l h−1 (6.9%), respectively. The amount of MPA recycled in the body was estimated to be 29.1% of the total amount absorbed. Covariate analysis showed that body weight was positively correlated with CL/F of MPA, intercompartment CL/F of MPA and distribution volume of MPA peripheral compartment. Polymorphisms of UGT1A9 did not show any effect on the pharmacokinetics of MPA and MPAG. The model evaluation tests indicated that the proposed model can describe the pharmacokinetic profiles of MPA and MPAG in healthy Chinese subjects.

CONCLUSIONS

The proposed model may provide a valuable approach for planning future pharmacokinetic–pharmacodynamic studies and for designing proper dosage regimens of MPA.
Transfer of chloroquine and desethylchloroquine across the placenta and into milk in Melanesian mothers
Authors: Law Irwin , Ilett Kenneth F. , Hackett L. Peter , Page‐Sharp Madhu , Baiwog Francesca , Gomorrai Servina , Mueller Ivo , Karunajeewa Harin A. , Davis Timothy M. E.
Published: February 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The literature on placental and milk transfer of chloroquine and its major bioactive metabolite desethylchloroquine is sparse and incomplete.

WHAT THIS STUDY ADDS

• We have provided data on the transplacental transfer of chloroquine and desethylchloroquine in Melanesian women (n = 19), measured transfer of these drugs into breast milk (n = 16) and estimated absolute and relative infant doses for the breastfed infant.

• The data for desethylchloroquine are novel.

• In all three areas we have significantly increased both quantity and quality of the available database.

AIMS

To investigate the transfer of chloroquine and its major bioactive metabolite desethylchloroquine across the placenta and into breast milk.

METHODS

In Papua New Guinea, chloroquine (CQ; 25 mg base kg−1) is recommended for prophylaxis of malaria during pregnancy, and at the Alexishafen Health Centre women are routinely prescribed CQ at the time of delivery. Fetal‐cord and maternal serum samples were collected at delivery (n = 19) and milk samples were collected from day 3 to day 17–21 after delivery (n = 16). CQ and its primary active metabolite desethylchloroquine (DECQ) were quantified by high‐performance liquid chromatography. For both CQ and DECQ cord/maternal ratios (C/M) were calculated to characterize placental transfer, and infant exposure via milk was estimated by standard methods.

RESULTS

The median (interquartile range) C/M was 1.1 (0.9, 1.6) for CQ and 1.2 (0.5, 1.8) for DECQ. The average concentration in milk over the time of sampling was 167 μg l−1 (27, 340) for CQ and 54 μg l−1 (22, 106) for DECQ. Estimated absolute and relative infant doses were 34 μg kg−1 day−1 (7, 50) and 15 μg kg−1 day−1 (4, 26), and 2.3% (0.5, 3.6) and 1.0% (0.4, 2.0) for CQ and DECQ (as CQ equivalents), respectively.

CONCLUSION

Infant exposure to CQ and DECQ during pregnancy will be similar to that in the maternal circulation, and dependent on maternal dose and frequency. The median CQ + DECQ relative infant dose of 3.2% (as CQ equivalents) was low, confirming that use of CQ during lactation is compatible with breastfeeding.