bluuebunny/crossref_metadata_2025 huggingface dataset:
Potassium-benzene interactions on Pt(111) studied by metastable atom electron spectroscopy
Authors: Sogo M. , Sakamoto Y. , Aoki M. , Masuda S.
Published: October 2010

Electron emission spectra obtained by thermal collisions of He∗(2S3) metastable atoms with C6H6/Pt(111), C6H6/K/Pt(111), and K/C6H6/Pt(111) were measured in the temperature range of 50–200 K to elucidate the adsorption/aggregation states, thermal stabilities of pure and binary films, and local electronic properties at the organic–metal interface. For C6H6/Pt(111), the He∗(2S3) atoms de-excite on the chemisorbed overlayer predominantly via resonance ionization followed by Auger neutralization and partly via Penning ionization (PI) yielding weak emission just below the Fermi level (EF). We assigned this emission to the C6H6 π-derived states delocalized over the Pt 5d bands on the basis of recent density functional calculations. During the layer-by-layer growth, the C6H6-derived bands via PI reveal a characteristic shift caused by the final-state effect (hole response at the topmost layer). C6H6 molecules chemisorb weakly on the bimetallic Pt(111) (θK=0.1) and physisorb on the K multilayer. In both cases, the sum rule was found to be valid between the K 4s and C6H6-derived bands. The band intensity versus exposure plot indicates that the C6H6 film grows on the K multilayer by the Volmer–Weber mechanism (island growth), reflecting the weak K–C6H6 interactions. In case of K/C6H6/Pt(111), the K atoms are trapped on the topmost C6H6 layer at 65 K, forming particlelike clusters. The surface plasmon satellite was identified for the first time and the loss energy increases with increasing cluster size. The K clusters are unstable above ∼100 K due to thermal migration into the C6H6 film. When the cluster coverage is low, the K 4s band extends below and above EF of the Pt substrate and the anomaly is discussed in terms of vacuum level bending around the cluster.
In situ observation of rapid reactions in nanoscale Ni–Al multilayer foils using synchrotron radiation
Authors: Fadenberger Konrad , Gunduz Ibrahim Emre , Tsotsos Chrysostomos , Kokonou Maria , Gravani Styliani , Brandstetter Stefan , Bergamaschi Anna , Schmitt Bernd , Mayrhofer Paul H. , Doumanidis Charalabos C. , Rebholz Claus
Published: October 2010

The observation of rapid reactions in nanoscale multilayers present challenges that require sophisticated analysis methods. We present high-resolution in situ x-ray diffraction analysis of reactions in nanoscale foils of Ni0.9V0.1–Al using the Mythen II solid-state microstrip detector system at the Material Science beamline of the Swiss Light Source Synchrotron at Paul Scherrer Institute in Villigen, Switzerland. The results reveal the temperature evolution corresponding to the rapid formation of NiAl intermetallic phase, vanadium segregation and formation of stresses during cooling, determined at high temporal (0.125 ms) and angular (0.004°) resolution over a full angular range of 120°.
Optical characteristics of a-plane ZnO/Zn0.8Mg0.2O multiple quantum wells grown by pulsed laser deposition
Authors: Ko T. S. , Lu T. C. , Zhuo L. F. , Wang W. L. , Liang M. H. , Kuo H. C. , Wang S. C. , Chang Li , Lin D. Y.
Published: October 2010

We reported optical properties of a-plane ZnO/ZnMgO multiple quantum wells (MQWs) structure grown by the pulse laser deposition system. The emission peak energy of a-plane ZnO/ZnMgO MQWs kept invariant in the power-dependent photoluminescence (PL) measurement, indicating the nonpolar characteristics due to the lack of built-in electric fields. Large exciton binding energy of 68 meV was deduced and no apparent S-curve appeared in temperature-dependent PL results, demonstrating less carrier localization effect in a-plane ZnO/ZnMgO MQWs. Large difference in electronic transition levels of 45 meV due to the valence band splitting was observed in the polarization dependent absorption spectrum. Furthermore, the high degree of polarization of 92% and 56% at 20 and 300 K in PL emission of a-plane ZnO/ZnMgO MQWs were obtained.
Chemical potentials for Au-assisted vapor-liquid-solid growth of III-V nanowires
Authors: Glas Frank
Published: October 2010

For use in quantitatively modeling the growth of gold-seeded semiconductor nanowires in the vapor-liquid-solid mode, we calculate the difference of chemical potential between a liquid melt formed of group III and group V atoms dissolved in gold and the corresponding solid III-V binary compound. Fits to our results are provided for seven compounds as simple polynomials of the concentrations in the III-V-Au liquid and temperature. We find that the difference of chemical potential increases with the group III and group V concentrations, decreases with increasing temperature, and can easily reach several hundreds of meV per III-V pair. We discuss these values and variations in the light of published experimental results, in particular as regards the crystalline structure adopted by the nanowires during growth.
Photoluminescence in electronic ferroelectric Er1−xYbxFe2O4
Authors: Wang R. , Yang H. X. , Qin Y. B. , Dong B. , Li J. Q. , Zhao Jimin
Published: October 2010

Strong Stark splitting, which is nearly independent of the R-ions replacement, has been observed through the photoluminescence investigation of electronic ferroelectric Er1−xYbxFe2O4 (x=0, 0.8, 0.9, and 0.95). Initially multiple radiative decay channels have been investigated, especially the visible transition F49/2→I415/2, of which a quenching effect has been observed. A series of small non-Raman peaks have been observed superimposed on a broadband photoluminescence spectrum, of which we tentatively assign Stark splitting to be the cause. The splitting of the F49/2 and I415/2 levels is found to be 54 meV and 66 meV, respectively. This unusually large Stark splitting at visible range indicates the existence of strong local field originated from the W-layer in the charge-frustrated ErFe2O4.
A bifunctional cloak using transformation media
Authors: Li J. Y. , Gao Y. , Huang J. P.
Published: October 2010

We theoretically explore a type of bifunctional cloak possessing both electrical and thermal cloaking functionality. We employ a composite material to design the cloak shell. By using effective medium theory, the effective electrical and thermal conductivities of the composite material should meet the perfect conductivity profile calculated from the coordinate transformation approach. In the design, we choose nonspherical nanoparticles with appropriate electrical and thermal conductivities, shape aspects, and volume fractions. Furthermore, finite element simulations are performed to verify the properties of such bifunctional cloaks.
Memory effects in nonadiabatic molecular dynamics at metal surfaces
Authors: Olsen Thomas , Schiøtz Jakob
Published: October 2010

We study the effect of temporal correlation in a Langevin equation describing nonadiabatic dynamics at metal surfaces. For a harmonic oscillator, the Langevin equation preserves the quantum dynamics exactly and it is demonstrated that memory effects are needed in order to conserve the ground state energy of the oscillator. We then compare the result of Langevin dynamics in a harmonic potential with a perturbative master equation approach and show that the Langevin equation gives a better description in the nonperturbative range of high temperatures and large friction. Unlike the master equation, this approach is readily extended to anharmonic potentials. Using density functional theory, we calculate representative Langevin trajectories for associative desorption of N2 from Ru(0001) and find that memory effects lower the dissipation of energy. Finally, we propose an ab initio scheme to calculate the temporal correlation function and dynamical friction within density functional theory.
Constrained-pairing mean-field theory. IV. Inclusion of corresponding pair constraints and connection to unrestricted Hartree–Fock theory
Authors: Tsuchimochi Takashi , Henderson Thomas M. , Scuseria Gustavo E. , Savin Andreas
Published: October 2010

Our previously developed constrained-pairing mean-field theory (CPMFT) is shown to map onto an unrestricted Hartree–Fock (UHF) type method if one imposes a corresponding pair constraint to the correlation problem that forces occupation numbers to occur in pairs adding to one. In this new version, CPMFT has all the advantages of standard independent particle models (orbitals and orbital energies, to mention a few), yet unlike UHF, it can dissociate polyatomic molecules to the correct ground-state restricted open-shell Hartree–Fock atoms or fragments.
Epithelial cell proliferation in the developing zebrafish intestine is regulated by the Wnt pathway and microbial signaling via Myd88
Authors: Cheesman Sarah E. , Neal James T. , Mittge Erika , Seredick Barbara M. , Guillemin Karen
Published: October 2010

Rates of cell proliferation in the vertebrate intestinal epithelium are modulated by intrinsic signaling pathways and extrinsic cues. Here, we report that epithelial cell proliferation in the developing zebrafish intestine is stimulated both by the presence of the resident microbiota and by activation of Wnt signaling. We find that the response to microbial proliferation-promoting signals requires Myd88 but not TNF receptor, implicating host innate immune pathways but not inflammation in the establishment of homeostasis in the developing intestinal epithelium. We show that loss of
axin1
, a component of the β-catenin destruction complex, results in greater than WT levels of intestinal epithelial cell proliferation. Compared with conventionally reared
axin1
mutants, germ-free
axin1
mutants exhibit decreased intestinal epithelial cell proliferation, whereas monoassociation with the resident intestinal bacterium
Aeromonas veronii
results in elevated epithelial cell proliferation. Disruption of β-catenin signaling by deletion of the β-catenin coactivator
tcf4
partially decreases the proliferation-promoting capacity of
A. veronii
. We show that numbers of intestinal epithelial cells with cytoplasmic β-catenin are reduced in the absence of the microbiota in both WT and
axin1
mutants and elevated in animals’ monoassociated
A. veronii
. Collectively, these data demonstrate that resident intestinal bacteria enhance the stability of β-catenin in intestinal epithelial cells and promote cell proliferation in the developing vertebrate intestine.
Direct and enantioselective α-allylation of ketones via singly occupied molecular orbital (SOMO) catalysis
Authors: Mastracchio Anthony , Warkentin Alexander A. , Walji Abbas M. , MacMillan David W. C.
Published: October 2010

The first enantioselective organocatalytic α-allylation of cyclic ketones has been accomplished via singly occupied molecular orbital catalysis. Geometrically constrained radical cations, forged from the one-electron oxidation of transiently generated enamines, readily undergo allylic alkylation with a variety of commercially available allyl silanes. A reasonable latitude in both the ketone and allyl silane components is readily accommodated in this new transformation. Moreover, three new oxidatively stable imidazolidinone catalysts have been developed that allow cyclic ketones to successfully participate in this transformation. The new catalyst platform has also been exploited in the first catalytic enantioselective α-enolation and α-carbooxidation of ketones.
Inhibition of brain tumor growth by intravenous poly(β-
l
-malic acid) nanobioconjugate with pH-dependent drug release
Authors: Ding Hui , Inoue Satoshi , Ljubimov Alexander V. , Patil Rameshwar , Portilla-Arias Jose , Hu Jinwei , Konda Bindu , Wawrowsky Kolja A. , Fujita Manabu , Karabalin Natalya , Sasaki Takako , Black Keith L. , Holler Eggehard , Ljubimova Julia Y.
Published: October 2010

Effective treatment of brain neurological disorders such as Alzheimer's disease, multiple sclerosis, or tumors should be possible with drug delivery through blood–brain barrier (BBB) or blood–brain tumor barrier (BTB) and targeting specific types of brain cells with drug release into the cell cytoplasm. A polymeric nanobioconjugate drug based on biodegradable, nontoxic, and nonimmunogenic polymalic acid as a universal delivery nanoplatform was used for design and synthesis of nanomedicine drug for i.v. treatment of brain tumors. The polymeric drug passes through the BTB and tumor cell membrane using tandem monoclonal antibodies targeting the BTB and tumor cells. The next step for polymeric drug action was inhibition of tumor angiogenesis by specifically blocking the synthesis of a tumor neovascular trimer protein, laminin-411, by attached antisense oligonucleotides (AONs). The AONs were released into the target cell cytoplasm via pH-activated trileucine, an endosomal escape moiety. Drug delivery to the brain tumor and the release mechanism were both studied for this nanobiopolymer. Introduction of a trileucine endosome escape unit resulted in significantly increased AON delivery to tumor cells, inhibition of laminin-411 synthesis in vitro and in vivo, specific accumulation in brain tumors, and suppression of intracranial glioma growth compared with pH-independent leucine ester. The availability of a systemically active polymeric drug delivery system that passes through the BTB, targets tumor cells, and inhibits glioma growth gives hope for a successful strategy of glioma treatment. This delivery system with drug release into the brain-specific cell type could be useful for treatment of various brain pathologies.
Control of salicylic acid synthesis and systemic acquired resistance by two members of a plant-specific family of transcription factors
Authors: Zhang Yaxi , Xu Shaohua , Ding Pingtao , Wang Dongmei , Cheng Yu Ti , He Jing , Gao Minghui , Xu Fang , Li Yan , Zhu Zhaohai , Li Xin , Zhang Yuelin
Published: October 2010

Salicylic acid (SA) is a defense hormone required for both local and systemic acquired resistance (SAR) in plants. Pathogen infections induce SA synthesis through up-regulating the expression of
Isochorismate Synthase 1
(
ICS1
), which encodes a key enzyme in SA production. Here we report that both SAR Deficient 1 (SARD1) and CBP60g are key regulators for
ICS1
induction and SA synthesis. Whereas knocking out
SARD1
compromises basal resistance and SAR, overexpression of
SARD1
constitutively activates defense responses. In the
sard1-1 cbp60g-1
double mutant, pathogen-induced
ICS1
up-regulation and SA synthesis are blocked in both local and systemic leaves, resulting in compromised basal resistance and loss of SAR. Electrophoretic mobility shift assays showed that SARD1 and CBP60g represent a plant-specific family of DNA-binding proteins. Both proteins are recruited to the promoter of
ICS1
in response to pathogen infections, suggesting that they control SA synthesis by regulating
ICS1
at the transcriptional level.
Regional differences in cellular mechanisms of adipose tissue gain with overfeeding
Authors: Tchoukalova Yourka D. , Votruba Susanne B. , Tchkonia Tamara , Giorgadze Nino , Kirkland James L. , Jensen Michael D.
Published: October 2010

Body fat distribution is an important predictor of the metabolic consequences of obesity, but the cellular mechanisms regulating regional fat accumulation are unknown. We assessed the changes in adipocyte size (photomicrographs) and number in response to overfeeding in upper- and lower-body s.c. fat depots of 28 healthy, normal weight adults (15 men) age 29 ± 2 y. We analyzed how these changes relate to regional fat gain (dual energy X-ray absorptiometry and computed tomography) and baseline preadipocyte proliferation, differentiation [peroxisome proliferator-activated receptor-γ2 (PPARγ2) and CCAAT/enhancer binding protein-α (C/EBPα) mRNA]), and apoptotic response to TNF-α. Fat mass increased by 1.9 ± 0.2 kg in the upper body and 1.6 ± 0.1 kg in the lower body. Average abdominal s.c. adipocyte size increased by 0.16 ± 0.06 μg lipid per cell and correlated with relative upper-body fat gain (
r
= 0.74,
P
< 0.0001). However, lower-body fat responded to overfeeding by fat-cell hyperplasia, with adipocyte number increasing by 2.6 ± 0.9 × 10
9
cells (
P
< 0.01). We found no depot-differences in preadipocyte replication or apoptosis that would explain lower-body adipocyte hyperplasia and abdominal s.c. adipocyte hypertrophy. However, baseline PPARγ2 and C/EBPα mRNA were higher in abdominal than femoral s.c. preadipocytes (
P
< 0.005 and
P
< 0.03, respectively), consistent with the ability of abdominal s.c. adipocytes to achieve a larger size. Inherent differences in preadipocyte cell dynamics may contribute to the distinct responses of different fat depots to overfeeding, and fat-cell number increases in certain depots in adults after only 8 wk of increased food intake.
Arc regulates spine morphology and maintains network stability in vivo
Authors: Peebles Carol L. , Yoo Jong , Thwin Myo T. , Palop Jorge J. , Noebels Jeffrey L. , Finkbeiner Steven
Published: October 2010

Long-term memory relies on modulation of synaptic connections in response to experience. This plasticity involves trafficking of AMPA receptors (AMPAR) and alteration of spine morphology. Arc, a gene induced by synaptic activity, mediates the endocytosis of AMPA receptors and is required for both long-term and homeostatic plasticity. We found that Arc increases spine density and regulates spine morphology by increasing the proportion of thin spines. Furthermore, Arc specifically reduces surface GluR1 internalization at thin spines, and Arc mutants that fail to facilitate AMPAR endocytosis do not increase the proportion of thin spines, suggesting that Arc-mediated AMPAR endocytosis facilitates alterations in spine morphology. Thus, by linking spine morphology with AMPAR endocytosis, Arc balances synaptic downscaling with increased structural plasticity. Supporting this, loss of Arc in vivo leads to a significant decrease in the proportion of thin spines and an epileptic-like network hyperexcitability.
Connexin 43 is critical to maintain the homeostasis of the blood–testis barrier via its effects on tight junction reassembly
Authors: Li Michelle W. M. , Mruk Dolores D. , Lee Will M. , Cheng C. Yan
Published: October 2010

In mammalian testes, the blood–testis barrier (BTB) or Sertoli cell barrier created by specialized junctions between Sertoli cells near the basement membrane confers an immunological barrier by sequestering the events of meiotic division and postmeiotic germ cell development from the systemic circulation. The BTB is constituted bycoexistingtight junctions (TJs), basal ectoplasmic specializations, desmosomes, and gap junctions. Despite being one of the tightest blood–tissue barriers, the BTB has to restructure cyclically during spermatogenesis. A recent study showed that gap junction protein connexin 43 (Cx43) and desmosome protein plakophilin-2 are working synergistically to modulate the BTB integrity by regulating the distribution of TJ-associated proteins at the Sertoli–Sertoli cell interface. However, the precise role of Cx43 in regulating the cyclical restructuring of junctions remains obscure. In this report, the calcium switch and the bisphenol A (BPA) models were used to induce junction restructuring in primary cultures of Sertoli cells isolated from rat testes that formed a TJ-permeability barrier that mimicked the BTB in vivo. The removal of calcium by EGTA perturbed the Sertoli cell tight junction barrier, but calcium repletion allowed the “resealing” of the disrupted barrier. However, a knockdown of Cx43 in Sertoli cells by RNAi significantly reduced the kinetics of TJ-barrier resealing. These observations were confirmed using the bisphenol A model in which the knockdown of Cx43 by RNAi also perturbed the TJ-barrier reassembly following BPA removal. In summary, Cx43 is crucial for TJ reassembly at the BTB during its cyclic restructuring throughout the seminiferous epithelial cycle of spermatogenesis.
Loss of
Goosecoid-like
and
DiGeorge syndrome critical region 14
in interpeduncular nucleus results in altered regulation of rapid eye movement sleep
Authors: Funato Hiromasa , Sato Makito , Sinton Christopher M. , Gautron Laurent , Williams S. Clay , Skach Amber , Elmquist Joel K. , Skoultchi Arthur I. , Yanagisawa Masashi
Published: October 2010

Sleep and wakefulness are regulated primarily by inhibitory interactions between the hypothalamus and brainstem. The expression of the states of rapid eye movement (REM) sleep and non-REM (NREM) sleep also are correlated with the activity of groups of REM-off and REM-on neurons in the dorsal brainstem. However, the contribution of ventral brainstem nuclei to sleep regulation has been little characterized to date. Here we examined sleep and wakefulness in mice deficient in a homeobox transcription factor,
Goosecoid-like
(
Gscl
), which is one of the genes deleted in DiGeorge syndrome or 22q11 deletion syndrome. The expression of
Gscl
is restricted to the interpeduncular nucleus (IP) in the ventral region of the midbrain–hindbrain transition. The IP has reciprocal connections with several cell groups implicated in sleep/wakefulness regulation. Although

Gscl
−/−

mice have apparently normal anatomy and connections of the IP, they exhibited a reduced total time spent in REM sleep and fewer REM sleep episodes. In addition,

Gscl
−/−

mice showed reduced theta power during REM sleep and increased arousability during REM sleep.

Gscl
−/−

mice also lacked the expression of
DiGeorge syndrome critical region 14
(
Dgcr14
) in the IP. These results indicate that the absence of
Gscl
and
Dgcr14
in the IP results in altered regulation of REM sleep.
Friends, colleagues, authors, lend us your data
Authors: deCathelineau Aimee , Williams Elizabeth H. , Misteli Tom , Rossner Mike
Published: October 2010

The JCB was founded by a group of scientists who needed a journal to showcase their micrographs with the highest quality reproduction. Our commitment to innovative presentation and sharing of image data continues today with the JCB DataViewer.
Bystander killing of cancer requires the cooperation of CD4+ and CD8+ T cells during the effector phase
Authors: Schietinger Andrea , Philip Mary , Liu Rebecca B. , Schreiber Karin , Schreiber Hans
Published: October 2010

Cancers frequently evade cytotoxic T lymphocyte–mediated destruction through loss or down-regulation of tumor antigens and antigen-presenting major histocompatibility complex molecules. Therefore, we have concentrated our efforts on immunological strategies that destroy nonmalignant stromal cells essential for the survival and growth of cancer cells. In this study, we developed a non–T cell receptor transgenic, immunocompetent tumor model to determine whether tumor-bearing hosts’ own immune systems could eliminate cancer cells through stromal targeting and what role CD4+ T cells play alongside CD8+ T cells in this process. We found that aggressive cancers could be eradicated by T cell targeting of tumor stroma. However, successful elimination required the cooperation of CD4+ and CD8+ T cells not only during the induction phase but also during the effector phase in the tumor microenvironment, implying a new role for CD4+ T cells that has not been previously described. Our study demonstrates the potential of stromal targeting as a cancer immunotherapy and suggests that successful anticancer strategies must facilitate cooperation between CD4+ and CD8+ T cells at the right times and the right places.
Effect of a Multifaceted Intervention on Adherence to Hand Hygiene among Healthcare Workers: A Cluster-Randomized Trial
Authors: Mertz Dominik , Dafoe Nancy , Walter Stephen D. , Brazil Kevin , Loeb Mark
Published: October 2010

Objectives.

Adherence to hand hygiene among healthcare workers (HCWs) is widely believed to be a key factor in reducing the spread of healthcare-associated infection. The objective of this study was to evaluate the impact of a multifaceted intervention to increase rates of adherence to hand hygiene among HCWs and to assess the effect on the incidence of hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) colonization.

Design.

Cluster-randomized controlled trial.

Setting.

Thirty hospital units in 3 tertiary care hospitals in Hamilton, Ontario, Canada.

Intervention.

After a 3-month baseline period of data collection, 15 units were randomly assigned to the intervention arm (with performance feedback, small-group teaching seminars, and posters) and 15 units to usual practice. Hand hygiene was observed during randomly selected 15-minute periods on each unit, and the incidence of MRSA colonization was measured using weekly surveillance specimens from June 2007 through May 2008.

Results.

We found that 3,812 (48.2%) of 7,901 opportunities for hand hygiene in the intervention group resulted in adherence, compared with 3,205 (42.6%) of 7,526 opportunities in the control group (P < .001; independent t test). There was no reduction in the incidence of hospital-acquired MRSA colonization in the intervention group.

Conclusion.

Among HCWs in Ontario tertiary care hospitals, the rate of adherence to hand hygiene had a statistically significant increase of 6% with a multifaceted intervention, but the incidence of MRSA colonization was not reduced.
Genetic data show that Carcharhinus tilstoni is not confined to the tropics, highlighting the importance of a multifaceted approach to species identification
Authors: Boomer J. J. , Peddemors V. , Stow A. J.
Published: October 2010

This study shows a range extension for the Australian blacktip shark Carcharhinus tilstoni, which was believed to be restricted to Australia's tropical waters, of >1000 km into temperate waters, revealing its vulnerability to a wider commercial fishery.
Using hierarchical models to estimate effects of ocean anomalies on north‐west Pacific Chinook salmonOncorhynchus tshawytscharecruitment
Authors: Sharma R. , Liermann M.
Published: October 2010

The high variability in survival over the past three decades of north‐west Pacific Chinook salmonOncorhynchus tshawytschais summarized for 24 stocks and analysed using hierarchical Bayesian models. Results from a simple model indicate that recruitment anomalies appear to be correlated in time and space. A simple model with a covariate based on basin‐scale effects (Pacific Decadal Oscillation and El Niño Southern Oscillation) and local‐scale effects (sea surface temperature, SST anomaly) was introduced to explain this variability. The model still exhibited residual patterns that were removed when a random‐walk component was added to the model. The analysis indicates that recruitment is negatively related to SST anomaly for all stocks and the effect of basin‐scale variables is negligible. The effect of climate over the next century is expected to result in estimated recruitment declining by an average of 13% forO. tshawytschastocks coastwide.
Effect of immunoglobulin G (IgG) interchain disulfide bond cleavage on efficacy of intravenous immunoglobulin for immune thrombocytopenic purpura (ITP)
Authors: Machino Y , Ohta H , Suzuki E , Higurashi S , Tezuka T , Nagashima H , Kohroki J , Masuho Y
Published: October 2010

Intravenous immunoglobulin (IVIG) has been used widely to treat immune thrombocytopenic purpura (ITP), but the mechanisms of its action remain unclear. We investigated the affinity for Fcγ receptors (FcγRs) and the thrombocytopenia-ameliorating effect of S-sulfonated gammaglobulin (SGG) and S-alkylated gammaglobulin (AGG), in comparison with unmodified gammaglobulin (GG), in a mouse ITP model. Cleavage of immunoglobulin (Ig)G interchain disulfide bonds by either S-sulfonation or S-alkylation did not decrease the affinity for FcγRIIA (CD32A) and FcγRIIB (CD32B), but did decrease the affinity for FcγRIA (CD64A) and FcγRIIIA (CD16A), presumably because of changes in H-chain configuration. The interchain disulfide bond cleavage decreased the affinity much more for mouse FcγRIV than for mouse FcγRIIB. The ability of AGG to ameliorate ITP was greatly diminished, while SGG, whose disulfide bonds are reconstituted in vivo, was as effective as GG. These results suggest that the interchain disulfide bonds are important for therapeutic effect. It is also suggested that the interaction of IVIG with the inhibitory receptor FcγRIIB is insufficient for effective amelioration of ITP and that, at least in this model, direct binding of IVIG to FcγRIIIA is also required.
Lack of anti-tumour reactivity despite enhanced numbers of circulating natural killer T cells in two patients with metastatic renal cell carcinoma
Authors: Vyth-Dreese F A , Sein J , Van De Kasteele W , Dellemijn T A M , Van Den Bogaard C , Nooijen W J , De Gast G C , Haanen J B A G , Bex A
Published: October 2010

Natural killer T (NK T) cells play a central role as intermediates between innate and adaptive immune responses important to induce anti-tumour reactivity in cancer patients. In two of 14 renal cell carcinoma (RCC) patients, treated with interferon (IFN)-α, we detected significantly enhanced numbers of circulating NK T cells which were typed phenotypically and analysed for anti-tumour reactivity. These NK T cells were T cell receptor (TCR) Vα24/Vβ11+, 6B11+ and bound CD1d tetramers. No correlation was observed between NK T frequencies and regulatory T cells (Tregs), which were also enhanced. NK T cells expressed CD56, CD161, CD45RO and CD69 and were predominantly CD8+, in contrast to the circulating T cell pool that contained both CD4+ and CD8+ T cells, as is found in healthy individuals. It is unlikely that IFN-α triggered the high NK T frequency, as all other patients expressed low to normal NK T numbers. A parallel was observed in IFN-α-related increase in activation of NK T cells with that in conventional T and non-T cells. Normal interleukin (IL)-7, IL-12 and IL-15 plasma levels were found. In one of the patients sporadic NK T cells were detected at the tumour site. α-Galactosylceramide (αGalCer) stimulation of peripheral blood mononuclear cells or isolated NK T cell lines from both patients induced IFN-γ, but no IL-4 and no response towards autologous tumour cells or lysates. The clinical course of disease in both patients was not exceptional with regard to histological subtype and extent of metastatic disease. Therefore, despite a constitutive high peripheral frequency and in vitroαGalCer responsiveness, the NK T cells in the two RCC patients did not show anti-tumour responsiveness.
Impact of practice recommendations on patient follow‐up and cystic fibrosis centres' activity in France
Authors: Decullier Evelyne , Touzet Sandrine , Bourdy Stéphanie , Termoz Anne , Bellon Gabriel , Pin Isabelle , Cracowski Claire , Colin Cyrille , Durieu Isabelle
Published: October 2010

Introduction  The French cystic fibrosis (CF) practice recommendations were published at the end of 2002. They advise each patient to be checked up at least once every 3 months in a reference centre for cystic fibrosis.

Objective  To describe the activity of the four reference centres in the Rhône‐Alpes area and the patients' follow‐up.

Methods  All patients with cystic fibrosis consulting one of the four CF centres between 1996 and 2005 were retrospectively included. All outpatient visits were recorded and classified according to (i) patient and year; and (ii) month and year. The two series were assessed graphically to determine a transition threshold, that is, the 2 consecutive years between which practices differed the most.

Results  A total of 616 patients were included, representing 17 594 outpatient visits. The average number of visits per patient increased from 3.7 in 1996 to 5.0 in 2005, the graphical representation showed a sharp change between 2000 and 2001. Among patients with less than 4 visits in 2000, 88 of them visited a centre 4 times or more in 2001 (44%).

The annual number of outpatient visits went from 1035 to 2420. The monthly average number of outpatient visits was 86 in 1996 and 202 in 2005. The graphical representation of activity also showed a sharp change from 2001.

Conclusion  We showed that the implementation of guidelines occurred the year before its official publication. We also showed that the growth of this implementation was sharp rather than gradual.
Implementing guidelines into clinical practice: what is the value?
Authors: Hoomans Ties , Ament André J.H.A. , Evers Silvia M.A.A. , Severens Johan L.
Published: October 2010

Rationale and objective In budget‐constrained health systems, decision makers need to consider both the costs and effects of introducing and actively implementing clinical guidance. We aim to demonstrate how, as an alternative to conventional methods, a total net benefit approach to economic evaluation can be used to inform decision making about guidelines and specific implementation strategies, like education or financial incentives.

Methods Aside from providing more detail on the decision framework, we describe how to collect and analyse the relevant data for calculating the total net benefit of guideline use and the value of implementation. We illustrate the process of decision analysis for a stylized example on improving diabetes care in the UK. For the analysis, economic evidence on intensified glycemic control and that on audit and feedback to promote control is combined with information on diabetes practice.

Results Our illustration demonstrates that the total net benefit of guideline use and the value of implementation can vary substantially, depending on the clinical intervention chosen, the health system being studied and the specific implementation strategies. This also holds for the threshold value for cost‐effectiveness, the duration of guideline usage or validity, the size of the patient population served, and the trends and ceiling rates in the implementation of clinical guidance.

Conclusions In comparison with conventional methods for health economic evaluation, a total net benefit approach allows for the explicit consideration of the current (or future) use of guidelines or guideline recommendations, the cost of implementation and the scope of clinical practice. Decisions made on the basis of the total net benefit of all plausible combinations of clinical guidance and implementation strategies provide optimal patient care and an efficient use of resources.
Most like it but some don't – attitudes of vocational trainees in general practice towards evidence‐based medicine
Authors: Blank Wolfgang A. , Meyer Thorsten , Schneider Antonius , Linde Klaus
Published: October 2010

Rationale and objectives  Vocational trainees in general practice are often confronted with new and unusual situations. The application of the principles and techniques of evidence‐based medicine (EBM) could often be appropriate in these situations. We aimed to investigate attitudes towards EBM among doctors undergoing postgraduate training in general practice in Germany. In particular, we were interested in which aspects the answers of doctors with an overall negative attitude towards EBM differed from those with a positive attitude.

Methods  A total of 153 doctors participating in courses for postgraduate medical training in general practice were asked to fill in a questionnaire on attitudes towards EBM and relevance of clinical research. Answers of doctors with a negative attitude towards EBM (negative sum in the questions asking personal judgment on EBM) were compared with those of the remaining doctors.

Results  A total of 142 (93%) doctors returned the questionnaire and 121 responded to the questions on EBM (21 responded that they had not heard about EBM). On average, attitudes towards EBM were positive; however, nine doctors gave negative ratings. EBM‐sceptics were similar regarding age, years working as doctors and working hours per week, but were more often male (P = 0.03). EBM‐sceptics considered keeping up to date as important as non‐sceptics but were significantly (P < 0.001) more negative regarding whether EBM is an important decision aid in one's personal work, whether it helps to identify the best clinical options and whether it constrains therapeutic freedom.

Conclusion  Overall, doctors specializing in general practice in Germany have a quite positive attitude towards EBM. A small minority, however, seems to consider EBM a threat to their professional autonomy.
The intradermal route for inoculation of sporozoites of rodent malaria parasites for immunological studies
Authors: INOUE M. , CULLETON R. L.
Published: October 2010

Rodent malaria parasites are commonly used for investigations into the immunology of pre‐erythrocytic stage malaria infection, as sporozoites can be easily produced in the laboratory. In the majority of past immunological studies using this system, sporozoites are inoculated into mice via the intravenous (IV) route. In natural situations, however, sporozoites are deposited into the skin by the bite of Anopheline mosquitoes, and it is likely that the immunological response to such natural intradermal (ID) inoculation will be different to that achieved through the IV route. Although infected mosquito bites are sometimes used during experimental induction of immunity in mice, this method is problematic because of the low numbers of sporozoites introduced to the skin and the large variation in sporozoite inoculation between individual mosquitoes. Here, we show that ID inoculation of dissected mosquito salivary gland sporozoites of Plasmodium yoelii allows the accurate introduction of known numbers of sporozoites into the skin and that these parasites successfully invade the liver. Furthermore, immunization of mice using ID inoculations of live sporozoites contemporaneously with mefloquine treatment induces an immune response that is protective against the development of liver stage parasites, and this protection does not differ significantly from that achieved with IV immunizations performed in the same manner.
Six aspects of supervision and the training of supervisors
Authors: Mason Barry
Published: October 2010

Arising out of a perceived contradiction in the implementation of a second order perspective, this article suggests a practice framework for inclusion in the training of systemic supervisors. Brief feedback from trainees is also presented.
Reducing Child Labour Through Conditional Cash Transfers: Evidence from Nicaragua's Red de Protección Social
Authors: Gee Kevin A.
Published: October 2010

Conditional Cash Transfer (CCT) programmes, providing eligible households with periodic cash payments, contingent on their children's adherence to school enrolment and attendance requirements, hold considerable promise for reducing levels of child labour across the developing world. This article presents the results of an analysis of a CCT programme in Nicaragua, Red de Protección Social, and compares them with those of other CCT programmes, discussing how the structure of each programme's incentives, including differences in targeting, subsidy amounts and educational requirements, contributes to the variation in their effectiveness at reducing child labour.
The Changing Pattern of Wage Returns to Education and its Implications
Authors: Colclough Christopher , Kingdon Geeta , Patrinos Harry
Published: October 2010

It is commonly believed that labour‐market returns to education are highest for the primary level of education and lower for subsequent levels. Recent evidence reviewed in this article suggests that the pattern is changing. The causes of such changes, and their implications for both education and labour‐market policy, are explored.
European outbreak of atypical myopathy in the autumn 2009
Authors: Van Galen Gaby , Amory Helene , Busschers Evita , Cassart Dominique , De Bruijn Marco , Gerber Vincent , Keen John , Lefere Laurence , Pitel Christel Marcillaud , Marr Celia , Müller Jessica‐M. V. , Pineau Xavier , Saegerman Claude , Sandersen Charlotte , Serteyn Didier , Torfs Sara , Unger Lucia , Verwilghen Denis , Votion Dominique‐Marie
Published: October 2010

Background –Atypical myopathy is an acute, severe rhabdomyolysis occurring in grazing horses. In the beginning of October 2009, a new outbreak occurred in several European countries. Geographic, demographic and clinical data of the reported cases in the month October 2009 are described.

Key Findings –The survival rate in this outbreak was 25%. The most frequently observed clinical signs were congested mucous membranes, dyspnea, tachycardia, depression, weakness, stiffness, recumbency, trembling, sweating, and myoglobinuria. Nonsurvivors were significantly more likely to be recumbent than survivors. Prognostic factors, symptomatic treatment, and preventive measures are discussed.

Significance –Differences were encountered during the described outbreak of atypical myopathy in October 2009 compared with previous outbreaks reported. Equine practitioners should be aware that previous epidemiological studies have shown that after a high prevalence in the autumn, new cases are likely to occur in the following spring.
The Association of Trauma and PTSD with the Substance Use Profiles of Alcohol‐ and Cocaine‐Dependent Out‐of‐Treatment Women
Authors: Johnson Sharon D. , Cottler Linda B. , O’Leary Catina Callahan , Abdallah Arbi Ben
Published: October 2010

The association of trauma and posttraumatic stress disorder (PTSD) with alcohol and cocaine use is explored to determine if there is additive risk associated with dual dependence. Data were collected from out‐of‐treatment women enrolled in an HIV‐prevention study. Women who experienced a DSM‐IV qualifying event (n = 791) were stratified into four substance use groups based on lifetime alcohol and cocaine use. Women with lifetime comorbid alcohol and cocaine dependence experienced significantly more traumatic events and had a higher prevalence of violent events and lifetime diagnosis of PTSD and PTSD‐related impairment. There is added risk for associated trauma and subsequent PTSD among women who have dual substance dependence. (Am J Addict 2010;00:1–6)
Examining Differences in Substance Use among Rural and Urban Pregnant Women
Authors: Shannon Lisa M. , Havens Jennifer R. , Hays Lon
Published: October 2010

Substance use during pregnancy is a major public health concern. This study examined differences in substance use among pregnant women from rural and urban areas. Participants were 114 pregnant women entering a hospital‐based inpatient detoxification unit primarily for Opiate Dependence who voluntarily agreed to a face‐to‐face interview. Substance use measures were based on the Addiction Severity Index gathering information about lifetime, past 12 months, and 30 days prior to admission. Rural pregnant women had higher rates of illicit opiate use, illicit sedative/benzodiazepine use, and injection drug use (IDU) in the 30 days prior to admission. Additionally, a greater proportion of rural pregnant women reported the use of multiple illegal/illicit substances in the 30 days prior to entering detoxification. More specifically, pregnant women from rural areas were 8.4 times more likely to report illicit opiate use, 5.9 times more likely to report IDU, 3.3 times more likely to report illicit sedative/benzodiazepine use, and 2.8 times more likely to report the use of multiple illegal/illicit substances in the 30 days prior to entering inpatient detoxification, after adjustment for socio‐demographic characteristics (including education and income), pregnancy characteristics, physical and mental health indicators, and criminal justice system involvement. The increased rates of prescription opiate and benzodiazepine use as well as IDU among rural pregnant women are concerning. In order to begin to understand the elevated rates of substance abuse among rural pregnant women, substance use must be considered within the context of demographic, geographic, social, and economic conditions of the region. (Am J Addict 2010;00:1–7)
Pilot Study of a Preliminary Criterion Standard for Prescription Opioid Misuse
Authors: Smith Robert C. , Frank Cathy , Gardiner Joseph C. , Lamerato Lois , Rost Kathryn M.
Published: October 2010

Multidisciplinary experts created a behaviorally defined preliminary criterion standard definition of probable prescription opioid misuse (PPOM) that could be rated from material found in administrative, pharmacy, and electronic health record databases. They then derived a scoring system to identify PPOM patients requiring referral to a specialist. Experts next rated cases of misuse and nonmisuse. Rater no. 1 correctly differentiated 37 of 40 cases (92.5%); kappa coefficient was .79 (CI: .57, 1.00). Rater no. 2 correctly identified 39 of 40 cases (97.5%); kappa was .94 (CI: .81, 1.00). Kappa for comparing raters was .73 (CI: .49, .98). This preliminary study demonstrates that multidisciplinary raters can use behaviorally based criteria to identify patients with known PPOM from health plan databases. (Am J Addict 2010;00:1–6)
Big Bad Banks? The Winners and Losers from Bank Deregulation in the United States
Authors: BECK THORSTEN , LEVINE ROSS , LEVKOV ALEXEY
Published: October 2010

We assess the impact of bank deregulation on the distribution of income in the United States. From the 1970s through the 1990s, most states removed restrictions on intrastate branching, which intensified bank competition and improved bank performance. Exploiting the cross‐state, cross‐time variation in the timing of branch deregulation, we find that deregulation materially tightened the distribution of income by boosting incomes in the lower part of the income distribution while having little impact on incomes above the median. Bank deregulation tightened the distribution of income by increasing the relative wage rates and working hours of unskilled workers.
Diversification and Its Discontents: Idiosyncratic and Entrepreneurial Risk in the Quest for Social Status
Authors: ROUSSANOV NIKOLAI
Published: October 2010

Social status concerns influence investors' decisions by driving a wedge in attitudes toward aggregate and idiosyncratic risks. I model such concerns by emphasizing the desire to “get ahead of the Joneses,” which implies that aversion to idiosyncratic risk is lower than aversion to aggregate risk. The model predicts that investors hold concentrated portfolios in equilibrium, which helps rationalize the small premium for undiversified entrepreneurial risk. In the model, status concerns are more important for wealthier households. Consequently, these households own a disproportionate share of risky assets, particularly private equity, and experience greater volatility of consumption, consistent with empirical evidence.
Structural and functional studies of the human phosphoribosyltransferase domain containing protein 1
Authors: Welin Martin , Egeblad Louise , Johansson Andreas , Stenmark Pål , Wang Liya , Flodin Susanne , Nyman Tomas , Trésaugues Lionel , Kotenyova Tetyana , Johansson Ida , Eriksson Staffan , Eklund Hans , Nordlund Pär
Published: October 2010

Human hypoxanthine‐guanine phosphoribosyltransferase (HPRT) (EC 2.4.2.8) catalyzes the conversion of hypoxanthine and guanine to their respective nucleoside monophosphates. Human HPRT deficiency as a result of genetic mutations is linked to both Lesch–Nyhan disease and gout. In the present study, we have characterized phosphoribosyltransferase domain containing protein 1 (PRTFDC1), a human HPRT homolog of unknown function. The PRTFDC1 structure has been determined at 1.7 Å resolution with bound GMP. The overall structure and GMP binding mode are very similar to that observed for HPRT. Using a thermal‐melt assay, a nucleotide metabolome library was screened against PRTFDC1 and revealed that hypoxanthine and guanine specifically interacted with the enzyme. It was subsequently confirmed that PRTFDC1 could convert these two bases into their corresponding nucleoside monophosphate. However, the catalytic efficiency (kcat/Km) of PRTFDC1 towards hypoxanthine and guanine was only 0.26% and 0.09%, respectively, of that of HPRT. This low activity could be explained by the fact that PRTFDC1 has a Gly in the position of the proposed catalytic Asp of HPRT. In PRTFDC1, a water molecule at the position of the aspartic acid side chain position in HPRT might be responsible for the low activity observed by acting as a weak base. The data obtained in the present study indicate that PRTFDC1 does not have a direct catalytic role in the nucleotide salvage pathway.

Structured digital abstract

 MINT‐7996314: PRTFDC1 (uniprotkb: Q9NRG1) and PRTFDC1 (uniprotkb: Q9NRG1) bind (MI:0407) by x‐ray crystallography (MI:0114)