bluuebunny/crossref_metadata_2025 huggingface dataset:
Muscarinic activation of Ca2+‐activated Cl− current in interstitial cells of Cajal
Authors: Zhu Mei Hong , Sung In Kyung , Zheng Haifeng , Sung Tae Sik , Britton Fiona C , O’Driscoll Kate , Koh Sang Don , Sanders Kenton M.
Published: July 2011

Non‐technical summary  Interstitial cells of Cajal (ICC) are tightly associated with excitatory and inhibitory motor neurons in the gastrointestinal tract, and these cells are also connected electrically to smooth muscle cells. We have suggested that ICC participate in responses to neurotransmitters released from neurons that drive motility and help move nutrients and wastes through the gut. We studied responses of isolated ICC to cholinergic neurotransmitter and found that a Ca2+‐activated Cl− current is activated in ICC in response to cholinergic stimulation. Such a current would result in depolarization that could be conducted to surrounding smooth muscle cells by the electrical connections. Exciting ICC would cause generalized excitation of the smooth muscle tissue. A different conductance is activated in smooth muscle cells by cholinergic stimulation. We tested drugs that blocked the Cl− current in ICC and found that responses to nerve stimulation in intact intestinal muscles were blocked by these drugs. This suggests that ICC mediate electrical responses to cholinergic nerve stimulation. In some human gastrointestinal motility disorders, ICC are damaged or lost. If these cells provide responses to neurotransmitters, this might provide an explanation for motor dysfunction in the gut.
SAP97 directs NMDA receptor spine targeting and synaptic plasticity
Authors: Li Dong , Specht Christian G. , Waites Clarissa L. , Butler‐Munro Charlotte , Leal‐Ortiz Sergio , Foote Janie W. , Genoux David , Garner Craig C. , Montgomery Johanna M.
Published: July 2011

Abstract  SAP97 is a multidomain scaffold protein implicated in the forward trafficking and synaptic localization of NMDA‐ and AMPA‐type glutamate receptors. Alternative splicing of SAP97 transcripts gives rise to palmitoylated αSAP97 and L27‐domain containing βSAP97 isoforms that differentially regulate the subsynaptic localization of GluR1 subunits of AMPA receptors. Here, we examined whether SAP97 isoforms regulate the mechanisms underlying long‐term potentiation (LTP) and depression (LTD) and find that both α‐ and β‐forms of SAP97 impair LTP but enhance LTD via independent isoform‐specific mechanisms. Live imaging of α‐ and βSAP97 revealed that the altered synaptic plasticity was not due to activity‐dependent changes in SAP97 localization or exchange kinetics. However, by recording from pairs of synaptically coupled hippocampal neurons, we show that αSAP97 occludes LTP by enhancing the levels of postsynaptic AMPA receptors, while βSAP97 blocks LTP by reducing the synaptic localization of NMDA receptors. Examination of the surface pools of AMPA and NMDA receptors indicates that αSAP97 selectively regulates the synaptic pool of AMPA receptors, whereas βSAP97 regulates the extrasynaptic pools of both AMPA and NMDA receptors. Knockdown of βSAP97 increases the synaptic localization of both AMPA and NMDA receptors, showing that endogenous βSAP97 restricts glutamate receptor expression at excitatory synapses. This isoform‐dependent differential regulation of synaptic versus extrasynaptic pools of glutamate receptors will determine how many receptors are available for the induction and the expression of synaptic plasticity. Our data support a model wherein SAP97 isoforms can regulate the ability of synapses to undergo plasticity by controlling the surface distribution of AMPA and NMDA receptors.
A Redesign Strategy to Improve the Efficiency of a 17-Stage Steam Turbine
Authors: Rubechini Filippo , Schneider Andrea , Arnone Andrea , Cecchi Stefano , Malavasi Francesco
Published: July 2011

A three-dimensional Reynolds averaged Navier–Stokes solver was applied to the aerodynamic redesigning of a 17-stage steam turbine. The redesign procedure was divided into three steps. In the first one, a single embedded stage was considered, and an optimization of stator lean and rotor twist was carried out by applying suitable repeating inlet/outlet boundary conditions. In the second step, a proper geometrical transformation between the original reference stage and the optimized one was identified and then applied to all other turbine stages, thus leading to a first approximation of the redesigned turbine. Finally, a neural-network-based refinement of the stator and rotor twist of each stage was performed to account for its actual position and operating conditions within the meridional channel. In this work, a detailed description of the redesign procedure is provided, and the aerodynamic characteristics of the optimized geometry are discussed and compared with the original ones.
Heat Transfer Characteristics of an Oblique Jet Impingement Configuration in a Passage With Ribbed Surfaces
Authors: Hoefler Florian , Schueren Simon , von Wolfersdorf Jens , Naik Shailendra
Published: July 2011

Heat transfer measurements of a confined impingement cooling configuration with ribs on the target surfaces are presented. The assembly consists of four nonperpendicular walls of which one holds two rows of staggered inclined jets, each impinging on a different adjacent wall. The ribs are aligned with the inclined jet axes, have the same pitch, and are staggered to the impinging jets. The flow exhausts through two staggered rows of holes opposing the impingement wall. The passage geometry is related to a modern gas turbine blade cooling configuration. A transient liquid crystal technique was used to take spatially resolved surface heat transfer measurements for the ground area between the ribs. A comparison with the smooth baseline configuration reveals local differences and a generally reduced heat transfer for the rib-roughened case. Furthermore, lumped heat capacity measurements of the ribs yielded area averaged heat transfer information for the ribs. From the combination of ground and rib heat transfer measurements, it is concluded that the overall performance of the ribbed configuration depends on the Reynolds number. Of the five investigated jet Reynolds numbers from 10,000 to 75,000, only for the highest Re the averaged Nusselt numbers increase slightly compared with the smooth baseline configuration.
Reduced Order Model of a Multistage Bladed Rotor With Geometric Mistuning via Modal Analyses of Finite Element Sectors
Authors: Bhartiya Yasharth , Sinha Alok
Published: July 2011

An algorithm to generate a reduced order model of a multistage rotor in which each stage has a different number of blades has been developed. It is shown that a reduced order model can be developed on the basis of tuned modes of certain bladed disks which can be easily obtained via sector analyses. Further, it is shown that the reduced order model can also be obtained when blades are geometrically mistuned. This algorithm is similar to the modified modal domain analysis, which has been recently developed for a single-stage bladed rotor with geometric mistuning. The validity of this algorithm is shown for the finite element model of a two-stage bladed rotor. In addition, the statistical distributions of peak maximum amplitudes and natural frequencies of a two-stage rotor are generated via Monte Carlo simulations for different patterns of geometric mistuning.
Unsteady Interactions Between Axial Turbine and Nonaxisymmetric Exhaust Hood Under Different Operational Conditions
Authors: Fu Jing-Lun , Liu Jian-Jun , Zhou Si-Jing
Published: July 2011

The exhaust system in condensing steam turbines is used to recover leaving kinetic energy of the last stage turbine, while guiding the flow from turbine to condenser. The flows in the exhaust system and the turbine stage are fully coupled and inherently unsteady. The unsteady flow interactions between the turbine and the exhaust system have a strong impact on the blade loading or blade aerodynamic force. This paper describes the unsteady flow interactions between a single-stage axial turbine and an exhaust system. The experimental and numerical studies on the coupled flow field in the single-stage turbine and the exhaust hood model under different operational conditions have been carried out. Unsteady pressure at the turbine rotor blade, turbine outlet, and exhaust outcasing are measured and compared with the numerical prediction. The details of unsteady flow in the exhaust system with the whole annulus stator and rotor blade rows are simulated by employing the computational fluid dynamics software CFX-5. Results show that for the investigated turbine-exhaust configuration the influence of the flow field in the exhaust system on the unsteady blade force is much stronger than that of the stator and rotor interaction. The flow pattern in the exhaust system changes with the turbine operational condition, which influences the unsteady flow in the turbine stage further.
Validation of Minimum Time-Jerk Algorithms for Trajectory Planning of Industrial Robots
Authors: Gasparetto A. , Lanzutti A. , Vidoni R. , Zanotto V.
Published: July 2011

In this paper, an experimental analysis and validation of a minimum time-jerk trajectory planning algorithm is presented. The technique considers both the execution time and the integral of the squared jerk along the whole trajectory, so as to take into account the need for fast execution and the need for a smooth trajectory, by adjusting the values of two weights. The experimental tests have been carried out by using an accelerometer mounted on a Cartesian robot. The algorithm does not require a dynamic model of the robot, but just its mechanical constraints, and can be implemented in any industrial robot. The outcomes of the tests have been compared with both simulation and experimental results yielded by two trajectory planning algorithms taken from the literature.
Methane Decarbonization in Indirect Heating Solar Reactors of 20 and 50 kW for a CO2-Free Production of Hydrogen and Carbon Black
Authors: Rodat Sylvain , Abanades Stéphane , Flamant Gilles
Published: July 2011

Solar methane decarbonization is an attractive pathway for a transition toward an hydrogen-based economy. In the frame of the European SOLHYCARB project, it was proposed to investigate this solar process extensively. At CNRS-PROMES, two indirect heating solar reactors (20 and 50 kW) were designed, built, and tested for methane decarbonization. They consist of graphite cavity-type receivers approaching the blackbody behavior. The CH4 dissociation reaction was carried out in tubular sections inserted in the solar absorber receiving concentrated solar irradiation. The 20 kW solar reactor (SR20) was especially suitable to study the chemical reaction and methane conversion performances depending on the experimental conditions (mainly temperature and residence time). The 50 kW solar reactor (SR50) was operated to produce significant amounts of carbon black for determining its properties and quality in the various possible commercial applications. The main encountered problem was the particle evacuation. Solutions were proposed for large-scale industrial applications. A process analysis was achieved for a 14.6 MW solar chemical plant on the basis of a process flow-sheet. A production of 436 kg/h of hydrogen and 1300 kg/h of carbon black could be obtained for 1737 kg/h of methane consumed, with an hydrogen cost competitive to conventional methane reforming. This paper summarizes the main results and conclusions of the project.
Molecular beam epitaxy growth of PbSe on Si (211) using a ZnTe buffer layer
Authors: Wang X. J. , Chang Y. , Hou Y. B. , Becker C. R. , Kodama R. , Aqariden F. , Sivananthan S.
Published: July 2011

The authors report the results of successful growth of single crystalline PbSe on Si (211) substrates with ZnTe as a buffer layer by molecular beam epitaxy. Single crystalline PbSe with (511) orientation was achieved on ZnTe/Si (211), as evidenced by RHEED patterns indicative of 2 dimensional (2D) growth, x ray diffraction rocking curves with a full width at half maximum as low as 153 arc sec and mobility as large as 1.1×104cm2V-1s-1 at 77 K. Cross hatch patterns were found on the PbSe(511) surface in Nomarski filtered microscope images suggesting the presence of a surface thermal strain relaxation mechanism, which was confirmed by Fourier transformed high resolution transmission electron microscope images.
Easy Strategy To Increase Salt Resistance of Antimicrobial Peptides
Authors: Yu Hui-Yuan , Tu Chih-Hsiung , Yip Bak-Sau , Chen Heng-Li , Cheng Hsi-Tsung , Huang Kuo-Chun , Lo Hsiu-Jung , Cheng Jya-Wei
Published: July 2011

The efficacies of many antimicrobial peptides are greatly reduced under high salt concentrations, limiting their development as pharmaceutical compounds. Here, we describe an easy strategy to increase salt resistance of antimicrobial peptides by replacing tryptophan or histidine residues with the bulky amino acids β-naphthylalanine and β-(4,4′-biphenyl)alanine. The activities of the salt-sensitive peptide P-113 were diminished at high salt concentrations, whereas the activities of its β-naphthylalanine and β-(4,4′-biphenyl)alanine-substituted variant were less affected.
Cryptic Species and Azole Resistance in the Aspergillus niger Complex
Authors: Howard Susan J. , Harrison Elizabeth , Bowyer Paul , Varga Janos , Denning David W.
Published: July 2011

Aspergillus niger
is a common clinical isolate. Multiple species comprise the
Aspergillus
section
Nigri
and are separable using sequence data. The antifungal susceptibility of these cryptic species is not known. We determined the azole MICs of 50 black aspergilli, 45 from clinical specimens, using modified EUCAST (mEUCAST) and Etest methods. Phylogenetic trees were prepared using the internal transcribed spacer, beta-tubulin, and calmodulin sequences to identify strains to species level and the results were compared with those obtained with
cyp51A
sequences. We attempted to correlate
cyp51A
mutations with azole resistance. Etest MICs were significantly different from mEUCAST MICs (
P
< 0.001), with geometric means of 0.77 and 2.79 mg/liter, respectively. Twenty-six of 50 (52%) isolates were itraconazole resistant by mEUCAST (MICs > 8 mg/liter), with limited cross-resistance to other azoles. Using combined beta-tubulin/calmodulin sequences, the 45 clinical isolates grouped into 5 clades,
A. awamori
(55.6%),
A. tubingensis
(17.8%),
A. niger
(13.3%),
A. acidus
(6.7%), and an unknown group (6.7%), none of which were morphologically distinguishable. Itraconazole resistance was found in 36% of the isolates in the
A. awamori
group, 90% of the
A. tubingensis
group, 33% of the
A. niger
group, 100% of the
A. acidus
group, and 67% of the unknown group. These data suggest that
cyp51A
mutations in section
Nigri
may not play as important a role in azole resistance as in
A. fumigatus
, although some mutations (G427S, K97T) warrant further study. Numerous cryptic species are found in clinical isolates of the
Aspergillus
section
Nigri
and are best reported as “
A. niger
complex” by clinical laboratories. Itraconazole resistance was common in this data set, but azole cross-resistance was unusual. The mechanism of resistance remains obscure.
Residual Activity of Two HIV Antiretroviral Regimens Prescribed without Virological Monitoring
Authors: Dunn D. T. , Goodall R. L. , Munderi P. , Kityo C. , Ranopa M. , Bacheler L. , Van Houtte M. , Gilks C. , Kaleebu P. , Pillay D.
Published: July 2011

Virological residual activity (VRA) denotes the degree of HIV RNA suppression achieved by antiretroviral therapy in the presence of resistant virus. This concept is particularly important in resource-limited settings, where rapid switching after detection of virological failure may not be feasible. Using data from the NORA trial, we estimated VRA for two regimens—zidovudine-lamivudine-abacavir (ZDV-3TC-ABC) and zidovudine-lamivudine-nevirapine (ZDV-3TC-NVP)—and related this to the phenotypic drug sensitivity of the component drugs in the two regimens. Plasma samples at weeks 0, 48, and 96 were retrospectively assayed for HIV-1 RNA, and genotypic/phenotypic resistance testing was performed if HIV-1 RNA exceeded 1,000 copies/ml. Virological residual activity (VRA) was defined as the difference between log10(HIV RNA) at week 48 or 96 and week 0 and related to 50% inhibitory concentration (IC50) relative to wild-type virus for ZDV and ABC (fold change [FC]). Twenty-seven samples in the ZDV-3TC-NVP group and 56 in the ZDV-3TC-ABC group contributed to the analysis. Mean VRA was significantly higher in the ZDV-3TC-ABC group than in the ZDV-3TC-NVP at week 48 (1.62 versus 0.90) and week 96 (1.29 versus 0.78). There was a weak and nonsignificant relationship between VRA and ZDV FC, with VRA decreasing by 0.1 log10copies/ml per 2-fold increase in ZDV. The association with ABC FC was much stronger, with a marked reduction in VRA occurring at ABC FC values greater than approximately 2. This information should be considered in future treatment guidelines relevant to resource-poor settings.
Pyrazinamide Susceptibility Testing in Mycobacterium tuberculosis: a Systematic Review with Meta-Analyses
Authors: Chang Kwok Chiu , Yew Wing Wai , Zhang Ying
Published: July 2011

Standard culture-based testing of the susceptibility of
Mycobacterium tuberculosis
to pyrazinamide is difficult to perform. This systematic review with meta-analyses evaluated the roles of molecular assays targeting
pncA
and of pyrazinamidase assays. PubMed and Embase were searched for relevant publications in English. Sensitivity and specificity were estimated in bivariate random-effects models. Of 128 articles identified, 73 sets of data involving culture isolates were initially included in meta-analyses. Summary estimates of sensitivity and specificity, respectively, were 87% and 93% for PCR-DNA sequencing (
n
= 29), 75% and 95% for PCR-single-stranded conformation polymorphism (SSCP) (
n
= 5), 96% and 97% for a mixture of other molecular assays (
n
= 6), and 89% and 97% for pyrazinamidase assays using the Wayne method (
n
= 33). The median prevalence (range) of pyrazinamide resistance was 51% (31% to 89%) in multidrug-resistant
M. tuberculosis
isolates and 5% (0% to 9%) in non-multidrug-resistant isolates. Excluding studies with possibly considerable false resistance in the reference assay gave the following estimates of sensitivity and specificity, respectively: 92% and 93% for PCR-DNA sequencing (
n
= 20), 98% and 96% for other molecular assays (
n
= 5), and 91% and 97% for the Wayne assay (
n
= 27). The Wayne assay had significant funnel plot asymmetry, so the test performance might have been overestimated. Considering the prevalence of pyrazinamide resistance in different clinical settings, PCR-DNA sequencing, and possibly other molecular assays targeting
pncA
, can detect pyrazinamide resistance in multidrug-resistant
M. tuberculosis
isolates, with predictive values largely exceeding 90%, and rule out pyrazinamide resistance in non-multidrug-resistant isolates, with predictive values exceeding 99%. Molecular assays are probably the way forward for detecting pyrazinamide resistance.
Expression of an Mg
2+
-Dependent HIV-1 RNase H Construct for Drug Screening
Authors: Farias Richard V. , Vargas Deborah A. , Castillo Andres E. , Valenzuela Beatriz , Coté Marie L. , Roth Monica J. , Leon Oscar
Published: July 2011

A single polypeptide of the HIV-1 reverse transcriptase that reconstituted Mg
2+
-dependent RNase H activity has been made. Using molecular modeling, the construct was designed to encode the p51 subunit joined by a linker to the thumb (T), connection (C), and RNase H (R) domains of p66. This p51-G-TCR construct was purified from the soluble fraction of an
Escherichia coli
strain, MIC2067(DE3), lacking endogenous RNase HI and HII. The p51-G-TCR RNase H construct displayed Mg
2+
-dependent activity using a fluorescent nonspecific assay and showed the same cleavage pattern as HIV-1 reverse transcriptase (RT) on substrates that mimic the tRNA removal required for second-strand transfer reactions. The mutant E706Q (E478Q in RT) was purified under similar conditions and was not active. The RNase H of the p51-G-TCR RNase H construct and wild type HIV-1 RT had similar

K
m

s for an RNA-DNA hybrid substrate and showed similar inhibition kinetics to two known inhibitors of the HIV-1 RT RNase H.
Observational Study of the Clinical Efficacy of Voriconazole and Its Relationship to Plasma Concentrations in Patients
Authors: Troke Peter F. , Hockey Hans P. , Hope William W.
Published: July 2011

Voriconazole is approved for treating invasive fungal infections. We examined voriconazole exposure-response relationships for patients from nine published clinical trials. The relationship between the mean voriconazole plasma concentration (
C
avg
) and clinical response and between the free
C
avg
/MIC ratio versus the clinical response were explored using logistic regression. The impact of covariates on response was also assessed. Monte Carlo simulation was used to estimate the relationship between the trough concentration/MIC ratio and the probability of response. The covariates individually related to response were as follows: study (
P
< 0.001), therapy (primary/salvage,
P
< 0.001), primary diagnosis (
P
< 0.001), race (
P
= 0.004), baseline bilirubin (
P
< 0.001), baseline alkaline phosphatase (
P
= 0.014), and pathogen (yeast/mold,
P
< 0.001). The
C
avg
for 72% of the patients was 0.5 to 5.0 μg/ml, with the maximum response rate (74%) at 3.0 to 4.0 μg/ml. The
C
avg
showed a nonlinear relationship to response (
P
< 0.003), with a lower probability at the extremes. For patients with
C
avg
< 0.5 μg/ml, the response rate was 57%. The lowest response rate (56%) was seen with a
C
avg
≥ 5.0 μg/ml (18% of patients) and was associated with significantly lower mold infection responses compared to yeasts (
P
< 0.001) but not with voriconazole toxicity. Higher free
C
avg
/MIC ratios were associated with a progressively higher probability of response. Monte Carlo simulation suggested that a trough/MIC ratio of 2 to 5 is associated with a near-maximal probability of response. The probability of response is lower at the extremes of
C
avg
. Patients with higher free
C
avg
/MIC ratios have a higher probability of clinical response. A trough/MIC ratio of 2 to 5 can be used as a target for therapeutic drug monitoring.
Mutations of the Listeria monocytogenes PeptidoglycanN-Deacetylase andO-Acetylase Result in Enhanced Lysozyme Sensitivity, Bacteriolysis, and Hyperinduction of Innate Immune Pathways
Authors: Rae Chris S. , Geissler Aimee , Adamson Paul C. , Portnoy Daniel A.
Published: July 2011

Listeria monocytogenesis a Gram-positive intracellular pathogen that is naturally resistant to lysozyme. Recently, it was shown that peptidoglycan modification by N-deacetylation or O-acetylation confers resistance to lysozyme in various Gram-positive bacteria, includingL. monocytogenes.L. monocytogenespeptidoglycan is deacetylated by the action ofN-acetylglucosamine deacetylase (Pgd) and acetylated byO-acetylmuramic acid transferase (Oat). We characterized Pgd−, Oat−, and double mutants to determine the specific role ofL. monocytogenespeptidoglycan acetylation in conferring lysozyme sensitivity during infection of macrophages and mice. Pgd−and Pgd−Oat−double mutants were attenuated approximately 2 and 3.5 logs, respectively,in vivo. In bone-marrow derived macrophages, the mutants demonstrated intracellular growth defects and increased induction of cytokine transcriptional responses that emanated from a phagosome and the cytosol. Lysozyme-sensitive mutants underwent bacteriolysis in the macrophage cytosol, resulting in AIM2-dependent pyroptosis. Each of thein vitrophenotypes was rescued upon infection of LysM−macrophages. The addition of extracellular lysozyme to LysM−macrophages restored cytokine induction, host cell death, andL. monocytogenesgrowth inhibition. This surprising observation suggests that extracellular lysozyme can access the macrophage cytosol and act on intracellular lysozyme-sensitive bacteria.
Role for the Burkholderia pseudomallei Type Three Secretion System Cluster 1
bpscN
Gene in Virulence
Authors: D'Cruze Tanya , Gong Lan , Treerat Puthayalai , Ramm Georg , Boyce John D. , Prescott Mark , Adler Ben , Devenish Rodney J.
Published: July 2011

Burkholderia pseudomallei
, the causal agent of melioidosis, employs a number of virulence factors during its infection of mammalian cells. One such factor is the type three secretion system (TTSS), which is proposed to mediate the transport and secretion of bacterial effector molecules directly into host cells. The
B. pseudomallei
genome contains three TTSS gene clusters (designated TTSS1, TTSS2, and TTSS3). Previous research has indicated that neither TTSS1 nor TTSS2 is involved in
B. pseudomallei
virulence in a hamster infection model. We have characterized a
B. pseudomallei
mutant lacking expression of the predicted TTSS1 ATPase encoded by
bpscN
. This mutant was significantly attenuated for virulence in a respiratory melioidosis mouse model of infection. In addition, analyses
in vitro
showed diminished survival and replication in RAW264.7 cells and an increased level of colocalization with the autophagy marker protein LC3 but an unhindered ability to escape from phagosomes. Taken together, these data provide evidence that the TTSS1
bpscN
gene product plays an important role in the intracellular survival of
B. pseudomallei
and the pathogenesis of murine infection.
Two DHH Subfamily 1 Proteins Contribute to Pneumococcal Virulence and Confer Protection against Pneumococcal Disease
Authors: Cron L. E. , Stol K. , Burghout P. , van Selm S. , Simonetti E. R. , Bootsma H. J. , Hermans P. W. M.
Published: July 2011

Streptococcus pneumoniae
is an important human bacterial pathogen, causing such infections as pneumonia, meningitis, septicemia, and otitis media. Current capsular polysaccharide-based conjugate vaccines protect against a fraction of the over 90 serotypes known, whereas vaccines based on conserved pneumococcal proteins are considered promising broad-range alternatives. The pneumococcal genome encodes two conserved proteins of an as yet unknown function, SP1298 and SP2205, classified as DHH (Asp-His-His) subfamily 1 proteins. Here we examined their contribution to pneumococcal pathogenesis using single and double knockout mutants in three different strains: D39, TIGR4, and BHN100. Mutants lacking both SP1298 and SP2205 were severely impaired in adherence to human epithelial Detroit 562 cells. Importantly, the attenuated phenotypes were restored upon genetic complementation of the deleted genes. Single and mixed mouse models of colonization, otitis media, pneumonia, and bacteremia showed that bacterial loads in the nasopharynx, middle ears, lungs, and blood of mice infected with the mutants were significantly reduced from those of wild-type-infected mice, with an apparent additive effect upon deletion of both genes. Minor strain-specific phenotypes were observed, i.e., deletion of SP1298 affected host-cell adherence in BHN100 only, and deletion of SP2205 significantly attenuated virulence in lungs and blood in D39 and BHN100 but not TIGR4. Finally, subcutaneous vaccination with a combination of both DHH subfamily 1 proteins conferred protection to nasopharynx, lungs, and blood of mice infected with TIGR4. We conclude that SP1298 and SP2205 play a significant role at several stages of pneumococcal infection, and importantly, these proteins are potential candidates for a multicomponent protein vaccine.
Importance of Antibodies to Lipopolysaccharide in Natural and Vaccine-Induced Serum Bactericidal Activity against Neisseria meningitidis Group B
Authors: Schmiel Deborah H. , Moran Elizabeth E. , Keiser Paul B. , Brandt Brenda L. , Zollinger Wendell D.
Published: July 2011

Analysis of the specificity of bactericidal antibodies in normal, convalescent, and postvaccination human sera is important in understanding human immunity to meningococcal infections and can aid in the design of an effective group B vaccine. A collection of human sera, including group C and group B convalescent-phase sera, normal sera with naturally occurring cross-reactive bactericidal activity, and some postvaccination sera, was analyzed to determine the specificity of cross-reactive bactericidal antibodies. Analysis of human sera using a bactericidal antibody depletion assay demonstrated that a significant portion of the bactericidal activity could be removed by purified lipopolysaccharide (LPS). LPS homologous to that expressed on the bactericidal test strain was most effective, but partial depletion by heterologous LPS suggested the presence of antibodies with various degrees of cross-reactivity. Binding of anti-L3,7 LPS bactericidal antibodies was affected by modification of the core structure, suggesting that these functional antibodies recognized epitopes consisting of both core structures and lacto-N-neotetraose (LNnT). When the target strain was grown with 5′-cytidinemonophospho-N-acetylneuraminic acid (CMP-NANA) to increase LPS sialylation, convalescent-phase serum bactericidal titers were decreased by only 2- to 4-fold, and most remaining bactericidal activity was still depleted by LPS. Highly sialylated LPS was ineffective in depleting bactericidal antibodies. We conclude that natural infections caused by strains expressing L3,7 LPS induce persistent, protective bactericidal antibodies and appear to be directed against nonsialylated bacterial epitopes. Additionally, subsets of these bactericidal antibodies are cross-reactive, binding to several different LPS immunotypes, which is a useful characteristic for an effective group B meningococcal vaccine antigen.
Stratified assessment of the role of inhaled hypertonic saline in reducing cystic fibrosis pulmonary exacerbations: a retrospective analysis
Authors: Dmello Dayton , Nayak Ravi P , Matuschak George M
Published: July 2011

Objective

Limited data exist concerning the role of inhaled hypertonic saline (HS) in decreasing pulmonary exacerbations in cystic fibrosis (CF), especially as more advanced stages of CF lung disease were excluded in prior studies. Herein, the authors retrospectively determined the efficacy of inhaled HS in reducing CF pulmonary exacerbations when stratified according to the severity of CF lung disease. Stratification was based on the framework of the Pulmonary Therapeutics Committee's published gradation of obstructive lung physiology in CF, that is, mild (FEV1>70%), moderate (FEV140–70%) and severe (FEV1<40%) lung disease, respectively.

Design

A retrospective review of the Port CF database over a 3-year period performed at an academic CF care centre.

Results

340 pulmonary exacerbations were identified; inhaled HS was being used in 99 of these cases. Univariate analysis demonstrated a significant reduction in pulmonary exacerbations only in mild obstruction (OR=0.09, CI 0.01 to 0.81, p=0.012); however, multivariate logistic regression that adjusted for confounding variables showed a reduction in pulmonary exacerbations across the entire spectrum of obstructive lung disease when using inhaled HS, that is, mild obstructive CF lung disease (OR=0.17, CI 0.05 to 0.58, p=0.004), moderate obstructive CF lung disease (OR=0.39, CI 0.16 to 0.93, p=0.034), as well as severe obstructive CF lung disease (OR=0.02, CI 0.001 to 0.45, p=0.015). Moreover, inhaled HS appeared reasonably well tolerated across all stages of lung-disease severity, and was discontinued in only 7% of cases (n=4) with severe lung disease.

Conclusion

In this study, inhaled HS appeared to reduce pulmonary exacerbations in CF lung disease at all stages of obstruction. This underscores the importance of therapeutic inhaled HS in CF lung disease, regardless of the severity of lung obstruction.
Differential effects of organic nitrates on arterial diameter among healthy Japanese participants with different mitochondrial aldehyde dehydrogenase 2 genotypes: randomised crossover trial
Authors: Sakata Satoko , Yoshihara Tatsuya , Arima Hisatomi , Shiraishi Fumie , Oniki Hideyuki , Takahashi-Yanaga Fumi , Matsumura Kiyoshi , Sasaguri Toshiyuki
Published: July 2011

Objectives

To determine whether polymorphisms at codon 487 (*1, GAA=Glu; *2, AAA=Lys) of mitochondrial aldehyde dehydrogenase 2 (ALDH2) influence nitroglycerine (glyceryl trinitrate (GTN))-induced vasodilation, and whether GTN or isosorbide dinitrate (ISDN) is a more effective antianginal agent in each ALDH2 genotype.

Design

A randomised, open-label, crossover trial with 117 healthy Japanese (20–39 years) whose genotypes were determined (*1/*1, n=47; *1/*2, n=48; *2/*2, n=22) was performed at Kyushu University Hospital, Fukuoka, Japan. Participants were randomly assigned to treatment: sublingual spray of GTN (0.3 mg) or ISDN (1.25 mg). After ≥1 week, measurements were repeated using the other drug. The main outcome measures were the maximal rate of increase in the brachial artery diameter determined by ultrasonography, the time required to attain maximal dilation (Tmax) and the time required to attain 90% maximal dilation (T0.9).

Results

The maximal artery diameter increase in response to GTN or ISDN did not differ among genotypes. However, GTN Tmaxwas significantly longer for *2/*2 (299.7 s, 269.0–330.4) than *1/*1 (254.7 s, 238.6–273.4; p=0.0190). GTN T0.9was significantly longer in the *1/*2 (206.1 s, 191.7–219.3) and *2/*2 (231.4 s, 211.8–251.0) genotypes than *1/*1 (174.9 s, 161.5–188.3; p=0.0068, p<0.0001, respectively). In contrast, the time-course of ISDN-induced vasodilation did not differ among genotypes. GTN Tmaxand T0.9among *1 allele carriers (*1/*1 and *1/*2) were significantly shorter than those of ISDN, whereas the time course of GTN and ISDN vasodilation did not differ among participants carrying *2/*2.

Conclusions

The amplitude of GTN-induced vasodilation was not influenced by the ALDH2 genotype, but the response was significantly delayed in *2 allele carriers, especially *2/*2. GTN dilated the artery more quickly than ISDN in *1/*1 and *1/*2, but not in *2/*2.

Trial registration number

UMIN000001492 (UMIN-CTR database).
Mortality following blood transfusion for non-variceal upper gastrointestinal bleeding
Authors: Taha Ali S , McCloskey Caroline , Craigen Theresa , Angerson Wilson J , Shah Amir A , Morran Christopher G
Published: July 2011

Objective

Blood transfusion remains an integral step in the management of acute non-variceal upper gastrointestinal bleeding (NV-UGIB), but its safety is being increasingly questioned in less severe cases. The authors aimed to measure 30-day and 2-year mortalities after blood transfusion for NV-UGIB.

Methods

Cox proportional hazards models were used to estimate the association of blood transfusion with mortality while adjusting for age, Charlson comorbidity score, the complete Rockall score for acute UGIB, admission status and medication intake prior to bleeding.

Main outcome measures

Death from any cause at 30 days and 2 years after NV-UGIB.

Results

1340 patients presented with NV-UGIB< (808 men (60.3%), median age 67 years) of whom 564 (42.1%) were transfused. The overall mortality was 5.3% at 30 days and 26.0% at 2 years in all patients. Comparing subjects with a haemoglobin concentration greater than 10.0 g/dl who were transfused with those who were not, 30-day mortalities (95% CIs) were 11.5% (6.7 to 18.0) versus 3.6% (2.3 to 5.3), respectively, p<0.001, and 2-year mortalities (95% CIs) were 40% (32 to 49) versus 20% (17 to 23), p<0.001. After adjusting for age, Charlson score, Rockall score and haemoglobin, the HRs (95% CIs) for death after transfusion were 1.88 (1.00 to 3.55) (p=0.051) at 30 days and 1.71 (1.28 to 2.28), (p<0.001) at 2 years.

Conclusion

In patients with moderately severe NV-UGIB, mortality is higher following blood transfusion. Whether this reflects selection bias, an effect of comorbidity or an effect of transfusion requires urgent prospective study.
Immunohistochemistry in the distinction between primary and metastatic ovarian mucinous neoplasms: Table 1
Authors: McCluggage W Glenn
Published: July 2011

The distinction between a primary and metastatic mucinous carcinoma within the ovary may be problematic. In most cases, the distinction can be made by careful pathological examination encompassing both the gross and microscopic findings and taking into account the distribution of the disease. However, immunohistochemistry may be of value in certain scenarios. In this review, I discuss the value of markers in the distinction between primary ovarian mucinous neoplasms and metastatic mucinous carcinomas from the colorectum, appendix, pancreas, biliary tract, stomach and cervix, the most common primary sites which give rise to metastatic mucinous carcinoma within the ovary. There is a significant degree of immunophenotypic overlap between primary ovarian mucinous neoplasms and metastatic mucinous carcinomas from the gastrointestinal tract, especially the upper gastrointestinal type; this is because most primary ovarian mucinous carcinomas and borderline tumours are of so-called intestinal or enteric type and exhibit some degree of positivity with enteric markers. Mullerian type primary ovarian mucinous neoplasms also exist and exhibit distinct immunohistochemical differences to the more common intestinal type.
Conscientious objection in medical students: a questionnaire survey
Authors: Strickland Sophie LM
Published: July 2011

Objective

To explore attitudes towards conscientious objections among medical students in the UK.

Methods

Medical students at St George's University of London, Cardiff University, King's College London and Leeds University were emailed a link to an anonymous online questionnaire, hosted by an online survey company. The questionnaire contained nine questions. A total of 733 medical students responded.

Results

Nearly half of the students in this survey stated that they believed in the right of doctors to conscientiously object toanyprocedure. Demand for the right to conscientiously object is greater in Muslim medical students when compared with other groups of religious medical students.

Discussion

Abortion continues to be a contentious issue among medical students and this may contribute to the looming crisis in abortion services over the coming years. This project sheds some light on how future doctors view some of their ethical rights and obligations. Using empirical evidence, it reveals that conscientious objection is an issue in the UK medical student body today. These data could help anticipate problems that may arise when these medical students qualify and practise medicine in the community.

Conclusion

Clearer guidance is needed for medical students about the issue of conscientious objection at medical school.
Computed tomographic angiography versus digital subtraction angiography for the postoperative detection of residual aneurysms: a single-institution series and meta-analysis
Authors: Thaker Nikhil Gautam , Turner Jay D , Cobb William S , Hussain Ibrahim , Janjua Nazli , He Wenzhuan , Gandhi Chirag D , Prestigiacomo Charles Joseph
Published: July 2011

Background

Computed tomographic angiography (CTA) has recently emerged as a non-invasive alternative to digital subtraction angiography (DSA) for the detection of residual cerebral aneurysms (RA).

Objective

To compare the diagnostic accuracy of CTA with the current ‘gold standard’, DSA, in the postoperative detection of RA.

Methods

Patient data from this single institution were prospectively gathered, and imaging results retrospectively blinded and analyzed. Between 2001 and 2005 eligible patients received microsurgical repair of cerebral aneurysms and were evaluated postoperatively by DSA and CTA. These single-institutional data were compiled with qualified studies published from 1997 to 2009, and a meta-analysis was performed.

Results

This institutional series reports sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of 100%. Eleven studies met the inclusion criteria for the meta-analysis. A total of 427 patients with 513 aneurysms were included, with 61 RA detected by DSA and 40 detected by CTA. Unweighted analysis resulted in pooled sensitivity of 73.8%, specificity of 96.3%, PPV of 91.0% and NPV of 86.1%. Stratified analysis of studies using 16-slice CTA versus 2D DSA reported pooled sensitivity of 92.6%, specificity of 99.3%, PPV of 95.8%, and NPV of 97.8%.

Conclusions

This meta-analysis supports CTA as an acceptable modality for postoperative detection of RA, although DSA remains the gold standard. By implementing multidetector CTA technology in experienced centers, the sensitivity and specificity of CTA may approach that of traditional DSA for detecting RA. As a cost-effective, non-invasive modality, CTA is a promising alternative to DSA for initial and long-term evaluation of RA.
Stent assisted coiling of the ruptured wide necked intracranial aneurysm
Authors: Lodi Y M , Latorre J G , El-Zammar Z , Swarnkar A , Deshaies E , Fessler R D
Published: July 2011

Background

Stent assisted coiling of unruptured wide necked intracranial aneurysms require antiplatelets to prevent stent thrombosis. The effect of the loading dose of antiplatelets prior to the stent coiling procedure in an unsecured wide necked ruptured intracranial aneurysm is not known.

Objective

To report any potential complication associated with the use of both aspirin and clopidogrel in stent assisted coiling of ruptured wide necked intracranial aneurysms.

Methods

Consecutive patients who underwent stent assisted coiling for ruptured wide necked intracranial aneurysm were enrolled from 2005 to 2009. Patients' demographics, including Hunt and Hess grade, Fisher scale, and location and size of aneurysms, were collected. Complications such as rupture of aneurysm, thromboembolic events, ventriculostomy associated or systemic hemorrhages were recorded. Additionally, a 90 day outcome measurement was obtained using the Glasgow Outcome Scale.

Results

22 patients with a mean age of 50±13 years underwent stent assisted coiling. A loading dose of clopidogrel 300 mg and aspirin 325 mg orally were given prior to stent placement. There was no intraoperative rupture of aneurysm, ventriculostomy associated hemorrhage or systemic hemorrhagic event. There were two episodes of stent thrombosis; one was an asymptomatic event which developed during the stent assisted coiling procedure and resolved spontaneously; the other was symptomatic which required intra-arterial administration of glycoprotein IIbIIIa receptor antagonist. There was no mortality and good outcome was observed in 82% of patients.

Conclusion

In our series of carefully selected patients, therapeutic dual antiplatelet loading prior to stent assisted coiling of ruptured wide necked intracranial aneurysm was not associated with increased bleeding complications. However, thromboembolic events remain the main challenge. Further study is required to confirm the safety of antiplatelet loading in stent assisted ruptured intracranial aneurysm coiling.
How to assess quality in your sexual health service: Table 1
Authors: Hathorn Emma , Land Lucy , Ross Jonathan D C
Published: July 2011

Previous improvements in NHS have largely focused on increasing service capacity to ensure the provision of universal, comprehensive healthcare at the point of need in the UK. However, public expectations of the NHS are changing, triggered by increased access to information and media coverage of a series of lapses in quality and geographical inequity of care. The NHS also faces the challenges posed by a changing family structure, an ageing population, advancing technology and economic uncertainty. To meet these challenges, improvements in quality rather than just quantity have become a focus of the new NHS. This article provides an overview of quality and how to measure it in sexual health services.
ENTROPY ENTRAINMENT AND DISSIPATION IN FINITE TEMPERATURE SUPERFLUIDS
Authors: ANDERSSON N. , COMER G. L.
Published: July 2011

Neutron stars are expected to contain several distinct superfluid components, ranging from the neutron superfluid which coexists with the elastic crust to the mixed neutron superfluid/proton superconductor in the outer core and more exotic phases like superfluid hyperons and colour-flavour-locked superconducting quarks in the deep core. These different phases may have significant effect on the dynamics of the system. Building on a general variational framework for multifluid dynamics, we consider the behaviour of superfluid systems at finite temperatures (as required to understand various dissipation channels). As a demonstration of the validity of the underlying principles, such as treating the excitations in the system as a massless "entropy" fluid, we show that the model is formally equivalent to the traditional two-fluid approach for superfluid helium. In particular, we demonstrate how the entropy entrainment is related to the "normal fluid density". We also show how the superfluid constraint of irrotationality reduces the number of dissipation coefficients in the system. The analysis provides insight into the more general problem where vortices are present in the superfluid, and we discuss how the so-called mutual friction force can be accounted for. The end product is a formalism for finite temperature effects in a single condensate that can be applied to both low temperature laboratory systems and the various superfluid phases in a neutron star. This provides a key step towards the modelling of more realistic neutron star dynamics, and the understanding of a range of phenomena from pulsar glitches to magnetar seismology and the gravitational-wave-driven r-mode instability.
EFFECT OF DILUTION RATE ON THE PREDICTABILITY OF A REALISTIC ECOSYSTEM MODEL WITH INSTANTANEOUS NUTRIENT RECYCLING
Authors: CHATTERJEE ANAL , PAL SAMARES
Published: July 2011

An analysis is made on a three dimensional mathematical model for the interaction of nutrient, phytoplankton and their predator zooplankton population in an open marine system. For a realistic representation of the open marine plankton ecosystem, we have incorporated various natural phenomena such as dissolved limiting nutrient with general nutrient uptake function, nutrient recycling, interspecies competition and grazing at a higher level. For the model with constant nutrient input and different constant washout rates, conditions for boundedness of the solutions, existence and stability of non negative equilibria, as well as persistence are given. The model system is studied analytically and the threshold values for the existence and stability of various steady states are worked out. It is observed that if the dilution rate of nutrient crosses certain critical value, the system enters into Hopf-bifurcation. Finally, it is observed that planktonic bloom can be controlled and stability around the equilibrium of coexistence can be obtained if the dilution rate of phytoplankton population is increased. Computer simulations have been carried out to illustrate different analytical results.
ENHANCEMENT OF SURFACE PLASMON RESONANCE USING COLLOIDAL GOLD NANOPARTICLES EMBEDDED IN A SILICA LAYER
Authors: JUNG JAEYEON , CHOI JAEYOO , CHENG JIE , PARK MINSUNG , CHO SEONGIN , HYUN JINHO , PARK SUNG HA
Published: July 2011

This paper presents a strategy for the signal enhancement of surface plasmon resonance biosensors using colloidal gold nanoparticles and a silica layer. We describe the method for the deposition of a silica-stabilized gold nanoparticle layer on a gold film, namely an enhanced surface plasmon resonance chip. This chip shows significant changes in its surface plasmon resonance signals when biomolecules are attached to its surface as compared to a normal gold surface. These characteristics are closely related to the surface plasmon resonance effect as determined using prostate-specific antigen. The detection limit of the enhanced surface plasmon resonance chip is determined to be 0.01 ng/mL for a prostate-specific antigen immunoassay. The use of an enhanced surface plasmon resonance chip makes it possible to enhance signals 1000-fold compared to the signals obtained by conventional surface plasmon resonance sensing. The enhancement of the surface plasmon resonance spectral shift results from the coupling of the surface and particle plasmons through the application of a silica-stabilized gold nanoparticle layer on the gold surface.