bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges in Uncertainty, Calibration, Validation and Predictability of Engineering Analysis Models
Authors: Wang Liping , Fang Xingjie , Subramaniyan Arun , Jothiprasad Giridhar , Gardner Martha , Kale Amit , Akkaram Srikanth , Beeson Don , Wiggs Gene , Nelson John
Published: May 2012

Model calibration, validation, prediction and uncertainty quantification have progressed remarkably in the past decade. However, many issues remain. This paper attempts to provide answers to the key questions: 1) how far have we gone? 2) what technical challenges remain? and 3) what are the future directions for this work? Based on a comprehensive literature review from academic, industrial and government research and experience gained at the General Electric (GE) Company, the paper will summarize the advancements of methods and the application of these methods to calibration, validation, prediction and uncertainty quantification. The latest research and application thrusts in the field will emphasize the extension of the Bayesian framework to validation of engineering analysis models. Closing remarks will offer insight into possible technical solutions to the challenges and future research directions.
Effects of Mesh Density on Static Load Performance of Metal Mesh Gas Foil Bearings
Authors: Lee Yong-Bok , Kim Chang Ho , Kim Tae Ho , Kim Tae Young
Published: May 2012

Metal mesh materials have been used successfully in vibration isolators and bearing dampers due to their superior friction or hysteresis damping mechanism. These materials are formed to metal mesh (or wire mesh) structures in ring-shape by compressing a weave of metal wires, in general. Recently, oil-free rotating machinery implement metal mesh structures into hydrodynamic gas foil bearings by replacing bump strip layers with them, to increase its bearing structural damping. A metal mesh foil bearing (MMFB) consists of a top foil and support elastic metal mesh pads installed between a rotating shaft and a housing. The present research presents load capacity tests of a MMFB at rotor rest (0 rpm) and 30 krpm for three metal mesh densities of 13.1%, 23.2%, and 31.6%. The metal mesh pad of test MMFB is made using a stainless steel wire with a diameter of 0.15 mm. Test rig comprises a rigid rotor with a diameter of 60 mm supported on two ball bearings at both ends and test MMFB with an axial length of 50 mm floats on the rotor. Static loads is provided with a mechanical loading device on test MMFB and a strain gauge type load cell measures the applied static loads. A series of static load versus deflection tests were conducted for selected metal mesh densities at rest (0 rpm). Test data are compared to further test results of static load versus journal eccentricity recorded at the rotor speed of 30 krpm. Test data show a strong nonlinearity of bearing deflection (journal eccentricity) with static load, independent of rotor spinning. Observed hysteresis loops imply significant structural damping of test MMFB. Measured journal deflections at 0 rpm are in similar trend to recorded journal eccentricities at the finite rotor speed, thus implying that the MMFB performance depends mainly on the metal mesh structures. The paper also estimates linearlized stiffness coefficient and damping loss factor of test MMFB using the measured static load versus deflection test data at 0 rpm and 30 krpm. The results show that the highest mesh density of 31.6% produces highest linearlized stiffness coefficient and damping loss factor. With rotor spinning at 30 krpm, the linearlized stiffness coefficient and damping loss factor decrease slightly, independent of metal mesh densities. The present test data will serve as a database for benchmarking MMFB predictive models.
Extending the Flexibility of Object Oriented Systems Modeling Architectures
Authors: Sirica Steven , Fuksman Igor
Published: May 2012

When adopting an industry-wide generalized modular based system simulation tool (such as the Numerical Propulsion System Simulation – NPSS™), the generic modules provided with the system do not typically provide the fidelity required for detailed engineering design and analysis nor do they necessarily align with company specific methods. The challenge is to develop company specific replacement modules that would promote standardized methodologies while still providing the flexibility required for unique methods and / or joint venture teaming arrangements. Pratt & Whitney (P&W) has developed such a system within the NPSS™ framework that leverages the intrinsic Object Oriented (OO) capabilities of this tool without compromising the integrity of the standard methodologies. This flexibility easily allows a single system to be used for engine systems modeling from Concept Initiation through Fielded Product Support. Additionally, the structure and capabilities of this newly developed system provides the means for a significant reduction in the manpower required to maintain / upgrade this toolset.
Effects of Core Flow Swirl on the Flow Characteristics of a Scalloped Forced Mixer
Authors: Lei Zhijun , Mahallati Ali , Cunningham Mark , Germain Patrick
Published: May 2012

This paper presents a detailed experimental investigation of the influence of core flow swirl on the mixing and performance of a scaled turbofan mixer with 12 scalloped lobes. Measurements were made downstream of the mixer in a co-annular wind tunnel. The core-to-bypass velocity ratio was set to 2:1, temperature ratio to 1.0, and pressure ratio to 1.03, giving a Reynolds number of 5.2 × 105, based on the core flow velocity and equivalent hydraulic diameter. In the core flow, the background turbulence intensity was raised to 5% and the swirl angle was varied using five vane geometries from 0° to 30°. Seven-hole pressure probe measurements and surface oil flow visualization were used to describe the flowfield and the mixer performance. At low swirl angles, additional streamwise vortices were generated by the deformation of normal vortices due to the scalloped lobes. With increased core swirl, greater than 10°, the additional streamwise vortices were generated mainly due to radial velocity deflection, rather than stretching and deformation of normal vortices. At high swirl angles, stronger streamwise vortices and rapid interaction between various vortices promoted downstream mixing. Mixing was enhanced with minimal or no total pressure and thrust losses for the inlet swirl angles less than 10°. However, the reversed flow downstream of the center-body was a dominant contributor to the loss of thrust at the maximum core flow swirl angle of 30°.
Mixture-Forced Flame Transfer Function Measurements and Mechanisms in a Single-Nozzle Combustor at Elevated Pressure
Authors: Bunce Nick , Lee Jong Guen , Quay Bryan D. , Santavicca Domenic A.
Published: May 2012

The mixture-forced flame transfer function of a lean fully premixed single-nozzle research combustor operating on natural gas is determined experimentally at combustor pressures from 1 to 4 atm. Measurements are made over a range of inlet temperatures (100–300°C), mean velocities (25–35 m/s), and equivalence ratios (0.5–0.75). A rotating siren device, located upstream of the nozzle, is used to modulate the flow rate of the premixed fuel-air mixture. The amplitude and phase of the resultant velocity fluctuation are measured near the exit of the nozzle using the two-microphone method. The measured normalized velocity fluctuation serves as the input to the flame transfer function. In this study, the amplitude of the normalized velocity fluctuation is fixed at 5% and the modulation frequency is varied from 100 to 500 Hz. The output of the flame transfer function is the normalized global heat release fluctuation, which is measured using a photomultiplier tube and interference filter which captures the CH* chemiluminescence from the entire flame. In addition, two-dimensional CH* chemiluminescence images are taken for both forced and unforced flames. Forced flame images are phase-synchronized with the velocity fluctuation. The flame transfer functions for all of the operating conditions tested exhibit similar behavior. At low frequencies, the gain is initially greater than one, but then decreases as the frequency increases. After reaching a minimum, the gain increases with increasing frequency to a second peak and then again decreases. At certain operating conditions, the gain exhibits a second minimum. At frequencies corresponding to the minima in gain the phase curve exhibits inflection points. Regions of maximum and minimum gain are explained in terms of the constructive and destructive interference of vorticity fluctuations generated in the inner and outer shear layers. Phase-synchronized images are analyzed to isolate the fluctuating component of heat release. At frequencies where the gain is amplified, this analysis shows that the heat release fluctuations caused by the vorticity fluctuations generated in the inner and outer shear layers are in phase. While when the gain is at its minimum value, the heat release fluctuations are out of phase and therefore destructively interfere.
Low Cycle Fatigue Characteristics of a Low-Thermal Expansion, High Strength Alloy (HAYNES 242 Alloy)
Authors: Pike L. M. , Srivastava S. K.
Published: May 2012

HAYNES® 242® alloy, based primarily on the Ni-25Mo-8Cr system, derives its low thermal expansion characteristics from its composition and its high strength concomitant with high ductility from a long-range ordering reaction upon an aging heat treatment. This combination has enabled the alloy continually to find a challenging range of applications in the aerospace industry at up to 1300°F (704°C). These include seal rings, containment rings, duct segments, casings, rocket nozzles, etc. In conjunction with the creep strength and environmental resistance, the low cycle fatigue (LCF) behavior is an important material property affecting the service life of 242 alloy components. The low cycle fatigue behavior of 242 alloy was studied under fully reversed strain-controlled mode at 800°F (427°C), 1000°F (538°C), 1200°F (649°C) and 1400°F (760°C) using a triangular wave form with a frequency of 0.33 Hz. Results are presented in terms of cycles to crack initiation and failure. The magnitudes of fatigue lives at total strain range ≤ 0.7% at 800, 1000 and 1200°F are significantly greater than those of solid solution strengthened alloys. Additionally, stress-controlled LCF tests were performed at 1200°F (649°C) on 242 alloy as well as 909 alloy (for comparison). The paper will discuss the results of these two test programs.
Study of Unforced and Modulated Inclined Film-Cooling Jets Using Proper Orthogonal Decomposition: Part II—Forced Jets
Authors: Bidan Guillaume , Vezier Clementine , Nikitopoulos Dimitris E.
Published: May 2012

The effects of jet flow-rate modulation were investigated in the case of a 35° inclined jet in cross-flow over a flat plate using Mie scattering visualizations, time-resolved flow rate records and large eddy simulations (LES). In forced experiments, average blowing ratios of 0.3 and 0.4 were investigated with a duty cycle of 50% and pulsing frequencies of St = 0.016 and 0.159. Time-resolved flow rate measurements during the experiments provided precise knowledge of the instantaneous jet blowing ratio and adequate inlet boundary conditions for large eddy simulations. The dynamics of the vortical structures generated during the transient parts of the forcing cycle as well as their impact on film cooling performance were investigated with respect of the forcing parameters. At the considered blowing ratios, a starting ring vortex was consistently generated at the transition from low to high blowing ratio. Ingestion of cross-flow fluid at the transition from high to low blowing ratio was also observed and had a negative impact on film cooling performance. All studied cases exhibited an overall decrease in coverage regardless of pulsing parameters over their corresponding steady jet cases at fixed mass flow rate. Comparisons between pulsed and steady jets at constant pressure supply (same high blowing ratio) did exhibit some film-cooling improvement with pulsing. 3D Proper orthogonal decomposition was performed on LES results at distinct forcing frequencies to provide an analysis of dominant modes in the velocity and temperature fields. Significantly different results were obtained depending on the forcing frequency.
Temperature dependent spin precession measurements in trilayer graphene utilizing co/graphene contacts
Authors: Abel Joseph , Matsubayashi Akitomo , Garramone John J. , LaBella Vincent P.
Published: May 2012

The temperature dependence of the spin lifetime and spin diffusion coefficient of exfoliated multilayer graphene is measured using nonlocal spin detection and spin precession measurements. Low impedance cobalt contacts are utilized for spin injection and readout. A decrease in spin lifetime with increasing temperature is observed as well as an increase in the spin diffusion coefficient with increasing temperature. This observation provides some insight into the relevant spin relaxation mechanisms that are occurring in this trilayer graphene sample.
Oseltamivir Pharmacokinetics and Clinical Experience in Neonates and Infants during an Outbreak of H1N1 Influenza A Virus Infection in a Neonatal Intensive Care Unit
Authors: Standing Joseph F. , Nika Angela , Tsagris Vasileios , Kapetanakis Ioannis , Maltezou Helena C. , Kafetzis Dimitris A. , Tsolia Maria N.
Published: May 2012

Detailed oseltamivir pharmacokinetics have yet to be reported in neonates and infants; this group is at high risk of serious influenza-associated complications. Extrapolation of doses from older patients is complicated by rapid organ and drug-metabolizing enzyme maturation. A pharmacokinetic study has been conducted during an influenza A(H1N1) outbreak in a neonatal intensive care unit. Each included patient provided 4 samples for oseltamivir and 4 samples for its active metabolite oseltamivir carboxylate. A population pharmacokinetic model was developed with NONMEM. Allometric weight scaling and maturation functions were added
a priori
to scale for size and age based on literature values. Nine neonates and infants were recruited. A physiologically parameterized pharmacokinetic model predicted typical day 1 area under the curve (AUC
0-12
) values of 1,966 and 2,484 μg · h/liter for neonates and infants of ≤37 weeks of postmenstrual age (PMA) and >37 weeks of PMA treated with 1 mg/kg of body weight and 2 mg/kg, respectively. The corresponding steady-state AUC
0-12
values were 3,670 and 4,559 μg · h/liter. Premature neonates treated with 1 mg/kg and term babies treated with 2 mg/kg should have average oseltamivir carboxylate concentrations in a range similar to that for adults treated with 75 mg, corresponding to >200-fold above the half-maximal inhibitory concentration (IC
50
) value for influenza A(H1N1) from the start of therapy.
Potent Synergistic Effect of Doxycycline with Fluconazole against Candida albicans Is Mediated by Interference with Iron Homeostasis
Authors: Fiori Alessandro , Van Dijck Patrick
Published: May 2012

Doxycycline was found to act synergistically with the antifungal fluconazole against
Candida albicans
. Combination with doxycycline converts fluconazole from fungistatic to fungicidal, prevents the onset of drug resistance, and is also effective against a clinical isolate characterized by elevated resistance to fluconazole. Investigation of the interactions between the two drugs by way of checkerboard assays indicated that doxycycline had an influence on the MIC for fluconazole, as defined by CLSI standards, only at high concentrations (200 μg/ml). However, lower concentrations were effective at eliminating residual cell growth at supra-MICs of fluconazole. Using MIC-0, defined as a drug combination resulting in optically clear wells, as an endpoint, doxycycline was found to be synergistic with fluconazole at a concentration as low as 25 μg/ml, with a fractional inhibitory concentration index of <0.5. Doxycycline-mediated growth inhibition can be reversed by externally added iron, indicating that iron depletion may account for the synergism. Consistently, we confirmed old literature data about iron-chelating activity of doxycycline. Synergism of fluconazole with doxycycline does not appear to be mediated by calcineurin, since doxycycline further aggravates the susceptibility to fluconazole of mutants lacking the catalytic or the regulatory subunits of calcineurin. Growth in the presence of fluconazole and doxycycline is restored by an elevated dosage of
ERG11
in
Saccharomyces cerevisiae
but not in
C. albicans
, despite the full competence of the pathogen's protein to act as a suppressor in baker's yeast.
Involvement of Trichoderma Trichothecenes in the Biocontrol Activity and Induction of Plant Defense-Related Genes
Authors: Malmierca M. G. , Cardoza R. E. , Alexander N. J. , McCormick S. P. , Hermosa R. , Monte E. , Gutiérrez S.
Published: May 2012

Trichoderma
species produce trichothecenes, most notably trichodermin and harzianum A (HA), by a biosynthetic pathway in which several of the involved proteins have significant differences in functionality compared to their
Fusarium
orthologues. In addition, the genes encoding these proteins show a genomic organization differing from that of the
Fusarium tri
clusters. Here we describe the isolation of
Trichoderma arundinaceum
IBT 40837 transformants which have a disrupted or silenced
tri4
gene, a gene encoding a cytochrome P450 monooxygenase that oxygenates trichodiene to give rise to isotrichodiol, and the effect of
tri4
gene disruption and silencing on the expression of other
tri
genes. Our results indicate that the
tri4
gene disruption resulted in a reduced antifungal activity against
Botrytis cinerea
and
Rhizoctonia solani
and also in a reduced ability to induce the expression of tomato plant defense-related genes belonging to the salicylic acid (SA) and jasmonate (JA) pathways against
B. cinerea
, in comparison to the wild-type strain, indicating that HA plays an important function in the sensitization of
Trichoderma
-pretreated plants against this fungal pathogen. Additionally, the effect of the interaction of
T. arundinaceum
with
B. cinerea
or
R. solani
and with tomato seedlings on the expressions of the
tri
genes was studied.
Human Milk Oligosaccharides Promote the Growth of Staphylococci
Authors: Hunt K. M. , Preuss J. , Nissan C. , Davlin C. A. , Williams J. E. , Shafii B. , Richardson A. D. , McGuire M. K. , Bode L. , McGuire M. A.
Published: May 2012

Human milk oligosaccharides (HMO), which constitute a major component of human milk, promote the growth of particular bacterial species in the infant's gastrointestinal tract. We hypothesized that HMO also interact with the bacterial communities present in human milk. To test this hypothesis, two experiments were conducted. First, milk samples were collected from healthy women (
n
= 16); culture-independent analysis of the bacterial communities was performed, HMO content was analyzed, and the relation between these factors was investigated. A positive correlation was observed between the relative abundance of
Staphylococcus
and total HMO content (
r
= 0.66). In a follow-up study, we conducted a series of
in vitro
growth curve experiments utilizing
Staphylococcus aureus
or
Staphylococcus epidermidis
and HMO isolated from human milk. HMO exhibited stimulatory effects on bacterial growth under various nutritional conditions. Analysis of culture supernatants from these experiments revealed that HMO did not measurably disappear from the culture medium, indicating that the growth-enhancing effects were not a result of bacterial metabolism of the HMO. Instead, stimulation of growth caused greater utilization of amino acids in minimal medium. Collectively, the data provide evidence that HMO may promote the growth of
Staphylococcus
species in the lactating mammary gland.
Analysis of Predicted Carbohydrate Transport Systems Encoded by Bifidobacterium bifidum PRL2010
Authors: Turroni Francesca , Strati Francesco , Foroni Elena , Serafini Fausta , Duranti Sabrina , van Sinderen Douwe , Ventura Marco
Published: May 2012

The
Bifidobacterium bifidum
PRL2010 genome encodes a relatively small set of predicted carbohydrate transporters. Growth experiments and transcriptome analyses of
B. bifidum
PRL2010 revealed that carbohydrate utilization in this microorganism appears to be restricted to a relatively low number of carbohydrates.
Banana-Associated Microbial Communities in Uganda Are Highly Diverse but Dominated by Enterobacteriaceae
Authors: Rossmann Bettina , Müller Henry , Smalla Kornelia , Mpiira Samuel , Tumuhairwe John Baptist , Staver Charles , Berg Gabriele
Published: May 2012

Bananas are among the most widely consumed foods in the world. In Uganda, the country with the second largest banana production in the world, bananas are the most important staple food. The objective of this study was to analyze banana-associated microorganisms and to select efficient antagonists against fungal pathogens which are responsible for substantial yield losses. We studied the structure and function of microbial communities (endosphere, rhizosphere, and soil) obtained from three different traditional farms in Uganda by cultivation-independent (PCR-SSCP fingerprints of 16S rRNA/ITS genes, pyrosequencing of enterobacterial 16S rRNA gene fragments, quantitative PCR, fluorescence
in situ
hybridization coupled with confocal laser scanning microscopy, and PCR-based detection of broad-host-range plasmids and sulfonamide resistance genes) and cultivation-dependent methods. The results showed microhabitat-specific microbial communities that were significant across sites and treatments. Furthermore, all microhabitats contained a high number and broad spectrum of indigenous antagonists toward identified fungal pathogens. While bacterial antagonists were found to be enriched in banana plants, fungal antagonists were less abundant and mainly found in soil. The banana stem endosphere was the habitat with the highest bacterial counts (up to 10
9
gene copy numbers g
−1
). Here, enterics were found to be enhanced in abundance and diversity; they provided one-third of the bacteria and were identified by pyrosequencing with 14 genera, including not only potential human (
Escherichia
,
Klebsiella
,
Salmonella
, and
Yersinia
spp.) and plant (
Pectobacterium
spp.) pathogens but also disease-suppressive bacteria (
Serratia
spp.). The dominant role of enterics can be explained by the permanent nature and vegetative propagation of banana and the amendments of human, as well as animal, manure in these traditional cultivations.
Effect of Phenotypic Residual Feed Intake and Dietary Forage Content on the Rumen Microbial Community of Beef Cattle
Authors: Carberry Ciara A. , Kenny David A. , Han Sukkyan , McCabe Matthew S. , Waters Sinead M.
Published: May 2012

Feed-efficient animals have lower production costs and reduced environmental impact. Given that rumen microbial fermentation plays a pivotal role in host nutrition, the premise that rumen microbiota may contribute to host feed efficiency is gaining momentum. Since diet is a major factor in determining rumen community structure and fermentation patterns, we investigated the effect of divergence in phenotypic residual feed intake (RFI) on ruminal community structure of beef cattle across two contrasting diets. PCR-denaturing gradient gel electrophoresis (DGGE) and quantitative PCR (qPCR) were performed to profile the rumen bacterial population and to quantify the ruminal populations ofEntodiniumspp., protozoa,Fibrobacter succinogenes,Ruminococcus flavefaciens,Ruminococcus albus,Prevotella brevis, the genusPrevotella, and fungi in 14 low (efficient)- and 14 high (inefficient)-RFI animals offered a low-energy, high-forage diet, followed by a high-energy, low-forage diet. Canonical correspondence and Spearman correlation analyses were used to investigate associations between physiological variables and rumen microbial structure and specific microbial populations, respectively. The effect of RFI on bacterial profiles was influenced by diet, with the association between RFI group and PCR-DGGE profiles stronger for the higher forage diet. qPCR showed thatPrevotellaabundance was higher (P< 0.0001) in inefficient animals. A higher (P< 0.0001) abundance ofEntodiniumandPrevotellaspp. and a lower (P< 0.0001) abundance ofFibrobacter succinogeneswere observed when animals were offered the low-forage diet. Thus, differences in the ruminal microflora may contribute to host feed efficiency, although this effect may also be modulated by the diet offered.
A Cytochrome
b
5
-Containing Plastid-Located Fatty Acid Desaturase from Chlamydomonas reinhardtii
Authors: Zäuner Simone , Jochum Wibke , Bigorowski Tara , Benning Christoph
Published: May 2012

Monogalactosyldiacylglycerol (MGDG) in
Chlamydomonas reinhardtii
and other green algae contains hexadeca-4,7,10,13-tetraenoic acid (16:4) in the glycerol
sn-
2 position. While many genes necessary for the introduction of acyl chain double bonds have been functionally characterized, the Δ4-desaturase remained unknown. Using a phylogenetic comparison, a candidate gene encoding the MGDG-specific Δ4-desaturase from
Chlamydomonas
(CrΔ4FAD) was identified. CrΔ4FAD shows all characteristic features of a membrane-bound desaturase, including three histidine boxes and a transit peptide for chloroplast targeting. But it also has an N-terminal cytochrome
b
5
domain, distinguishing it from other known plastid desaturases. Cytochrome
b
5
is the primary electron donor for endoplasmic reticulum (ER) desaturases and is often fused to the desaturase domain in desaturases modifying the carboxyl end of the acyl group. Difference absorbance spectra of the recombinant cytochrome
b
5
domain of CrΔ4FAD showed that it is functional
in vitro
. Green fluorescent protein fusions of CrΔ4FAD localized to the plastid envelope in
Chlamydomonas
. Interestingly, overproduction of CrΔ4FAD in
Chlamydomonas
not only increased levels of 16:4 acyl groups in cell extracts but specifically increased the total amount of MGDG. Vice versa, the amount of MGDG was lowered in lines with reduced levels of CrΔ4FAD. These data suggest a link between MGDG molecular species composition and galactolipid abundance in the alga, as well as a specific function for this fatty acid in MGDG.
The Tlo Proteins Are Stoichiometric Components of Candida albicans Mediator Anchored via the Med3 Subunit
Authors: Zhang Anda , Petrov Kostadin O. , Hyun Emily R. , Liu Zhongle , Gerber Scott A. , Myers Lawrence C.
Published: May 2012

The amplification of the
TLO
(for
t
e
lo
mere-associated) genes in
Candida albicans
, compared to its less pathogenic, close relative
Candida dubliniensis
, suggests a role in virulence. Little, however, is known about the function of the Tlo proteins. We have purified the Mediator coactivator complex from
C. albicans
(caMediator) and found that Tlo proteins are a stoichiometric component of caMediator. Many members of the Tlo family are expressed, and each is a unique member of caMediator. Protein expression analysis of individual Tlo proteins, as well as the purification of tagged Tlo proteins, demonstrate that there is a large free population of Tlo proteins in addition to the Mediator-associated population. Coexpression and copurification of Tloα12 and caMed3 in
Escherichia coli
established a direct physical interaction between the two proteins. We have also made a
C. albicans
med3Δ/Δ
strain and purified an intact Mediator from this strain. The analysis of the composition of the
med3Δ
Mediator shows that it lacks a Tlo subunit. Regarding Mediator function, the
med3Δ/Δ
strain serves as a substitute for the difficult-to-make
tloΔ/Δ C. albicans
strain. A potential role of the
TLO
and
MED3
genes in virulence is supported by the inability of the
med3Δ/Δ
strain to form normal germ tubes. This study of caMediator structure provides initial clues to the mechanism of action of the Tlo genes and a platform for further mechanistic studies of caMediator's involvement in gene regulatory patterns that underlie pathogenesis.
Role of Actin-Bundling Protein Sac6 in Growth of Cryptococcus neoformans at Low Oxygen Concentration
Authors: Chang Yun C. , Lamichhane Ami Khanal , Kwon-Chung Kyung J.
Published: May 2012

Cryptococcus neoformans
, the etiologic agent of cryptococcosis, is an obligately aerobic yeast that inhabits an environmental niche exposed to ambient air. The cell doubling time was significantly prolonged under 1% O
2
relative to that under normoxic conditions. No apparent cell cycle arrest occurred following a shift from ambient air to 1% O
2
. However, yeast cells became hypersensitive to the actin monomer-sequestering agent latrunculin A at 1% O
2
, indicating that proper actin function is critical for growth at low oxygen concentrations. We showed that Sac6, an actin-binding protein, played an important role in cell growth under low oxygen conditions. Sac6 colocalized with cortical actin patches and with the ring structures between mother cells and buds. Under low oxygen conditions, the
sac6
deletion mutant grew poorly, and accumulation of the actin capping protein Cap1 was observed in the vacuole of the
sac6Δ
strain. Furthermore, endocytic processes were hampered in the
sac6Δ
mutant, but cell polarity and cytokinesis were not visibly disturbed. The deficiency of endocytosis in the
sac6Δ
strain could be rescued by 1 M sorbitol under 1% O
2
, but growth remained retarded. These results suggest an absence of a direct link in
C. neoformans
between endocytosis and coping with the stress of low oxygen conditions. This interpretation is further supported by the observation that deletion of three conserved genes,
ABP1
,
CRN1
, and
SLA2
, which play important roles in endocytosis, had no effect on growth under 1% O
2
. Interestingly, deletion of
SAC6
in
C. neoformans
had no effect on virulence in mice.
Oxidative Stress Modulates the Nitric Oxide Defense Promoted by Escherichia coli Flavorubredoxin
Authors: Baptista Joana M. , Justino Marta C. , Melo Ana M. P. , Teixeira Miguel , Saraiva Lígia M.
Published: May 2012

Mammalian cells of innate immunity respond to pathogen invasion by activating proteins that generate a burst of oxidative and nitrosative stress. Pathogens defend themselves from the toxic compounds by triggering a variety of detoxifying enzymes.
Escherichia coli
flavorubredoxin is a nitric oxide reductase that is expressed under nitrosative stress conditions. We report that in contrast to nitrosative stress alone, exposure to both nitrosative and oxidative stresses abolishes the expression of flavorubredoxin. Electron paramagnetic resonance (EPR) experiments showed that under these conditions, the iron center of the flavorubredoxin transcription activator NorR loses the ability to bind nitric oxide. Accordingly, triggering of the NorR ATPase activity, a requisite for flavorubredoxin activation, was impaired by treatment of the protein with the double stress. Studies of macrophages revealed that the contribution of flavorubredoxin to the survival of
E. coli
depends on the stage of macrophage infection and that the lack of protection observed at the early phase is related to inhibition of NorR activity by the oxidative burst. We propose that the time-dependent activation of flavorubredoxin contributes to the adaptation of
E. coli
to the different fluxes of hydrogen peroxide and nitric oxide to which the bacterium is subjected during the course of macrophage infection.
SalB Inactivation Modulates Culture Supernatant Exoproteins and Affects Autolysis and Viability in Enterococcus faecalis OG1RF
Authors: Shankar Jayendra , Walker Rachel G. , Wilkinson Mark C. , Ward Deborah , Horsburgh Malcolm J.
Published: May 2012

The culture supernatant fraction of an
Enterococcus faecalis gelE
mutant of strain OG1RF contained elevated levels of the secreted antigen SalB. Using differential fluorescence gel electrophoresis (DIGE) the
salB
mutant was shown to possess a unique complement of exoproteins. Differentially abundant exoproteins were identified using matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry. Stress-related proteins including DnaK, Dps family protein, SOD, and NADH peroxidase were present in greater quantity in the OG1RF
salB
mutant culture supernatant. Moreover, several proteins involved in cell wall synthesis and cell division, including
d
-Ala-
d
-Lac ligase and EzrA, were present in reduced quantity in OG1RF
salB
relative to the parent strain. The
salB
mutant displayed reduced viability and anomalous cell division, and these phenotypes were exacerbated in a
gelE salB
double mutant. An epistatic relationship between
gelE
and
salB
was not identified with respect to increased autolysis and cell morphological changes observed in the
salB
mutant. SalB was purified as a six-histidine-tagged protein to investigate peptidoglycan hydrolytic activity; however, activity was not evident. High-pressure liquid chromatography (HPLC) analysis of reduced muropeptides from peptidoglycan digested with mutanolysin revealed that the
salB
mutant and OG1RF were indistinguishable.
Risk factors affecting inhospital mortality after hip fracture: retrospective analysis using the Japanese Diagnosis Procedure Combination Database
Authors: Shoda Naoko , Yasunaga Hideo , Horiguchi Hiromasa , Matsuda Shinya , Ohe Kazuhiko , Kadono Yuho , Tanaka Sakae
Published: May 2012

Objective

To identify risk factors for inhospital mortality in patients with hip fractures using the Japanese Diagnosis Procedure Combination (DPC) nationwide administrative claims database.

Design

Retrospective observational study.

Setting

Hospitals adopting the DPC system during 2007–2009.

Participants

The authors analysed a total of 80 800 eligible patients aged ≥60 years with a single hip fracture (International Classification of Diseases, 10th Revision codes: S72.0 and S72.1). The DPC database includes patients treated between July and December each year.

Main outcome measures

Inhospital mortality after hip fracture.

Results

The overall inhospital mortality rate after hip fractures was 3.3%. Multivariate analysis indicated that inhospital mortality was significantly associated with male gender (OR 2.12, 95% CI 1.94 to 2.31), advancing age and number of comorbidities. Significantly higher mortality was observed in those treated conservatively (OR 4.25, 95% CI 3.92 to 4.61). Surgical delays of 5 days or more were significantly associated with higher rates of inhospital mortality (OR 1.34, 95% CI 1.20 to 1.50).

Conclusions

In patients with hip fractures, male gender, advancing age, high number of comorbidities, conservative treatment and the surgical delay of 5 days or more were associated with higher rates of inhospital mortality.
A cost-utility analysis of transcatheter aortic valve implantation in Belgium: focusing on a well-defined and identifiable population
Authors: Neyt Mattias , Van Brabandt Hans , Devriese Stephan , Van De Sande Stefaan
Published: May 2012

Background

Patients with severe aortic stenosis and coexisting non-cardiac conditions may be at high risk for surgical replacement of the aortic valve or even be no candidates for surgery. In these patients, transcatheter aortic valve implantation (TAVI) is suggested as an alternative. Results of the PARTNER (Placement of AoRTic TraNscathetER Valve) trial comparing the clinical effectiveness of TAVI with surgical valve replacement and standard therapy were published. The authors assessed the cost-effectiveness of TAVI in Belgium.

Methods

A Markov model of incremental costs, effects (survival and quality of life) and incremental cost-effectiveness of TAVI was developed. The impact on survival, number of events and quality of life was based on the PARTNER trial. Costs per event were context specific.

Results

In high-risk operable patients, even if the minor differences in 30-day and 1-year mortality are taken into account, the incremental cost-effectiveness ratio (ICER) remains on average above €750 000 per quality-adjusted life-year (QALY) gained (incremental cost: €20 400; incremental effect: 0.03 QALYs). In inoperable patients, an ICER of €44 900 per QALY (incremental cost: €33 200; incremental effect: 0.74 QALYs) is calculated, including a life-long extrapolation of the mortality benefit. This result was sensitive to the assumed time horizon. The subgroup of anatomically inoperable patients had better outcomes than medically inoperable patients, with ICERs decreasing more than €10 000/QALY.

Conclusions

It is inappropriate to consider reimbursement of TAVI for high-risk operable patients. Reimbursing TAVI in inoperable patients in essence is a political decision. From an economic perspective, it would be prudent to first target patients that are inoperable because of anatomical prohibitive conditions. In the search for evidence, the authors identified non-published negative results from a randomised controlled TAVI trial. The study sponsor should be more willing to share this information to allow balanced evaluations and policy recommendations. Payers should require these data before taking reimbursement decisions.
Risk Factors for Alloimmunisation after red blood Cell Transfusions (R-FACT): a case cohort study
Authors: Zalpuri Saurabh , Zwaginga Jaap Jan , van der Bom J G
Published: May 2012

Introduction

Individuals exposed to red blood cell alloantigens through transfusion, pregnancy or transplantation may produce antibodies against the alloantigens. Alloantibodies can pose serious clinical problems such as delayed haemolytic reactions and logistic problems, for example, to obtain timely and properly matched transfusion blood for patients in which new alloantibodies are detected.

Objective

The authors hypothesise that the particular clinical conditions (eg, used medication, concomitant infection, cellular immunity) during which transfusions are given may contribute to the risk of immunisation. The aim of this research was to examine the association between clinical, environmental and genetic characteristics of the recipient of erythrocyte transfusions and the risk against erythrocyte alloimmunisation during that transfusion episode.

Methods and analysis Study design

Incident case–cohort study.

Setting

Secondary care, nationwide study (within the Netherlands) including seven hospitals, from January 2005 to December 2011.

Study population

Consecutive red cell transfused patients at the study centres.

Inclusion

The study cohort comprises of consecutive red blood cell transfused patients at the study centre.

Exclusion

Patients with transfusions before the study period and/or pre-existing alloantibodies.Cases defined as first time alloantibody formers; Controls defined as transfused individuals matched (on number of transfusions) to cases and have not formed an alloantibody.

Statistical analysis

Logistic regression models will be used to assess the association between the risk to develop antibodies and potential risk factors, adjusted for other risk factors.

Ethics and dissemination

Approval at each local ethics regulatory committee will be obtained. Data will be coded for privacy reasons. Patients will be sent a letter and an information brochure explaining the purpose of the study. A consent form in presence of the study coordinator will be signed before the blood taking commences. Investigators will submit progress summary of the study to study sponsor regularly. Investigators will notify the accredited ethics board of the end of the study within a period of 8 weeks.
Becoming an effective learner
Authors: Parry Sally D , Barton Roger
Published: May 2012

The teaching of medicine and the expectations of trainees has changed enormously over the past two decades in parallel to changes in medical technology, advances in information technology and the provision of healthcare. With a shortened time in medical training efficient learning is ever more crucial and the skills with which to optimise and enhance our learning opportunities are discussed.
Association between prospective owner viewing of the parents of a puppy and later referral for behavioural problems
Authors: Westgarth C. , Reevell K. , Barclay R.
Published: May 2012

A case‐control study was designed to test whether there is an association between the owners seeing the mother of a puppy, and later development of behavioural problems. The sample consisted of dogs that were seen by animal behaviourists (members of the Association of Pet Behaviour Counsellors) and equivalent dogs (without a behavioural problem, but the owners would consider referral to an animal behaviourist were the dog to develop a behavioural problem) seen at a veterinary practice that referred to each animal behaviourist. After adjustment for confounding factors using multivariable logistic regression, case dogs were more likely to be younger than controls (P < 0.001); less likely to be obtained at six (OR = 0.27, 95 per cent CI = 0.09 to 0.85, P = 0.03), nine (OR = 0.22, 95 per cent CI = 0.06 to 0.80, P = 0.02) or 10 weeks (OR = 0.35, 95 per cent CI = 0.12 to 1.01, P = 0.05), than eight weeks; more likely for the owner to have seen only one parent (OR = 2.49, 95 per cent CI = 1.15 to 5.37, P = 0.02) than both parents, and more likely to have not seen either parent (OR = 3.82, 95 per cent CI = 1.12 to 12.97, P = 0.03) than both. Advice to ‘see the mother’ has been shown to be partly scientifically accurate in relation to future unwanted behavioural problems among dogs; in fact, it may be better for prospective owners to be recommended to view both parents.
Pretreatment withBacopa monnieriextract offsets 3-nitropropionic acid induced mitochondrial oxidative stress and dysfunctions in the striatum of prepubertal mouse brain
Authors: Shinomol George K. , Bharath M.M. Srinivas , Muralidhara
Published: May 2012

The present investigation was designed to determine the efficacy of Bacopa monnieri (Brahmi; BM) to offset 3-nitropropionic acid (3-NPA) induced oxidative stress and mitochondrial dysfunction in dopaminergic (N27) cells and prepubertal mouse brain. Pretreatment of N27 cells with BM ethanolic extract (BME) significantly attenuated 3-NPA-induced cytotoxicity. Further, we determined the degree of oxidative stress induction, redox status, enzymic antioxidants, and protein oxidation in the striatal mitochondria of mice given BME prophylaxis followed by 3-NPA challenge. While 3-NPA-induced marked oxidative stress in the mitochondria of the striatum, BME prophylaxis markedly prevented 3-NPA-induced oxidative dysfunctions and depletion of reduced glutathione and thiol levels. The activities of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, glutathione reductase, thioredoxin reductase), Na+,K+-ATPase, and citric acid cycle enzymes in the striatum discernible among 3-NPA mice were significantly restored with BME prophylaxis. Interestingly, BME offered protection against 3-NPA-induced mitochondrial dysfunctions as evidenced by the restoration of the activities of ETC enzymes (NADH:ubiquinone oxidoreductase, NADH:cytochrome c reductase, succinate–ubiquinone oxidoreductase, and cytochrome c oxidase) and mitochondrial viability. We hypothesize that the neuroprotective effects of BME may be wholly or in part related to its propensity to scavenge free radicals, maintain redox status, and upregulate antioxidant machinery in striatal mitochondria.
Endothelium-dependent vascular relaxation induced by Globularia alypum extract is mediated by EDHF in perfused rat mesenteric arterial bed
Authors: Chokri Aziz , El Abida Kaouakib , Zegzouti Younes Filali , Ben Cheikh Rachid
Published: May 2012

The vasodilatory effect of Globularia alypum L. (GA) extract was evaluated in rat mesenteric arterial bed pre-contracted by continuous infusion of phenylephrine (2–4 ng/mL). Bolus injections of GA elicited dose–response vasodilation, which was abolished after endothelium removal. Addition of a nitric oxide synthase inhibitor, NG-nitro-l-arginine methyl ester (100 µmol/L), alone or in the presence of a cyclooxygenase inhibitor, indomethacin (10 µmol/L), did not significantly affect the vasodilation of the mesenteric arterial bed in response to GA extract. These results suggest that GA-induced vasodilation is endothelium dependent but nitric oxide and prostacyclin independent. In the presence of high K+ (60 mmol/L), the GA vasodilatory effect was completely abolished, suggesting that the vasodilation effect is mediated by hyperpolarization of the vascular cells. Also, pre-treatment with atropine (a muscarinic receptors antagonist) antagonized the GA-induced vasodilation, suggesting that the vasodilatory effect is mainly mediated by the endothelium-derived hyperpolarizing factor through activation of endothelial muscarinic receptors.
Carbohydrate- and lipid-enriched meals acutely disrupt glycemic homeostasis by inducing transient insulin resistance in rats
Authors: Campello Raquel Saldanha , Alves-Wagner Ana Barbara Teixeira , Abdulkader Fernando , Mori Rosana Cristina Tieko , Machado Ubiratan Fabres
Published: May 2012

Chronic intake of high-carbohydrate or high-lipid diets is a well-known insulin resistance inducer. This study investigates the immediate effect (1–6 h) of a carbohydrate- or lipid-enriched meal on insulin sensitivity. Fasted rats were refed with standard, carbohydrate-enriched (C), or lipid-enriched (L) meal. Plasma insulin, glucose, and non-esterified fatty acids (NEFA) were measured at 1, 2, 4, and 6 h of refeeding. The glucose–insulin index showed that either carbohydrates or lipids decreased insulin sensitivity at 2 h of refeeding. At this time point, insulin tolerance tests (ITTs) and glucose tolerance tests (GTTs) detected insulin resistance in C rats, while GTT confirmed it in L rats. Reduced glycogen and phosphorylated AKT and GSK3 content revealed hepatic insulin resistance in C rats. Reduced glucose uptake in skeletal muscle subjected to the fatty acid concentration that mimics the high NEFA level of L rats suggests insulin resistance in these animals is mainly in muscle. In conclusion, carbohydrate- or lipid-enriched meals acutely disrupt glycemic homeostasis, inducing a transient insulin resistance, which seems to involve liver and skeletal muscle, respectively. Thus, the insulin resistance observed when those types of diets are chronically consumed may be an evolution of repeated episodes of this transient insulin resistance.
CONSTRUCTION COMPONENTS ENGINEERING IN INTERMEDIATE BAND SOLAR CELLS
Authors: GORJI N. E. , HOUSHMAND M. , DEHKORDI S. S.
Published: May 2012

The parameter electron filling factor can be taken as a scale for the electronic states in the intermediate band which should be de-localized and thus the unconfined electrons at the quantum dots. For three different value of electron filling factor, the sunlight concentration effect on the efficiency of a quantum dot solar cell is calculated. The maximum point of efficiency and optimum thickness of the cell obtained under three different sunlight concentrations. We show the importance of electron filling factor as a parameter to be more considered. This parameter can be controlled by the quantum dots size and distance between quantum dot layers in the active region. Analysis of above mentioned parameters suggest that to attain a maximum efficiency, the size of the quantum dots and the distance between the periodically arrayed dot layers have to be optimized. In addition, sunlight concentration is recommended as an effective approach to have high efficiency and low cost level solar cells.