bluuebunny/crossref_metadata_2025 huggingface dataset:
Solar Turbo Power Plant Design
Authors: Mackay D. B. , Leventhal E. L.
Published: January 2012

This paper discusses the design of a lunar-based power plant powered entirely by solar radiation. Factors affecting power plant design and a discussion of a performance basis for a working fluid are also presented. Graphs and equations which illustrate theory, optimize results, and demonstrate inter-component relationships are included. Also, a design for a novel, compact power plant is introduced.
Analysis of Solar-Furnace Performance in Mechanical Testing at Extremely High Temperatures
Authors: Leon G. S. , Shank M. E.
Published: January 2012

The use of the solar furnace for investigating properties of materials has received increased attention. However, such work has been limited to determining physical properties of refractory materials. Analyses of performance, related to such work, have been confined to investigations of flux distribution and temperature on flat-plate, hemispherical, and cavity receivers at the focal spot. Heat conduction away from the focal spot usually has not been considered. The present investigation is concerned with the analysis of fluxes and temperatures that can be attained in tensile specimens undergoing mechanical tests. Account is taken of heat loss by conduction and reradiation. It is shown that, (a) attainable temperatures are considerably lower than those reached in flat-plate receivers, (b) with normal low-aperture furnaces (i. e., 60 deg) a large furnace is necessary to reach high temperatures with adequately large specimens, and (c) furnaces best-adapted to mechanical testing would have larger apertures (120 deg) than are now commonly conceived.
Efficiency Improvement of an Automatic Ball Balancer
Authors: Ishida Yukio , Matsuura Tomonori , Long Zhang Xiao
Published: January 2012

An automatic ball balancer is a unique vibration suppression device for rotor systems. Theoretically, two balls in a cylindrical chamber of the rotor are located at the optimal positions on the opposite side to the unbalance and cancel the unbalance automatically in the super-critical speed range. However, this device is not used widely due to two malfunctions. One is the influence of friction. Due to the inevitable friction between the balls and the inside wall of the channel, the balls stop near the optimal positions and do not balance the rotor perfectly. The other is the self-excited oscillation which occurs near and above the major critical speed. The objectives of the present paper are to clarify the fundamental characteristics of a ball balancer and to introduce some simple methods to eliminate these malfunctions.
Fully Coupled Finite-Element Modeling of Active Sandwich Panels With Poroelastic Core
Authors: Zieliński Tomasz G. , Galland Marie-Annick , Ichchou Mohamed N.
Published: January 2012

Active sandwich panels are an example of smart noise attenuators and a realization of hybrid active-passive approach for the problem of broadband noise reduction. The panels are composed of thin elastic faceplates linked by the core of a lightweight absorbent material of high porosity. Moreover, they are active, so piezoelectric actuators in the form of thin patches are fixed to their faceplates. Therefore, the passive absorbent properties of porous core, effective at high and medium frequencies, can be combined with the active vibroacoustic reduction necessary in a low frequency range. Important convergence issues for fully coupled finite-element modeling of such panels are investigated on a model of a disk-shaped panel under a uniform acoustic load by plane harmonic waves, with respect to the important parameter of the total reduction of acoustic transmission. Various physical phenomena are considered, namely, the wave propagation in a porous medium, the vibrations of elastic plate and the piezoelectric behavior of actuators, the acoustics-structure interaction and the wave propagation in a fluid. The modeling of porous core requires the usage of the advanced biphasic model of poroelasticity, because the vibrations of the skeleton of porous core cannot be neglected; they are in fact induced by the vibrations of the faceplates. Finally, optimal voltage amplitudes for the electric signals used in active reduction, with respect to the relative size of the piezoelectric actuator, are computed in some lower-to-medium frequency range.
Thermodynamics and Transport Phenomena in High Temperature Steam Electrolysis Cells
Authors: O’Brien James E.
Published: January 2012

Hydrogen can be produced from water splitting with relatively high efficiency using high temperature electrolysis. This technology makes use of solid-oxide cells, running in the electrolysis mode to produce hydrogen from steam, while consuming electricity and high temperature process heat. The overall thermal-to-hydrogen efficiency for high temperature electrolysis can be as high as 50%, which is about double the overall efficiency of conventional low-temperature electrolysis. Current large-scale hydrogen production is based almost exclusively on steam reforming of methane, a method that consumes a precious fossil fuel while emitting carbon dioxide to the atmosphere. An overview of high temperature electrolysis technology will be presented, including basic thermodynamics, experimental methods, heat and mass transfer phenomena, and computational fluid dynamics modeling.
Computational Heat Transfer in Complex Systems: A Review of Needs and Opportunities
Authors: Murthy Jayathi Y. , Mathur Sanjay R.
Published: January 2012

During the few decades, computational techniques for simulating heat transfer in complex industrial systems have reached maturity. Combined with increasingly sophisticated modeling of turbulence, chemistry, radiation, phase change, and other physics, powerful computational fluid dynamics (CFD) and computational heat transfer (CHT) solvers have been developed which are beginning to enter the industrial design cycle. In this paper, an overview of emerging simulation needs is first given, and currently-available CFD techniques are evaluated in light of these needs. Emerging computational methods which address some of the failings of current techniques are then reviewed. New research opportunities for computational heat transfer, such as in submicron and multiscale heat transport, are reviewed. As computational techniques and physical models become mature, there is increasing demand for predictive simulation, that is, simulation which is not only verified and validated, but whose uncertainty is also quantified. Current work in the area of sensitivity computation and uncertainty propagation is described.
Genetic Algorithm Optimization on a Venting System With Three-Chamber Hybrid Mufflers Within a Constrained Back Pressure and Space
Authors: Chiu Min-Chie
Published: January 2012

Recently, research on new techniques for dissipative mufflers in dealing with the higher frequencies has been addressed. However, the shape optimization of hybrid mufflers in reducing broadband noise within a constrained space as well as a pressure-drop limit which are both concerned with the necessity of operation and system venting in practical engineering work was rarely tackled. Therefore, this study will not only analyze the sound transmission loss (STL) of a space-constrained multichamber hybrid muffler but also optimize the best design shape under a specified pressure drop. In this paper, the generalized decoupling technique and plane wave theory used to solve the coupled acoustical problem of perforated mufflers with/without sound absorbing material are presented. The four-pole system matrix used to evaluate acoustic performance is also introduced in conjunction with a genetic algorithm (GA). A numerical case for eliminating a broadband venting noise emitted from a pressure relief valve using four kinds of hybrid mufflers is also introduced. To verify the reliability of the GA optimization, optimal noise abatement for a pure tone (1000 Hz) is exemplified. Before the GA operation can be carried out, the accuracy of the mathematical models need to be checked using the experimental data. The optimal result in eliminating broadband noise reveals that the overall noise reductions with respect to various mufflers under a maximal allowable pressure drop of 100 Pa can achieve 62.6, 54.8, 32.3 and 87.8 dB. Consequently, the approach used for the optimal design of the multichamber hybrid mufflers under space and back pressure constrained conditions is indeed easy and quite effective.
Preexposure Prophylaxis with Albumin-Conjugated C34 Peptide HIV-1 Fusion Inhibitor in SCID-hu Thy/Liv Mice
Authors: Stoddart Cheryl A. , Nault Geneviève , Galkina Sofiya A. , Bousquet-Gagnon Nathalie , Bridon Dominique , Quraishi Omar
Published: January 2012

PC-1505 is a C34 peptide derived from the heptad repeat 2 region of HIV-1 gp41 conjugated to human serum albumin for sustained
in vivo
activity. One single preexposure dose of PC-1505 reduced viral RNA in HIV-1-infected SCID-hu Thy/Liv mice by 3.3 log
10
and protected T cells from virus-mediated depletion. In contrast, a single preexposure dose of Truvada reduced viral RNA by only 0.8 log
10
and was substantially less effective in preventing T cell depletion.
Klebsiella pneumoniae ST258 Producing KPC-3 Identified in Italy Carries Novel Plasmids and OmpK36/OmpK35 Porin Variants
Authors: García-Fernández Aurora , Villa Laura , Carta Claudio , Venditti Carolina , Giordano Alessandra , Venditti Mario , Mancini Carlo , Carattoli Alessandra
Published: January 2012

A carbapenemase-resistant
Klebsiella pneumoniae
strain, clone ST258 producing KPC-3, was fully characterized. The entire plasmid content was investigated, thereby identifying plasmids of the IncFII
k
(two of them similar to pKPQIL and pKPN3, respectively), IncX, and ColE types, carrying a formidable set of resistance genes against toxic compounds, metals, and antimicrobial drugs and a novel iron(III) uptake system.
Tolerability and Safety of Primaquine in Papua New Guinean Children 1 to 10 Years of Age
Authors: Betuela Inoni , Bassat Quique , Kiniboro Benson , Robinson Leanne J. , Rosanas-Urgell Anna , Stanisic Danielle , Siba Peter M. , Alonso Pedro L. , Mueller Ivo
Published: January 2012

Primaquine is currently the only drug available for radical cure of
Plasmodium vivax
and
P. ovale
liver infection stages, but limited safety data exist for children <10 years of age. Detailed daily assessments of side effects in glucose-6-phosphate dehydrogenase (G6PD)-normal children treated with 14 days of primaquine plus chloroquine (3 days;
n
= 252) or artesunate (7 days;
n
= 141) (0.5 mg/kg of body weight) showed that both treatments are well tolerated, do not lead to reductions in hemoglobin levels, and can thus safely be used in children 1 to 10 years of age.
Population Pharmacokinetics of Dihydroartemisinin and Piperaquine in Pregnant and Nonpregnant Women with Uncomplicated Malaria
Authors: Tarning Joel , Rijken Marcus J. , McGready Rose , Phyo Aung Pyae , Hanpithakpong Warunee , Day Nicholas P. J. , White Nicholas J. , Nosten François , Lindegardh Niklas
Published: January 2012

Pregnant women are particularly vulnerable to malaria. The pharmacokinetic properties of antimalarial drugs are often affected by pregnancy, resulting in lower drug concentrations and a consequently higher risk of treatment failure. The objective of this study was to evaluate the population pharmacokinetic properties of piperaquine and dihydroartemisinin in pregnant and nonpregnant women with uncomplicated malaria. Twenty-four pregnant and 24 matched nonpregnant women on the Thai-Myanmar boarder were treated with a standard fixed oral 3-day treatment, and venous plasma concentrations of both drugs were measured frequently for pharmacokinetic evaluation. Population pharmacokinetics were evaluated with nonlinear mixed-effects modeling. The main pharmacokinetic finding was an unaltered total exposure to piperaquine but reduced exposure to dihydroartemisinin in pregnant compared to nonpregnant women with uncomplicated malaria. Piperaquine was best described by a three-compartment disposition model with a 45% higher elimination clearance and a 47% increase in relative bioavailability in pregnant women compared with nonpregnant women. The resulting net effect of pregnancy was an unaltered total exposure to piperaquine but a shorter terminal elimination half-life. Dihydroartemisinin was best described by a one-compartment disposition model with a 38% lower relative bioavailability in pregnant women than nonpregnant women. The resulting net effect of pregnancy was a decreased total exposure to dihydroartemisinin. The shorter terminal elimination half-life of piperaquine and lower exposure to dihydroartemisinin will shorten the posttreatment prophylactic effect and might affect cure rates. The clinical impact of these pharmacokinetic findings in pregnant women with uncomplicated malaria needs to be evaluated in larger series.
Randomized, Double-Blind, Placebo-Controlled Trial of Monthly versus Bimonthly Dihydroartemisinin-Piperaquine Chemoprevention in Adults at High Risk of Malaria
Authors: Lwin Khin Maung , Phyo Aung Pyae , Tarning Joel , Hanpithakpong Warunee , Ashley Elizabeth A. , Lee Sue J. , Cheah Phaikyeong , Singhasivanon Pratap , White Nicholas J. , Lindegårdh Niklas , Nosten François
Published: January 2012

Intermittent preventive treatment (IPT) is increasingly used to reduce malaria morbidity and mortality in children and pregnant women. The efficacy of IPT depends on the pharmacokinetic and pharmacodynamic properties of the antimalarial drugs used. Healthy adult male volunteers whose occupation put them at high risk of malaria on the Northwest border of Thailand were randomized to receive a 3-day-treatment dose of dihydroartemisinin-piperaquine monthly (DPm) or every 2 months (DPalt) or an identical placebo with or without fat (6.4g/dose) over a 9-month period. All volunteers were monitored weekly. One thousand adults were recruited. Dihydroartemisinin-piperaquine was well tolerated. There were 114 episodes of malaria (49
Plasmodium falciparum
, 63
P. vivax
, and 2
P. ovale)
. The protective efficacy against all malaria at 36 weeks was 98% (95% confidence interval [CI], 96% to 99%) in the DPm group and 86% (95% CI, 81% to 90%) in the DPalt group (for both,
P
< 0.0001 compared to the placebo group). As a result, the placebo group also had lower hematocrits during the study (
P
< 0.0001). Trough plasma piperaquine concentrations were the main determinant of efficacy; no malaria occurred in participants with a trough concentration above 31 ng/ml. Neither plasma piperaquine concentration nor efficacy was influenced by the coadministration of fat. DPm is safe to use and is effective in the prevention of malaria in adult males living in an area where
P. vivax
and multidrug-resistant
P. falciparum
malaria are endemic.
Structural and Inhibition Studies of the RNase H Function of Xenotropic Murine Leukemia Virus-Related Virus Reverse Transcriptase
Authors: Kirby Karen A. , Marchand Bruno , Ong Yee Tsuey , Ndongwe Tanyaradzwa P. , Hachiya Atsuko , Michailidis Eleftherios , Leslie Maxwell D. , Sietsema Daniel V. , Fetterly Tracy L. , Dorst Christopher A. , Singh Kamalendra , Wang Zhengqiang , Parniak Michael A. , Sarafianos Stefan G.
Published: January 2012

RNase H inhibitors (RNHIs) have gained attention as potential HIV-1 therapeutics. Although several RNHIs have been studied in the context of HIV-1 reverse transcriptase (RT) RNase H, there is no information on inhibitors that might affect the RNase H activity of other RTs. We performed biochemical, virological, crystallographic, and molecular modeling studies to compare the RNase H function and inhibition profiles of the gammaretroviral xenotropic murine leukemia virus-related virus (XMRV) and Moloney murine leukemia virus (MoMLV) RTs to those of HIV-1 RT. The RNase H activity of XMRV RT is significantly lower than that of HIV-1 RT and comparable to that of MoMLV RT. XMRV and MoMLV, but not HIV-1 RT, had optimal RNase H activities in the presence of Mn
2+
and not Mg
2+
. Using hydroxyl-radical footprinting assays, we demonstrated that the distance between the polymerase and RNase H domains in the MoMLV and XMRV RTs is longer than that in the HIV-1 RT by ∼3.4 Å. We identified one naphthyridinone and one hydroxyisoquinolinedione as potent inhibitors of HIV-1 and XMRV RT RNases H with 50% inhibitory concentrations ranging from ∼0.8 to 0.02 μM. Two acylhydrazones effective against HIV-1 RT RNase H were less potent against the XMRV enzyme. We also solved the crystal structure of an XMRV RNase H fragment at high resolution (1.5 Å) and determined the molecular details of the XMRV RNase H active site, thus providing a framework that would be useful for the design of antivirals that target RNase H.
Population Pharmacokinetics of Metronidazole Evaluated Using Scavenged Samples from Preterm Infants
Authors: Cohen-Wolkowiez Michael , Ouellet Daniele , Smith P. Brian , James Laura P. , Ross Ashley , Sullivan Janice E. , Walsh Michele C. , Zadell Arlene , Newman Nancy , White Nicole R. , Kashuba Angela D. M. , Benjamin Daniel K.
Published: January 2012

Pharmacokinetic (PK) studies in preterm infants are rarely conducted due to the research challenges posed by this population. To overcome these challenges, minimal-risk methods such as scavenged sampling can be used to evaluate the PK of commonly used drugs in this population. We evaluated the population PK of metronidazole using targeted sparse sampling and scavenged samples from infants that were ≤32 weeks of gestational age at birth and <120 postnatal days. A 5-center study was performed. A population PK model using nonlinear mixed-effect modeling (NONMEM) was developed. Covariate effects were evaluated based on estimated precision and clinical significance. Using the individual Bayesian PK estimates from the final population PK model and the dosing regimen used for each subject, the proportion of subjects achieving the therapeutic target of trough concentrations >8 mg/liter was calculated. Monte Carlo simulations were performed to evaluate the adequacy of different dosing recommendations per gestational age group. Thirty-two preterm infants were enrolled: the median (range) gestational age at birth was 27 (22 to 32) weeks, postnatal age was 41 (0 to 97) days, postmenstrual age (PMA) was 32 (24 to 43) weeks, and weight was 1,495 (678 to 3,850) g. The final PK data set contained 116 samples; 104/116 (90%) were scavenged from discarded clinical specimens. Metronidazole population PK was best described by a 1-compartment model. The population mean clearance (CL; liter/h) was determined as 0.0397 × (weight/1.5) × (PMA/32)
2.49
using a volume of distribution (
V
) (liter) of 1.07 × (weight/1.5). The relative standard errors around parameter estimates ranged between 11% and 30%. On average, metronidazole concentrations in scavenged samples were 30% lower than those measured in scheduled blood draws. The majority of infants (>70%) met predefined pharmacodynamic efficacy targets. A new, simplified, postmenstrual-age-based dosing regimen is recommended for this population. Minimal-risk methods such as scavenged PK sampling provided meaningful information related to development of metronidazole PK models and dosing recommendations.
Polymorphisms in the
lcrV
Gene of Yersinia enterocolitica and Their Effect on Plague Protective Immunity
Authors: Miller Nathan C. , Quenee Lauriane E. , Elli Derek , Ciletti Nancy A. , Schneewind Olaf
Published: January 2012

Current efforts to develop plague vaccines focus on LcrV, a polypeptide that resides at the tip of type III secretion needles. LcrV-specific antibodies block
Yersinia pestis
type III injection of Yop effectors into host immune cells, thereby enabling phagocytes to kill the invading pathogen. Earlier work reported that antibodies against
Y. pestis
LcrV cannot block type III injection by
Yersinia enterocolitica
strains and suggested that
lcrV
polymorphisms may provide for escape from LcrV-mediated plague immunity. We show here that polyclonal or monoclonal antibodies raised against
Y. pestis
KIM D27 LcrV (LcrV
D27
) bind LcrV from
Y. enterocolitica
O:9 strain W22703 (LcrV
W22703
) or O:8 strain WA-314 (LcrV
WA-314
) but are otherwise unable to block type III injection by
Y. enterocolitica
strains. Replacing the
lcrV
gene on the pCD1 virulence plasmid of
Y. pestis
KIM D27 with either

lcrV
W22703

or

lcrV
WA-314

does not affect the ability of plague bacteria to secrete proteins via the type III pathway, to inject Yops into macrophages, or to cause lethal plague infections in mice. LcrV
D27
-specific antibodies blocked type III injection by
Y. pestis
expressing

lcrV
W22703

or

lcrV
WA-314

and protected mice against intravenous lethal plague challenge with these strains. Thus, although antibodies raised against LcrV
D27
are unable to block the type III injection of
Y. enterocolitica
strains, expression of

lcrV
W22703

or

lcrV
WA-314

in
Y. pestis
did not allow these strains to escape LcrV-mediated plague protective immunity in the intravenous challenge model.
Characterization of the Burkholderia pseudomallei K96243 Capsular Polysaccharide I Coding Region
Authors: Cuccui Jon , Milne Timothy S. , Harmer Nicholas , George Alison J. , Harding Sarah V. , Dean Rachel E. , Scott Andrew E. , Sarkar-Tyson Mitali , Wren Brendan W. , Titball Richard W. , Prior Joann L.
Published: January 2012

Burkholderia pseudomallei
is the causative agent of melioidosis, a disease endemic to regions of Southeast Asia and Northern Australia. Both humans and a range of other animal species are susceptible to melioidosis, and the production of a group 3 polysaccharide capsule in
B. pseudomallei
is essential for virulence.
B. pseudomallei
capsular polysaccharide (CPS) I comprises unbranched
manno
-heptopyranose residues and is encoded by a 34.5-kb locus on chromosome 1. Despite the importance of this locus, the role of all of the genes within this region is unclear. We inactivated 18 of these genes and analyzed their phenotype using Western blotting and immunofluorescence staining. Furthermore, by combining this approach with bioinformatic analysis, we were able to develop a model for CPS I biosynthesis and export. We report that inactivating
gmhA
,
wcbJ
, and
wcbN
in
B. pseudomallei
K96243 retains the immunogenic integrity of the polysaccharide despite causing attenuation in the BALB/c murine infection model. Mice immunized with the
B. pseudomallei
K96243 mutants lacking a functional copy of either
gmhA
or
wcbJ
were afforded significant levels of protection against a wild-type
B. pseudomallei
K96243 challenge.
Molecular Characterizations of Cytolethal Distending Toxin Produced by Providencia alcalifaciens Strains Isolated from Patients with Diarrhea
Authors: Shima Ayaka , Hinenoya Atsushi , Asakura Masahiro , Sugimoto Norihiko , Tsukamoto Teizo , Ito Hideaki , Nagita Akira , Faruque Shah M. , Yamasaki Shinji
Published: January 2012

Cytolethal distending toxins (CDTs), which block eukaryotic cell proliferation by acting as inhibitory cyclomodulins, are produced by diverse groups of Gram-negative bacteria. Active CDT is composed of three polypeptides—CdtA, CdtB, and CdtC—encoded by the genes
cdtA
,
cdtB
, and
cdtC
, respectively. We developed a PCR-restriction fragment length polymorphism assay for the detection and differentiation of five alleles of
cdtB
(Cdt-I through Cdt-V) in
Escherichia coli
and used the assay to investigate the prevalence and characteristic of CDT-producing
E. coli
in children with diarrhea (A. Hinenoya et al., Microbiol. Immunol. 53:206–215, 2009). In these assays, two untypable
cdtB
genes were detected and the organisms harboring the
cdtB
gene were identified as
Providencia alcalifaciens
(strains AH-31 and AS-1). Nucleotide sequence analysis of the
cdt
gene cluster revealed that the
cdtA
,
cdtB
, and
cdtC
genes of
P. alcalifaciens
are of 750, 810, and 549 bp, respectively. To understand the possible horizontal transfer of the
cdt
genes among closely related species, the presence of
cdt
genes was screened in various
Providencia
spp. by colony hybridization assay, and the
cdt
gene cluster was found in only limited strains of
P. alcalifaciens
. Genome walking revealed that the
cdt
gene cluster of
P. alcalifaciens
is located adjacent to a putative transposase gene, suggesting the locus might be horizontally transferable. Interestingly, the CDT of
P. alcalifaciens
(PaCDT) showed some homology with the CDT of
Shigella boydii
. Whereas filter-sterilized lysates of strains AH-31 and AS-1 showed distention of CHO but not of HeLa cells,
E. coli
CDT-I exhibited distention of both cells. This activity of PaCDT was confirmed by generating recombinant PaCDT protein, which could also be neutralized by rabbit anti-PaCdtB antibody. Furthermore, recombinant PaCDT was found to induce G
2
/M cell cycle arrest and phosphorylation of host histone H2AX, a sensitive marker of DNA double-strand breaks. To our knowledge, this is the first report showing that certain clinical
P. alcalifaciens
strains could produce variants of the CDTs compared.
Plasmodium yoelii Macrophage Migration Inhibitory Factor Is Necessary for Efficient Liver-Stage Development
Authors: Miller Jessica L. , Harupa Anke , Kappe Stefan H. I. , Mikolajczak Sebastian A.
Published: January 2012

Mammalian macrophage migration inhibitory factor (MIF) is a multifaceted cytokine involved in both extracellular and intracellular functions. Malaria parasites express a MIF homologue that might modulate host immune responses against blood-stage parasites, but the potential importance of MIF against other life cycle stages remains unstudied. In this study, we characterized the MIF homologue ofPlasmodium yoeliithroughout the life cycle, with emphasis on preerythrocytic stages.P. yoeliiMIF (Py-MIF) was expressed in blood-stage parasites and detected at low levels in mosquito salivary gland sporozoites. MIF expression was strong throughout liver-stage development and localized to the cytoplasm of the parasite, with no evidence of release into the host hepatocyte. To examine the importance of Py-MIF for liver-stage development, we generated a Py-mifknockout parasite (P. yoeliiΔmif).P. yoeliiΔmifparasites grew normally as asexual erythrocytic-stage parasites and showed normal infection of mosquitoes. In contrast, theP. yoeliiΔmifstrain was attenuated during the liver stage. Mice infected withP. yoeliiΔmifsporozoites either did not develop blood-stage parasitemia or exhibited a delay in the onset of blood-stage patency. Furthermore,P. yoeliiΔmifparasites exhibited growth retardationin vivo. Combined, the data indicate thatPlasmodiumMIF is important for liver-stage development ofP. yoelii, during which it is likely to play an intrinsic role in parasite development rather than modulating host immune responses to infection.
Hypoxia-Mediated Impairment of the Mitochondrial Respiratory Chain Inhibits the Bactericidal Activity of Macrophages
Authors: Wiese Melanie , Gerlach Roman G. , Popp Isabel , Matuszak Jasmin , Mahapatro Mousumi , Castiglione Kirstin , Chakravortty Dipshikha , Willam Carsten , Hensel Michael , Bogdan Christian , Jantsch Jonathan
Published: January 2012

In infected tissues oxygen tensions are low. As innate immune cells have to operate under these conditions, we analyzed the ability of macrophages (Mϕ) to killEscherichia coliorStaphylococcus aureusin a hypoxic microenvironment. Oxygen restriction did not promote intracellular bacterial growth but did impair the bactericidal activity of the host cells against both pathogens. This correlated with a decreased production of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates. Experiments with phagocyte NADPH oxidase (PHOX) and inducible NO synthase (NOS2) double-deficient Mϕ revealed that inE. coli- orS. aureus-infected cells the reduced antibacterial activity during hypoxia was either entirely or partially independent of the diminished PHOX and NOS2 activity. Hypoxia impaired the mitochondrial activity of infected Mϕ. Inhibition of the mitochondrial respiratory chain activity during normoxia (using rotenone or antimycin A) completely or partially mimicked the defective antibacterial activity observed in hypoxicE. coli- orS. aureus-infected wild-type Mϕ, respectively. Accordingly, inhibition of the respiratory chain ofS. aureus-infected, normoxic PHOX−/−NOS2−/−Mϕ further raised the bacterial burden of the cells, which reached the level measured in hypoxic PHOX−/−NOS2−/−Mϕ cultures. Our data demonstrate that the reduced killing ofS. aureusorE. coliduring hypoxia is not simply due to a lack of PHOX and NOS2 activity but partially or completely results from an impaired mitochondrial antibacterial effector function. Since pharmacological inhibition of the respiratory chain raised the generation of ROI but nevertheless phenocopied the effect of hypoxia, ROI can be excluded as the mechanism underlying the antimicrobial activity of mitochondria.
Interplay between Candida albicans and the Mammalian Innate Host Defense
Authors: Cheng Shih-Chin , Joosten Leo A. B. , Kullberg Bart-Jan , Netea Mihai G.
Published: January 2012

Candida albicansis both the most common fungal commensal microorganism in healthy individuals and the major fungal pathogen causing high mortality in at-risk populations, especially immunocompromised patients. In this review, we summarize the interplay between the host innate system andC. albicans, ranging from how the host recognizes, responds, and clearsC. albicansinfection to howC. albicansevades, dampens, and escapes from host innate immunity.
Analysis of Cell Cycle and Replication of Mouse Macrophages after
In Vivo
and
In Vitro
Cryptococcus neoformans Infection Using Laser Scanning Cytometry
Authors: Coelho Carolina , Tesfa Lydia , Zhang Jinghang , Rivera Johanna , Gonçalves Teresa , Casadevall Arturo
Published: January 2012

We investigated the outcome of the interaction of
Cryptococcus neoformans
with murine macrophages using laser scanning cytometry (LSC). Previous results in our lab had shown that phagocytosis of
C. neoformans
promoted cell cycle progression. LSC allowed us to simultaneously measure the phagocytic index, macrophage DNA content, and 5-ethynyl-2′-deoxyuridine (EdU) incorporation such that it was possible to study host cell division as a function of phagocytosis. LSC proved to be a robust, reliable, and high-throughput method for quantifying phagocytosis. Phagocytosis of
C. neoformans
promoted cell cycle progression, but infected macrophages were significantly less likely to complete mitosis. Hence, we report a new cytotoxic effect associated with intracellular
C. neoformans
residence that manifested itself in impaired cell cycle completion as a consequence of a block in the G
2
/M stage of the mitotic cell cycle. Cell cycle arrest was not due to increased cell membrane permeability or DNA damage. We investigated alveolar macrophage replication
in vivo
and demonstrated that these cells are capable of low levels of cell division in the presence or absence of
C. neoformans
infection. In summary, we simultaneously studied phagocytosis, the cell cycle state of the host cell and pathogen-mediated cytotoxicity, and our results demonstrate a new cytotoxic effect of
C. neoformans
infection on murine macrophages: fungus-induced cell cycle arrest. Finally, we provide evidence for alveolar macrophage proliferation
in vivo
.
The Interplay between the Escherichia coli Rho Guanine Nucleotide Exchange Factor Effectors and the Mammalian RhoGEF Inhibitor EspH
Authors: Wong Alexander R. C. , Clements Abigail , Raymond Benoit , Crepin Valerie F. , Frankel Gad
Published: January 2012

Rho GTPases are important regulators of many cellular processes. Subversion of Rho GTPases is a common infection strategy employed by many important human pathogens. Enteropathogenic
Escherichia coli
and enterohemorrhagic
Escherichia coli
(EPEC and EHEC) translocate the effector EspH, which inactivates mammalian Rho guanine exchange factors (GEFs), as well as Map, EspT, and EspM2, which, by mimicking mammalian RhoGEFs, activate Rho GTPases. In this study we found that EspH induces focal adhesion disassembly, triggers cell detachment, activates caspase-3, and induces cytotoxicity. EspH-induced cell detachment and caspase-3 activation can be offset by EspT, EspM2, and the
Salmonella
Cdc42/Rac1 GEF effector SopE, which remain active in the presence of EspH. EPEC and EHEC therefore use a novel strategy of controlling Rho GTPase activity by translocating one effector to inactivate mammalian RhoGEFs, replacing them with bacterial RhoGEFs. This study also expands the functional range of bacterial RhoGEFs to include cell adhesion and survival.

IMPORTANCE
Many human pathogens use a type III secretion system to translocate effectors that can functionally be divided into signaling, disabling, and countervirulence effectors. Among the signaling effectors are those that activate Rho GTPases, which play a central role in coordinating actin dynamics. However, many pathogens also translocate effectors with antagonistic or counteractive functions. For example,
Salmonella
translocates SopE and SptP, which sequentially turn Rac1 and Cdc42 on and off. In this paper, we show that enteropathogenic
E. coli
translocates EspH, which inactivates mammalian RhoGEFs and triggers cytotoxicity and at the same time translocates the bacterial RhoGEFs EspM2 and EspT, which are insensitive to EspH, and so neutralizes EspH-induced focal adhesion disassembly, cell detachment, and caspase-3 activation. Our data point to an intriguing infection strategy in which EPEC and EHEC override cellular Rho GTPase signaling by disabling mammalian RhoGEFs and replacing them with with bacterial RhoGEFs that promote cell adhesion and survival.
Syncope and profound bradycardia associated with intrauterine contraceptive procedures
Authors: Baird Aisling , Dickson Jane , Jensen Mary , Talbot Martin
Published: January 2012

There has been recent interest in this Journal concerning the occurrence of profound bradycardia with impaired consciousness during insertion of intrauterine contraceptive devices or systems. Questions have been raised regarding the requirement for medication for reversal of the condition, the role of the nurse practitioner in the light of this, and the effects upon sexual and reproductive health care service delivery. We present three cases where this condition affected patients under our care and suggest that although very infrequent, it is important. Medication for treatment and staff trained to administer it should always be available.
Epidemiology of, and behavioural risk factors for, sexually transmitted human papillomavirus infection in men and women in Britain
Authors: Johnson Anne M , Mercer Catherine H , Beddows Simon , de Silva Natasha , Desai Sarika , Howell-Jones Rebecca , Carder Caroline , Sonnenberg Pam , Fenton Kevin A , Lowndes Catherine , Soldan Kate
Published: January 2012

Objectives

Persistent infection with high-risk sexually transmitted human papillomaviruses (HR-HPVs) can lead to development of cervical and other cancers, while low-risk types (low-risk HPV) may cause genital warts. We explored the epidemiology of different HPV types in men and women and their association with demographic and behavioural variables.

Methods

We analysed data collected for the British National Survey of Sexual Attitudes and Lifestyles, a cross-sectional survey undertaken in 1999–2001. Half of all sexually experienced male and female respondents aged 18–44 years were invited to provide a urine sample. We tested 3123 stored urine samples using an in-house Luminex-based HPV genotyping system.

Results

HPV DNA was detected in 29.0% (95% CI 26.7% to 31.3%) of samples from women and 17.4% (95% CI 15.1% to 19.8%) from men. Any of 13 HR-HPV types was detected in 15.9% (95% CI 14.1% to 17.8%) of women and 9.6% (95% CI 8.0% to 11.6%) of men. HPV types 16/18 were found in 5.5% (95% CI 4.5% to 6.8%) of women and 3.0% (95% CI 2.1% to 4.3%) of men; and types 6/11 in 4.7% (95% CI 1.8% to 5.9%) of women and 2.2% (95% CI 1.5% to 3.1%) of men. In multivariate analysis, HR-HPV was associated with new partner numbers, in women with younger age, single status and partner concurrency, and in men with number of partners without using condom(s) and age at first intercourse.

Conclusions

HPV DNA was detectable in urine of a high proportion of the sexually active British population. In both genders, HR-HPV was strongly associated with risky sexual behaviour. The minority of HPV infections were of vaccine types. It is important to monitor HPV prevalence and type distribution following the introduction of vaccination of girls.
Rapid synthesis of homoallylic alcohol from aldehyde with allyltributylstannane under solvent-free conditions
Authors: Bora Pranjal P. , Sema H. Atoholi , Wahlang Barisha , Bez Ghanashyam
Published: January 2012

A catalytic amount (2 mol %) of phosphotungstic acid (PTA) is sufficient to synthesize homoallylic alcohol in excellent yields from aldehyde with allyltributylstannane upon grinding under solvent-free reaction conditions. Easy handling, very short reaction time, solvent-free reaction conditions, and aqueous workup free isolation protocol may make our method very useful for synthetic chemists.
Separation and determination of ephedra alkaloids in traditional Chinese medicine and human urines by capillary electrophoresis coupled with electrochemiluminescence detection
Authors: Liu Yan-Ming , Li Jie , Yang Yang , Du Junjun , Mei Lin
Published: January 2012

A new approach for the simultaneous determination of ephedrine, methylephedrine, and pseudoephedrine is developed, using capillary electrophoresis coupled with electrochemiluminescence detection with internal standard method. Separation efficiency and sensitivity were improved by use of an ionic liquid. Parameters affecting separation and detection were investigated in detail. Under optimum conditions, the three ephedra alkaloids were well separated and detected. The limits of detection (S/N = 3) of ephedrine, methylephedrine and pseudoephedrine are 4.0 × 10−8, 6.5 × 10−8, and 4.6 × 10−8 mol/L, respectively. The limits of quantitation (S/N = 10) in human urine are 5.3 × 10−7 mol/L for ephedrine, 9.1 × 10−7 mol/L for methylephedrine, and 6.9 × 10−7 mol/L for pseudoephedrine, respectively. The precision (RSD%) of the peak area and the migration time were from 2.2% to 2.5% and from 0.1% to 0.2% within a day and from 2.7% to 3.9% and from 0.4% to 0.8% in three days. The proposed method was successfully applied to the determination of three analytes in traditional Chinese medicine and human urine, and the monitoring of pharmacokinetics of pseudoephedrine in human body.
Four new triterpenoids from Chisocheton paniculatus and their anti-inflammatory activities
Authors: Yang Ming-Hua , Wang Jun-Song , Luo Jian-Guang , Wang Xiao-Bing , Kong Ling-Yi
Published: January 2012

As part of our continuing effort to discover new potential anti-inflammatory agents, four new triterpenoids, chisopanins L-O (1–4), were isolated from the twigs of Chisocheton paniculatus. Their structures were established on the basis of detailed analysis of spectroscopic data, including IR, NMR (1D and 2D NMR), and HR-ESI-MS. Their inhibitory effects against nitric oxide (NO) production were evaluated in an in vitro model of lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Compounds 1, 3, and 4 were found to exhibit moderate activity with IC50 values less than 10 μmol/L.
Synthesis and intramolecular hydrogen bonding of syn-9-hydroxy-18-substituted [3.3]metacyclophanes
Authors: Tazoe Kazuya , Feng Xing , Sharma Bigyan , Miyamoto Shinpei , Yamato Takehiko
Published: January 2012

Various anti-9-methoxy[3.3]metacyclophane-2,11-diones are exclusively obtained by the coupling reaction of the corresponding 1,3-bis(bromomethyl)benzenes and 2,6-bis[2-isocyano-2-(tolylsulfonyl)ethyl]-4-tert-butylanisole in dimethylformamide (DMF) with an excess of sodium hydride, from which the corresponding syn-[3.3]metacyclophanes (MCPs) are synthesized via anti/syn-isomerization during the Wolff–Kishner reduction. Demethylation of syn-9-methoxy[3.3]MCPs with BBr3 afforded the corresponding syn-9-hydroxy[3.3]MCPs in good yields. The existence of the strong intramolecular hydrogen bonding between the 9-hydroxy group and the 18-substituents, such as F, OH, and OMe groups at the opposing aromatic rings, are observed in solution and in the solid state. A distinct low-field shift of the phenolic OH proton was observed in the 1H NMR spectrum compared with that of the 18-unsubstituted analog. Furthermore, O–H···F through-space coupling was observed.
WEAK RESONANT DOUBLE HOPF BIFURCATIONS IN AN INERTIAL FOUR-NEURON MODEL WITH TIME DELAY
Authors: GE JUHONG , XU JIAN
Published: January 2012

In this paper, a four-neuron delayed bidirectional associative memory (BAM) model with inertia is considered. Weak resonant double Hopf bifurcations are completely analyzed in the parameter space of the coupling weight and the coupling delay by the perturbation-incremental scheme (PIS). Numerical simulations are given for justifying the theoretical results. To the best of our knowledge, the paper is the first one to introduce inertia to a four-neuron delayed system and clarify the relationship between system parameters and dynamical behaviors.
ADAPTIVE CONTROL FOR MIMO UNCERTAIN NONLINEAR SYSTEMS USING RECURRENT WAVELET NEURAL NETWORK
Authors: LIN CHIH-MIN , TING ANG-BUNG , HSU CHUN-FEI , CHUNG CHAO-MING
Published: January 2012

Recurrent wavelet neural network (RWNN) has the advantages such as fast learning property, good generalization capability and information storing ability. With these advantages, this paper proposes an RWNN-based adaptive control (RBAC) system for multi-input multi-output (MIMO) uncertain nonlinear systems. The RBAC system is composed of a neural controller and a bounding compensator. The neural controller uses an RWNN to online mimic an ideal controller, and the bounding compensator can provide smooth and chattering-free stability compensation. From the Lyapunov stability analysis, it is shown that all signals in the closed-loop RBAC system are uniformly ultimately bounded. Finally, the proposed RBAC system is applied to the MIMO uncertain nonlinear systems such as a mass-spring-damper mechanical system and a two-link robotic manipulator system. Simulation results verify that the proposed RBAC system can achieve favorable tracking performance with desired robustness without any chattering phenomenon in the control effort.
A NOVEL EFFICIENT LEARNING ALGORITHM FOR SELF-GENERATING FUZZY NEURAL NETWORK WITH APPLICATIONS
Authors: LIU FAN , ER MENG JOO
Published: January 2012

In this paper, a novel efficient learning algorithm towards self-generating fuzzy neural network (SGFNN) is proposed based on ellipsoidal basis function (EBF) and is functionally equivalent to a Takagi-Sugeno-Kang (TSK) fuzzy system. The proposed algorithm is simple and efficient and is able to generate a fuzzy neural network with high accuracy and compact structure. The structure learning algorithm of the proposed SGFNN combines criteria of fuzzy-rule generation with a pruning technology. The Kalman filter (KF) algorithm is used to adjust the consequent parameters of the SGFNN. The SGFNN is employed in a wide range of applications ranging from function approximation and nonlinear system identification to chaotic time-series prediction problem and real-world fuel consumption prediction problem. Simulation results and comparative studies with other algorithms demonstrate that a more compact architecture with high performance can be obtained by the proposed algorithm. In particular, this paper presents an adaptive modeling and control scheme for drug delivery system based on the proposed SGFNN. Simulation study demonstrates the ability of the proposed approach for estimating the drug's effect and regulating blood pressure at a prescribed level.
ENSEMBLES OF NEURAL NETWORKS BASED ON THE ALTERATION OF INPUT FEATURE VALUES
Authors: AKHAND M. A. H. , MURASE K.
Published: January 2012

An ensemble performs well when the component classifiers are diverse yet accurate, so that the failure of one is compensated for by others. A number of methods have been investigated for constructing ensemble in which some of them train classifiers with the generated patterns. This study investigates a new technique of training pattern generation. The method alters input feature values of some patterns using the values of other patterns to generate different patterns for different classifiers. The effectiveness of neural network ensemble based on the proposed technique was evaluated using a suite of 25 benchmark classification problems, and was found to achieve performance better than or competitive with related conventional methods. Experimental investigation of different input values alteration techniques finds that alteration with pattern values in the same class is better for generalization, although other alteration techniques may offer more diversity.
THE PHANTOM OF THE OPERA: SUPERLUMINAL NEUTRINOS
Authors: MA BO-QIANG
Published: January 2012

This is a brief review on the experimental measurements of the muon neutrino velocities from the OPERA, Fermilab and MINOS experiments and that of the (anti)-electron neutrino velocities from the supernova SN1987A, and consequently on the theoretical attempts to attribute the data as signals for superluminality of neutrinos. Different scenarios on how to understand and treat the background fields in the effective field theory frameworks are pointed out. Challenges on interpreting the OPERA result as a signal of neutrino superluminality are briefly reviewed and discussed. It is also pointed out that a covariant picture of Lorentz violation can avoid the refutation on the OPERA experiment.
PROTON INELASTIC DIFFRACTION BY A BLACK NUCLEUS AND THE SIZE OF EXCITED NUCLEI
Authors: IIDA KEI , KOIDE SHINYA , KOHAMA AKIHISA , OYAMATSU KAZUHIRO
Published: January 2012

We systematically derive a length scale characterizing the size of a low-lying, β stable nucleus from empirical data for the diffraction peak angle in the proton inelastic differential cross-section of incident energy of ~ 1 GeV. In doing so, we assume that the target nucleus in the ground state is a completely absorptive "black" sphere of radius a. The cross-section πa2, where a is determined in such a way as to reproduce the empirical proton diffraction peak angle in the elastic channel, is known to agree with empirical total reaction cross-sections for incident protons to within error bars. By comparing the inelastic diffraction patterns obtained in the Fraunhofer approximation with the experimental ones, one can likewise derive the black sphere radius al for the excited state with spin l. We find that for 12 C , 58, 60, 62, 64 Ni , and 208 Pb , the value of al obtained from the inelastic channel is generally larger than the value of a from the elastic channel and tends to increase with the excitation energy. This increase is remarkable for the Hoyle state. Finally, we discuss the relation between al and the size of excited nuclei.
OBSERVATION OF THE PREDICTED CHARGE COLLECTIVE MODE OF THE Tc = 45 K SUPERCONDUCTING PHASE OF La2CuO4+δ
Authors: KIM Y. H. , SONG Y. S. , HOR P. H.
Published: January 2012

We report the far-infrared (far-IR) observation of the Goldstone mode at ~ 72 cm-1 (~ 9 meV) predicted to exist in the superconducting phase of the transition temperature (Tc) at 45 K in the La 2 CuO 4-based superconductors. Our observation furthers the experimental support for the two-component picture where the localized charge texture, formed at a specific planar hole density (Ppl), is tied to the high temperature super-conductivity (HTS) at Tc = 15 K , 30 K, and 45 K in a hierarchical fashion at the so-called "magic" doping level at Ppl = 1/16, 2/16, and 3/16 respectively.
CONTROL OF QUANTUM ROTOR WITH SPIN-1/2
Authors: SCHMIDT ALEXANDRE G. M. , MARTINS BRUNO N.
Published: January 2012

In this work, we study the time evolution of a quantum rotor with spin-1/2 interacting with a time-dependent magnetic flux. Choosing an adequate magnetic flux and applying it at certain special switching times ti and tf, we show how to drive a wave-packet from a starting position to a final one maximizing its probability.