bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimized Bands: A New Design Concept for Concentrating Solar Parabolic Mirrors
Authors: Li Lifang , Kecskemethy Andres , Arif A. F. M. , Dubowsky Steven
Published: July 2011

Parabolic concentrator mirrors are an important component of many solar energy systems, particularly solar mirror collectors. Precision parabolic mirrors are expensive to fabricate and to transport. Here, a new concept for designing and fabricating precision parabolic mirrors is presented. The mirror is formed from a thin flat very flexible metal sheet with a highly reflective surface. Attached to the rear surface of the mirror sheet is a backbone band whose figure is optimized to form the reflective sheet into a precision parabola when its two ends are pulled toward each other. An analytical model to optimize the shape and thickness of the band is presented. The validity of the concept is demonstrated using Finite Element Analysis (FEA) and laboratory experiments. The concept would permit flat mirror elements to be easily fabricated and efficiently packaged and shipped to field sites and assembled into the parabolic trough concentrators with potentially substantial costs reductions compared with the conventional methods.
Thermal Performances of a High Temperature Air Solar Absorber Based on Compact Heat Exchange Technology
Authors: Grange B. , Ferrière A. , Bellard D. , Vrinat M. , Couturier R. , Pra F. , Fan Y.
Published: July 2011

In the framework of the French PEGASE project (Production of Electricity by GAs turbine and Solar Energy), CNRS/PROMES laboratory is developing a 4 MWth pressurized air solar receiver with a surface absorber based on a compact heat exchanger technology. The first step of this development consists in designing and testing a pilot scale (1/10 scale, e.g., 360 kWth) solar receiver based on a metallic surface absorber. This paper briefly presents the hydraulic and thermal performances of the innovative pressurized air solar absorber developed in a previous work. The goal is to be capable of preheating pressurized air from 350 °C at the inlet to 750 °C at the outlet, with a maximum pressure drop of 300 mbar. The receiver is a cavity of square aperture 120 cm × 120 cm and 1 m deepness with an average concentration in the aperture of more than 300. The square shaped aperture is chosen due to the small scale of the receiver; indeed, the performances are not enhanced that much with a round aperture, while the manufacturability is much more complicated. However in the perspective of PEGASE, a round aperture is likely to be used. The back of the cavity is covered by modules arranged in two series making the modular and multistage absorber. The thermal performances of one module are considered to simulate the thermal exchange within the receiver and to estimate the energy efficiency of this receiver. The results of the simulation show that the basic design yields an air outlet temperature of 739 °C under design operation conditions (1000 W/m2 solar irradiation, 0.8 kg/s air flow rate). Using the cavity walls as air preheating elements allows increasing the air outlet temperature above 750 °C as well as the energy efficiency up to 81% but at the cost of a critical absorber wall temperature. However, this wall temperature can be controlled by applying an aiming point strategy with the heliostat field.
Wall Pressure Profile Around Cylindrical Rods in Yawed Gas Flow
Authors: Marino R. G. , Clausse A. , Herrero V. A. , Silin N. , Saravia G.
Published: July 2011

The distribution of wall pressures in yawed flow through an array of cylindrical tubes inclined at different angles between 30° and 90° was experimentally studied using air at atmospheric pressure for 2290 ≤ Re ≤ 6100. The experiments show that the pressure coefficient is strongly influenced by the inclination angle, and only marginally affected by the flow rate within the tested range. The pressure behavior at the gap was calculated by assuming curved streamlines and inviscid flow, showing good agreement with measurements performed at the rod wall in the gap position.
Experimental verification of the shape of the excitation depth distribution function for AES
Authors: Tougaard S. , Jablonski A.
Published: July 2011

In the common formalism of AES, it is assumed that the in-depth distribution of ionizations is uniform. There are experimental indications that this assumption may not be true for certain primary electron energies and solids. The term “excitation depth distribution function” (EXDDF) has been introduced to describe the distribution of ionizations at energies used in AES. This function is conceptually equivalent to the Phi-rho-z function of electron microprobe analysis (EPMA). There are, however, experimental difficulties to determine this function in particular for energies below ∼ 10 keV. In the present paper, we investigate the possibility of determining the shape of the EXDDF from the background of inelastically scattered electrons on the low energy side of the Auger electron features in the electron energy spectra. The experimentally determined EXDDFs are compared with the EXDDFs determined from Monte Carlo simulations of electron trajectories in solids. It is found that this technique is useful for the experimental determination of the EXDDF function.
Investigation of crystal structure and optical properties of Cd1−xMnxS epilayers
Authors: Kim D. J. , Choi Y. D. , Lee J. W.
Published: July 2011

High quality Cd1−xMnxS epilayers were grown on GaAs (100) substrates via the hot-wall epitaxy method. The crystal structure of the grown Cd1−xMnxS epilayers was changed from cubic to hexagonal with Mn compositions higher than x = 0.05, as determined from x-ray diffraction patterns and scanning electron microscope images. In order to investigate the binding states and their chemical composition, Cd1−xMnxS epilayers have been characterized using x-ray photoelectron spectroscopy. The optical properties of the Cd1−xMnxS epilayers were investigated in a wide photon energy range between 2.0 and 8.5 eV using spectroscopic ellipsometry (SE) at room temperature. The data obtained using SE were analyzed in order to find the critical points of the pseudodielectric function spectra, <ɛ(E)> = <ɛ1(E)> + i<ɛ2(E)>. In addition, the second derivative spectra, d2ɛ(E)/dE2, of the pseudodielectric function of the Cd1−xMnxS epilayers were numerically calculated in order to determine the critical structures. Four structures, E0′ (H3v→H3c), F1 (M4v→M3c), and two E2 (K3v→K2c,K2v→K2c) structures from 6.0 eV to 8.0 eV, were observed with variation of the Mn composition at 300 K via ellipsometric measurements for the Cd1−xMnxS epilayers. The phase transition process from a cubic structure to a hexagonal structure was observed and investigated, for the first time, for Cd1−xMnxS epilayers via SE.
Humanized θ-Defensins (Retrocyclins) Enhance Macrophage Performance and Protect Mice from Experimental Anthrax Infections
Authors: Welkos S. , Cote C. K. , Hahn U. , Shastak O. , Jedermann J. , Bozue J. , Jung G. , Ruchala P. , Pratikhya P. , Tang T. , Lehrer R. I. , Beyer W.
Published: July 2011

Retrocyclins are humanized versions of the θ-defensin peptides expressed by the leukocytes of several nonhuman primates. Previous studies, performed in serum-free media, determined that retrocyclins 1 (RC1) and RC2 could prevent successful germination ofBacillus anthracisspores, kill vegetativeB. anthraciscells, and inactivate anthrax lethal factor. We now report that retrocyclins are extensively bound by components of native mouse, human, and fetal calf sera, that heat-inactivated sera show greatly enhanced retrocyclin binding, and that native and (especially) heat-inactivated sera greatly reduce the direct activities of retrocyclins against spores and vegetative cells ofB. anthracis. Nevertheless, we also found that retrocyclins protected mice challengedin vivoby subcutaneous, intraperitoneal, or intranasal instillation ofB. anthracisspores. Retrocyclin 1 bound extensively toB. anthracisspores and enhanced their phagocytosis and killing by murine RAW264.7 cells. Based on the assumption that spore-bound RC1 enters phagosomes by “piggyback phagocytosis,” model calculations showed that the intraphagosomal concentration of RC1 would greatly exceed its extracellular concentration. Murine alveolar macrophages took up fluorescently labeled retrocyclin, suggesting that macrophages may also acquire extracellular RC1 directly. Overall, these data demonstrate that retrocyclins are effectivein vivoagainst experimental murine anthrax infections and suggest that enhanced macrophage function contributes to this property.
The Quorum-Sensing Molecule Farnesol Is a Modulator of Drug Efflux Mediated by ABC Multidrug Transporters and Synergizes with Drugs in Candida albicans
Authors: Sharma Monika , Prasad Rajendra
Published: July 2011

Overexpression of the
CaCDR1
-encoded multidrug efflux pump protein CaCdr1p (
Candida
drug resistance protein 1), belonging to the ATP binding cassette (ABC) superfamily of transporters, is one of the most prominent contributors of multidrug resistance (MDR) in
Candida albicans
. Thus, blocking or modulating the function of the drug efflux pumps represents an attractive approach in combating MDR. In the present study, we provide first evidence that the quorum-sensing molecule farnesol (FAR) is a specific modulator of efflux mediated by ABC multidrug transporters, such as CaCdr1p and CaCdr2p of
C. albicans
and ScPdr5p of
Saccharomyces cerevisiae
. Interestingly, FAR did not modulate the efflux mediated by the multidrug extrusion pump protein CaMdr1p, belonging to the major facilitator superfamily (MFS). Kinetic data revealed that FAR competitively inhibited rhodamine 6G efflux in CaCdr1p-overexpressing cells, with a simultaneous increase in an apparent

K
m

without affecting the
V
max
values and the ATPase activity. We also observed that when used in combination, FAR at a nontoxic concentration synergized with the drugs at their respective nonlethal concentrations, as was evident from their <0.5 fractional inhibitory concentration index (FICI) values and from the drop of 14- to 64-fold in the MIC
80
values in the wild-type strain and in azole-resistant clinical isolates of
C. albicans
. Our biochemical experiments revealed that the synergistic interaction of FAR with the drugs led to reactive oxygen species accumulation, which triggered early apoptosis, and that both could be partly reversed by the addition of an antioxidant. Collectively, FAR modulates drug extrusion mediated exclusively by ABC proteins and is synergistic to fluconazole (FLC), ketoconazole (KTC), miconazole (MCZ), and amphotericin (AMB).
In Vitro
Efficacy of Dicationic Compounds and Mefloquine Enantiomers against Echinococcus multilocularis Metacestodes
Authors: Stadelmann Britta , Küster Tatiana , Scholl Sabrina , Barna Fabienne , Kropf Christian , Keiser Jennifer , Boykin David W. , Stephens Chad E. , Hemphill Andrew
Published: July 2011

The current chemotherapy of alveolar echinococcosis (AE) is based on benzimidazoles such as albendazole and has been shown to be parasitostatic rather than parasiticidal, requiring lifelong duration. Thus, new and more efficient treatment options are urgently needed. By employing a recently validated assay based on the release of functional phosphoglucose isomerase (PGI) from dying parasites, the activities of 26 dicationic compounds and of the (+)- and (−)-
erythro
-enantiomers of mefloquine were investigated. Initial screening of compounds was performed at 40 μM, and those compounds exhibiting considerable antiparasitic activities were also assessed at lower concentrations. Of the dicationic drugs, DB1127 (a diguanidino compound) with activities comparable to nitazoxanide was further studied. The activity of DB1127 was dose dependent and led to severe structural alterations, as visualized by electron microscopy. The (+)- and (−)-
erythro
-enantiomers of mefloquine showed similar dose-dependent effects, although higher concentrations of these compounds than of DB1127 were required for metacestode damage. In conclusion, of the drugs investigated here, the diguanidino compound DB1127 represents the most promising compound for further study in appropriate
in vivo
models for
Echinococcus multilocularis
infection.
Characterization of OXA-181, a Carbapenem-Hydrolyzing Class D β-Lactamase from Klebsiella pneumoniae
Authors: Potron Anaïs , Nordmann Patrice , Lafeuille Emilie , Al Maskari Zaina , Al Rashdi Fatma , Poirel Laurent
Published: July 2011

Klebsiella pneumoniae
KP3 was isolated from a patient transferred from India to the Sultanate of Oman.
K. pneumoniae
KP3 was resistant to all β-lactams, including carbapenems, and expressed the carbapenem-hydrolyzing β-lactamase OXA-181, which differs from OXA-48 by four amino acid substitutions. Compared to OXA-48, OXA-181 possessed a very similar hydrolytic profile. The
bla
OXA-181
gene was located on a 7.6-kb ColE-type plasmid and was linked to the insertion sequence IS
Ecp1
. The IS
Ecp1
-mediated one-ended transposition of
bla
OXA-181
was also demonstrated.
New Transposon Tn
6133
in Methicillin-Resistant Staphylococcus aureus ST398 Contains
vga
(E), a Novel Streptogramin A, Pleuromutilin, and Lincosamide Resistance Gene
Authors: Schwendener Sybille , Perreten Vincent
Published: July 2011

A novel streptogramin A, pleuromutilin, and lincosamide resistance determinant, Vga(E), was identified in porcine methicillin-resistant
Staphylococcus aureus
(MRSA) ST398. The
vga
(E) gene encoded a 524-amino-acid protein belonging to the ABC transporter family. It was found on a multidrug resistance-conferring transposon, Tn
6133
, which was comprised of Tn
554
with a stably integrated 4,787-bp DNA sequence harboring
vga
(E). Detection of Tn
6133
in several porcine MRSA ST398 isolates and its ability to circularize suggest a potential for dissemination.
Cytotoxicity of Voriconazole on Cultured Human Corneal Endothelial Cells
Authors: Han Sang Beom , Shin Young Joo , Hyon Joon Young , Wee Won Ryang
Published: July 2011

The purpose of the present study was to evaluate the toxicity of voriconazole on cultured human corneal endothelial cells (HCECs). HCECs were cultured and exposed to various concentrations of voriconazole (5.0 to 1,000 μg/ml). Cell viability was measured using a Cell Counting Kit-8 (CCK-8) and live/dead viability/cytotoxicity assays. Cell damage was assessed using phase-contrast microscopy after 24 h of exposure to voriconazole. To analyze the effect of voriconazole on the intercellular barrier, immunolocalization of zonula occludens 1 (ZO1) was performed. A flow cytometric assay was performed to evaluate the apoptotic and necrotic effects of voriconazole on HCECs. Cytotoxicity tests demonstrated the dose-dependent toxic effect of voriconazole on HCECs. Voriconazole concentrations of ≥100 μg/ml led to a significant reduction in cell viability. The morphological characteristics of HCECs also changed in a dose-dependent manner. Increasing concentrations of voriconazole resulted in fading staining for ZO1. Higher concentrations of voriconazole resulted in an increased number of propidium iodide (PI)-positive cells, indicating activation of the proapoptotic pathway. In conclusion, voriconazole may have a dose-dependent toxic effect on cultured HCECs. The results of this study suggest that although voriconazole concentrations of up to 50 μg/ml do not decrease cell viability, intracameral voriconazole concentrations of ≥100 μg/ml may increase the risk of corneal endothelial damage.
Molecular Basis for the Selectivity of Antituberculosis Compounds Capreomycin and Viomycin
Authors: Akbergenov Rashid , Shcherbakov Dmitri , Matt Tanja , Duscha Stefan , Meyer Martin , Wilson Daniel N. , Böttger Erik C.
Published: July 2011

Capreomycin and the structurally similar compound viomycin are cyclic peptide antibiotics which are particularly active against
Mycobacterium tuberculosis
, including multidrug resistant strains. Both antibiotics bind across the ribosomal interface involving 23S rRNA helix 69 (H69) and 16S rRNA helix 44 (h44). The binding site of tuberactinomycins in h44 partially overlaps with that of aminoglycosides, and they share with these drugs the side effect of irreversible hearing loss. Here we studied the drug target interaction on ribosomes modified by site-directed mutagenesis. We identified rRNA residues in h44 as the main determinants of phylogenetic selectivity, predict compensatory evolution to impact future resistance development, and propose mechanisms involved in tuberactinomycin ototoxicity, which may enable the development of improved, less-toxic derivatives.
DNA Gyrase Inhibition Assays Are Necessary To Demonstrate Fluoroquinolone Resistance Secondary to
gyrB
Mutations in Mycobacterium tuberculosis
Authors: Pantel Alix , Petrella Stéphanie , Matrat Stéphanie , Brossier Florence , Bastian Sylvaine , Reitter Delphine , Jarlier Vincent , Mayer Claudine , Aubry Alexandra
Published: July 2011

The main mechanism of fluoroquinolone (FQ) resistance in
Mycobacterium tuberculosis
is mutation in DNA gyrase (GyrA
2
GyrB
2
), especially in
gyrA
. However, the discovery of unknown mutations in
gyrB
whose implication in FQ resistance is unclear has become more frequent. We investigated the impact on FQ susceptibility of eight
gyrB
mutations in
M. tuberculosis
clinical strains, three of which were previously identified in an FQ-resistant strain. We measured FQ MICs and also DNA gyrase inhibition by FQs in order to clarify the role of these mutations in FQ resistance. Wild-type GyrA, wild-type GyrB, and mutant GyrB subunits produced from engineered
gyrB
alleles by mutagenesis were overexpressed in
Escherichia coli
, purified to homogeneity, and used to reconstitute highly active gyrase complexes. MICs and DNA gyrase inhibition were determined for moxifloxacin, gatifloxacin, ofloxacin, levofloxacin, and enoxacin. We demonstrated that the eight substitutions in GyrB (D473N, P478A, R485H, S486F, A506G, A547V, G551R, and G559A), recently identified in FQ-resistant clinical strains or encountered in
M. tuberculosis
strains isolated in France, are not implicated in FQ resistance. These results underline that, as opposed to phenotypic FQ susceptibility testing, the DNA gyrase inhibition assay is the only way to prove the role of a DNA gyrase mutation in FQ resistance. Therefore, the use of FQ in the treatment of tuberculosis (TB) patients should not be ruled out only on the basis of the presence of mutations in
gyrB
.
Salmonella enterica Serovar Typhimurium Colonizing the Lumen of the Chicken Intestine Grows Slowly and Upregulates a Unique Set of Virulence and Metabolism Genes
Authors: Harvey P. C. , Watson M. , Hulme S. , Jones M. A. , Lovell M. , Berchieri A. , Young J. , Bumstead N. , Barrow P.
Published: July 2011

The pattern of global gene expression in
Salmonella enterica
serovar Typhimurium bacteria harvested from the chicken intestinal lumen (cecum) was compared with that of a late-log-phase LB broth culture using a whole-genome microarray. Levels of transcription, translation, and cell division
in vivo
were lower than those
in vitro
.
S.
Typhimurium appeared to be using carbon sources, such as propionate, 1,2-propanediol, and ethanolamine, in addition to melibiose and ascorbate, the latter possibly transformed to
d
-xylulose. Amino acid starvation appeared to be a factor during colonization. Bacteria in the lumen were non- or weakly motile and nonchemotactic but showed upregulation of a number of fimbrial and
Salmonella
pathogenicity island 3 (SPI-3) and 5 genes, suggesting a close physical association with the host during colonization.
S.
Typhimurium bacteria harvested from the cecal mucosa showed an expression profile similar to that of bacteria from the intestinal lumen, except that levels of transcription, translation, and cell division were higher and glucose may also have been used as a carbon source.
Pneumocystis carinii Interactions with Lung Epithelial Cells and Matrix Proteins Induce Expression and Activity of the PcSte20 Kinase with Subsequent Phosphorylation of the Downstream Cell Wall Biosynthesis Kinase PcCbk1
Authors: Kottom Theodore J. , Burgess Joshua W. , Limper Andrew H.
Published: July 2011

Eukaryotic cell proliferation and phenotype are highly regulated by contact-dependent mechanisms. We have previously shown that the binding and interaction of the opportunistic fungal pathogen
Pneumocystis carinii
to lung epithelial cells and extracellular matrix proteins induces mRNA expression of both the mitogen-activated protein (MAP) kinase
P. carinii
Ste20 (PcSte20) and the cell wall-remodeling enzyme
PcCbk1
(16). Herein, we report that in addition to
PcSte20
mRNA expression being upregulated,
Pneumocystis
PcSte20 kinase activity is increased upon interacting with these same lung targets. This activity is also significantly suppressed by
Clostridium difficile
toxin B, a pan-specific inhibitor of small GTPases, demonstrating the potential role of a Cdc42-like molecule in this signaling cascade. We further observed that the PcSte20 kinase physically interacts with a specific region of the
P. carinii
cell wall biosynthesis kinase, PcCbk1, a downstream kinase important for mating projection formation and cell wall remodeling. This direct binding was mapped to a specific region of the PcCbk1 protein. We also demonstrated that PcSte20 obtained from whole
P. carinii
lysates has the ability to phosphorylate PcCbk1 after the organism interacts with lung epithelial cells and extracellular matrix components. These observations provide new insights into
P. carinii
signaling induced by interactions of this important opportunistic fungal pathogen with lung epithelial cells and matrix.
Protective Live Oral Brucellosis Vaccines Stimulate Th1 and Th17 Cell Responses
Authors: Clapp Beata , Skyberg Jerod A. , Yang Xinghong , Thornburg Theresa , Walters Nancy , Pascual David W.
Published: July 2011

Zoonotic transmission of brucellosis often results from exposure to
Brucella
-infected livestock, feral animals, or wildlife or frequently via consumption of unpasteurized milk products or raw meat. Since natural infection of humans often occurs by the oral route, mucosal vaccination may offer a means to confer protection for both mucosal and systemic tissues. Significant efforts have focused on developing a live brucellosis vaccine, and deletion of the
znuA
gene involved in zinc transport has been found to attenuate
Brucella abortus
. A similar mutation has been adapted for
Brucella melitensis
and tested to determine whether oral administration of Δ
znuA
B. melitensis
can confer protection against nasal
B. melitensis
challenge. A single oral vaccination with Δ
znuA
B. melitensis
rapidly cleared from mice within 2 weeks and effectively protected mice upon nasal challenge with wild-type
B. melitensis
16M. In 83% of the vaccinated mice, no detectable brucellae were found in their spleens, unlike with phosphate-buffered saline (PBS)-dosed mice, and vaccination also enhanced the clearance of brucellae from the lungs. Moreover, vaccinated gamma interferon-deficient (IFN-γ
−/−
) mice also showed protection in both spleens and lungs, albeit protection that was not as effective as in immunocompetent mice. Although IFN-γ, interleukin 17 (IL-17), and IL-22 were stimulated by these live vaccines, only RB51-mediated protection was codependent upon IL-17 in BALB/c mice. These data suggest that oral immunization with the live, attenuated Δ
znuA
B. melitensis
vaccine provides an attractive strategy to protect against inhalational infection with virulent
B. melitensis
.
Type 1 Fimbrial Adhesin FimH Elicits an Immune Response That Enhances Cell Adhesion of Escherichia coli
Authors: Tchesnokova Veronika , Aprikian Pavel , Kisiela Dagmara , Gowey Sarah , Korotkova Natalia , Thomas Wendy , Sokurenko Evgeni
Published: July 2011

Escherichia coli
causes about 90% of urinary tract infections (UTI), and more than 95% of all UTI-causing
E. coli
express type 1 fimbriae. The fimbrial tip-positioned adhesive protein FimH utilizes a shear force-enhanced, so-called catch-bond mechanism of interaction with its receptor, mannose, where the lectin domain of FimH shifts from a low- to a high-affinity conformation upon separation from the anchoring pilin domain. Here, we show that immunization with the lectin domain induces antibodies that exclusively or predominantly recognize only the high-affinity conformation. In the lectin domain, we identified four high-affinity-specific epitopes, all positioned away from the mannose-binding pocket, which are recognized by 20 separate clones of monoclonal antibody. None of the monoclonal or polyclonal antibodies against the lectin domain inhibited the adhesive function. On the contrary, the antibodies enhanced FimH-mediated binding to mannosylated ligands and increased by severalfold bacterial adhesion to urothelial cells. Furthermore, by natural conversion from the high- to the low-affinity state, FimH adhesin was able to shed the antibodies bound to it. When whole fimbriae were used, the antifimbrial immune serum that contained a significant amount of antibodies against the lectin domain of FimH was also able to enhance FimH-mediated binding. Thus, bacterial adhesins (or other surface antigens) with the ability to switch between alternative conformations have the potential to induce a conformation-specific immune response that has a function-enhancing rather than -inhibiting impact on the protein. These observations have implications for the development of adhesin-specific vaccines and may serve as a paradigm for antibody-mediated enhancement of pathogen binding.
Membrane Translocation of Binary Actin-ADP-Ribosylating Toxins from Clostridium difficile and Clostridium perfringens Is Facilitated by Cyclophilin A and Hsp90
Authors: Kaiser Eva , Kroll Claudia , Ernst Katharina , Schwan Carsten , Popoff Michel , Fischer Gunter , Buchner Johannes , Aktories Klaus , Barth Holger
Published: July 2011

Some hypervirulent strains of
Clostridium difficile
produce the binary actin-ADP-ribosylating toxin
C. difficile
transferase (CDT) in addition to Rho-glucosylating toxins A and B. It has been suggested that the presence of CDT increases the severity of
C. difficile
-associated diseases, including pseudomembranous colitis. CDT contains a binding and translocation component, CDTb, that mediates the transport of the separate enzyme component CDTa into the cytosol of target cells, where CDTa modifies actin. Here we investigated the mechanism of cellular CDT uptake and found that bafilomycin A1 protects cultured epithelial cells from intoxication with CDT, implying that CDTa is translocated from acidified endosomal vesicles into the cytosol. Consistently, CDTa is translocated across the cytoplasmic membranes into the cytosol when cell-bound CDT is exposed to acidic medium. Radicicol and cyclosporine A, inhibitors of the heat shock protein Hsp90 and cyclophilins, respectively, protected cells from intoxication with CDT but not from intoxication with toxins A and B. Moreover, both inhibitors blocked the pH-dependent membrane translocation of CDTa, strongly suggesting that Hsp90 and cyclophilin are crucial for this process. In contrast, the inhibitors did not interfere with the ADP-ribosyltransferase activity, receptor binding, or endocytosis of the toxin. We obtained comparable results with the closely related iota-toxin from
Clostridium perfringens
. Moreover, CDTa and Ia, the enzyme component of iota-toxin, specifically bound to immobilized Hsp90 and cyclophilin A
in vitro
. In combination with our recently obtained data on the C2 toxin from
C. botulinum
, these results imply a common Hsp90/cyclophilin A-dependent translocation mechanism for the family of binary actin-ADP-ribosylating toxins.
Effect of Deletion of Genes Involved in Lipopolysaccharide Core and O-Antigen Synthesis on Virulence and Immunogenicity of Salmonella enterica Serovar Typhimurium
Authors: Kong Qingke , Yang Jiseon , Liu Qing , Alamuri Praveen , Roland Kenneth L. , Curtiss Roy
Published: July 2011

Lipopolysaccharide (LPS) is a major virulence factor ofSalmonella entericaserovar Typhimurium and is composed of lipid A, core oligosaccharide (C-OS), and O-antigen polysaccharide (O-PS). While the functions of the gene products involved in synthesis of core and O-antigen have been elucidated, the effect of removing O-antigen and core sugars on the virulence and immunogenicity ofSalmonella entericaserovar Typhimurium has not been systematically studied. We introduced nonpolar, defined deletion mutations inwaaG(rfaG),waaI(rfaI),rfaH,waaJ(rfaJ),wbaP(rfbP),waaL(rfaL), orwzy(rfc) into wild-typeS.Typhimurium. The LPS structure was confirmed, and a number ofin vitroandin vivoproperties of each mutant were analyzed. All mutants were significantly attenuated compared to the wild-type parent when administered orally to BALB/c mice and were less invasive in host tissues. Strains with ΔwaaGand ΔwaaImutations, in particular, were deficient in colonization of Peyer's patches and liver. This deficiency could be partially overcome in the ΔwaaImutant when it was administered intranasally. In the context of an attenuated vaccine strain delivering the pneumococcal antigen PspA, all of the mutations tested resulted in reduced immune responses against PspA andSalmonellaantigens. Our results indicate that nonreversible truncation of the outer core is not a viable option for developing a live oralSalmonellavaccine, while awzymutant that retains one O-antigen unit is adequate for stimulating the optimal protective immunity to homologous or heterologous antigens by oral, intranasal, or intraperitoneal routes of administration.
Systematic review of genome-wide expression studies in multiple sclerosis
Authors: Kemppinen A K , Kaprio J , Palotie A , Saarela J
Published: July 2011

Background

Although recent genome-wide association studies have identified several genetic variants contributing to the complex aetiology of multiple sclerosis (MS), expression and functional studies are required to further understand its molecular basis.

Objectives

To identify genes and pathways with differential expression in MS.

Design

The authors conducted a systematic review of seven microarray studies, in which expression in immune cells was compared between MS patients and controls. These studies include a previously unpublished study, which is described here in detail.

Results and conclusion

Although in general the overlap between studies was poor, 229 genes were found to be differentially expressed in MS in at least two studies, of which 11 were in three studies andHSPA1Ain four studies. After excluding the authors' unpublished experiment which may have been affected by certain confounding factors and inclusion of treated subjects, 135 genes were identified in at least two studies. The differentially expressed genes were significantly associated with several immunological pathways, including interleukin (IL)-4, IL-6, IL-17 and glucocorticoid receptor signalling pathways. 15 of the 229 loci have shown some association with MS in published genome-wide association studies (p<0.0001), including three loci with confirmed MS risk variants.
Heterogeneity of the efficacy of the 23-valent pneumococcal polysaccharide vaccine caused by various underlying conditions of chronic pulmonary disease in older patients: prospective cohort study
Authors: Inoue Satoshi , Watanuki Yuji , Kaneko Tetsuji , Sato Takashi , Miyazawa Naoki , Kaneko Takeshi , Ishigatsubo Yoshiaki , Morita Satoshi , Natsumeda Yutaka , Mizushima Shunsaku
Published: July 2011

Objective

To determine the ideal conditions for use of the 23-valent pneumococcal polysaccharide vaccine (PPV23) in older outpatients with chronic pulmonary diseases.

Design

Prospective cohort study.

Participants

1378 outpatients with chronic pulmonary diseases ≥60 years of age.

Intervention

Participants were educated about PPV23, and those who responded affirmatively were vaccinated between August and November 2002. The participants who chose no intervention served as controls. The prevaccine period was defined as August 2001 to August 2002. Participants were followed for 2 years from December 2002 or until death.

Main outcome measures

Events of interest included the first episode of bacterial (including pneumococcal) pulmonary infection (primary endpoint) and death of any cause (secondary endpoint).

Results

Frequent episodes of pulmonary infection during the prevaccine period significantly decreased event-free survival during the 2-year observation period (p<0.001). Chronic respiratory failure was associated with a decreased event-free survival only when the pulmonary infection episode did not occur in the prevaccine period (p<0.001). No significant differences in event-free survival were observed between the vaccinated and unvaccinated group during analysis of the entire cohort. In the Cox proportional hazards regression model, event-free survival decreased significantly when pulmonary infection occurred in the prevaccine period. In the subgroup analysis, the first episode of bacterial pulmonary infection (but not death of any cause) was reduced significantly by PPV23 only in patients with chronic respiratory failure who had no episodes of pulmonary infection during the prevaccine period (p=0.019).

Conclusion

The efficacy of PPV23 against pulmonary infection and death of any cause might be unachievable if pulmonary infection occurs during the prevaccine period. PPV23 needs to be given to older patients with chronic pulmonary disease at an earlier time in which infectious complications in the lung have not yet occurred.
Improved communication in post-ICU care by improving writing of ICU discharge letters: a longitudinal before‐after study
Authors: Medlock Stephanie , Eslami Saeid , Askari Marjan , van Lieshout Erik Jan , Dongelmans Dave A , Abu-Hanna Ameen
Published: July 2011

Background

The discharge letter is the primary means of communication at patient discharge, yet discharge letters are often not completed on time. A multifaceted intervention was performed to improve communication in patient hand-off from the intensive care unit (ICU) to the wards by improving the timeliness of discharge letters.

Methods

A management directive was operationalised by a working group of ICU staff in a longitudinal before–after study. The intervention consisted of (a) changing policy to require a letter for use as a transfer note at the time of ICU discharge, (b) changing the assignment of responsibility to an automatic process, (c) leveraging positive peer pressure by making the list of patients in need of letters visible to colleagues and (d) provision of decision support, through automatic copying of important content from the patient record to the letter and email reminders if letters were not written on time. Statistical process control charts were used to monitor the longitudinal effect of the intervention.

Results

The intervention resulted in a 77.9% absolute improvement in the proportion of patients with a complete transfer note at the time of discharge, and an 85.2% absolute improvement in the number of discharge letters written. Statistical process control shows that the effect was sustained over time.

Conclusions

A multifaceted intervention can be highly effective for improving discharge communication from the ICU.
The comparative behaviour of two combat boots under impact
Authors: Newell Nicolas , Masouros Spyros D , Pullen Andy D , Bull Anthony M J
Published: July 2011

Background

Improvised explosive devices have become the characteristic weapon of conflicts in Iraq and Afghanistan. While little can be done to mitigate against the effects of blast in free-field explosions, scaled blast simulations have shown that the combat boot can attenuate the effects on the vehicle occupants of anti-vehicular mine blasts. Although the combat boot offers some protection to the lower limb, its behaviour at the energies seen in anti-vehicular mine blast has not been documented previously.

Methods

The sole of eight same-size combat boots from two brands currently used by UK troops deployed to Iraq and Afghanistan were impacted at energies of up to 518 J, using a spring-assisted drop rig.

Results

The results showed that the Meindl Desert Fox combat boot consistently experienced a lower peak force at lower impact energies and a longer time-to-peak force at higher impact energies when compared with the Lowa Desert Fox combat boot.

Discussion

This reduction in the peak force and extended rise time, resulting in a lower energy transfer rate, is a potentially positive mitigating effect in terms of the trauma experienced by the lower limb.

Conclusion

Currently, combat boots are tested under impact at the energies seen during heel strike in running. Through the identification of significantly different behaviours at high loading, this study has shown that there is rationale in adding the performance of combat boots under impact at energies above those set out in international standards to the list of criteria for the selection of a combat boot.
THE PROBLEM OF INERTIA IN FRIEDMANN UNIVERSES
Authors: SULTANA JOSEPH , KAZANAS DEMOSTHENES
Published: July 2011

In this paper we study the origin of inertia in a curved spacetime, particularly the spatially flat, open and closed Friedmann universes. This is done using Sciama's law of inertial induction, which is based on Mach's principle, and expresses the analogy between the retarded far fields of electrodynamics and those of gravitation. After obtaining covariant expressions for electromagnetic fields due to an accelerating point charge in Friedmann models, we adopt Sciama's law to obtain the inertial force on an accelerating mass m by integrating over the contributions from all the matter in the universe. The resulting inertial force has the form F = -kma, where k < 1 depends on the choice of the cosmological parameters such as ΩM, ΩΛ and ΩR and is also redshift-dependent.
DYNAMICS OF AN HIV-1 INFECTION MODEL WITH CELL-MEDIATED IMMUNE RESPONSE AND STOCHASTIC PERTURBATION
Authors: JI CHUNYAN , JIANG DAQING
Published: July 2011

In this paper, we introduce the stochasticity into an HIV-1 infection model with cytotoxic T lymphocytes (CTLs) immune response via the technique of parameter perturbation. We show that there is a positive solution as desired in any population dynamics. Then we analyze the long time behavior of this model. We obtain a sufficient condition for the stochastic asymptotic stability in the large of the infection-free equilibrium and give the conditions for the solution fluctuating around the two infection equilibria (one without CTLs being activated and the other with). Finally, we make simulations to conform to our analytical results.
Investigation of Annealing and Blend Concentration Effects of Organic Solar Cells Composed of Small Organic Dye and Fullerene Derivative
Authors: Ismail Yasser A. M. , Soga Tetsuo , Jimbo Takashi
Published: July 2011

We have fabricated bulk heterojunction organic solar cells using coumarin 6 (C6) as a small organic dye, for light harvesting and electron donation, with fullerene derivative [6,6]-phenyl-C61 butyric acid methyl ester (PCBM), acting as an electron acceptor, by spin-coating technique. We have investigated thermal annealing and blend concentration effects on light harvesting, photocurrent, and performance parameters of the solar cells. In this work, we introduced an experimental method by which someone can easily detect the variation in the contact between active layer and cathode due to thermal annealing after cathode deposition. We have showed, in this work, unusual behavior of solar cell composed of small organic molecules under the influence of thermal annealing at different conditions. This behavior seemed uncommon for polymer solar cells. We try from this work to understand device physics and to locate a relationship between production parameters and performance parameters of the solar cell based on small organic molecules.
Treatment of Severe Hypertriglyceridemia with Continuous Insulin Infusion
Authors: Rodríguez Santana Yesica , Nimo Román Andrea , García Sáez Iker , López Alvarez José Manuel , Consuegra Llapur Eduardo , González Jorge Rafael
Published: July 2011

Severe hypertriglyceridemia (SH) represents a therapeutic emergency because of the possibility of developing cardiovascular events and hyperlipemic acute pancreatitis (PA). Most patients with SH suffer primary or genetic abnormality in lipid metabolism in combination with a precipitating factor such as uncontrolled diabetes mellitus, alcoholism, and drug intake. The standard treatment of hypertriglyceridemia (HTG) with omega 3 fatty acids and fibrates, along with dietary changes, has no effect on an emergency situation. There are no clinical guidelines to SH, but therapy with insulin, heparin, a combination of both, plasmapheresis, or octreotide have been tested succesfully. We report the case of a 10-year-old girl with clinical acute pancreatitis and diabetic ketoacidosis debut, along with incidental finding of an SH, who had a good outcome after treatment with insulin intravenous infusion.
The Planetary Wave Activity in Temperatures of the Stratosphere, Mesosphere and in Critical Frequencies of Ionospheric F2 Layer
Authors: Polekh N. M. , Vergasova G. V. , Kazimirovsky E. S. , Perevalova N. P. , Kurkin V. I. , Chernigovskaya M. A.
Published: July 2011

A large body of experimental evidence lends credit to the existence of a close relationship between ionospheric parameters and the underlying atmosphere. Vertical-incidence ionospheric sounding data and temperature measurements at stratospheric (30 km) and mesospheric (80 km) heights have been used in investigating the interrelation between the occurrence of fluctuations with periods of planetary waves in temperature variations at different heights and inF2layer critical frequency variations (foF2) under low solar activity conditions for the time interval 2006-2007. The distinctive characteristics of the manifestation of common periodicities of the wave structures under consideration are discussed. The statistically significant periods of stratospheric and mesospheric temperature fluctuations vary from 11 to 49 days, whereas foF2 periodograms show higher-frequency fluctuations with periods of 5, 8, 9, and 10 days. The study revealed a similarity between periodic structures for the variations in the parameters involved.
Histological Chorioamnionitis Is Increased at Extremes of Gestation in Stillbirth: A Population-Based Study
Authors: Gordon Adrienne , Lahra Monica , Raynes-Greenow Camille , Jeffery Heather
Published: July 2011

Objective. To determine the incidence of histological chorioamnionitis and a fetal response in stillbirths in New South Wales (NSW), and to examine any relationship of fetal response to spontaneous onset of labour and to unexplained antepartum death.Study Design. Population-based cohort study.Setting. New South Wales Australia.Population. All births between 2002 and 2004 with stillbirths reviewed and classified by the state perinatal mortality review committee.Methods. Record linkage of the Midwives Data Collection and the Perinatal Death Database including placental histopathology and standardised cause of death classification.Results. 952 stillbirths were included. The incidence of histopathological chorioamnionitis was 22.6%, with a bimodal distribution. A fetal inflammatory response was present in 10.1% and significantly correlated with spontaneous onset of labour. The absence of a fetal inflammatory response was strongly associated with unexplained antepartum death.Conclusions. The increased incidence of histological chorioamnionitis at extremes of gestation is confirmed in the largest dataset to date using population data. This has important implications for late gestation stillbirth as the percentage of unexplained stillbirths increases near term.
Mandibular Fracture in a Child Resulting from a Dog Attack: A Case Report
Authors: Cottom Hannah , Tuopar Dery , Ameerally Phillip
Published: July 2011

Dog attacks are extremely frequent and are thought to be responsible for an average of 250,000 minor injuries and emergency unit attendances each year. Children in particular are more likely to experience dog-bite injuries with 5–9-year olds most susceptible. The majority of injuries are to the head region, with the lips, cheeks, and nose often affected. Most injuries experienced are confined to the soft tissues; nevertheless, maxillofacial fracture is a potential albeit rare complication. The incidence of facial fractures in relation to dog bites is unknown; however, some have estimated that facial fractures could occur in 5% of dog attacks. However mandibular fracture following a dog bite is extremely rare, with review of the literature only identifying three cases. We present a further case in which a five-year-old sustained numerous soft-tissue lacerations to the face and hand, together with fracture of the mandibular symphysis following a dog attack. The fracture was successfully repaired using open reduction and internal fixation with titanium plates and screws. The case emphasises that although maxillofacial fracture is rare, it may occur following a dog bite and that thorough and systematic examination of the facial skeleton is crucial to exclude the presence of such injuries.
Immune Efficacy of a Genetically Engineered Vaccine against Lymphocystis Disease Virus: Analysis of Different Immunization Strategies
Authors: Zheng Fengrong , Sun Xiuqin , Wu Xing′an , Liu Hongzhan , Li Jiye , Wu Suqi , Zhang Jinxing
Published: July 2011

Here, we report the construction of a vaccine against lymphocystis disease virus (LCDV) using nucleic acid vaccination technology. A fragment of the major capsid protein encoding gene from an LCDV isolated from China (LCDV‐cn) was cloned into an eukaryotic expression vector pEGFP‐N2, yielding a recombinant plasmid pEGFP‐N2‐LCDV‐cn0.6 kb. This plasmid was immediately expressed after liposomal transfer into the Japanese flounder embryo cell line. The recombinant plasmid was inoculated into Japanese flounder via two routes (intramuscular injection and hypodermic injection) at three doses (0.1, 5, and 15 μg), and then T‐lymphopoiesis in different tissues and antibodies raised against LCDV were evaluated. The results indicated that this recombinant plasmid induced unique humoral or cell‐mediated immune responses depending on the inoculation route and conferred immune protection. Furthermore, the humoral immune responses and protective effects were significantly increased at higher vaccine doses via the two injection routes. Plasmid pEGFP‐N2‐LCDV0.6 kb is therefore a promising vaccine candidate against LCDV in Japanese flounder.
A Preliminary Study of the Microbial Resources and Their Biological Activities of the East China Sea
Authors: Lu Xiaoling , Liu Xiaoyu , Long Cong , Wang Guoxiang , Gao Yun , Liu Junhua , Jiao Binghua
Published: July 2011

East China Sea is one of the four sea areas in China, which possesses peculiar ecological environment and many kinds of living creatures, especially the microorganisms. We established the East China Sea microorganism library (during 2006–2010) for the first time, which stored about 30000 strains that covered most kinds of the species. In this paper, 395 pure strains of East China Sea microorganism library which belong to 33 different genera were mainly introduced. Sulfitobacter, Halomonas, Bacillus, Pseudoalteromonas, and Idiomarina were the most dominant species. On the large‐scale biological activity screening of the 395 strains, 100 strains possess different biological activities based on different screening models, of which 11.4% strains have antibacterial activities, 15.9% have cytotoxicity activities, and 6.1% have antioxidation activities. Besides, the secondary metabolites of 6 strains with strong biological activities were studied systematically; diketopiperazines and macrocyclic lactones are the active secondary metabolites. The species and the biological activity of microorganisms diversity, the abundant structure type of the secondary metabolites, and their bioactivities all indicate that East China Sea is a potent marine microorganisms‐derived developing resource for drug discovery.