bluuebunny/crossref_metadata_2025 huggingface dataset:
A Unified Finite Element Approach for the Study of Postyielding Deformation Behavior of Formable Sheet Materials
Authors: Duan Xinjian , Jain Mukesh , Metzger Don. R. , Wilkinson David S.
Published: October 2007

Deformation and fracture behavior of several formable automotive aluminum alloys and steels have been assessed experimentally at room temperature through standard uniaxial tension, plane strain tension, and hemispherical dome tests. These materials exhibit the same deformation sequence: normally uniform elongation followed by diffuse necking, then localized necking in the form of crossed intense-shear bands, and finally fracture. The difference among these alloys lies primarily with respect to the point at which damage (i.e., voiding) starts. Damage develops earlier in the steel samples, although in all cases very little damage is observed prior to the onset of shear instability. A unified finite element model has been developed to reproduce this characteristic deformation sequence. Instability is triggered by the introduction of microstructural inhomogeneities rather than through the commonly utilized Gurson-Tvergaard-Needleman damage model. The predicted specimen shape change, shear band characteristics, distribution of strain, and the fracture modes for steels and aluminum alloys are all in good agreement with the experimental observations.
Ultrasonic Creep Damage Detection by Frequency Analysis for Boiler Piping
Authors: Hatanaka Hiroaki , Ido Nobukazu , Ito Takuya , Uemichi Ryota , Tagami Minoru , Nakagawa Hirokatsu
Published: October 2007

Boiler piping of fossil-fuel combustion power generation plants are exposed to high-temperature and high-pressure environments, and failure of high-energy piping due to creep damage has been a concern. Therefore, a precise creep damage assessment method is needed. This paper proposes a nondestructive method for creep damage detection of piping in fossil-fuel combustion power generation plants by ultrasonic testing. Ultrasonic signals are transformed to signals in a frequency domain by Fourier transform, and a specific frequency band is chosen. To determine the creep damage, the spectrum intensities are calculated. Calculated intensities have a good correlation to life consumption of the weld joints, and this method is able to predict the remaining life of high-temperature piping, which has been already installed.
A Nondestructive Strategy for the Distinction of Natural Fatigue and Stress Corrosion Cracks Based on Signals From Eddy Current Testing
Authors: Chen Zhenmao , Janousek Ladislav , Yusa Noritaka , Miya Kenzo
Published: October 2007

In this paper, a novel nondestructive strategy is proposed for distinguishing differences between a stress corrosion crack (SCC) and a fatigue crack (FC) based on signals from eddy current testing (ECT). The strategy consists of measurement procedures with a special ECT probe and crack type judgment scheme based on an index parameter that is defined as the amplitude ratio of the measured signals. An ECT probe, which can induce eddy current flowing mainly in a selected direction, is proposed and applied to detect crack signals by scanning along the crack with different probe orientations. It is clear that the ratio of the amplitudes of signals detected for parallel and perpendicular probe orientations is sensitive to the microstructure of the crack, i.e., the parameter is much bigger for a fatigue crack than that of a SCC. Therefore, whether a crack is a SCC or a FC can be recognized nondestructively by comparing the index parameter with a threshold value that can be previously determined. In order to verify the validity of the proposed strategy, many artificial SCC and FC test pieces were fabricated and ECT inspections were performed to measure the corresponding crack signals. Numerical simulations were also conducted to investigate the physical principles of the new methodology. From both the numerical and experimental results, it is demonstrated that the strategy is very promising for the distinction of artificial SCC and FC; there is also good possibility that this method can be applied to natural cracks if the threshold value can be properly determined.
Anodic Behavior of Specimens Prepared From a Full-Diameter Alloy 22 Fabricated Mockup Container for Nuclear Waste
Authors: Estill John C. , Rebak Raul B.
Published: October 2007

Alloy 22 (N06022) has been extensively tested for general and localized corrosion behavior both in the wrought annealed condition and in the as-welded condition. In general, the specimens for laboratory testing are mostly prepared from flat plates of material. It is important to determine if the process of fabricating a container will affect the corrosion performance of this alloy. Thus, specimens for corrosion testing were prepared directly from a fabricated full-diameter Alloy 22 container. Results show that both the anodic corrosion behavior and the localized corrosion resistance of specimens prepared from a welded container were the same as those from flat welded plates.
Urea Reactor Integrity Evaluation Based on Failure Analysis
Authors: Song Mingda , Wang Weiqiang , Zhao Yafan , Cui Yuliang
Published: October 2007

Multilayered pressure vessels tend to induce stress corrosion cracking (SCC) in the heavy weld. This conclusion is based on the recent ruptured urea reactor failure analysis. Finite element simulation proved that multilayered urea reactors have yielded zones at the heavy weld where the SCC crack initiated. Acoustic emission (AE) examination conducted for two in-service urea reactors revealed AE event clusters at the heavy weld and subsequent phased array reexamination confirmed the existence of propagating defects in the heavy weld. The results also showed that AE evaluation and phased array reexamination are sound combination methods to evaluate the integrity of multilayered urea reactors. Besides, they are superior to γ-ray inspection because of the uncertain propagation direction of SCC cracks.
Acoustic Resonance in a Package Boiler and Its Solution—A Case Study
Authors: Eisinger Frantisek L. , Sullivan Robert E.
Published: October 2007

Strong acoustic resonance with acoustic pressures reaching up to 165dB developed in the boiler bank of a package boiler at full load. At first, the resonance developed at a lower frequency in the downstream portion of the tube bank and was suppressed by an acoustic baffle covering the downstream section of the flow channel. After about one year of operation, a second resonant condition developed. Tests confirmed that, again, a strong resonant condition developed at a higher frequency in the unbaffled upstream portion of the flow channel. Computer analysis confirmed that the initial resonance occurred at the first acoustic mode of the flow channel while the follow-up resonance occurred at the second mode of the flow channel expressed as a first-mode resonance in a different (upstream) location. An extension of the acoustic baffle covering the entire depth of the tube bank eliminated the vibration. This paper gives a description of the problem and summarizes the theoretical and experimental results substantiating the findings.
Comparative Study for Stresses in Nozzle and Flange Welds Generated During Conventional Pressure Testing and Local Pressure Testing Using Bolted Devices
Authors: Cheta Ayman M. , Brodzinski Richard
Published: October 2007

Weld repairs and alterations of pressure vessels and piping built to ASME codes may require pressure testing to prove the integrity of the weld and/or design. Conventional hydrostatic pressure testing requires filling an entire vessel or piping system with water and pressurizing it to the test pressure. In recent years, several designs were developed to employ bolted devices to perform local pressure testing of flange-to-nozzle, flange-to-pipe, and nozzle-to-shell attachment welds. Due to the cost and equipment downtime associated with performing a full conventional pressure test and the desire to reduce repair costs, several petrochemical companies adopted the use of such devices. The purpose of this paper is to compare the stress values and stress distribution associated with conventional and local pressure testing techniques. The advantages and disadvantages of both approaches are discussed and the conclusions are supported by a practical example.
Significance of Fracture Toughness Test Results of Beam Welds in
Evaluation of Brittle Fracture Performance of Girth Welded Pipe
Joints
Authors: Ohata Mitsuru , Toyoda Masao , Ishikawa Nobuyuki , Shinmiya Toyohisa
Published: October 2007

High power beam welds, such as electron beam welds or laser welds, sometimes provide fracture path deviation (FPD) in standardized Charpy V-notch fracture toughness testing due to narrow bead profile together with higher overmatching in strength between weld metal and base metal. Moreover, it should be noted that these typical features of beam welds might result in a plastic constraint loss around both the notch and crack tip in fracture toughness test specimens. Even in the temperature range where FPD would not occur, the fracture toughness test results could not necessarily be an intrinsic value of such beam welds. These fracture properties make it difficult to evaluate fracture performance of girth welded pipe joints. In this paper, the estimation method of intrinsic fracture toughness of beam weld metal itself using standard toughness test specimens is proposed on the basis of “Weibull stress criterion.” The predicted intrinsic fracture toughness was found to be lower than the test results both in standard Charpy specimen and in three-point bend specimen with fatigue precrack. The assessment of brittle fracture performance of girth welded pipeline was conducted from the estimated intrinsic fracture toughness of girth welds by means of Weibull stress criterion. It was demonstrated that the low intrinsic fracture toughness of beam welds could not directly lead to the low fracture performance of a pipe joint under tensile loading. This is because of a lower plastic constraint compared to a three-point bend specimen due to difference in loading mode together with constraint loss in pipe joints and shielding effect of straining in weld metal due to highly overmatched narrow welds.
Artemisinin and a Series of Novel Endoperoxide Antimalarials Exert Early Effects on Digestive Vacuole Morphology
Authors: del Pilar Crespo Maria , Avery Thomas D. , Hanssen Eric , Fox Emma , Robinson Tony V. , Valente Peter , Taylor Dennis K. , Tilley Leann
Published: October 2007

Artermisinin and its derivatives are now the mainstays of antimalarial treatment; however, their mechanism of action is only poorly understood. We report on the synthesis of a novel series of epoxy-endoperoxides that can be prepared in high yields from simple starting materials. Endoperoxides that are disubstituted with alkyl or benzyl side chains show efficient inhibition of the growth of both chloroquine-sensitive and -resistant strains of
Plasmodium falciparum
. A
trans
-epoxide with respect to the peroxide linkage increases the activity compared to that of its
cis
-epoxy counterpart or the parent endoperoxide. The novel endoperoxides do not show a strong interaction with artemisinin. We have compared the mechanism of action of the novel endoperoxides with that of artemisinin. Electron microscopy reveals that the novel endoperoxides cause the early accumulation of endocytic vesicles, while artemisinin causes the disruption of the digestive vacuole membrane. At longer incubation times artemisinin causes extensive loss of organellar structures, while the novel endoperoxides cause myelin body formation as well as the accumulation of endocytic vesicles. An early event following endoperoxide treatment is the redistribution of the pH-sensitive probe LysoSensor Blue from the digestive vacuole to punctate structures. By contrast, neither artemisinin nor the novel endoperoxides caused alterations in the morphology of the endoplasmic reticulum nor showed antagonistic antimalarial activity when they were used with thapsigargin. Analysis of rhodamine 123 uptake by
P. falciparum
suggests that disruption of the mitochondrial membrane potential occurs as a downstream effect rather than as an initiator of parasite killing. The data suggest that the digestive vacuole is an important initial site of endoperoxide antimalarial activity.
Comparative In Vitro Pharmacodynamics of Caspofungin, Micafungin, and Anidulafungin against Germinated and Nongerminated
Aspergillus
Conidia
Authors: Antachopoulos Charalampos , Meletiadis Joseph , Sein Tin , Roilides Emmanuel , Walsh Thomas J.
Published: October 2007

The concentration-dependent effects of echinocandins on the metabolic activity of
Aspergillus
spp. were comparatively studied by using nongerminated and germinated conidia. The susceptibilities of 11
Aspergillus fumigatus
, 8
A. terreus
and 8
A. flavus
isolates to caspofungin, micafungin, and anidulafungin were studied by a CLSI (formerly NCCLS) M38-A broth microdilution-based method. After 48 h of incubation the minimum effective concentration (MEC) was defined microscopically. Metabolic activity was assessed by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2
H
-tetrazolium-5-carboxanilide assay and modeled by using the sigmoid (
E
max
) or “bell-shaped” model. The median MEC values of caspofungin (0.5 to 1 μg/ml), micafungin (0.06 to 0.12 μg/ml), and anidulafungin (0.03 μg/ml) against nongerminated conidia increased by 0 to 1, 1 to 2, and 2 to 3 twofold dilutions, respectively (depending on the species), over those against germinated conidia. A similar shift to the right was demonstrated for the corresponding curves of metabolic activity. There was a significant correlation between the degrees of maximal metabolic inhibition caused by different echinocandins at both the species level (greater inhibition for
A. flavus
) and the strain level (
r
= 0.84 to 0.93;
P
< 0.0001). Paradoxical increases in metabolism in the presence of higher concentrations of caspofungin, micafungin, and anidulafungin were detected in 6, 2, and 5 of the
A. fumigatus
isolates, respectively; 5, 1, and 2 of the
A. terreus
isolates, respectively; and 1, 0, and 0 of the
A. flavus
isolates, respectively. Based on the model, 50% of the maximal paradoxical increase was detected with 4.2, 11.1, and 10.8 μg/ml of caspofungin, micafungin, and anidulafungin, respectively. All echinocandins therefore exerted comparable levels of maximal metabolic inhibition against
Aspergillus
spp. at concentrations that were differentially increased for germinated versus nongerminated conidia. The paradoxical increase in metabolism occurred more frequently and at lower concentrations with caspofungin than with micafungin and anidulafungin.
Phenotypic Characterization of Resistant Val36Variants of Hepatitis C Virus NS3-4A Serine Protease
Authors: Zhou Yi , Bartels Doug J. , Hanzelka Brian L. , Müh Ute , Wei Yunyi , Chu Hui-May , Tigges Ann M. , Brennan Debra L. , Rao B. Govinda , Swenson Lora , Kwong Ann D. , Lin Chao
Published: October 2007

In patients chronically infected with hepatitis C virus (HCV) strains of genotype 1, rapid and dramatic antiviral activity has been observed with telaprevir (VX-950), a highly selective and potent inhibitor of the HCV NS3-4A serine protease. HCV variants with substitutions in the NS3 protease domain were observed in some patients during telaprevir dosing. In this study, purified protease domain proteins and reconstituted HCV subgenomic replicons were used for phenotypic characterization of many of these substitutions. V36A/M or T54A substitutions conferred less than eightfold resistance to telaprevir. Variants with double substitutions at Val36plus Thr54had ∼20-fold resistance to telaprevir, and variants with double substitutions at Val36plus Arg155or Ala156had >40-fold resistance to telaprevir. An X-ray structure of the HCV strain H protease domain containing the V36M substitution in a cocomplex with an NS4A cofactor peptide was solved at a 2.4-Å resolution. Except for the side chain of Met36, the V36M variant structure is identical to that of the wild-type apoenzyme. The in vitro replication capacity of most variants was significantly lower than that of the wild-type replicon in cells, which is consistent with the impaired in vivo fitness estimated from telaprevir-dosed patients. Finally, the sensitivity of these replicon variants to alpha interferon or ribavirin remained unchanged compared to that of the wild-type.
Time of Incubation for Antifungal Susceptibility Testing of
Aspergillus fumigatus
: Can MIC Values Be Obtained at 24 Hours?
Authors: Rodriguez-Tudela Juan Luis , Alcazar-Fuoli Laura , Alastruey-Izquierdo Ana , Monzon Araceli , Mellado Emilia , Cuenca-Estrella Manuel
Published: October 2007

A collection of
Aspergillus fumigatus
isolates was used to check if MICs can be read at 24 h. At 24 h, the geometric mean MIC of itraconazole for resistant isolates was determined to be 5.11 mg/liter, but the MIC was read as 16 mg/liter at 48 h. At 24 h, MICs for 51.5% of resistant strains were determined to be ≤2 mg/liter. MICs must be obtained at 48 h.
In Vivo Validation of the Mutant Selection Window Hypothesis with Moxifloxacin in a Murine Model of Tuberculosis
Authors: Almeida Deepak , Nuermberger Eric , Tyagi Sandeep , Bishai William R. , Grosset Jacques
Published: October 2007

Combination therapy is the most effective strategy to prevent emergence of resistance during tuberculosis (TB) treatment. Another strategy, albeit theoretical, is to limit the time that drug concentrations fall in the “mutant selection window” (MSW) between the MIC and the mutant prevention concentration (MPC). Drug concentrations above the MPC prevent selective amplification of resistant mutants in vitro even with a single drug exposure. The MSW concept has been validated using fluoroquinolones against
Mycobacterium tuberculosis
in vitro but not in vivo. Using a mouse model in which serum moxifloxacin (MXF) concentrations were maintained above the MPC, we tested whether this strategy prevents selection of MXF-resistant mutants. Beginning 2 weeks after aerosol infection with
M. tuberculosis
, when the mean lung log
10
CFU count was 7.9 ± 0.2, mice received either no treatment or MXF in the diet at 0.25% to approximate the conventional human dose or 1.5% to maintain serum concentrations above the MPC (8 μg/ml). After 56 days of treatment, lung CFU counts were 3.5 ± 0.8 and 0.9 ± 0.6 in 0.25% and 1.5% of the MXF-treated mice, respectively. In mice given 0.25% MXF, MXF-resistant mutants were selected by day 28 and detected in 16% (3/19) of mice tested on day 56. No selection of MXF-resistant mutants was detected in mice given 1.5% MXF. We conclude that maintaining serum concentrations of MXF above the MPC prevents selection of MXF-resistant mutants. Although this target cannot be achieved clinically with MXF, it might be possible with new fluoroquinolones with more potent activity and/or improved pharmacokinetics.
First Occurrence of an IMP Metallo-β-Lactamase in
Aeromonas caviae
: IMP-19 in an Isolate from France
Authors: Neuwirth Catherine , Siebor Eliane , Robin Frederic , Bonnet Richard
Published: October 2007

We describe the first IMP metallo-β-lactamase in
Aeromonas caviae
: IMP-19, which differed from IMP-2 by a single amino acid change (Arg to Ala at position 38).
bla
IMP-19
was found within a class 1 integron located on a 35-kb plasmid. This is also the first description of an IMP producer in France.
Cytotoxicity in Macrophages Infected with Rough
Brucella
Mutants Is Type IV Secretion System Dependent
Authors: Pei Jianwu , Wu Qingmin , Kahl-McDonagh Melissa , Ficht Thomas A.
Published: October 2007

Smooth
Brucella
spp. inhibit macrophage apoptosis, whereas rough
Brucella
mutants induce macrophage oncotic and necrotic cell death. However, the mechanisms and genes responsible for
Brucella
cytotoxicity have not been identified. In the current study, a random mutagenesis approach was used to create a mutant bank consisting of 11,354 mutants by mariner transposon mutagenesis using
Brucella melitensis
rough mutant 16MΔ
manBA
as the parental strain. Subsequent screening identified 56 mutants (0.49% of the mutant bank) that failed to cause macrophage cell death (release of 10% or less of the lactate dehydrogenase). The absence of cytotoxicity during infection with these mutants was independent of demonstrable defects in in vitro bacterial growth or uptake and survival in macrophages. Interrupted genes in 51 mutants were identified by DNA sequence analysis, and the mutations included interruptions in
virB
encoding the type IV secretion system (T4SS) (
n
= 36) and in
vjbR
encoding a LuxR-like regulatory element previously shown to be required for
virB
expression (
n
= 3), as well as additional mutations (
n
= 12), one of which also has predicted roles in
virB
expression. These results suggest that the T4SS is associated with
Brucella
cytotoxicity in macrophages. To verify this, deletion mutants were constructed in
B. melitensis
16M by removing genes encoding phosphomannomutase/phosphomannoisomerase (Δ
manBA
) and the T4SS (Δ
virB
). As predicted, deletion of
virB
from 16MΔ
manBA
and 16M resulted in a complete loss of cytotoxicity in rough strains, as well as the low level cytotoxicity observed with smooth strains at extreme multiplicities of infection (>1,000). Taken together, these results demonstrate that
Brucella
cytotoxicity in macrophages is T4SS dependent.
Functional Role of the PE Domain and Immunogenicity of the
Mycobacterium tuberculosis
Triacylglycerol Hydrolase LipY
Authors: Mishra Kanhu C. , de Chastellier Chantal , Narayana Yeddula , Bifani Pablo , Brown Alistair K. , Besra Gurdyal S. , Katoch Vishwa M. , Joshi Beenu , Balaji Kithiganahalli N. , Kremer Laurent
Published: October 2007

PE and PPE proteins appear to be important for virulence and immunopathogenicity in mycobacteria, yet the functions of the PE/PPE domains remain an enigma. To decipher the role of these domains, we have characterized the triacylglycerol (TAG) hydrolase LipY from
Mycobacterium tuberculosis
, which is the only known PE protein expressing an enzymatic activity. The overproduction of LipY in mycobacteria resulted in a significant reduction in the pool of TAGs, consistent with the lipase activity of this enzyme. Unexpectedly, this reduction was more pronounced in mycobacteria overexpressing LipY lacking the PE domain [LipY(ΔPE)], suggesting that the PE domain participates in the modulation of LipY activity. Interestingly,
Mycobacterium marinum
contains a protein homologous to LipY, termed LipY
mar
, in which the PE domain is substituted by a PPE domain. As for LipY, overexpression of LipY
mar
in
Mycobacterium smegmatis
significantly reduced the TAG pool, and this was further pronounced when the PPE domain of LipY
mar
was removed. Fractionation studies and Western blot analysis demonstrated that both LipY and LipY(ΔPE) were mainly present in the cell wall, indicating that the PE domain was not required for translocation to this site. Furthermore, electron microscopy immunolabeling of LipY(ΔPE) clearly showed a cell surface localization, thereby suggesting that the lipase may interact with the host immune system. Accordingly, a strong humoral response against LipY and LipY(ΔPE) was observed in tuberculosis patients. Together, our results suggest for the first time that both PE and PPE domains can share similar functional roles and that LipY represents a novel immunodominant antigen.
L-Ficolin/Mannose-Binding Lectin-Associated Serine Protease Complexes Bind to Group B Streptococci Primarily throughN-Acetylneuraminic Acid of Capsular Polysaccharide and Activate the Complement Pathway
Authors: Aoyagi Youko , Adderson Elisabeth E. , Rubens Craig E. , Bohnsack John F. , Min Jin G. , Matsushita Misao , Fujita Teizo , Okuwaki Yoshiyuki , Takahashi Shinji
Published: October 2007

Group B streptococci (GBS) are the most common cause of neonatal sepsis and meningitis. Most infants who are colonized with GBS at birth do not develop invasive disease, although many of these uninfected infants lack protective levels of capsular polysaccharide (CPS)-specific antibody. The lectin pathway of complement is a potential mechanism for initiating opsonization of GBS with CPS-specific antibody-deficient serum. In this study, we determined whether mannose-binding lectin (MBL)/MBL-associated serine protease (MASP) complexes and L-ficolin/MASP complexes bind to different strains of GBS to activate the lectin pathway, and we identified the molecules recognized by lectins on the GBS surface. We found that MBL did not bind to any GBS examined, whereas L-ficolin bound to GBS cells of many serotypes. L-ficolin binding to GBS cells correlated with the CPS content in serotypes Ib, III (restriction digestion pattern types III-2 and III-3), and V but not with the group B-specific polysaccharide (GBPS) content or with the lipoteichoic acid (LTA) content. L-ficolin bound to purified CPS and GBPS in a concentration-dependent manner but not to purified LTA. All strains to which L-ficolin/MASP complexes bound consumed C4. WhenN-acetylneuraminic acid (NeuNAc) was selectively removed from GBS cells by treatment with neuraminidase, the reduction in L-ficolin binding was correlated with the amount of NeuNAc removed. Additionally, L-ficolin was able to bind to wild-type strains but was able to bind only weakly to unencapsulated mutants and a mutant strain in which the CPS lacks NeuNAc. We concluded that L-ficolin/MASP complexes bind to GBS primarily through an interaction with NeuNAc of CPS.
Identification of NovelListeria monocytogenesSecreted Virulence Factors following Mutational Activation of the Central Virulence Regulator, PrfA
Authors: Port Gary C. , Freitag Nancy E.
Published: October 2007

Upon bacterial entry into the cytosol of infected mammalian host cells, the central virulence regulator PrfA ofListeria monocytogenesbecomes activated and induces the expression of numerous factors which contribute to bacterial pathogenesis. The mechanism or signal by which PrfA becomes activated during the course of infection has not yet been determined; however, several amino acid substitutions within PrfA (known as PrfA* mutations) that appear to lock the protein into a constitutively activated state have been identified. In this study, the PrfA activation statuses of severalL. monocytogenesmutant strains were subjected to direct isogenic comparison and the mutant with the highest activity, theprfA(L140F) mutant, was identified. TheprfA(L140F) strain was subsequently used as a tool to identify gene products secreted as a result of PrfA activation. By use of two-dimensional gel electrophoresis followed by liquid chromatography-electrospray ionization-tandem mass spectroscopy analyses, 15 proteins were identified as up-regulated in theprfA(L140F) secretome, while the secretion of two proteins was found to be reduced. Although some of the proteins identified were known to be subject to direct regulation by PrfA, the majority have not previously been associated with PrfA regulation and their expression or secretion may be influenced indirectly by a PrfA-dependent regulatory pathway. Plasmid insertion inactivation of the genes encoding four novel secreted products indicated that three of the four have significant roles inL. monocytogenesvirulence. The use of mutationally activatedprfAalleles therefore provides a useful approach towards identifying gene products that contribute toL. monocytogenespathogenesis.
Use of Peptide-Major Histocompatibility Complex Tetramer Technology To Study Interactions betweenStaphylococcus aureusProteins and Human Cells
Authors: Massey Ruth C. , Scriba Thomas J. , Brown Eric L. , Phillips Rodney E. , Sewell Andrew K.
Published: October 2007

In this study, we report the use of peptide-major histocompatibility complex tetramer technology to study the interactions that occur betweenStaphylococcus aureusproteins and human leukocytes. We demonstrated that this technology can be used to study the activity of superantigens such as toxic shock syndrome toxin 1 and also found that despite similarities to known proteins (i.e., major histocompatibility complex [MHC] class II molecules and superantigens), theS. aureusEap protein does not block MHC-T-cell receptor interactions and is not a superantigen. Instead, it has nonspecific cross-linking activity that is dependent upon having at least two of its six 110-amino-acid repeats.
A Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Homologue Plays a Pivotal Role in Nontypeable
Haemophilus influenzae
Colonization of the Chinchilla Nasopharynx via the Outer Membrane Protein P5-Homologous Adhesin
Authors: Bookwalter James E. , Jurcisek Joseph A. , Gray-Owen Scott D. , Fernandez Soledad , McGillivary Glen , Bakaletz Lauren O.
Published: October 2007

In vitro studies suggest an important role for CEACAM1 (
c
arcino
e
mbryonic
a
ntigen-related
c
ell
a
dhesion
m
olecule 1) in infection by multiple gram-negative bacteria. However, in vivo evidence supporting this role is lacking, largely because the bacterial adhesins involved in this host-microbe association do not bind to murine-derived CEACAM1. One of several adhesins expressed by nontypeable
Haemophilus influenzae
(NTHI), the outer membrane protein P5-homologous adhesin (or P5), is essential for colonization of the chinchilla nasopharynx and infection of the middle ear. Here we reveal that NTHI P5 binds to the chinchilla homologue of CEACAM1 and that rabbit anti-human carcinoembryonic antigen blocks NTHI colonization of the chinchilla nasopharynx, providing the first demonstration of a role for CEACAM receptor binding by any bacterial pathogen in vivo.
Highly Polymorphic Family of Glycosylphosphatidylinositol-Anchored Surface Antigens with Evidence of Developmental Regulation in
Toxoplasma gondii
Authors: Pollard Angela M. , Onatolu Krystal N. , Hiller Luisa , Haldar Kasturi , Knoll Laura J.
Published: October 2007

The life cycle of the apicomplexan parasite
Toxoplasma gondii
requires that an infectious cyst develop and be maintained throughout the life of the host. The molecules displayed on the parasite surface are important in controlling the immune response to the parasite.
T. gondii
has a superfamily of glycosylphosphatidylinositol (GPI)-anchored surface antigens, termed the surface antigen (SAG) and SAG-related surface antigens, that are developmentally regulated during infection. Using a clustering algorithm, we identified a new family of 31 surface proteins that are predicted to be GPI anchored but are unrelated to the SAG proteins, and thus we named these proteins SAG-unrelated surface antigens (SUSA). Analysis of the single nucleotide polymorphism density showed that the members of this family are the most polymorphic genes within the
T. gondii
genome. Immunofluorescence of SUSA1 and SUSA2, two members of the family, revealed that they are found on the parasite surface. We confirmed that SUSA1 and SUSA2 are GPI anchored by phospholipase cleavage. Analysis of expressed sequence tags (ESTs) revealed that SUSA1 had 22 of 23 ESTs from chronic infection. Analysis of mRNA and protein confirmed that SUSA1 is highly expressed in the chronic form of the parasite. Sera from mice with chronic
T. gondii
infection reacted to SUSA1, indicating that SUSA1 interacts with the host immune system during infection. This group of proteins likely represents a new family of polymorphic GPI-anchored surface antigens that are recognized by the host's immune system and whose expression is regulated during infection.
Malaria Vaccine-Related Benefits of a Single Protein ComprisingPlasmodium falciparumApical Membrane Antigen 1 Domains I and II Fused to a Modified Form of the 19-Kilodalton C-Terminal Fragment of Merozoite Surface Protein 1
Authors: Faber Bart W. , Remarque Edmond J. , Morgan William D. , Kocken Clemens H. M. , Holder Anthony A. , Thomas Alan W.
Published: October 2007

We show that the smallest module ofPlasmodium falciparumAMA1 (PfAMA1) that can be expressed in the yeastPichia pastoriswhile retaining the capacity to induce high levels of parasite-inhibitory antibodies comprises domains I and II. Based on this, two fusion proteins, differing in the order of the modules, were developed. Each comprised one module of PfAMA1 (FVO strain, amino acids [aa] 97 to 442) (module A) and one module of PfMSP119(Wellcome strain, aa 1526 to 1621) (module Mm) in which a cystine had been removed to improve immune responses. Both fusion proteins retained the antigenicity of each component and yielded over 30 mg/liter purified protein under fed-batch fermentation. Rabbits immunized with purified fusion proteins MmA and AMm had up to eightfold-higher immune responses to MSP119than those of rabbits immunized with module Mm alone or Mm mixed with module A. In terms of parasite growth inhibition, fusion did not diminish the induction of inhibitory antibodies compared with immunization with module A alone or module A mixed with module Mm, and fusion outperformed antibodies induced by immunization with module M or Mm alone. When tested against parasites expressing AMA1 heterologous to the immunogen, antibodies to the fusion proteins inhibited parasite growth to a greater extent than did antibodies either to the individual antigens or to the mixture. These results suggest that compared with the individual modules delivered separately or as a mixture, fusion proteins containing these two modules offer the potential for significant vaccine-related advantages in terms of ease of production, immunogenicity, and functionality.
What is a significant difference between sequential laboratory results?Calf muscle pain can indicate localised vasculitis
Authors: Smellie W S A
Published: October 2007

The uncertainty of a numerical laboratory result can be masked by the fact that the laboratory reports an absolute number, whereas users have limited knowledge of the confidence interval of the result. Interpretation of laboratory tests is in reality therefore an inexact science, a balance between clinical context and the likely relevance of a laboratory result.

This review considers the factors which contribute to result variability and examines the implications for interpreting differences between sequential laboratory results. It offers suggestions to deal with a problem which has not yet been much addressed in routine practice. The examples used are restricted to the discipline of clinical biochemistry, although the issues and principles apply to numerical (and indeed qualitative) results in other disciplines.

Laboratories could provide more guidance on the likelihood of a result being significant to assist users. There is a need for discussion about how this is best done, and compatible with electronic result delivery. Options for providing this information are considered.
Inflammatory myofibroblastic tumours: where are we now?
Authors: Gleason B C , Hornick J L
Published: October 2007

Inflammatory pseudotumour is a generic term applied to a variety of neoplastic and non-neoplastic entities that share a common histological appearance, namely a cytologically bland spindle cell proliferation with a prominent, usually chronic inflammatory infiltrate. Over the last two decades, inflammatory myofibroblastic tumour (IMT) has emerged from within the broad category of inflammatory pseudotumour, with distinctive clinical, pathological and molecular features. IMT shows a predilection for the visceral soft tissues of children and adolescents and has a tendency for local recurrence, but only a small risk of distant metastasis. Characteristic histological patterns include the fasciitis-like, compact spindle cell and hypocellular fibrous patterns, which are often seen in combination within the same tumour. Chromosomal translocations leading to activation of the ALK tyrosine kinase can be detected in approximately 50% of IMTs, particularly those arising in young patients. This review will examine the clinical, pathological, and molecular genetic features of IMT and discuss an approach to diagnosis and differential diagnosis.
Mozart's movements and behaviour: a case of Tourette's syndrome?
Authors: Ashoori A , Jankovic J
Published: October 2007

In this review, we intend to explore the often asked question: “Did Mozart have Tourette's syndrome?” Although there are numerous reports attributing Mozart's peculiar personality and behaviour to a spectrum of neurobehavioural disorders such as Tourette's syndrome, autistic disorder, Asperger's syndrome, attention deficit hyperactivity disorder, obsessive–compulsive disorder and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection, the evidence for any of these disorders is lacking. Whether Mozart's behaviour was nothing more than a reflection of his unique personality or a more complex neurological disorder, aggravated later in life by enormous demands by his father and society, his behaviour has been the subject of many biographies. It will also remain unknown to what extent his accomplishments and failures were shaped by his childhood experiences, pressured lifestyle, and his innate genius and extraordinary talent. Lessons from his life may have important implications for other gifted individuals and savants whose special attributes may lead them to succeed or, on the other hand, suppress their emotional growth and make them more vulnerable to stress and failure.
Effects of multidisciplinary inpatient rehabilitation for chronic back or neck pain: a register-linkage study of sickness absences and analgesic purchases in an occupational cohort
Authors: Suoyrjö H , Hinkka K , Oksanen T , Kivimäki M , Klaukka T , Pentti J , Vahtera J
Published: October 2007

Objective:

To determine the effects of multidisciplinary in-patient rehabilitation for chronic back or neck pain on sickness absences and analgesic purchases.

Design:

A prospective observational study.

Setting:

10 towns in Finland.

Participants:

34 838 local government employees, including 418 participants in rehabilitation for chronic back pain and 195 participants in rehabilitation for chronic neck pain between 1994 and 2002.

Main outcome measures:

The annual rates of short (1–3 days), long (>3 days), and very long (>21 days) sickness absences and the defined daily doses (DDD) of prescribed analgesics.

Results:

The rate of very long (>21 days) sickness absence among the chronic back pain rehabilitees was 3.03-fold (95% CI 2.55 to 3.60) compared to the non-rehabilitees in the year before rehabilitation. This ratio declined to 1.88 (95% CI 1.65 to 2.37) three years after rehabilitation. No further decline in the rate of very long sickness absence was observed in the subsequent years. For chronic neck pain rehabilitees, no evidence of the effectiveness of rehabilitation on sickness absence was found. In relation to consumption of analgesics, the mean rate of DDDs declined among the back and neck pain rehabilitees after rehabilitation compared to the non-rehabilitees.

Conclusions:

Multidisciplinary in-patient rehabilitation for chronic back pain may decrease the risk of very long sickness absence for three years. In relation to rehabilitation for chronic neck pain, no changes in sickness absences were found.
MAJORITY-VOTE ON DIRECTED SMALL-WORLD NETWORKS
Authors: LUZ EDINA M. S. , LIMA F. W. S.
Published: October 2007

On directed small-world networks the majority-vote model with noise is now studied through Monte Carlo simulations. In this model, the order-disorder phase transition of the order parameter is well defined. We calculate the value of the critical noise parameter qc for several values of rewiring probability p of the directed small-world network. The critical exponents β/ν, γ/ν and 1/ν were calculated for several values of p.
TIME-DELAY ROBUSTNESS OF CONSENSUS PROBLEMS IN REGULAR AND COMPLEX NETWORKS
Authors: WU ZHENGPING , GUAN ZHI-HONG
Published: October 2007

Recent advances in complex network research have stimulated increasing interests in understanding the relationship between the topology and dynamics of complex networks. Based on the theory of complex networks and computer simulation, we analyze the robustness to time-delay in linear consensus problem with different network topologies, such as global coupled network, star network, nearest-neighbor coupled network, small-world network, and scale-free network. It is found that global coupled network, star network, and scale-free network are vulnerable to time-delay, while nearest-neighbor coupled network and small-world network are robust to time-delay. And it is found that the maximum node degree of the network is a good predictor for time-delay robustness. And it is found that the robustness to time-delay can be improved significantly by a decoupling process to a small part of edges in scale-free network.
STRUCTURALLY DYNAMIC SPIN MARKET NETWORKS
Authors: HORVÁTH DENIS , KUSCSIK ZOLTÁN
Published: October 2007

The agent-based model of stock price dynamics on a directed evolving complex network is suggested and studied by direct simulation. The stationary regime is maintained as a result of the balance between the extremal dynamics, adaptivity of strategic variables and reconnection rules. The inherent structure of node agent "brain" is modeled by a recursive neural network with local and global inputs and feedback connections. For specific parametric combination the complex network displays small-world phenomenon combined with scale-free behavior. The identification of a local leader (network hub, agent whose strategies are frequently adapted by its neighbors) is carried out by repeated random walk process through network. The simulations show empirically relevant dynamics of price returns and volatility clustering. The additional emerging aspects of stylized market statistics are Zipfian distributions of fitness.
GAUGED SYSTEM MIMICKING THE GÜRSEY MODEL
Authors: HORTAÇSU M. , LÜTFÜOḠLU B. C. , TAŞKIN F.
Published: October 2007

We comment on the changes in the constrained model studied earlier when constituent massless vector fields are introduced. The new model acts like a gauge-Higgs–Yukawa system, although its origin is different.
PROGRESS IN THE STUDY OF THE γ-DECAY OF THE GIANT DIPOLE RESONANCE IN HOT NUCLEI
Authors: BRACCO A. , CAMERA F. , WIELAND O. , ORMAND W. E.
Published: October 2007

The problem of the damping of the Giant Dipole Resonance (GDR) at finite temperature at T>2 MeV is discussed here. The experimental results are based on fusion evaporation reactions. The most recent results on the mass region A = 132 ( Ce isotopes) obtained in exclusive measurements are compared with the existing results on the A = 110–120 region ( Sn isotopes). The comparison with the theoretical predictions based on thermal shape fluctuations is also discussed. The GDR width is found to increase also in the region T>2 MeV and this is accounted by the combined effect of the increase of the compound nucleus width (smaller lifetime) and to the increase of the average deformation of the nucleus.
SHORT-BASELINE ACTIVE-STERILE NEUTRINO OSCILLATIONS?
Authors: GIUNTI CARLO , LAVEDER MARCO
Published: October 2007

We suggest the possibility that the anomalies observed in the LSND experiment and the Gallium radioactive source experiments may be due to neutrino oscillations generated by a large squared-mass difference of about 20–30 eV2. We consider the simplest 3+1 four-neutrino scheme that can accommodate also the observed solar and atmospheric neutrino oscillations. We show that, in this framework, the disappearance of [Formula: see text] and [Formula: see text] in short-baseline neutrino oscillation experiments is mainly due to active-sterile transitions. The implications of the first MiniBooNE results, appeared after the completion of this paper, are discussed in an addendum.
Nanotechnology and Cancer
Authors: Heath James R. , Davis Mark E.
Published: October 2007

The biological picture of cancer is rapidly advancing from models built from phenomenological descriptions to network models derived from systems biology, which can capture the evolving pathophysiology of the disease at the molecular level. The translation of this (still academic) picture into a clinically relevant framework can be enabling for the war on cancer, but it is a scientific and technological challenge. In this review, we discuss emerging in vitro diagnostic technologies and therapeutic approaches that are being developed to handle this challenge. Our discussion of in vitro diagnostics is guided by the theme of making large numbers of measurements accurately, sensitively, and at very low cost. We discuss diagnostic approaches based on microfluidics and nanotechnology. We then review the current state of the art of nanoparticle-based therapeutics that have reached the clinic. The goal of the presentation is to identify nanotherapeutic strategies that are designed to increase efficacy while simultaneously minimizing the toxic side effects commonly associated with cancer chemotherapies.
Medical Management of Influenza Infection
Authors: Moscona Anne
Published: October 2007

Antiviral drugs are important in the management of seasonal influenza and critical to pandemic planning. Although several other classes of anti-influenza compounds exist, the neuraminidase (NA) inhibitors are currently the only option in most clinical settings. These drugs, zanamivir and oseltamivir, prevent the release of newly replicated influenza virions from infected cells. They are highly effective when used for treatment of seasonal influenza early in the course of infection, or for prevention when given soon after exposure. Treatment strategies for avian influenza infections in humans are still provisional owing to inadequate clinical data. As predicted by molecular studies, resistance to the NA inhibitors is now emerging, although at a level less significant than adamantane resistance. NA inhibitor resistance is a cause for concern if indeed some mutant strains of avian influenza are transmissible and pathogenic. In the near term, appropriate use of the available NA inhibitors will be of major benefit in lessening morbidity and mortality due to influenza infection. Priorities include developing appropriate formulations and guidelines for use of these drugs in children and people infected with avian influenza, study of the mechanisms and clinical significance of drug resistance, and identification of new antiviral therapies that target different points in the viral life cycle in order to limit the effect of emerging drug resistance.
Cancer Epigenetics: Modifications, Screening, and Therapy
Authors: Einav Nili Gal-Yam , Saito Yoshimasa , Egger Gerda , Jones Peter A.
Published: October 2007

Deregulation of gene expression is a hallmark of cancer. Although genetic lesions have been the focus of cancer research for many years, it has become increasingly recognized that aberrant epigenetic modifications also play major roles in the tumorigenic process. These modifications are imposed on chromatin, do not change the nucleotide sequence of DNA, and are manifested by specific patterns of gene expression that are heritable through many cell divisions. We review these modifications in normal and cancer cells and the evolving approaches used to study them. Additionally, we outline advances in their potential use for cancer diagnostics and targeted epigenetic therapy.
Genetic Susceptibility to Type 2 Diabetes and Implications for Antidiabetic Therapy
Authors: Moore Allan F. , Florez Jose C.
Published: October 2007

Despite major advances in our knowledge of glycemic pathophysiology and the availability of multiple therapeutic options to confront type 2 diabetes, unraveling the complex link between genetic risk and environmental factors in this burgeoning epidemic has proven difficult. Linkage approaches have clarified the etiology of monogenic diabetic syndromes and congenital lipodystrophies, and candidate gene association studies have identified a number of common variants implicated in type 2 diabetes. This year we have witnessed the advent of genome-wide association scanning: As many as nine genetic loci have now been reproducibly associated with type 2 diabetes in five genome-wide scans. Of particular interest are preliminary explorations of the connections between genetic risk and pharmacologic response. An improved understanding of genetic mechanisms should allow us to test whether behavioral or pharmacologic therapies can be tailored and thus the tremendous disease burden inflicted by type 2 diabetes alleviated.