bluuebunny/crossref_metadata_2025 huggingface dataset:
The
Campylobacter jejuni
Thiol Peroxidases Tpx and Bcp Both Contribute to Aerotolerance and Peroxide-Mediated Stress Resistance but Have Distinct Substrate Specificities
Authors: Atack John M. , Harvey Philippa , Jones Michael A. , Kelly David J.
Published: May 2008

The microaerophilic food-borne pathogen
Campylobacter jejuni
experiences variable oxygen concentrations during its life cycle, especially during transitions between the external environment and the avian or mammalian gut. Single knockout mutations in either one of two related thiol peroxidase genes,
tpx
and
bcp
, resulted in normal microaerobic growth (10% [vol/vol] oxygen) but poorer growth than that of the wild type under high-aeration conditions (21% [vol/vol] oxygen). However, a
tpx/bcp
double mutant had a severe microaerobic growth defect and did not grow at high aeration in shake flasks. Although the single mutant strains were no more sensitive than the wild-type strains in disc diffusion assays with hydrogen peroxide, organic peroxides, superoxide, or nitrosative stress agents, in all cases the double mutant was hypersensitive. Quantitative cell viability and cellular lipid peroxidation assays indicated some increased sensitivity of the single
tpx
and
bcp
mutants to peroxide stress. Protein carbonylation studies revealed that the
tpx/bcp
double mutant had a higher degree of oxygen- and peroxide-induced oxidative protein damage than did either of the single mutants. An analysis of the peroxidase activity of the purified recombinant enzymes showed that, surprisingly, Tpx reduced only hydrogen peroxide as substrate, whereas Bcp also reduced organic peroxides. Immunoblotting of wild-type cell extracts with Tpx- or Bcp-specific antibodies showed increased abundance of both proteins under high aeration compared to that under microaerobic growth conditions. Taken together, the results suggest that Tpx and Bcp are partially redundant antioxidant enzymes that play an important role in protection of
C. jejuni
against oxygen-induced oxidative stress.
A Plasmid-Borne
Shewanella algae
Gene,
qnrA3
, and Its Possible Transfer In Vivo between
Kluyvera ascorbata
and
Klebsiella pneumoniae
Authors: Lascols Christine , Podglajen Isabelle , Verdet Charlotte , Gautier Valérie , Gutmann Laurent , Soussy Claude-James , Collatz Ekkehard , Cambau Emmanuelle
Published: May 2008

The plasmid-borne quinolone resistance gene
qnrA1
is prevalent in multidrug-resistant
Enterobacteriaceae
. A chromosomally encoded homologue in
Shewanella algae
,
qnrA3
, has been described. We isolated two
qnrA3
-positive strains, one of
Klebsiella pneumoniae
(He96) and one of
Kluyvera ascorbata
(Kas96), from the feces of an immunocompromised outpatient. The
qnrA3
allele was identical to that of
S. algae
except for 5 nucleotides and differed from
qnrA1
by 29 nucleotides affecting three amino acids. The analysis of the
qnrA3
genetic environment showed that
qnrA3
was inserted downstream from an IS
CR1
element at a recombination crossover site described for other resistance genes, including
qnrA1
, and immediately upstream from IS
26
, a situation not described before. IS
26
preceded an incomplete class 1 integron which contained, among other genes,
aac
(
6
′)-
Ib-cr
, another transferable quinolone resistance gene, and the β-lactamase gene
bla
OXA-1/30
. The 10-kb fragment encompassing
qnrA3
was compared to previously described
qnrA1
-containing plasmids and multidrug-resistant plasmids; it shares identical sequences with pC15a, pHSH2, pQR1, pQKp311H, and pSAL-1 but with rearrangements, deletions, and mutations. Conjugal transfer of
qnrA3
was highly efficient (10
−2
) from
K. pneumoniae
He96 or
K. ascorbata
Kas96 to
Escherichia coli
J53 but less so (10
−5
) from either donor to a clinical strain of
Enterobacter cloacae
. This first description of a plasmid-borne copy and of the in vitro transfer of
qnrA3
is taken to illustrate its likely in vivo transfer from
S. algae
to the
Enterobacteriaceae
.
Opposite Effects of Mn2+and Zn2+on PsaR-Mediated Expression of the Virulence GenespcpA,prtA, andpsaBCAofStreptococcus pneumoniae
Authors: Kloosterman Tomas G. , Witwicki Robert M. , van der Kooi-Pol Magdalena M. , Bijlsma Jetta J. E. , Kuipers Oscar P.
Published: May 2008

Homeostasis of Zn2+and Mn2+is important for the physiology and virulence of the human pathogenStreptococcus pneumoniae. Here, transcriptome analysis was used to determine the response ofS. pneumoniaeD39 to a high concentration of Zn2+. Interestingly, virulence genes encoding the choline binding protein PcpA, the extracellular serine protease PrtA, and the Mn2+uptake system PsaBC(A) were strongly upregulated in the presence of Zn2+. Using random mutagenesis, a previously described Mn2+-responsive transcriptional repressor, PsaR, was found to mediate the observed Zn2+-dependent derepression. In addition, PsaR is also responsible for the Mn2+-dependent repression of these genes. Subsequently, we investigated how these opposite effects are mediated by the same regulator. In vitro binding of purified PsaR to theprtA,pcpA, andpsaBpromoters was stimulated by Mn2+, whereas Zn2+destroyed the interaction of PsaR with its target promoters. Mutational analysis of thepcpApromoter demonstrated the presence of a PsaR operator that mediates the transcriptional effects. In conclusion, PsaR is responsible for the counteracting effects of Mn2+and Zn2+on the expression of several virulence genes inS. pneumoniae, suggesting that the ratio of these metal ions exerts an important influence on pneumococcal pathogenesis.
Modulation of Hexa-Acyl Pyrophosphate Lipid A Population underEscherichia coliPhosphate (Pho) Regulon Activation
Authors: Lamarche Martin G. , Kim Sang-Hyun , Crépin Sébastien , Mourez Michael , Bertrand Nicolas , Bishop Russell E. , Dubreuil J. Daniel , Harel Josée
Published: May 2008

Environmental phosphate is an important signal for microorganism gene regulation, and it has recently been shown to trigger some key bacterial virulence mechanisms. In many bacteria, the Pho regulon is the major circuit involved in adaptation to phosphate limitation. The Pho regulon is controlled jointly by the two-component regulatory system PhoR/PhoB and by the phosphate-specific transport (Pst) system, which both belong to the Pho regulon. We showed that apstmutation results in virulence attenuation in extraintestinal pathogenicEscherichia coli(ExPEC) strains. Our results indicate that the bacterial cell surface of thepstmutants is altered. In this study, we show thatpstmutants of ExPEC strains display an increased sensitivity to different cationic antimicrobial peptides and vancomycin. Remarkably, the hexa-acylated 1-pyrophosphate form of lipid A is significantly less abundant inpstmutants. Among differentially expressed genes in thepstmutant,lpxTcoding for an enzyme that transfers a phosphoryl group to lipid A, forming the 1-diphosphate species, was found to be downregulated. Our results strongly suggest that the Pho regulon is involved in lipid A modifications, which could contribute to bacterial surface perturbations. Since the Pho regulon and the Pst system are conserved in many bacteria, such a lipid A modification mechanism could be widely distributed among gram-negative bacterial species.
The Role of Prophage for Genome Diversification within a Clonal Lineage ofLactobacillus johnsonii: Characterization of the Defective Prophage LJ771
Authors: Denou Emmanuel , Pridmore Raymond David , Ventura Marco , Pittet Anne-Cécile , Zwahlen Marie-Camille , Berger Bernard , Barretto Caroline , Panoff Jean-Michel , Brüssow Harald
Published: May 2008

Two independent isolates of the gut commensalLactobacillus johnsoniiwere sequenced. These isolates belonged to the same clonal lineage and differed mainly by a 40.8-kb prophage, LJ771, belonging to the Sfi11 phage lineage. LJ771 shares close DNA sequence identity withLactobacillus gasseriprophages. LJ771 coexists as an integrated prophage and excised circular phage DNA, but phage DNA packaged into extracellular phage particles was not detected. Between the phage lysin gene andattRa likelymazE(“antitoxin”)/pemK(“toxin”) gene cassette was detected in LJ771 but not in theL. gasseriprophages. ExpressedpemKcould be cloned inEscherichia colionly together with themazEgene. LJ771 was shown to be highly stable and could be cured only by coexpression ofmazEfrom a plasmid. The prophage was integrated into the methionine sulfoxide reductase gene (msrA) and complemented the 5′ end of this gene, creating a protein with a slightly altered N-terminal sequence. The twoL. johnsoniistrains had identical in vitro growth and in vivo gut persistence phenotypes. Also, in an isogenic background, the presence of the prophage resulted in no growth disadvantage.
Pathology of sentinel lymph nodes for melanoma
Authors: Cook M G , Di Palma S
Published: May 2008

As a concept sentinel lymph node biopsy seems attractive in that it attempts to identify the first lymph node, rather than the nearest node, draining a particular anatomic area where a tumour has arisen. Pathological assessment can then indicate whether metastases are present and the procedure is either a strong prognostic indicator or possibly therapeutic in itself. These comments apply to any tumour type, but with melanoma the pathological procedure is more problematic and any benefits above prognosis and staging are not universally accepted. The procedure does give accurate staging without the extra morbidity of regional node dissection and many patients gain psychological support from the information gained.
Impact of standardised reporting in adrenocortical carcinoma: a single centre clinicopathological review
Authors: Advani A , Vaikkakara S , Gill M S , Arun C S , Pearce S H , Ball S G , James R A , Lennard T W J , Bliss R D , Quinton R , Johnson S J
Published: May 2008

Aims:

Structured multicentre efforts are needed if the prognosis of adrenocortical carcinoma (ACC) is to be improved. Data collection may be enhanced through standardised histopathological reporting using criteria such as the recently published Royal College of Pathologists’ (UK) minimum dataset (MDS). This study aimed to perform a clinicopathological review of the adult patients treated at the Royal Victoria Infirmary, Newcastle upon Tyne, in the 10 years preceding the MDS.

Methods:

Case records were examined for all patients diagnosed with ACC between 1996 and 2006. Pathology was reviewed and compared with the Royal College of Pathologists’ MDS along with the original reports. A systematic evaluation of Ki-67 immunolabelling was also performed.

Results:

Eleven patients with ACC were diagnosed and treated. Histopathological reporting according to the MDS identified more features of malignancy than in the original reports (8.5±1.2 versus 5.1±0.8, p<0.02). The median number of microscopic criteria of malignancy was 7 (range 5–10), with ⩾5 features occurring in all cases. The most commonly observed features of malignancy were diffuse architecture, <25% clear cells, confluent necrosis, abnormal mitoses and mitotic count ⩾6 per 50 high-power fields. Capsular invasion and ⩾8 MDS criteria of malignancy were associated with a worse outcome (each p<0.01). Median Ki-67 index was 19.0% (range 3.7–44.1%) and was not apparently related to survival.

Conclusions:

Standardised criteria for histopathological reporting of ACC will improve the accuracy of data for cancer registration and may also assist in individual patient stratification. An elevated Ki-67 index is a feature of ACC, although it does not appear to predict individual patient survival.
Genetic variation in the diameter–height relationship in Scots pine (Pinus sylvestris)
Authors: Kroon Johan , Andersson Bengt , Mullin Tim J.
Published: June 2008

Genetic parameters were estimated for the diameter–height (d-h) relationship and three other tree stem-form characteristics (total height, breast height diameter, and total tree volume) for data from 10 diallel progeny trials of Scots pine ( Pinus sylvestris L.), at about 30 years of age in Sweden. Linear mixed models were fit to the data, where adjustments for intertree competition and microsite heterogeneity were made by means of covariates in a nearest-neighbour analysis. The d-h relationship was analyzed with a covariate (tree height) adjusted model of diameter. Average estimates of the additive coefficient of variation and narrow-sense heritability for the d-h relationship were 7.4% and 0.22, respectively. Estimates of dominance were comparatively small (average dominance: phenotypic variance ratio of 0.04). The results indicate that there is scope to modify the d-h relationship by selection and breeding. Additive genetic correlations between the d-h relationship and height were negative, with a mean of –0.62. Selection for height would thus result in stems that are more slender than average, suggesting that tall trees allocate relatively more resources to height growth than to diameter growth. Selection based on height alone will negatively affect volume gain.
REBOUND BEHAVIOUR OF SPHERES DURING ELASTIC-PLASTIC OBLIQUE IMPACTS
Authors: WU CHUAN-YU , THORNTON COLIN , LI LONG-YUAN
Published: June 2008

In this paper, the influence of plastic deformation on the rebound behaviour of spheres during oblique impacts with a substrate at various impact angles is analysed using Finite Element Methods (FEM). Both oblique impacts of the elastic spheres with an elastic-plastic substrate and those of an elastic-plastic sphere with an elastic substrate are considered. For each impact case, impact angles ranging from 0° to 85° are specified by either keeping the impact speed constant, i.e, changing impact angle will vary both the normal impact velocities and tangential velocities, or keeping the normal impact velocity constant, i.e., only the tangential velocities are changed for different impact angles. It has been found that, during oblique impacts, the plastic deformation not only dissipates the initial impact kinetic energy but also leads to permanent deformation of the impacting bodies that significantly affect the rebound behaviour of the spheres, especially at relatively high impact angles. Consequently, the rebound behaviour of spheres during oblique impacts depends upon which of contacting bodies (the sphere or the substrate) deforms plastically and different rebound behaviours were observed between the impacts of an elastic sphere with an elastic-plastic substrate and those of an elastic-plastic spheres with an elastic substrate.
IMPACT TENSILE PROPERTIES IN AL-MG-SI BASE ALLOYS FOR AUTOMOTIVE USE
Authors: YAMADA HIROYUKI , HORIKAWA KEITARO , KOBAYASHI HIDETOSHI
Published: June 2008

Effect of alloy composition on impact tensile properties [Formula: see text] in Al - Mg - Si base alloys was investigated by means of the split Hopkinson pressure bar method. As a result of the impact test, it was proved that the nominal stress for 5% plastic strain was not changed by changing the strain rate regardless of the alloy composition. In the impact test, the elongation was decreased with increasing the amount of excess Si , while that was increased by the addition of Cu . Fractography revealed that the reduction of the elongation in the excess Si alloy was caused by the change of the fracture mode from the mixture of transgranular and intergranular fracture to the intergranular fracture.
DYNAMIC DEFORMATION AND FRACTURE BEHAVIOR OF ULTRA-FINE-GRAINED DUAL PHASE STEELS FABRICATED BY EQUAL CHANNEL ANGULAR PRESSING
Authors: KIM YANG GON , HWANG BYOUNGCHUL , LEE SUNGHAK , SHIN DONG HYUK
Published: June 2008

In this study, dynamic deformation and fracture behavior of ultra-fine-grained dual phase steels fabricated by equal channel angular pressing (ECAP) was compared with that of conventionally annealed ultra-fine-grained steels. In the ECAPed conventionally annealed specimen, pearlites were decomposed, and the ferrite grain size increased up to 0.5 μm. The intercritically annealed specimen consisted of dual phases of equiaxed ferrites and blocky martensites (volume fraction; 35%, size; 1 μm). The dynamic torsional test results indicated that maximum shear stress of the annealed specimens was lower than that of the as-pressed specimen, but fracture shear strain was higher. These results suggested that annealing or promoting dual phase microstructures of the ECAPed specimens could be a good way to increase the fracture resistance under dynamic loading, as it reduced or prevented the formation of adiabatic shear bands or voids. In particular, the ECAPed ultra-fine-grained dual phase steel can be more reliably used under dynamic conditions since it overcomes the shortcomings of reduced strain hardenability, ductility, and dynamic properties.
EXPLOSIVE INDENTATION STUDY OF B4C-TiAlx COMPOSITES FABRICATED BY THE DIPPING EXOTHERMIC REACTION PROCESS
Authors: KIM JONG HO , ANSARI HARIS MASOOD , KIM HANEUL , KIM DO KYUNG , CHANG SOON NAM
Published: June 2008

The aim of this study is to fabricate a high volume fraction B 4 C -reinforced intermetallic matrix composite by the dipping exothermic reaction process and investigate the shock impact damage response of composites by explosive indentation experiment. It has been shown that the final microstructure of the dipping exothermic reaction process-fabricated composite can be tailored by treatment of the constituent powders and post heat treatment. The hardness and impact damage resistance of the fabricated composites were evaluated.
ON THE PROTECTION CAPABILITY OF THE FLYING PLATE AGAINST TO LONG-ROD PENETRATORS
Authors: ROLC STANISLAV , BUCHAR JAROSLAV , AKSTEIN ZBYNEK
Published: June 2008

The interaction of the flying plate with the Long-rod penetrator has been studied both experimentally and numerically using the LS DYNA 3D finite element code. The influence of the plate velocity and plate material on this interaction has been investigated in details. Numerical results show that there was a relatively large damage of the projectiles. The extent of this damage well agree with our experimental foundings. The numerical simulation of the damaged projectiles with some targets has been also performed
DESENSITIZATION OF HETEROGENEOUS HIGH EXPLOSIVES UNDER INITIATION THROUGH HIGH MODULUS ELASTIC ELEMENTS
Authors: BALAGANSKY I. A. , GLUMOV A. I. , SAMSONOV A. V. , MATROSOV A. D. , STADNICHENKO I. A.
Published: June 2008

We have experimentally investigated the influence of fluoroplastic, copper, and silicon carbide inert inserts on the process of detonation transmission through water. Active and passive HE charges were molded from high explosive (HE) Comp. B. The diameter and height of HE cartridges were 40 and 40 mm, respectively. On the rear end of the passive HE charge a steel witness plate was mounted, which detected presence or absence of detonation. Inert inserts were shaped as 20 mm × 20 mm square prisms of varying lengths, and were contained between active and passive HE charges without any clearance on the way of initiating shock wave with partial overlap of HE cross sections. We demonstrate that preloading a passive HE charge with a shock wave transmitted through a copper or a ceramic insert causes considerable desensitization of the Comp. B. Other conditions being the same, the crash distance of detonation transmission for copper was equal to 74%, and for silicon carbide – to 60% of the distance for fluoroplastic. This desensitization phenomenon may be used for development of protective shells for HE. While performing experiments with 20 mm ceramic inserts we have observed unknown cumulation phenomenon, which manifested itself as a hole in identification steel specimen with depth of about 10 mm.
NONLINEAR IMPACT DYNAMIC ANALYSIS AND COMPARISON WITH EXPERIMENTAL DATA FOR THE SKID GEAR
Authors: KIM DONG-HYUN , KIM YU-SUNG
Published: June 2008

In this study, nonlinear crash analyses have been conducted for the skid landing gear of helicopter. The realistic configuration of skid landing gear system is considered. Detailed three-dimensional finite element model with variable thickness and material nonlinearity is constructed for required impact design conditions. Advanced computational approach is used to conduct nonlinear transient impact dynamic analyses for different collision models. Characteristics of impact dynamic responses due to the ground crash are practically investigated in detail. It is also shown that the exact consideration of friction effect is very important to accurately predict the crash behavior of the skid type landing gear system. Finally, two typical landing conditions are analyzed and correlated with drop test results.
EFFECT OF TENSILE SPEED ON THE FAILURE LOAD OF A SPOT WELD UNDER COMBINED LOADING CONDITIONS
Authors: SONG JUNG-HAN , HUH HOON , LIM JI-HO , PARK SUNG-HO
Published: June 2008

This paper is concerned with the evaluation of the dynamic failure load of the spot weld under combined axial and shear loading conditions. The testing fixture are designed to impose the combined axial and shear load on the spot weld. Using the proposed testing fixtures and specimens, quasi-static and dynamic failure tests of the spot weld are conducted with seven different combined loading conditions. The failure load and failure behavior of the spot weld are investigated with different loading conditions. Dynamic effects on the failure load of the spot weld, which is critical for structural crashworthiness, are also examined based on the experimental data. In order to evaluate the effect of the strain rate on the failure contour of the spot weld under combined axial and shear loads, the failure loads measured from the experiment are decomposed into the two components along the axial and shear directions. Experimental results indicate that the failure contour is expanded with increasing strain rates according to the rate sensitivity of the ultimate stress for welded material.
NON-LINEAR DYNAMIC MODEL OF ROCK BURST BASED ON EVOLUTIONARY NEURAL NETWORK
Authors: GAO WEI
Published: June 2008

The theory studies have showed that, rock burst is a kind of dynamic phenomenon of rock mass in mining, and is a kind of dynamic disaster from mining. The time series of magnitude is a very important exterior behavior of rock burst. The previous studies show that, to model this complicated non-linear time series, the neural network is a very good method. To overcome the shortcomings of traditional neural network, a new kind of evolutionary neural network based on immunized evolutionary programming proposed by author is proposed here. At last, the proposed evolutionary neural network model is verified by a real magnitude series of rock burst. And the result is compared with other method, such as grey system method. The results have showed that, evolutionary neural network model not only has high approaching precision, but also has high predicting precision, and is a good method to construct the non-linear model of rock burst. And this method can be used in a large number of engineering examples.
SPH SIMULATIONS OF HYPERVELOCITY IMPACT OF AL SPHERES ON MULTI-PLATE STRUCTURES
Authors: ZHANG QING-MING , LONG REN-RONG , LIU ZHI-FANG , HUANG FENG-LEI
Published: June 2008

A series of numerical simulations using SPH (Smoothed Particle Hydrodynamics) method were carried out to study the hypervelocity impact of aluminum spheres on multi-plate structures. Both the morphologic characteristics of debris clouds and the damage of intermediate plates were investigated. The possible damage effects of debris cloud threat on back wall were also described qualitatively. Results showed that, comparing with single plate or double-plate structures, the multi-plate structure has higher resistance capacity to the impact from hypervelocity particles. Hence the multi-plate shield structure has a better shielding performance with a reduction in weight of the structure. It provides a promising alternative to the traditional shield in the spacecraft shield design.
MOLECULAR-DYNAMICS STUDY OF ENERGETIC CLUSTER IMPACT ON SILICON
Authors: KIM DONG-EARN , OH SOO-IK , RHIM SUNG-HAN
Published: June 2008

To investigate the dynamic deformation behavior of silicon induced by the energetic cluster impact at an atomistic level, cluster impact simulations are carried out using molecular dynamics. Clusters are emitted to the silicon (100) surface with external kinetic energies varying from 1 to 10 eV/atom. While a structural phase transformation is identified as the dominant deformation mechanism in silicon due to the increased pressure caused by the energetic cluster impact, its deformation pathway tends to change according to the kinetic energy of cluster. In the lower energy region, the initial diamond structure of silicon is first transformed into the beta-tin structure during the impact process, and then this high-pressure structure is transformed into an amorphous structure after the impact process is completed. This result is very similar to those computed in the quasi-static deformation. On the other hand, amorphous structures are directly transformed from initial diamond structure in the higher energy region. Additionally, the propagation of the shock-wave is accompanied in this deformation.
A METHOD OF 3D FREEFORM FABRICATION USING A CURING OF PHOTOPOLYMER RESIN
Authors: KIM JUNG SU , KIM DONG SOO , LEE MIN CHEOL , LEE WON HEE
Published: June 2008

Recently, Study of 3D freeform fabrication method was working in the various applications. For example, in the powder base, it's laminated using a binding method or laser sintering method. However, the demerits of these methods are to take long time for post process and not enough to keep high strength of manufacturing part. The binding method needs the post process and the time for post process needs longer time than a manufacturing time. The sintering method has huge size of system with module of the laser. In this paper, we introduce a method of 3D freeform fabrication using a curing of photopolymer resin. A photopolymer curing method has simply fabrication process and high strength of manufacturing part. So, we are configuration the system with compact type module for the office environment and experiment a UV curing test with photopolymer resin in the 3D freeform fabrication method. In the conclusion, we fabricate the 3D freeform part, which is suitable to the office environment using a photopolymer curing method.
THE RUINOUS-THIN RELATIONSHIP FOR THREE ELEMENT SETS
Authors: DONNELLY JOHN
Published: June 2008

Richard Thompson's group F is nonamenable if and only if there exists a ruinous set. It is known that no three element set is ruinous. Here we explicitly construct a family of thin sets for any three element set each of whose trees has three carets. We then show where this construction fails when each of the trees has four or more carets.
FLOW REPRESENTATION OF THE BOSE–HUBBARD HAMILTONIAN: GENERAL CASE
Authors: FUJII KAZUYUKI , SUZUKI TATSUO
Published: June 2008

In this paper the explicit flow representation to the Bose–Hubbard Hamiltonian is given in the general case. This representation may be useful in creating cat states for the system of atoms trapped in the optical ring.
MOYAL STAR PRODUCT OF μ-HOLOMORPHIC j-DIFFERENTIALS
Authors: KACHKACHI M.
Published: June 2008

It was shown in [1], only for scalar conformal fields, that the Moyal–Weyl star product can introduce the quantum effect as the phase factor to the ordinary product.

In this paper we show that, even on the same complex structure, the Moyal–Weyl star product of two j-differentials (conformal fields of weights (j, 0)) does not vanish but it generates the quantum effect at the first order of its perturbative series.

More generally, we get the explicit expression of the Moyal–Weyl star product of j-differentials defined on any complex structure of a bi-dimensional Riemann surface Σ. We show that the star product of two j-differentials is not a j-differential and does not preserve the conformal covariance character.

This can shed some light on the Moyal–Weyl deformation quantization procedure connection's with the deformation of complex structures on a Riemann surface. Hence, the situation might relate the star products to the Moduli and Teichmüller spaces of Riemann surfaces.
FLUCTONS
Authors: CARTAS-FUENTEVILLA R. , SOLANO-ALTAMIRANO J. M.
Published: June 2008

From the perspective of topological field theory we explore the physics beyond instantons. We propose the fluctons as nonperturbative topological fluctuations of vacuum, from which the self-dual domain of instantons is attained as a particular case. Invoking the Atiyah–Singer index theorem, we determine the dimension of the corresponding flucton moduli space, which gives the number of degrees of freedom of the fluctons. An important consequence of these results is that the topological phases of vacuum in non-Abelian gauge theories are not necessarily associated with self-dual fields, but only with smooth fields. Fluctons in different scenarios are considered, the basic aspects of the quantum mechanical amplitude for fluctons are discussed. A possible application of fluctons in the N = 4 Topologically Twisted Supersymmetric Yang–Mills Theory is explored and the case of gravity is discussed briefly.
Mechanical discoordination rather than dyssynchrony predicts reverse remodeling upon cardiac resynchronization
Authors: Kirn Borut , Jansen Annemieke , Bracke Frank , van Gelder Berry , Arts Theo , Prinzen Frits W.
Published: May 2008

By current guidelines a considerable part of the patients selected for cardiac resynchronization therapy (CRT) do not respond to the therapy. We hypothesized that mechanical discoordination [opposite strain within the left ventricular (LV) wall] predicts reversal of LV remodeling upon CRT better than mechanical dyssynchrony. MRI tagging images were acquired in CRT candidates ( n = 19) and in healthy control subjects ( n = 9). Circumferential strain (εcc) was determined in 160 regions. From εcc signals we derived 1) an index of mechanical discoordination [internal stretch fraction (ISF), defined as the ratio of stretch to shortening during ejection] and 2) indexes of mechanical dyssynchrony: the 10–90% width of time to onset of shortening, time to peak shortening, and end-systolic strain. LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), and ejection fraction (LVEF) were determined before and after 3 mo of CRT. Responders were defined as those patients in whom LVESV decreased by >15%. In responders ( n = 10), CRT increased LVEF and decreased LVEDV and LVESV (11 ± 6%, 21 ± 16%, and 30 ± 16%, respectively) significantly more ( P < 0.05) than in nonresponders (1 ± 6%, 3 ± 4%, and 5 ± 10%, respectively). Among mechanical indexes, only ISF was different between responders and nonresponders (0.53 ± 0.25 vs. 0.31 ± 0.16; P < 0.05). In patients with ISF >0.4 ( n = 10), LVESV decreased by 31 ± 18% vs. 5 ± 11% in patients with ISF <0.4 ( P < 0.05). We conclude that mechanical discoordination, as estimated from ISF, is a better predictor of reverse remodeling after CRT than differences in time to onset and time to peak shortening. Therefore, discoordination rather than dyssynchrony appears to reflect the reserve contractile capacity that can be recruited by CRT.
Changes in regional myocardial volume during the cardiac cycle: implications for transmural blood flow and cardiac structure
Authors: Ashikaga Hiroshi , Coppola Benjamin A. , Yamazaki Katrina G. , Villarreal Francisco J. , Omens Jeffrey H. , Covell James W.
Published: May 2008

Although previous studies report a reduction in myocardial volume during systole, myocardial volume changes during the cardiac cycle have not been quantitatively analyzed with high spatiotemporal resolution. We studied the time course of myocardial volume in the anterior mid-left ventricular (LV) wall of normal canine heart in vivo ( n = 14) during atrial or LV pacing using transmurally implanted markers and biplane cineradiography (8 ms/frame). During atrial pacing, there was a significant transmural gradient in maximum volume decrease (4.1, 6.8, and 10.3% at subepi, midwall, and subendo layer, respectively, P = 0.002). The rate of myocardial volume increase during diastole was 4.7 ± 5.8, 6.8 ± 6.1, and 10.8 ± 7.7 ml·min−1·g−1, respectively, which is substantially larger than the average myocardial blood flow in the literature measured by the microsphere method (0.7–1.3 ml·min−1·g−1). In the early activated region during LV pacing, myocardial volume began to decrease before the LV pressure upstroke. We conclude that the volume change is greater than would be estimated from the known average transmural blood flow. This implies the existence of blood-filled spaces within the myocardium, which could communicate with the ventricular lumen. Our data in the early activated region also suggest that myocardial volume change is caused not by the intramyocardial tissue pressure but by direct impingement of the contracting myocytes on the microvasculature.
Proteasome inhibition attenuates coxsackievirus-induced myocardial damage in mice
Authors: Gao Guang , Zhang Jingchun , Si Xiaoning , Wong Jerry , Cheung Caroline , McManus Bruce , Luo Honglin
Published: May 2008

Coxsackievirus B3 (CVB3) is one of the most prevalent pathogens of viral myocarditis, which may persist chronically and progress to dilated cardiomyopathy. We previously demonstrated a critical role of the ubiquitin-proteasome system (UPS) in the regulation of coxsackievirus replication in mouse cardiomyocytes. In the present study, we extend our interest to an in vivo animal model to examine the regulation and role of the UPS in CVB3-induced murine myocarditis. Male myocarditis-susceptible A/J mice at age 4–5 wk were randomized to four groups: sham infection + vehicle ( n = 10), sham infection + proteasome inhibitor ( n = 10), virus + vehicle ( n = 20), and virus + proteasome inhibitor ( n = 20). Proteasome inhibitor was administered subcutaneously once a day for 3 days. Mice were killed on day 9 after infection, and infected hearts were harvested for Western blot analysis, plaque assay, immunostaining, and histological examination. We showed that CVB3 infection led to an accumulation of ubiquitin conjugates at 9 days after infection. Protein levels of ubiquitin-activating enzyme E1A/E1B, ubiquitin-conjugating enzyme UBCH7, as well as deubiquitinating enzyme UCHL1 were markedly increased in CVB3-infected mice compared with sham infection. However, there was no significant alteration in proteasome activities at 9 days after infection. Immunohistochemical staining revealed that increased expression of E1A/E1B was mainly localized to virus-damaged cells. Finally, we showed that application of a proteasome inhibitor significantly reduced CVB3-induced myocardial damage. This observation reveals a novel mechanism of coxsackieviral pathogenesis, and suggests that the UPS may be an attractive therapeutic target against coxsackievirus-induced myocarditis.
Three-dimensional localization and quantification of PAF-induced gap formation in intact venular microvessels
Authors: Jiang Yanyan , Wen Ke , Zhou Xueping , Schwegler-Berry Diane , Castranova Vince , He Pingnian
Published: May 2008

Combining single-vessel perfusion technique with confocal microscopy, this study presents a new approach that allows three-dimensional visualization and quantification of endothelial gaps under experimental conditions identical to those used to measure permeability coefficients, endothelial calcium concentration, and nitric oxide production in individually perfused intact microvessels. This approach provides an efficient means for defining the transport pathways and cellular mechanisms of increased microvascular permeability during inflammation. Platelet-activating factor (PAF) was used to increase the permeability of individually perfused rat mesenteric venules. Fluorescent microspheres (FMs, 100 nm) were used as leakage markers, and confocal images were acquired at successive focal planes through the perfused microvessel. Perfusion of FMs under control conditions produced a thin, uniform layer of FMs in the vessel lumen, but in PAF-stimulated microvessels significant amounts of FMs accumulated at endothelial junctions. Reconstructed confocal images three-dimensionally delineated the temporal and spatial development of endothelial gaps in PAF-stimulated microvessels. The FM accumulation, quantified as the total fluorescence intensity per square micrometer of vessel wall, was 8.4 ± 1.8 times the control value within 10 min of PAF perfusion and declined to 5.0 ± 0.6 and 1.4 ± 0.2 times the control value when FMs were applied 30 and 60 min after PAF perfusion. The changes in the magnitude of FM accumulation closely correlated with the time course of PAF-induced increases in hydraulic conductivity ( Lp), indicating that the opening and closing of endothelial gaps contributed to the transient increase in Lpin PAF-stimulated microvessels. Electron microscopic evaluations confirmed PAF-induced gap formation and FM accumulation at endothelial clefts.
Endothelin type A receptor antagonist normalizes blood pressure in rats exposed to eucapnic intermittent hypoxia
Authors: Allahdadi Kyan J. , Cherng Tom W. , Pai Hemanth , Silva Ana Q. , Walker Benjimen R. , Nelin Leif D. , Kanagy Nancy L.
Published: May 2008

We have reported that eucapnic intermittent hypoxia (E-IH) causes systemic hypertension, elevates plasma endothelin 1 (ET-1) levels, and augments vascular reactivity to ET-1 and that a nonspecific ET-1 receptor antagonist acutely lowers blood pressure in E-IH-exposed rats. However, the effect of chronic ET-1 receptor inhibition has not been evaluated, and the ET receptor subtype mediating the vascular effects has not been established. We hypothesized that E-IH causes systemic hypertension through the increased ET-1 activation of vascular ET type A (ETA) receptors. We found that mean arterial pressure (MAP) increased after 14 days of 7 h/day E-IH exposure (109 ± 2 to 137 ± 4 mmHg; P < 0.005) but did not change in sham-exposed rats. The ETAreceptor antagonist BQ-123 (10 to 1,000 nmol/kg iv) acutely decreased MAP dose dependently in conscious E-IH but not sham rats, and continuous infusion of BQ-123 (100 nmol·kg−1·day−1sc for 14 days) prevented E-IH-induced increases in MAP. ET-1-induced constriction was augmented in small mesenteric arteries from rats exposed 14 days to E-IH compared with those from sham rats. Constriction was blocked by the ETAreceptor antagonist BQ-123 (10 μM) but not by the ET type B (ETB) receptor antagonist BQ-788 (100 μM). ETAreceptor mRNA content was greater in renal medulla and coronary arteries from E-IH rats. ETBreceptor mRNA was not different in any tissues examined, whereas ET-1 mRNA was increased in the heart and in the renal medulla. Thus augmented ET-1-dependent vasoconstriction via vascular ETAreceptors appears to elevate blood pressure in E-IH-exposed rats.
Chemical conjugation of ΔF508-CFTR corrector deoxyspergualin to transporter human serum albumin enhances its ability to rescue Cl−channel functions
Authors: Norez Caroline , Pasetto Matteo , Dechecchi Maria Cristina , Barison Erika , Anselmi Cristina , Tamanini Anna , Quiri Federica , Cattel Luigi , Rizzotti Paolo , Dosio Franco , Cabrini Giulio , Colombatti Marco
Published: May 2008

The most common mutation of the cystic fibrosis (CF) gene, the deletion of Phe508, encodes a protein (ΔF508-CFTR) that fails to fold properly, thus mutated ΔF508-cystic fibrosis transmembrane conductance regulator (CFTR) is recognized and degraded via the ubiquitin-proteasome endoplasmic reticulum-associated degradation pathway. Chemical and pharmacological chaperones and ligand-induced transport open options for designing specific drugs to control protein (mis)folding or transport. A class of compounds that has been proposed as having potential utility in ΔF508-CFTR is that which targets the molecular chaperone and proteasome systems. In this study, we have selected deoxyspergualin (DSG) as a reference molecule for this class of compounds and for ease of cross-linking to human serum albumin (HSA) as a protein transporter. Chemical cross-linking of DSG to HSA via a disulfide-based cross-linker and its administration to cells carrying ΔF508-CFTR resulted in a greater enhancement of ΔF508-CFTR function than when free DSG was used. Function of the selenium-dependent oxidoreductase system was required to allow intracellular activation of HSA-DSG conjugates. The principle that carrier proteins can deliver pharmacological chaperones to cells leading to correction of defective CFTR functions is therefore proven and warrants further investigations.
Role of brain-derived neurotrophic factor in hyperoxia-induced enhancement of contractility and impairment of relaxation in lung parenchyma
Authors: Sopi Ramadan B. , Martin Richard J. , Haxhiu Musa A. , Dreshaj Ismail A. , Yao Qin , Jafri Anjum , Zaidi Syed I. A.
Published: May 2008

Prolonged hyperoxic exposure contributes to neonatal lung injury, and airway hyperreactivity is characterized by enhanced contraction and impaired relaxation of airway smooth muscle. Our previous data demonstrate that hyperoxia in rat pups upregulates expression of brain-derived neurotrophic factor (BDNF) mRNA and protein, disrupts NO-cGMP signaling, and impairs cAMP production in airway smooth muscle. We hypothesized that BDNF-tyrosine kinase B (TrkB) signaling plays a functional role in airway hyperreactivity via upregulation of cholinergic mechanisms in hyperoxia-exposed lungs. Five-day-old rat pups were exposed to ≥95% oxygen or room air for 7 days and administered daily tyrosine kinase inhibitor K-252a (50 μg·kg−1·day−1 ip) to block BDNF-TrkB signaling or vehicle. Lungs were removed for HPLC measurement of ACh or for in vitro force measurement of lung parenchymal strips. ACh content doubled in hyperoxic compared with room air-exposed lungs. K-252a treatment of hyperoxic pups restored ACh content to room air levels. Hyperoxia increased contraction and impaired relaxation of lung strips in response to incremental electrical field stimulation. K-252a administration to hyperoxic pups reversed this increase in contraction and decrease in relaxation. K-252a or TrkB-Fc was used to block the effect of exogenous BDNF in vitro. Both K-252a and TrkB-Fc blocked the effects of exogenous BDNF. Hyperoxia decreased cAMP and cGMP levels in lung strips, and blockade of BDNF-TrkB signaling restored cAMP but not cGMP to control levels. Therefore, hyperoxia-induced increase in activity of BDNF-TrkB receptor signaling appears to play a critical role in enhancing cholinergically mediated contractile responses of lung parenchyma.
Retention of human bone marrow-derived cells in murine lungs following bleomycin-induced lung injury
Authors: Liebler Janice M. , Lutzko Carolyn , Banfalvi Agnes , Senadheera Dinithi , Aghamohammadi Neema , Crandall Edward D. , Borok Zea
Published: May 2008

We studied the capacity of adult human bone marrow-derived cells (BMDC) to incorporate into distal lung of immunodeficient mice following lung injury. Immunodeficient NOD/SCID and NOD/SCID/β2microglobulin (β2M)nullmice were administered bleomycin (bleo) or saline intranasally. One, 2, 3 and 4 days after bleo or saline, human BMDC labeled with CellTracker Green CMFDA (5-chloromethylfluorescein diacetate) were infused intravenously. Retention of CMFDA+cells was maximal when delivered 4 days after bleo treatment. Seven days after bleo, <0.005% of enzymatically dispersed lung cells from NOD/SCID mice were CMFDA+, which increased 10- to 100-fold in NOD/SCID/β2Mnullmice. Preincubation of BMDC with Diprotin A, a reversible inhibitor of CD26 peptidase activity that enhances the stromal-derived factor-1 (SDF-1/CXCL12)/CXCR4 axis, resulted in a 30% increase in the percentage of CMFDA+cells retained in the lung. These data indicate that human BMDC can be identified in lungs of mice following injury, albeit at low levels, and this may be modestly enhanced by manipulation of the SDF-1/CXCR4 axis. Given the overall low number of human cells detected, methods to increase homing and retention of adult BMDC, and consideration of other stem cell populations, will likely be required to facilitate engraftment in the treatment of lung injury.
Effect of severe calorie restriction on the lung in two strains of mice
Authors: Bishai John M. , Mitzner Wayne
Published: May 2008

There is a body of literature in animal models that has suggested the development of emphysema following severe calorie restriction. This has led to the notion of “nutritional emphysema” that might have relevance in COPD patients. There have been few studies, however, that have looked closely at both the mechanics and lung structure in the same animals. In the present work, we examined lung mechanics and histological changes in two strains of mice that have substantial differences in alveolar size, the C57BL/6 and C3H/HeJ strains. We quantified the dynamic elastance and resistance at 2.5 Hz, the quasistatic pressure volume curve, and the alveolar chord lengths in lungs inflated to a lung capacity at 25–30 cmH2O. We found that after 2 or 3 wk of calorie restriction to 1/3 their normal diet, the lungs became stiffer with increased resistance. In addition, the lung capacity was also decreased. These mechanical changes were reversed after 2 wk on a normal ad libitum diet. Histology of the postmortem fixed lungs showed no changes in the mean alveolar chord lengths with calorie restriction. Although the baseline mechanics and alveolar size were quantitatively different in the two strains, both strains showed similar qualitative changes during the starvation and refeeding periods. Thus, in two strains of mice with genetically determined differences in alveolar size, neither the mechanics nor the histology show any evidence of emphysema-like changes with this severe caloric insult.
Critical role of Cdc42 in mediating endothelial barrier protection in vivo
Authors: Ramchandran Ramaswamy , Mehta Dolly , Vogel Stephen M. , Mirza Muhammad K. , Kouklis Panos , Malik Asrar B.
Published: May 2008

Activation of the Rho GTPase Cdc42 has been shown in endothelial cell monolayers to prevent disassembly of interendothelial junctions and the increase in endothelial permeability. Here, we addressed the in vivo role of Cdc42 activity in mediating endothelial barrier protection in lungs by generating mice expressing the dominant active mutant V12Cdc42 protein in vascular endothelial cells targeted via the VE-cadherin promoter. These mice developed normally and exhibited constitutively active GTP-bound Cdc42. The increase in lung vascular permeability and gain in tissue water content in response to intraperitoneal lipopolysaccharide challenge (7 mg/kg) were markedly attenuated in the transgenic mice. To address the basis of the protective effect, we observed that expression of V12Cdc42 mutant in endothelial monolayers reduced the decrease in transendothelial electrical resistance, a measure of opening of interendothelial junctions, thus indicating that Cdc42 activity preserved junctional integrity. RhoA activity in V12Cdc42-expressing endothelial monolayers was reduced compared with untransfected cells, suggesting that activated Cdc42 functions by counteracting the canonical RhoA-mediated mechanism of endothelial hyperpermeability. Therefore, Cdc42 activity of microvessel endothelial cells is a critical determinant of junctional barrier restrictiveness and may represent a means of therapeutically modulating increased lung vascular permeability and edema formation.