bluuebunny/crossref_metadata_2025 huggingface dataset:
TACHYON MONOPOLE
Authors: LI XIN-ZHOU , LIU DAO-JUN
Published: September 2005

The property and gravitational field of global monopole of tachyon are investigated in a four-dimensional static space–time. We give an exact solution of the tachyon field in the flat space–time background. Using the linearized approximation of gravity, we get the approximate solution of the metric. We also solve analytically the coupled Einstein and tachyon field equations which is beyond the linearized approximation to determine the gravitational properties of the monopole solution. We find that the metric of tachyon monopole represents an asymptotically AdS space–time with a small effective mass at the origin. We show that this relatively tiny mass is actually negative, as it is in the case of ordinary scalar field.
CONSTRAINTS ON A NEW ALTERNATIVE MODEL TO DARK ENERGY
Authors: GONG YUNGUI , CHEN XI-MING
Published: September 2005

The recent type Ia supernova data suggest that the Universe is accelerating now and had decelerated in recent past. This may provide the evidence that the standard Friedmann equation needs to be modified. We analyze in detail a new model in the context of modified Friedmann equation using the supernova data published by the High-z Supernova Search Team and the Supernova Cosmology Project. The new model explains recent acceleration and past deceleration. Furthermore, the acceleration of the expansion of the Universe is almost zero in the future.
AN ORIGIN FOR THE MAIN PULSATION AND OVERTONES OF SGR1900+14 DURING THE AUGUST 27 (1998) SUPEROUTBURST
Authors: MOSQUERA CUESTA HERMAN J.
Published: September 2005

The crucial observation on the occurrence of subpulses (overtones) in the Power Spectral Density of the August 27 (1998) event from SGR1900+14, as discovered by BeppoSAX,7 has received no consistent explanation in the context of the competing theories to explain the SGRs phenomenology: the magnetar and accretion-driven models. Based on the ultra-relativistic, ultracompact X-ray binary model introduced in the accompanying paper,20 I present here a self-consistent explanation for such an striking feature. I suggest that both the fundamental mode and the overtones observed in SGR1900+14 stem from pulsations of a massive white dwarf (WD). The fundamental mode (and likely some of its harmonics) is excited because of the mutual gravitational interaction with its orbital companion (a NS, envisioned here as point mass object) whenever the binary Keplerian orbital frequency is a multiple integer number (m) of that mode frequency.28 Besides, a large part of the powerful irradiation from the fireball-like explosion occurring on the NS (after partial accretion of disk material) is absorbed in different regions of the star driving the excitation of other multipoles,25,26 i.e., the overtones (fluid modes of higher frequency). Part of this energy is then reemitted into space from the WD surface or atmosphere. This way, the WD lightcurve carries with it the signature of these pulsations inasmuch the way as it happens with the Sun pulsations in Helioseismology. It is shown that our theoretical prediction on the pulsation spectrum agrees quite well with the one found by BeppoSAX,7 a feature confirmed by numerical simulations (Montgomery & Winget 2000).
A WHITE DWARF-NEUTRON STAR RELATIVISTIC BINARY MODEL FOR SOFT GAMMA-RAY REPEATERS
Authors: MOSQUERA CUESTA HERMAN J.
Published: September 2005

A scenario for soft gamma-ray repeaters (SGRs) is introduced in which gravitational radiation reaction (GRR) effects drive the dynamics of an ultrashort orbital period X-ray binary embracing a high-mass donor white dwarf (WD) to a rapidly rotating low magnetized massive neutron star (NS) surrounded by a thick, dense and massive accretion torus. Driven by GRR, over timescales of ΔTrep~ 10 years, the binary separation reduces, the WD overflows its Roche lobe and the mass transfer drives unstable the accretion disk around the NS. As the binary circular orbital period is a multiple integer number (m) of the period of the WD fundamental mode,37the WD is since long pulsating at its fundamental mode; and most of its harmonics, due to the tidal interaction with its NS orbital companion. Hence, when the powerful irradiation glows onto the WD; from the fireball ejected as part of the disk matter slumps onto the NS, it is partially absorbed. This huge energy excites other WD radial (p-mode) pulsations.34,35After each mass-transfer episode the binary separation (and orbital period) is augmented significantly1,5due to the binary's angular momentum redistribution. Thus a new adiabatic inspiral phase driven by GRR reaction starts which brings the binary close again, and the process repeats after a time span ΔTrep. This model allows to explain most of SGRs observational features: their recurrent activity, energetics of giant superoutbursts and quiescent stages, and particularly the intriguing subpulses discovered by BeppoSAX,10which are suggested here to be overtones of the WD radial fundamental mode (see the accompanying paper).31
THE FUTURE OF A Λ-UNIVERSE
Authors: GONZÁLEZ-DÍAZ PEDRO F. , SIGÜENZA CARMEN L.
Published: September 2005

It is argued that the accretion of phantom energy onto a wormhole in a universe with a positive cosmological constant leads also to a gradual increase of the wormhole throat radius, which eventually overtakes the super-accelerated expansion of the universe and becomes infinite at a time in the future before the big rip. Thus, the universe as a whole can time travel toward the past or the future.
RELATIVISTIC HYDRODYNAMICS WITH SOURCES FOR COSMOLOGICAL K-FLUIDS
Authors: DIEZ-TEJEDOR ALBERTO , FEINSTEIN ALEXANDER
Published: September 2005

We consider hydrodynamics with non-conserved number of particles and show that it can be modeled with effective fluid Lagrangians which explicitly depend on the velocity potentials. For such theories, the "shift symmetry" ϕ → ϕ + const leading to the conserved number of fluid particles in conventional hydrodynamics is globally broken and, as a result, the non-conservation of particle number appears as a source term in the continuity equation. The non-conservation of particle number is balanced by the entropy change, with both the entropy and the source term expressed in terms of the fluid velocity potential. Equations of hydrodynamics are derived using a modified version of Schutz's variational principle method. Examples of fluids described by such Lagrangians (tachyon condensate, K-essence) in spatially flat isotropic universe are briefly discussed.
ON INHOMOGENEITY OF A STRING BIT MODEL FOR QUANTUM GRAVITY
Authors: LEE C.-W. H. , MANN R. B.
Published: September 2005

We study quantum gravitational effect on a two-dimensional open universe with one particle by means of a string bit model. We find that matter is necessarily homogeneously distributed if the influence of the particle on the size of the universe is optimized.
GRAVITATION AND DUALITY SYMMETRY
Authors: DE ANDRADE V. C. , BARBOSA A. L. , PEREIRA J. G.
Published: September 2005

By generalizing the Hodge dual operator to the case of soldered bundles, and working in the context of the teleparallel equivalent of general relativity, an analysis of the duality symmetry in gravitation is performed. Although the basic conclusion is that, at least in the general case, gravitation is not dual symmetric, there is a particular theory in which this symmetry shows up. It is a self dual (or anti-self dual) teleparallel gravity in which, due to the fact that it does not contribute to the interaction of fermions with gravitation, the purely tensor part of torsion is assumed to vanish. The ensuing fermionic gravitational interaction is found to be chiral. Since duality is intimately related to renormalizability, this theory may eventually be more amenable to renormalization than teleparallel gravity or general relativity.
STATEFINDER DIAGNOSTIC FOR HOLOGRAPHIC DARK ENERGY MODEL
Authors: ZHANG XIN
Published: September 2005

In this paper, we study the holographic dark energy model proposed by Li from the statefinder viewpoint. We plot the evolutionary trajectories of the model with c = 1 in the statefinder parameter-planes. The statefinder diagrams characterize the properties of the holographic dark energy and show the discrimination between this scenario and other dark energy models. We also perform a statefinder diagnostic to the holographic dark energy model in cases of different c which given by three fits to observational data. The result indicates that from the statefinder viewpoint c plays a significant role in this model and should thus be determined seriously by future high precision experiments.
STRING DUST COSMOLOGICAL MODEL IN HIGHER-DIMENSIONAL SPACE–TIME
Authors: KHADEKAR G. S. , PATKI VRISHALI , RADHA R.
Published: September 2005

We have investigated the bulk viscous fluid string dust cosmological model in the higher dimensional space–time. To obtain a determinate solution, it is assumed that the coefficient of bulk viscosity is a power function of the energy density τ = τcρm(t) and the scalar of expansion is proportional to shear scalar, which leads to a relation between metric potentials A = KRnwhere A and R are functions of time. It is also observed that models appear to be singular at [Formula: see text] and [Formula: see text] in the presence and absence of bulk viscosity and for n = 1, the model represent an isotropic universe. The physical and geometrical aspects of the model are also discussed.
LIMITS ON THE TIME EVOLUTION OF SPACE DIMENSIONS FROM NEWTON'S CONSTANT
Authors: NASSERI FOROUGH
Published: September 2005

Limits are imposed upon the possible rate of change of extra spatial dimensions in a decrumpling model Universe with time variable spatial dimensions (TVSD) by considering the time variation of (1+3)-dimensional Newton's constant. Previous studies on the time variation of (1+3)-dimensional Newton's constant in TVSD theory had not include the effects of the volume of the extra dimensions and the effects of the surface area of the unit sphere in D-space dimensions. Our main result is that the absolute value of the present rate of change of spatial dimensions to be less than about 10-14 yr-1. Our results would appear to provide a prima facie case for ruling the TVSD model out. We show that based on observational bounds on the present variation of Newton's constant, one would have to conclude that the spatial dimension of the Universe when the Universe was "at the Planck scale" to be less than or equal to 3.09. If the dimension of space when the Universe was "at the Planck scale" is constrained to be fractional and very close to 3, then the whole edifice of TVSD model loses credibility.
ON ASTROPHYSICAL BOUNDS OF THE COSMOLOGICAL CONSTANT
Authors: BALAGUERA-ANTOLÍNEZ ANDRÉS , NOWAKOWSKI MAREK , BÖHMER CHRISTIAN G.
Published: September 2005

Astrophysical bounds on the cosmological constant are examined for spherically symmetric bodies. Similar limits emerge from the hydrostatical and gravitational equilibrium and the validity of the Newtonian limit. The methods in use seem to be disjoint from the basic principles, however they have the same implication regarding the upper bounds. Therefore we will compare different inequalities and comment on the possible relationship between them. These inequalities are of relevance for the so-called coincidence problem and for the bound of the cosmological constant which comes surprisingly close to the "experimental" value.
ENERGY–MOMENTUM OF A REGULAR MMaS–CLASS BLACK HOLE
Authors: PATASHNICK OWEN
Published: September 2005

We compute the energy and momentum of a regular black hole of type defined by Mars, Martín-Prats, and Senovilla by using the Einstein and Papapetrou definitions for energy–momentum density. Some other definitions of energy–momentum density are shown to give mutually contradictory and less reasonable results. In addition, the resuts support the Cooperstock hypothesis.
Insulin secretion after dietary supplementation with conjugated linoleic acids and n-3 polyunsaturated fatty acids in normal and insulin-resistant mice
Authors: Winzell Maria Sörhede , Pacini Giovanni , Ahrén Bo
Published: September 2005

Conjugated linoleic acids (CLAs) and n-3 polyunsaturated fatty acids (PUFAs) improve insulin sensitivity in insulin-resistant rodents. However, the effects of these fatty acids on insulin secretion are not known but are of importance to completely understand their influence on glucose homeostasis. We therefore examined islet function after dietary supplementation consisting of 1% CLAs in combination with 1% n-3 enriched PUFAs for 12 wk to mice on a normal diet and to insulin-resistant mice fed a high-fat diet (58% fat). In the mice fed a normal diet, CLA/PUFA supplementation resulted in insulin resistance associated with low plasma adiponectin levels and low body fat content. Intravenous and oral glucose tolerance tests revealed a marked increase in insulin secretion, which nevertheless was insufficient to counteract the insulin resistance, resulting in glucose intolerance. In freshly isolated islets from mice fed the normal diet, both basal and glucose-stimulated insulin secretion were adaptively augmented by CLA/PUFA, and at a high glucose concentration this was accompanied by elevated glucose oxidation. In contrast, in high-fat-fed mice, CLA/PUFA did not significantly affect insulin secretion, insulin resistance, or glucose tolerance. It is concluded that dietary supplementation of CLA/PUFA in mice fed the normal diet augments insulin secretion, partly because of increased islet glucose oxidation, but that this augmentation is insufficient to counterbalance the induction of insulin resistance, resulting in glucose intolerance. Furthermore, the high-fat diet partly prevents the deleterious effects of CLA/PUFA, but this dietary supplementation was not able to counteract high-fat-diet-induced insulin resistance.
Effects of gastric emptying on the postprandial ghrelin response
Authors: Blom Wendy A. M. , Lluch Anne , Vinoy Sophie , Stafleu Annette , van den Berg Robin , Holst Jens J. , Kok Frans J. , Hendriks Henk F. J.
Published: September 2005

Distension and chemosensitization of the stomach are insufficient to induce a ghrelin response, suggesting that postgastric feedback is required. This postgastric feedback may be regulated through insulin. We investigated the relation between gastric emptying rate and the postprandial ghrelin response as well as the role of insulin and other hormones possibly mediating this response. Fifteen healthy men [BMI 21.6 kg/m2 (SD 1.9), age 20.5 yr (SD 2.5)] were studied in a single-blind, crossover design. Subjects received two treatments separated by 1 wk: 1) a dairy breakfast in combination with a 3-h intravenous infusion of glucagon-like peptide-1 (GLP-1), which delays gastric emptying, and 2) a dairy breakfast in combination with a 3-h intravenous infusion of saline. Blood samples were drawn before breakfast and during the infusion. Postprandial ghrelin (total) responses were lower following the saline infusion compared with the GLP-1 infusion ( P < 0.05). Acetaminophen concentrations, an indirect measurement of gastric emptying rate, were inversely correlated with total ghrelin concentrations (saline r = −0.76; 95% CI = −0.90, −0.49, GLP-1 r = −0.47; 95% CI = −0.76, −0.04). Ghrelin concentrations were only weakly correlated with insulin concentrations (saline r = −0.36; 95% CI = −0.69, 0.09; GLP- 1 r = −0.42; 95% CI = −0.73, 0.03), but strongly inversely correlated with GIP concentrations (saline r = −0.74; 95% CI= −0.89, −0.45; GLP-1 r = −0.63; 95% CI = −0.84, −0.27). In conclusion, our results support the hypothesis that ghrelin requires postgastric feedback, which may not be regulated through insulin. Conversely, our data suggest a role of glucose-dependent insulinotropic polypeptide in ghrelin secretion.
Medroxyprogesterone acetate binds the glucocorticoid receptor to stimulate α-ENaC and sgk1 expression in renal collecting duct epithelia
Authors: Thomas Christie P. , Liu Kang Z. , Vats Hemender S.
Published: September 2005

Medroxyprogesterone acetate (MPA), a widely used synthetic progestational contraceptive, occasionally leads to Cushingoid side effects such as hypertension, fluid retention, and centripetal obesity. We investigated the effect of MPA on classic mineralocorticoid target genes, α-epithelial Na channel (ENaC) and sgk1, in the collecting duct. In adrenalectomized mice, aldosterone, dexamethasone, and MPA increased α-ENaC mRNA levels in kidney cortex. MPA and dexamethasone, but not progesterone, dose dependently increased α-ENaC and sgk1 mRNA in M-1 and in Madin-Darby canine kidney-C7 cells, both collecting duct cell lines. The stimulatory effect of MPA and dexamethasone on α-ENaC expression was inhibited by RU-38486, a combined glucocorticoid receptor (GR) and progesterone receptor (PR) antagonist, but not by Org31710 , a pure PR antagonist. MPA and dexamethasone dose dependently increased α-ENaC promoter-driven luciferase activity in M-1 cells, which was not inhibited by Org31710 , indicating that MPA regulates α-ENaC in a PR-independent manner. When tested in HT29 cells, MPA could only stimulate α-ENaC-driven reporter activity when GR was coexpressed, confirming the requirement for functional GR in the transcriptional effect of MPA. The activation of steroid receptors such as GR can explain the apparent glucocorticoid effects of MPA, independent of PR activation.
Identification of potential caloric restriction mimetics by microarray profiling
Authors: Dhahbi Joseph M. , Mote Patricia L. , Fahy Gregory M. , Spindler Stephen R.
Published: September 2005

To facilitate the development of assays for the discovery of pharmaceuticals capable of mimicking the effects of caloric restriction (CR) on life- and healthspan (CR mimetics), we evaluated the effectiveness of glucoregulatory and putative cancer chemopreventatives in reproducing the hepatic gene expression profile produced by long-term CR (LTCR), using Affymetrix microarrays. We have shown that CR initiated late in life begins to extend lifespan, reduce cancer as a cause of death, and reproduce approximately three-quarters of the genomic effects of LTCR in 8 wk (CR8). Eight weeks of metformin treatment was superior to CR8 at reproducing LTCR-like gene expression changes, maintaining a superior number of such changes over a broad range of statistical stringencies, and producing more Gene Ontology terms overlapping those produced by LTCR. Consistent with these results, metformin has been shown to reduce cancer incidence in mice and humans. Phenformin, a chemical cousin of metformin, extends lifespan and reduces tumor incidence in mice. Taken together, these results indicate that gene expression biomarkers can be used to identify promising candidate CR mimetics.
Possible Role of Brain-Derived Neurotrophic Factor in the Pathogenesis of Coronary Artery Disease
Authors: Ejiri Junya , Inoue Nobutaka , Kobayashi Seiichi , Shiraki Rio , Otsui Kazunori , Honjo Tomoyuki , Takahashi Motonori , Ohashi Yoshitaka , Ichikawa Shinobu , Terashima Mitsuyasu , Mori Takao , Awano Kojiro , Shinke Toshiro , Shite Junya , Hirata Ken-ichi , Yokozaki Hiroshi , Kawashima Seinosuke , Yokoyama Mitsuhiro
Published: September 2005

Background—

The neurotrophin (NT) family, including nerve growth factor NT-3 and brain-derived neurotrophic factor (BDNF), has a critical role in the survival, growth, maintenance, and death of central and peripheral neurons. NTs and their receptors are expressed in atherosclerotic lesions; however, their significance in cardiovascular disease remains unclear.

Methods and Results—

To clarify the role of NTs in the pathogenesis of coronary artery disease, NT plasma levels in the aorta, coronary sinus, and peripheral veins of patients with unstable angina (n=38), stable effort angina (n=45), and non–coronary artery disease (n=24) were examined. In addition, regional expression of BDNF in coronary arteries was examined in autopsy cases and patients with angina pectoris by directional coronary atherectomy. The difference in BDNF levels, but not NT-3, between the coronary sinus and aorta was significantly greater in the unstable angina group compared with the stable effort angina and non–coronary artery disease groups. Immunohistochemical investigations demonstrated BDNF expression in the atheromatous intima and adventitia in atherosclerotic coronary arteries. BDNF expression was enhanced in macrophages and smooth muscle cells in atherosclerotic coronary arteries. Stimulation with recombinant BDNF significantly enhanced NAD(P)H oxidase activity and the generation of reactive oxygen species in cultured human coronary artery smooth muscle cells.

Conclusions—

BDNF has an important role in atherogenesis and plaque instability via the activation of NAD(P)H oxidase.
Enhanced Plasma Levels of LIGHT in Unstable Angina
Authors: Scholz Hanne , Sandberg Wiggo , Damås Jan Kristian , Smith Camilla , Andreassen Arne K. , Gullestad Lars , Frøland Stig S. , Yndestad Arne , Aukrust Pål , Halvorsen Bente
Published: September 2005

Background—

Numerous studies have demonstrated the ability of oxidized LDL [(ox)LDL] to promote an inflammatory response in macrophages. Several inflammatory mediators have been reported to increase after oxLDL stimulation of such cells, but their relative importance is still unknown. In the present study, we used microarrays to identify genes in THP-1 macrophages that were upregulated by oxLDL.

Methods and Results—

Our main findings were as follows. In a microarray screening experiment, we identified LIGHT, a ligand in the tumor necrosis factor superfamily, as one of the genes that were markedly upregulated in oxLDL-stimulated THP-1 macrophages. We showed significantly raised plasma levels of LIGHT in patients with stable angina (n=40) and particularly in those with unstable angina (n=40) compared with healthy controls (n=20), which underscores the clinical relevance of the in vitro finding. We also showed that LIGHT enhanced lipid accumulation in oxLDL-stimulated THP-1 macrophages, possibly through upregulation of class A scavenger receptor (SR-A). This increased lipid accumulation was accompanied by enhanced expression of tissue factor and plasminogen activator inhibitor-1, as well as enhanced thrombin formation, transforming macrophages into a prothrombotic phenotype. The LIGHT-mediated increase in SR-A, tissue factor, and plasminogen activator inhibitor-1 was also seen in human monocyte-derived macrophages. Finally, the LIGHT-mediated enhancement of SR-A and TF expression appears to involve nuclear factor-κB activation.

Conclusions—

These findings suggest that LIGHT could serve as a molecular link between lipid metabolism, inflammation, and thrombus formation, which are all features of atherosclerotic plaques.
Prognostic Value of N-Terminal Pro–Brain Natriuretic Peptide in Patients With Chronic Stable Angina
Authors: Ndrepepa Gjin , Braun Siegmund , Niemöller Kathrin , Mehilli Julinda , von Beckerath Nicolas , von Beckerath Olga , Vogt Wolfgang , Schömig Albert , Kastrati Adnan
Published: September 2005

Background—

Patients with chronic stable angina are poorly characterized in terms of biomarkers that help in the assessment of prognosis. We investigated whether plasma levels of N-terminal pro–brain natriuretic peptide (NT-proBNP) may be used as a prognostic marker in patients with chronic stable angina treated with coronary stenting.

Methods and Results—

Plasma levels of NT-proBNP were measured in 1059 patients with chronic stable angina and coronary angiographic confirmation of significant coronary artery disease. The primary end point of the study was mortality. After a median of 3.6 years (interquartile range, 3.3 to 4.5 years), there were 106 deaths. Kaplan-Meier estimates of 5-year mortality were 4.7% in the first quartile, 7.8% in the second quartile, 11.4% in the third quartile, and 32.7% in the fourth quartile of NT-proBNP (
P
<0.001). A Cox proportional hazards model showed that NT-proBNP was the strongest correlate of mortality (adjusted hazards ratio [HR], 5.83 [95% confidence interval: 2.07 to 16.44] for the fourth versus the first quartile). A similar prognostic value of NT-proBNP was demonstrated for cardiovascular mortality (HR, 5.98 [1.55 to 23.13] for the fourth versus the first quartile) and for patients with New York Heart Association class I and II (HR, 6.03 [2.07 to 17.52] for the fourth versus the first quartile).

Conclusions—

Circulating levels of NT-proBNP are a strong prognostic biomarker for patients with chronic stable angina.
Hypercholesterolemia Abrogates Late Preconditioning via a Tetrahydrobiopterin-Dependent Mechanism in Conscious Rabbits
Authors: Tang Xian-Liang , Takano Hitoshi , Xuan Yu-Ting , Sato Hiroshi , Kodani Eitaro , Dawn Buddhadeb , Zhu Yanqing , Shirk Gregg , Wu Wen-Jian , Bolli Roberto
Published: September 2005

Background—

Although the late phase of ischemic preconditioning (PC) is known to confer cardioprotection in healthy animal models, it is unknown whether this phenomenon exists in the presence of hypercholesterolemia. The goal of this study was to determine whether the infarct-sparing effect of late PC is affected by hypercholesterolemia and, if so, whether a tetrahydrobiopterin (BH
4
)-dependent mechanism is responsible for the loss of late PC.

Methods and Results—

Conscious rabbits fed a normal diet or a 1% cholesterol diet for 6 weeks were subjected to ischemic PC (six 4-minute coronary occlusion/4-minute reperfusion cycles) and, 24 hours later, underwent a 30-minute occlusion followed by 3 days of reperfusion. A total of 125 rabbits were used. In normocholesterolemic rabbits, ischemic PC reduced infarct size, an effect that was abrogated by administration of the BH
4
synthesis inhibitor
N
-acetylserotonin (15 mg/kg IV) before the 30-minute occlusion. In hypercholesterolemic rabbits, however, ischemic PC failed to reduce infarct size. Myocardial BH
4
levels in the ischemic zone increased 24 hours after ischemic PC in normocholesterolemic rabbits but not in hypercholesterolemic rabbits. In addition, in normocholesterolemic rabbits, pretreatment with
N
-acetylserotonin completely abolished the ischemic PC-induced increase in myocardial BH
4
levels.

Conclusions—

This study demonstrates that (1) hypercholesterolemia abrogates both the infarct-sparing effect of late PC and the concomitant upregulation of myocardial BH
4
, and (2) inhibition of myocardial BH
4
synthesis in the absence of hypercholesterolemia is sufficient to abolish the infarct-sparing effect of late PC. The results support the concept that hypercholesterolemia abrogates late PC by preventing the upregulation of BH
4
, an essential cofactor for inducible nitric oxide synthase.
E1A expression dysregulates IL-8 production and suppresses IL-6 production by lung epithelial cells
Authors: van den Berg Arjen , Snoek Mieke , Jansen Henk M , Lutter René
Published: September 2005

Background

The adenoviral protein E1A has been proposed to play a role in the pathophysiology of COPD, in particular by increasing IL-8 gene transcription of lung epithelial cells in response to cigarette smoke-constituents such as LPS. As IL-8 production is also under tight post-transcriptional control, we planned to study whether E1A affected IL-8 production post-transcriptionally. The production of IL-6 by E1A-positive cells had not been addressed and was studied in parallel. Based on our previous work into the regulation of IL-8 and IL-6 production in airway epithelial cells, we used the lung epithelial-like cell line NCI-H292 to generate stable transfectants expressing either E1A and/or E1B, which is known to frequently co-integrate with E1A. We analyzed IL-8 and IL-6 production and the underlying regulatory processes in response to LPS and TNF-α.

Methods

Stable transfectants were generated and characterized with immunohistochemistry, western blot and flow cytometry. IL-8 and IL-6 protein production was measured by ELISA. Levels of IL-8 and IL-6 mRNA were measured using specific radiolabeled probes. EMSA was used to assess transcriptional activation of relevant transcription factors. Post-transcriptional regulation of mRNA half-life was measured by Actinomycin D chase experiments.

Results

Most of the sixteen E1A-expressing transfectants showed suppression of IL-6 production, indicative of biologically active E1A. Significant but no uniform effects on IL-8 production, nor on transcriptional and post-transcriptional regulation of IL-8 production, were observed in the panel of E1A-expressing transfectants. E1B expression exerted similar effects as E1A on IL-8 production.

Conclusion

Our results indicate that integration of adenoviral DNA and expression of E1A and E1B can either increase or decrease IL-8 production. Furthermore, we conclude that expression of E1A suppresses IL-6 production. These findings question the unique role of E1A protein in the pathophysiology of COPD, but do not exclude a role for adenoviral E1A/E1B DNA in modulating inflammatory responses nor in the pathogenesis of COPD.
Quality determination and the repair of poor quality spots in array experiments
Authors: Tom Brian DM , Gilks Walter R , Brooke-Powell Elizabeth T , Ajioka James W
Published: September 2005

Background

A common feature of microarray experiments is the occurence of missing gene expression data. These missing values occur for a variety of reasons, in particular, because of the filtering of poor quality spots and the removal of undefined values when a logarithmic transformation is applied to negative background-corrected intensities. The efficiency and power of an analysis performed can be substantially reduced by having an incomplete matrix of gene intensities. Additionally, most statistical methods require a complete intensity matrix. Furthermore, biases may be introduced into analyses through missing information on some genes. Thus methods for appropriately replacing (imputing) missing data and/or weighting poor quality spots are required.

Results

We present a likelihood-based method for imputing missing data or weighting poor quality spots that requires a number of biological or technical replicates. This likelihood-based approach assumes that the data for a given spot arising from each channel of a two-dye (two-channel) cDNA microarray comparison experiment independently come from a three-component mixture distribution – the parameters of which are estimated through use of a constrained E-M algorithm. Posterior probabilities of belonging to each component of the mixture distributions are calculated and used to decide whether imputation is required. These posterior probabilities may also be used to construct quality weights that can down-weight poor quality spots in any analysis performed afterwards. The approach is illustrated using data obtained from an experiment to observe gene expression changes with 24 hr paclitaxel (Taxol®) treatment on a human cervical cancer derived cell line (HeLa).

Conclusion

As the quality of microarray experiments affect downstream processes, it is important to have a reliable and automatic method of identifying poor quality spots and arrays. We propose a method of identifying poor quality spots, and suggest a method of repairing the arrays by either imputation or assigning quality weights to the spots. This repaired data set would be less biased and can be analysed using any of the appropriate statistical methods found in the microarray literature.
Mitochondrial-encoded membrane protein transcripts are pyrimidine-rich while soluble protein transcripts and ribosomal RNA are purine-rich
Authors: Bradshaw Patrick C , Rathi Anand , Samuels David C
Published: September 2005

Background

Eukaryotic organisms contain mitochondria, organelles capable of producing large amounts of ATP by oxidative phosphorylation. Each cell contains many mitochondria with many copies of mitochondrial DNA in each organelle. The mitochondrial DNA encodes a small but functionally critical portion of the oxidative phosphorylation machinery, a few other species-specific proteins, and the rRNA and tRNA used for the translation of these transcripts. Because the microenvironment of the mitochondrion is unique, mitochondrial genes may be subject to different selectional pressures than those affecting nuclear genes.

Results

From an analysis of the mitochondrial genomes of a wide range of eukaryotic species we show that there are three simple rules for the pyrimidine and purine abundances in mitochondrial DNA transcripts. Mitochondrial membrane protein transcripts are pyrimidine rich, rRNA transcripts are purine-rich and the soluble protein transcripts are purine-rich. The transitions between pyrimidine and purine-rich regions of the genomes are rapid and are easily visible on a pyrimidine-purine walk graph. These rules are followed, with few exceptions, independent of which strand encodes the gene. Despite the robustness of these rules across a diverse set of species, the magnitude of the differences between the pyrimidine and purine content is fairly small. Typically, the mitochondrial membrane protein transcripts have a pyrimidine richness of 56%, the rRNA transcripts are 55% purine, and the soluble protein transcripts are only 53% purine.

Conclusion

The pyrimidine richness of mitochondrial-encoded membrane protein transcripts is partly driven by U nucleotides in the second codon position in all species, which yields hydrophobic amino acids. The purine-richness of soluble protein transcripts is mainly driven by A nucleotides in the first codon position. The purine-richness of rRNA is also due to an abundance of A nucleotides. Possible mechanisms as to how these trends are maintained in mtDNA genomes of such diverse ancestry, size and variability of A-T richness are discussed.
A Bacillus thuringiensis isolation method utilizing a novel stain, low selection and high throughput produced atypical results
Authors: Rampersad Joanne , Ammons David
Published: September 2005

Background

Bacillus thuringiensis is a bacterium known for producing protein crystals with insecticidal properties. These toxins are widely sought after for controlling agricultural pests due to both their specificity and their applicability in transgenic plants. There is great interest in isolating strains with improved or novel toxin characteristics, however isolating B. thuringiensis from the environment is time consuming and yields relatively few isolates of interest. New approaches to B. thuringiensis isolation have been, and continue to be sought. In this report, candidate B. thuringiensis isolates were recovered from environmental samples using a combination of a novel stain, high throughput and reduced selection. Isolates were further characterized by SDS-PAGE, light microscopy, PCR, probe hybridization, and with selected isolates, DNA sequencing, bioassay or Electron Microscopy.

Results

Based on SDS-PAGE patterns and the presence of cry genes or a crystal, 79 candidate, non-clonal isolates of B. thuringiensis were identified from 84 samples and over 10,000 colonies. Although only 16/79 (20%) of the isolates showed DNA homology by Probe Hybridization or PCR to common cry genes, initial characterization revealed a surprisingly rich library that included a putative nematocidal gene, a novel filamentous structure associated with a crystal, a spore with spikes originating from a very small parasporal body and isolates with unusually small crystals. When compared to reports of other screens, this screen was also atypical in that only 3/79 isolates (3.8%) produced a bipyramidal crystal and 24/79 (30%) of the isolates' spores possessed an attached, dark-staining body.

Conclusion

Results suggest that the screening methodology adopted in this study might deliver a vastly richer and potentially more useful library of B. thuringiensis isolates as compared to that obtained with commonly reported methodologies, and that by extension, methodologies fundamentally different from current methods should also be explored.
Purification and kinetic studies of recombinant gibberellin dioxygenases
Authors: Lester Diane R , Phillips Andy , Hedden Peter , Andersson Inger
Published: September 2005

Background

The 2-oxoglutarate-dependent dioxygenases (2ODDs) of gibberellin (GA) biosynthesis have a key role in the metabolism of a major plant hormone. The activity of recombinant GA 2ODDs from many species has been characterised in detail, however little information relates to enzyme purification. Native GA 2ODDs displayed lability during purification.

Results

Two GA 2ODDs were expressed in Escherichia coli and purified to homogeneity. The GA 2-oxidase from Pisum sativum L., PsGA2OX1, was expressed as a glutathione s-transferase (GST) fusion. It was purified in the three steps of affinity chromatography, GST removal and gel filtration. Highly pure PsGA2OX1 was obtained at a yield of 0.3 mg/g of cells. It displayed a K

m
of 0.024 μM and a V

max
of 4.4 pkat/mg toward [1β,2β,3β-3H3]GA20. The GA 3-oxidase from Arabidopsis thaliana, AtGA3OX4, was expressed as a poly(His)-tagged thioredoxin fusion. It was purified by Immobilised Metal Affinity Chromatography followed by gel filtration. Cleavage of the fusion took place between the two purification steps. Highly pure AtGA3OX4 was obtained at a yield of 0.01 mg/g of cells. It displayed a K

m
of 0.82 μM and V

max
of 52,500 pkat/mg toward [1β,2β,3β-3H3]GA20.

Conclusion

Fusion tags were required to stabilise and solubilise PsGA2OX1 and AtGA3OX4 during E. coli expression. The successful purification of milligram quantities of PsGA2OX1 enables mechanistic and structural studies not previously possible on GA 2ODDs. A moderate yield of pure AtGA3OX4 requires the further optimisation of the latter stages of the enzyme purification schedule. PsGA2OX1's action in planta as deduced from the effect of the null mutation sln on GA levels in seeds is in agreement with the kinetic parameters of the recombinant enzyme.
Accuracy of popular automatic QT Interval algorithms assessed by a 'Gold Standard' and comparison with a Novel method: computer simulation study
Authors: Hunt Anthony Charles
Published: September 2005

Background

Accurate measurement of the QT interval is very important from a clinical and pharmaceutical drug safety screening perspective. Expert manual measurement is both imprecise and imperfectly reproducible, yet it is used as the reference standard to assess the accuracy of current automatic computer algorithms, which thus produce reproducible but incorrect measurements of the QT interval. There is a scientific imperative to evaluate the most commonly used algorithms with an accurate and objective 'gold standard' and investigate novel automatic algorithms if the commonly used algorithms are found to be deficient.

Methods

This study uses a validated computer simulation of 8 different noise contaminated ECG waveforms (with known QT intervals of 461 and 495 ms), generated from a cell array using Luo-Rudy membrane kinetics and the Crank-Nicholson method, as a reference standard to assess the accuracy of commonly used QT measurement algorithms. Each ECG contaminated with 39 mixtures of noise at 3 levels of intensity was first filtered then subjected to three threshold methods (T1, T2, T3), two T wave slope methods (S1, S2) and a Novel method. The reproducibility and accuracy of each algorithm was compared for each ECG.

Results

The coefficient of variation for methods T1, T2, T3, S1, S2 and Novel were 0.36, 0.23, 1.9, 0.93, 0.92 and 0.62 respectively. For ECGs of real QT interval 461 ms the methods T1, T2, T3, S1, S2 and Novel calculated the mean QT intervals(standard deviations) to be 379.4(1.29), 368.5(0.8), 401.3(8.4), 358.9(4.8), 381.5(4.6) and 464(4.9) ms respectively. For ECGs of real QT interval 495 ms the methods T1, T2, T3, S1, S2 and Novel calculated the mean QT intervals(standard deviations) to be 396.9(1.7), 387.2(0.97), 424.9(8.7), 386.7(2.2), 396.8(2.8) and 493(0.97) ms respectively. These results showed significant differences between means at >95% confidence level. Shifting ECG baselines caused large errors of QT interval with T1 and T2 but no error with Novel.

Conclusion

The algorithms T2, T1 and Novel gave low coefficients of variation for QT measurement. The Novel technique gave the most accurate measurement of QT interval, T3 (a differential threshold method) was the next most accurate by a large margin. The objective and accurate 'gold standard' presented in this paper may be useful to assess new QT measurement algorithms. The Novel algorithm may prove to be more accurate and reliable method to measure the QT interval.
Dog filariosis in the Lazio region (Central Italy): first report on the presence of Dirofilaria repens
Authors: Scaramozzino Paola , Gabrielli Simona , Di Paolo Michele , Sala Marcello , Scholl Francesco , Cancrini Gabriella
Published: September 2005

Background

Epidemiological investigations were carried out in the Lazio Region to assess the status of canine filariosis and to evaluate the actual risk for veterinary and medical public health.

Methods

Since August 2001 to June 2003, a total of 972 canine blood samples, collected in public kennels and from private owners animals of the 5 Provinces of the Region, were tested. The presence of filarial parasites was evaluated by microscopy and bio-molecular techniques; the species identification was performed by means of the same diagnostic tools.

Results

A total of 17/972 (1.75%; 95%CI 1.06%–2.85%) blood samples were parasitized by D. repens,13 out them drawn by dogs resident in the Province of Roma, and 4 in the other provinces. Multivariate analysis was performed in order to evaluate the association between filariosis and risk factors. The origin from coastal territories seems to be a significant risk factor to acquire the infection.

Conclusion

This is the first report of canine filariosis in the Lazio Region, where D. repens was before reported only in foxes. The risk of human zoonotic infection is stressed, and the absence of other filarial species is discussed
Use of a nested PCR-enzyme immunoassay with an internal control to detect Chlamydophila psittaciin turkeys
Authors: Van Loock Marnix , Verminnen Kristel , Messmer Trudy O , Volckaert Guido , Goddeeris Bruno M , Vanrompay Daisy
Published: September 2005

Background

Laboratory diagnosis of Chlamydophila psittaci, an important turkey respiratory pathogen, is difficult. To facilitate the diagnosis, a nested PCR-enzyme immunoassay (PCR-EIA) was developed to detect the Cp. psittaci outer membrane protein A (ompA) gene in pharyngeal swabs.

Methods

The fluorescein-biotin labelled PCR products were immobilized on streptavidin-coated microtiter plates and detected with anti-fluorescein peroxidase conjugate and a colorimetric substrate. An internal inhibition control was included to rule out the presence of inhibitors of DNA amplification. The diagnostic value of the ompA nested PCR-EIA in comparison to cell culture and a 16S-rRNA based nested PCR was assessed in pharyngeal turkey swabs from 10 different farms experiencing respiratory disease.

Results

The sensitivity of the nested PCR-EIA was established at 0.1 infection forming units (IFU). Specificity was 100%. The ompA nested PCR-EIA was more sensitive than the 16S-rRNA based nested PCR and isolation, revealing 105 out of 200 (52.5%) positives against 13 and 74 for the latter two tests, respectively. Twenty-nine (23.8%) out of 122 ompA PCR-EIA negatives showed the presence of inhibitors of DNA amplification, although 27 of them became positive after diluting (1/10) the specimens in PCR buffer or after phenol-chloroform extraction and subsequent ethanol precipitation.

Conclusion

The present study stresses the need for an internal control to confirm PCR true-negatives and demonstrates the high prevalence of chlamydiosis in Belgian turkeys and its potential zoonotic risk. The ompA nested PCR-EIA described here is a rapid, highly sensitive and specific diagnostic assay and will help to facilitate the diagnosis of Cp. psittaci infections in both poultry and man.
Visual recovery after perinatal stroke evidenced by functional and diffusion MRI: case report
Authors: Seghier Mohamed L , Lazeyras François , Zimine Slava , Saudan-Frei Sonja , Safran Avinoam B , Huppi Petra S
Published: September 2005

Background

After perinatal brain injury, clinico-anatomic correlations of functional deficits and brain plasticity remain difficult to evaluate clinically in the young infant. Thus, new non-invasive methods capable of early functional diagnosis are needed in young infants.

Case Presentation

The visual system recovery in an infant with perinatal stroke is assessed by combining diffusion tensor imaging (DTI) and event-related functional MRI (ER-fMRI). All experiments were done at 1.5T. A first DTI experiment was performed at 12 months of age. At 20 months of age, a second DTI experiment was performed and combined with an ER-fMRI experiment with visual stimuli (2 Hz visual flash). At 20 months of age, ER-fMRI showed significant negative activation in the visual cortex of the injured left hemisphere that was not previously observed in the same infant. DTI maps suggest recovery of the optic radiation in the vicinity of the lesion. Optic radiations in the injured hemisphere are more prominent in DTI at 20 months of age than in DTI at 12 months of age.

Conclusion

Our data indicate that functional cortical recovery is supported by structural modifications that concern major pathways of the visual system. These neuroimaging findings might contribute to elaborate a pertinent strategy in terms of diagnosis and rehabilitation.
Chances of late surgery in relation to length of wait lists
Authors: Sobolev Boris G , Levy Adrian R , Kuramoto Lisa , Hayden Robert
Published: September 2005

Background

The proportion of patients who undergo surgery within a clinically safe time is an important performance indicator in health systems that use wait lists to manage access to care. However, little is known about chances of on-time surgery according to variations in existing demand. We sought to determine what proportion of patients have had late coronary bypass surgery after registration on wait lists of different size in a network of hospitals with uniform standards for timing of surgery.

Methods

Using records from a population-based registry, we studied wait-list times prospectively collected in a cohort of patients registered on wait lists for coronary artery bypass grafting procedures. We compared the number of weeks from registration to surgery against target access times established for three urgency groups. The chances of undergoing surgery within target time have been evaluated in relation to wait-list size at registration and the number of surgeries performed without registration on a wait list.

Results

In 1991–2001, two in three patients were at risk of late surgery when registered on wait lists for isolated coronary bypass procedures in British Columbia, Canada. Although urgent patients had never seen a wait list with clearance time exceeding one week, the odds of on-time surgery were reduced by 25%, odds ratio [OR] = 0.75 (95% confidence interval [CI] 0.65–0.87) for every additional operation performed without registration on a list. When the wait list at registration required a clearance time of over one month, semi-urgent patients had 51% lower odds of on-time surgery as compared to lists with clearance time less than one week, OR = 0.49 (95%CI 0.41–0.60), after adjustment for age, sex, comorbidity, calendar period, hospital and week on the list. In the non-urgent group, the odds were 69% lower, OR = 0.31 (95%CI 0.20–0.47). Every time an operation in the same hospital was performed without registration on a wait list, the odds of on-time surgery for listed patients were reduced by 7%, OR = 0.93 (95%CI 0.91–0.95) in the semi-urgent group, and by 10%, OR = 0.90 (95%CI 0.87–0.94), in the non-urgent group.

Conclusion

Chances of late surgery increase with the wait-list size for semi-urgent and non-urgent patients needing coronary bypass surgery. The weekly number of patients who move immediately from angiography to the operation without registration on a wait list reduced chances of surgery within target time in all urgency groups of listed patients. When advising patients who will be placed on the wait list about the expected time to treatment, hospital managers should take into account the current list size as well as the weekly number of patients who require CABG immediately after undergoing coronary angiography.