bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECTS OF OPEN STRING MODULI ON RACETRACK INFLATION
Authors: WEN WEN-YU
Published: July 2008

In this note, we refine the racetrack inflation model constructed in Ref. 3 by including the open string modulus. This modulus encodes the embedding of our braneworld inside some Calabi-Yau throat. We argue that in generic this open string modulus dynamically runs with the inflaton field thanks to its nonlinear coupling. A full analysis becomes difficult because the scalar potential changes progressively during the inflation epoch. Nevertheless, by explicit construction we are still able to build a realistic model through appropriate choices of the initial conditions.
ASTRO-QUARK MATTER: A CHALLENGE FACING ASTROPARTICLE PHYSICS
Authors: XU RENXIN
Published: July 2008

Quark matter both in terrestrial experiment and in astrophysics is briefly reviewed. Astrophysical quark matter could appear in the early Universe, in compact stars, and as cosmic rays. Emphasis is put on quark star as the nature of pulsars. Possible astrophysical implications of experiment-discovered sQGP are also concisely discussed.
MULTIRESOLUTION SIGNAL DECOMPOSITION AND APPROXIMATION BASED ON SUPPORT VECTOR MACHINES
Authors: SHANG ZHAOWEI , TANG YUAN YAN , FANG BIN , WEN JING , ONG YAT ZHOU
Published: July 2008

The fusion of wavelet technique and support vector machines (SVMs) has become an intensive study in recent years. Considering that the wavelet technique is the theoretical foundation of multiresolution analysis (MRA), it is valuable for us to investigate the problem of whether a good performance could be obtained if we combine the MRA with SVMs for signal approximation. Based on the fact that the feature space of SVM and the scale subspace in MRA can be viewed as the same Reproducing Kernel Hilbert Spaces (RKHS), a new algorithm named multiresolution signal decomposition and approximation based on SVM is proposed. The proposed algorithm which approximates the signals hierarchically at different resolutions, possesses better approximation of smoothness for signal than conventional MRA due to using the approximation criterion of the SVM. Experiments illustrate that our algorithm has better approximation of performance than the MRA when being applied to stationary and non-stationary signals.
LOCALLY ADAPTIVE MULTISCALE BAYESIAN METHOD FOR IMAGE DENOISING BASED ON BIVARIATE NORMAL INVERSE GAUSSIAN DISTRIBUTIONS
Authors: FOROUZANFAR MOHAMAD , MOGHADDAM HAMID ABRISHAMI , GHADIMI SONA
Published: July 2008

Recently, the use of wavelet transform has led to significant advances in image denoising applications. Among wavelet-based denoising approaches, the Bayesian techniques give more accurate estimates. Considering interscale dependencies, these estimates become closer to the original image. In this context, the choice of an appropriate model for wavelet coefficients is an important issue. The performance can also be improved by estimating model parameters in a local neighborhood. In this paper, we propose the bivariate normal inverse Gaussian (NIG) distribution, which can model a wide range of heavy-tailed to less heavy-tailed processes, to model the local wavelet coefficients at adjacent scales. We will show that this new statistical model is superior to the conventional generalized Gaussian (GG) model. Then, a minimum mean square error-based (MMSE-based) Bayesian estimator is designed to effectively remove noise from wavelet coefficients. Exploiting this new statistical model in the dual-tree complex wavelet domain, we achieved state-of-the-art performance among related recent denoising approaches, both visually and in terms of peak signal-to-noise ratio (PSNR).
Role of MutS homolog 2 (MSH2) in intestinal myofibroblast proliferation during Crohn's disease stricture formation
Authors: Floer Martin , Binion David G. , Nelson Victoria M. , Manley Sharon , Wellner Michael , Sadeghi Saba , Behmaram Behnaz , Sewell Chloe , Otterson Mary F. , Kucharzik Torsten , Rafiee Parvaneh
Published: July 2008

Tissue remodeling and mesenchymal cell accumulation accompanies chronic inflammatory disorders involving joints, lung, vasculature, and bowel. Chronic inflammation may alter DNA-mismatch repair (MMR) systems in mesenchymal cells, but is not defined in Crohn's disease (CD) and its associated intestinal remodeling and stricture formation. We determined whether DNA-MMR alteration plays a role in the pathogenesis of CD tissue remodeling. Control and CD bowel tissues were used to generate primary cultures of muscularis mucosa myofibroblasts, which were assessed directly or following stimulation with TNF-α/LPS or H2O2. MutS homolog (MSH)2, MSH3, and MSH6 expression in tissues and myofibroblasts was determined. Immunohistochemical staining revealed an increased expression of MSH2 in CD muscularis mucosa and submucosal tissues compared with controls or uninvolved CD tissue, and MSH2 expression was increased in CD myofibroblasts compared with control cells. TNF-α/LPS and H2O2 further enhanced MSH2 expression in both control and CD cells, which were decreased by simvastatin. There were no significant changes in MSH3 and MSH6 expression. Proliferating cell nuclear antigen and Ki67 staining of CD tissue revealed increased proliferation in the muscularis mucosa and submucosa of chronically inflamed tissues, and enhanced proliferation was seen in CD myofibroblasts compared with controls. Simvastatin reversed the effects of inflammatory stress on the DNA-MMR and inhibited proliferation of control and CD myofibroblasts. Gene silencing with MSH2 siRNA selectively decreased CD myofibroblast proliferation. These data demonstrate a potential role for MSH2 in the pathogenesis of nonneoplastic mesenchymal cell accumulation and intestinal remodeling in CD chronic inflammation.
Stimulation of ecto-5′-nucleotidase in human umbilical vein endothelial cells by lipopolysaccharide
Authors: Li R. W. S. , Man Ricky Y. K. , Vanhoutte Paul M. , Leung George P. H.
Published: July 2008

The involvement of ecto-5′-nucleotidase (E-5′Nu) in the elevation of extracellular adenosine during inflammation is unclear. In the present study, the effect of lipopolysaccharide (LPS), an inflammation inducer, was investigated on E-5′Nu in human umbilical vein endothelial cells (HUVECs). E-5′Nu activity was enhanced after a 24 h exposure to LPS. This effect was dose dependent, with an EC50 of 1.66 ng/ml. At 10 μM, the phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002 abolished the LPS-induced E-5′Nu activity. However, at 10 μM, the NF-κB inhibitor ammonium pyrrolidine dithiocarbamate had no effect. LPS upregulated the protein expression but not the messenger RNA expression of E-5′Nu. The inhibition of E-5′Nu by 100 μM α,β-methylene adenosine-5′-diphosphate increased the LPS-induced inflammation, suggesting that E-5′Nu plays a significant role in reducing inflammation, probably through the generation of adenosine. In conclusion, the experiments indicate that LPS upregulates E-5′Nu activity in HUVECs through a PI3K-dependent increase in the abundance of E-5′Nu on cell membranes. Since adenosine is an anti-inflammatory molecule, E-5′Nu upregulation may be crucial in protecting endothelial cells against inflammatory damage.
Sectorial Angioarchitecture of the Human Tibia
Authors: Menck J. , Bertram Ch. , Lierse W.
Published: July 2008

The blood supply of the periosteum of the human tibia was investigated by anatomical dissection of 12 lower extremities which were filled with injection mass. By division of the tibia into 4 segments (proximal and distal fifths; proximal and distal diaphysis) a general supplying system of the periosteum was found. The proximal fifth of the tibial periosteum is nourished by branches of the arteriae recurrentes tibiales anterior et posterior and the aa. inferiores medialis et lateralis genus. At the proximal diaphysis (next three tenths of the tibia) periosteal branches arise from the aa. tibialis anterior and posterior, whereas the distal diaphysis is nourished exclusively by semicircular vessels of the a. tibialis anterior which twine around the bone and merge with each other at the facies medialis. Concerning the periosteal blood supply of the distal fifth of the tibia, two different types were found. In two thirds of the cases the lateral side was nourished by branches of the a. tibialis anterior, which are supported by vessels from the a. fibularis. In one third the latter branch was absent so that the rami periostales arising from the a. tibialis anterior nourished the lateral aspect of the distal tibia alone. The dorsal region was supplied in all cases by rami of the a. fibularis and a. tibialis posterior. On the medial side the periosteal nourishment is ensured only by anastomosis. Branches of the a. tibialis anterior supply the facies lateralis and facies posterior where it is supported by vessels of the a. tibialis posterior and in a minor region of rami of the a. fibularis (distal) and a. poplitea (proximal). Both the facies lateralis and facies posterior are nourished by direct branches which arise from the main arteries of the lower leg, whereas the facies medialis is supplied only by capillary anastomosis. The a. tibialis anterior is the artery of great importance concerning the arterial supply of the periosteum and the outer aspect of the cortex of the tibia. The autonomous region of this vessel is the periosteum of the distal diaphysis. It is known that this region has the highest incidence of congenital and acquired pseudarthrosis. Therefore an osteo- or corticotomy should be avoided in the distal diaphysis.
Absence of Foramen Transversarium in the Human Atlas Vertebra: A Case Report
Authors: Vasudeva N. , Kumar R.
Published: July 2008

Anatomical texts allude to many variations in the foramen transversarium of the seventh cervical vertebra, including its absence, but absent foramen transversarium of the atlas vertebra has not been mentioned. This is the case report of an atlas vertebra, the transverse process of which did not exhibit this foramen on the left side. However, the groove for the vertebral artery was present bilaterally on the posterior arch. The possible factors responsible for this interesting variant are discussed.
Effects of Six
APOA5
Variants, Identified in Patients With Severe Hypertriglyceridemia, on In Vitro Lipoprotein Lipase Activity and Receptor Binding
Authors: Dorfmeister B. , Zeng W.W. , Dichlberger A. , Nilsson S.K. , Schaap F.G. , Hubacek J.A. , Merkel M. , Cooper J.A. , Lookene A. , Putt W. , Whittall R. , Lee P.J. , Lins L. , Delsaux N. , Nierman M. , Kuivenhoven J.A. , Kastelein J.J.P. , Vrablik M. , Olivecrona G. , Schneider W.J. , Heeren J. , Humphries S.E. , Talmud P.J.
Published: July 2008

Objective—

The purpose of this study was to identify rare
APOA5
variants in 130 severe hypertriglyceridemic patients by sequencing, and to test their functionality, since no patient recall was possible.

Methods and Results—

We studied the impact in vitro on LPL activity and receptor binding of 3 novel heterozygous variants, apoAV-E255G, -G271C, and -H321L, together with the previously reported -G185C, -Q139X, -Q148X, and a novel construct -Δ139 to 147. Using VLDL as a TG-source, compared to wild type, apoAV-G255, -L321 and -C185 showed reduced LPL activation (−25% [
P
=0.005], −36% [
P
<0.0001], and −23% [
P
=0.02]), respectively). ApoAV-C271, -X139, -X148, and Δ139 to 147 had little affect on LPL activity, but apoAV-X139, -X148, and -C271 showed no binding to LDL-family receptors, LR8 or LRP1. Although the G271C proband carried no
LPL
and
APOC2
mutations, the H321L carrier was heterozygous for
LPL
P207L. The E255G carrier was homozygous for
LPL
W86G, yet only experienced severe hypertriglyceridemia when pregnant.

Conclusion—

The in vitro determined function of these apoAV variants only partly explains the high TG levels seen in carriers. Their occurrence in the homozygous state, coinheritance of
LPL
variants or common
APOA5
TG-raising variant in
trans
, appears to be essential for their phenotypic expression.
G Protein–Coupled Receptor Kinase 2 Ablation in Cardiac Myocytes Before or After Myocardial Infarction Prevents Heart Failure
Authors: Raake Philip W. , Vinge Leif E. , Gao Erhe , Boucher Matthieu , Rengo Giuseppe , Chen Xiongwen , DeGeorge Brent R. , Matkovich Scot , Houser Steven R. , Most Patrick , Eckhart Andrea D. , Dorn Gerald W. , Koch Walter J.
Published: July 2008

Myocardial G protein–coupled receptor kinase (GRK)2 is a critical regulator of cardiac β-adrenergic receptor (βAR) signaling and cardiac function. Its upregulation in heart failure may further depress cardiac function and contribute to mortality in this syndrome. Preventing GRK2 translocation to activated βAR with a GRK2-derived peptide that binds G
β
γ (βARKct) has benefited some models of heart failure, but the precise mechanism is uncertain, because GRK2 is still present and βARKct has other potential effects. We generated mice in which cardiac myocyte GRK2 expression was normal during embryonic development but was ablated after birth (αMHC-Cre×GRK2 fl/fl) or only after administration of tamoxifen (αMHC-MerCreMer×GRK2 fl/fl) and examined the consequences of GRK2 ablation before and after surgical coronary artery ligation on cardiac adaptation after myocardial infarction. Absence of GRK2 before coronary artery ligation prevented maladaptive postinfarction remodeling and preserved βAR responsiveness. Strikingly, GRK2 ablation initiated 10 days after infarction increased survival, enhanced cardiac contractile performance, and halted ventricular remodeling. These results demonstrate a specific causal role for GRK2 in postinfarction cardiac remodeling and heart failure and support therapeutic approaches of targeting GRK2 or restoring βAR signaling by other means to improve outcomes in heart failure.
Superficial Siderosis
Authors: Feldman Howard H. , Maia Luis F. , Mackenzie Ian R.A. , Forster Bruce B. , Martzke Jeff , Woolfenden Andrew
Published: July 2008

Background and Purpose—

Superficial siderosis of the central nervous system results from chronic bleeding in the superficial layers of the cortex and spinal cord. In cerebral amyloid angiopathy (CAA), there is amyloid deposition in meningeal and meningo-cortical arteries and capillaries, predisposing them to rupture. CAA is frequently associated with Alzheimer disease (AD).

Methods and Results—

We report a series of 3 AD patients with MRI evidence of superficial siderosis. Two had neuropathological examination confirming superficial siderosis, AD, and CAA.

Conclusions—

Superficial siderosis should be recognized within the spectrum of AD with CAA and considered as a possible antemortem diagnostic feature.
In-Hospital Stroke Treated With Intravenous Tissue Plasminogen Activator
Authors: Masjuan Jaime , Simal Patricia , Fuentes Blanca , Egido José Antonio , Díaz-Otero Fernando , Gil-Núñez Antonio , Novillo-López Maria Elena , Díez-Tejedor Exuperio , Alonso de Leciñana María
Published: July 2008

Background and Purpose—

In-hospital strokes (IHSs) are potential candidates for thrombolysis. We analyzed the treatment procedures, safety, and efficacy of intravenous tissue plasminogen activator (IV-tPA) in IHSs compared with out-of-hospital strokes (OHSs).

Methods—

This study was based on a multicenter prospective registry of patients treated with IV-tPA divided into IHSs and OHSs. We recorded intrahospital delays and stroke outcomes.

Results—

Among 367 patients treated with IV-tPA, 30 were IHSs. Baseline characteristics were similar except for a greater proportion of diabetes (36.7% vs 17.5%,
P
=0.01), cardiac failure (16.7% vs 5.3%,
P
=0.014), and atrial fibrillation (33.3% vs 17.5%,
P
=0.034) in IHSs than OHSs. In-hospital delays were significantly longer in IHSs for door-to-computed tomography time (39.5±18.7 vs 22.6±19.7 minutes,
P
<0.0001) and computed tomography-to-treatment time (92.0±26.1 vs 65.4±25.8 minutes,
P
<0.0001). No differences were observed in safety or efficacy.

Conclusions—

In-hospital procedures for thrombolysis proceed more slowly in IHSs than in OHSs. Thrombolysis is safe and efficient in IHS.
Evidence for the Efficacy of NXY-059 in Experimental Focal Cerebral Ischaemia Is Confounded by Study Quality
Authors: Macleod Malcolm R. , van der Worp H. Bart , Sena Emily S. , Howells David W. , Dirnagl Ulrich , Donnan Geoffrey A.
Published: July 2008

Background and Purpose—

The neutral results of the SAINT II trial have again highlighted difficulties translating neuroprotective efficacy from bench to bedside. Animal studies are susceptible to study quality biases, which may lead to overstatement of efficacy. We report the impact of study quality on published estimates of the efficacy of NXY-059 in animal models of stroke.

Methods—

We conducted a systematic review and stratified meta-analysis of published studies describing the efficacy of NXY-059 in experimental focal cerebral ischemia.

Results—

Overall, NXY-059 improved infarct volume by 43.3% (95% CI, 34.7 to 52.8). Only 2 of 9 publications reported randomization, concealment of treatment allocation, and blinded outcome assessment. Studies not reporting these quality items gave substantially higher estimates of efficacy than did higher-quality studies.

Conclusions—

The reported efficacy of NXY-059 in animal models of stroke is confounded by low study quality. The failure of SAINT II highlights the need for substantial improvements in the design, conduct, and reporting of animal studies; journals can play an important role in this by adopting standards for animal studies similar to those agreed over 10 years ago for clinical trials.
Evaluation of the Simultaneous Multiple Pulse Repetition Frequency Algorithm for Weather Radar
Authors: Ruzanski Evan , Hubbert John C. , Chandrasekar V.
Published: July 2008

Performance of the simultaneous multiple pulse repetition frequency algorithm (SMPRF) for recovery of mean power and mean Doppler velocity is investigated using simulated weather radar data. Operation and functionality of the algorithm is described; methods to estimate mean power values using statistical inversion and to estimate mean velocity from unevenly spaced autocorrelation function samples are presented and analyzed. A simulation technique for constructing multiple pulse repetition interval data is described and the algorithm performance results are presented for an example SMPRF code using three weather profiles. This leads to the development of an error structure related to factors influencing moment recovery, including finite-length time series effects, the effects of overlaid echoes that create an effective signal-to-noise ratio that limits moment recovery performance, and the effects of spectrum width and radar frequency related to coherence time.
Investigating Seasonal PR–TMI Calibration Differences
Authors: Dinku Tufa , Anagnostou Emmanouil N.
Published: July 2008

Seasonal differences in the calibration of overland passive microwave rain retrieval are investigated using Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI) and precipitation radar (PR). Four geographic regions from southern Africa, South Asia, the Amazon basin, and the southeastern United States are selected. Three seasons are compared for each region. Two scenarios of algorithm calibration are considered. In the first, the parameter sets are derived by calibrating the TMI algorithm with PR in each season. In the second scenario, common parameter sets are derived from the combined dataset of all three seasons. The parameter sets from both scenarios are then applied to the validation dataset of each season to determine the effect of seasonal calibration. Furthermore, calibration parameters from one season are also applied to another season, and results are compared against those derived using the season’s own parameters. Appreciable seasonal differences are observed for the U.S. region, while there are no significant differences between using individual seasonal calibration and the all-season calibration for the other regions. However, using one season’s parameter set to retrieve rainfall for another season is associated with increased uncertainty. It is also shown that the performance of the retrieval varies by season.
Boundary Layer Energy Transport and Cumulus Development over a Heated Mountain: An Observational Study
Authors: Demko J. Cory , Geerts Bart , Miao Qun , Zehnder Joseph A.
Published: July 2008

Aircraft and surface measurements of the boundary layer transport of mass and moisture toward an isolated, heated mountain are presented. The data were collected around the Santa Catalina Mountains in Arizona, 20–30 km in diameter, during the North American monsoon, on days with weak winds and cumulus congestus to cumulonimbus development over the mountain. Flights in the boundary layer around the mountain and surface station data indicate that mountain-scale anabatic surface wind generally develops shortly after sunrise, peaking at ∼1 m s−1 in strength close to solar noon. There is some evidence for a toroidal heat island circulation, with divergence in the upper boundary layer. The aircraft data and mainly the diurnal surface temperature and pressure patterns confirm that this circulation is driven by surface heating over the mountain. Three case studies suggest that growth spurts of orographic cumulus and cumulonimbus are not preceded by enhanced mountain-scale mass convergence near the surface, and that the decay of orographic deep convection is associated with divergence around the mountain.
A Sequential Variational Algorithm for Data Assimilation in Oceanography and Meteorology
Authors: Dobricic Srdjan
Published: July 2008

This study theoretically establishes a sequential variational (SVAR) method for the data assimilation in oceanography and meteorology defined on the model space. Requiring a significantly smaller amount of computer memory, theoretically SVAR gives the same optimal model state estimate as the four-dimensional variational data assimilation method. Its computational cost is similar to that of the four-dimensional variational data assimilation and representer methods. In addition to the optimal state estimates, SVAR computes error covariances at the end of the assimilation window. These advantageous properties of the new algorithm are obtained by combining the sequential methodology with suitable definitions of several new l2 norms, which implicitly provide required estimates.
Attributions for psychobiological changes in ecstasy/MDMA and other polydrug users
Authors: Soar K , Parrott A , Turner J
Published: July 2008

Abstract

Ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] use has been associated with a number of psychopathological problems. However, research suggests that reported symptoms might be associated more with heavy polydrug use in general rather than ecstasy per se. The current study aimed to determine the role of other drug use in reports of long-term effects by some ecstasy-polydrug users. Problematic ecstasy users ( n = 53), reporting problems which they attributed to ecstasy use, were compared with non-problematic ecstasy users ( n = 62), polydrug ( n = 62) and alcohol/nicotine using controls ( n = 111). Drug use was recorded, and positive and negative life changes were assessed along with which previous drug use, if any, they attributed these changes too. Both ecstasy groups reported higher drug use compared with polydrug controls. Polydrug and ecstasy users more often reported life changes compared with non-drug users, and ecstasy users appeared to experience more life changes than polydrug users, with problematic ecstasy users experiencing most alterations. Ecstasy users reported changes more to a combination of drugs than to one specific drug, suggesting that polydrug use in these groups has an impact on their life experiences. These findings emphasise that research into the psychological effects of ecstasy should not underestimate the role of other polydrug use.
Review: Problems associated with long-term treatment with selective serotonin reuptake inhibitors
Authors: Moret C. , Isaac M. , Briley M.
Published: July 2008

Although the selective serotonin reuptake inhibitors (SSRIs), which are now widely used as a first-line treatment for depression and many other psychiatric conditions, are generally well tolerated, they are not devoid of side effects. Most short-term treatment-related side effects of SSRIs are transient and disappear after a few days or weeks. However, following long-term treatment with the SSRIs, some serious adverse events may occur. Some of them can be difficult to recognise because they can resemble residual symptoms of depression. The most serious can be life threatening. They all have a negative influence on the patient’s quality of life and are frequently a prime reason for a lack of long-term compliance with the associated increased risk of recurrence of a depressive episode. This article is an overview of the more common adverse events, which are seen with non-acute treatment with the SSRIs.
Individual Values and Social Exchange Variables
Authors: Cohen Aaron , Keren Danny
Published: July 2008

This study examines the relationship between individual values and organizational commitment and the joint effect of commitment dimensions and individual values on employees' in-role performance and organizational citizenship behavior (OCB). The sample includes 539 secular Israeli teachers employed in 20 secular schools. The OCB data were provided by each school's principal. Hierarchical linear modeling analyses showed individual values, particularly collectivism, were related to affective and normative commitment above and beyond the effect of organizational justice. The findings also showed that individual values were related to three of the behavioral outcomes, also above and beyond the effect of the social exchange variables. The relationship of commitment forms to in-role performance and OCB was rather weak and raises some questions about the utility of organizational commitment in predicting these outcomes. The findings' implications for the continuation of research on the relationship between individual values and workplace attitudes and behaviors are discussed.
Strong position-dependent effects of sequence mismatches on signal ratios measured using long oligonucleotide microarrays
Authors: Rennie Catriona , Noyes Harry A , Kemp Stephen J , Hulme Helen , Brass Andy , Hoyle David C
Published: July 2008

Background

Microarrays are an important and widely used tool. Applications include capturing genomic DNA for high-throughput sequencing in addition to the traditional monitoring of gene expression and identifying DNA copy number variations. Sequence mismatches between probe and target strands are known to affect the stability of the probe-target duplex, and hence the strength of the observed signals from microarrays.

Results

We describe a large-scale investigation of microarray hybridisations to murine probes with known sequence mismatches, demonstrating that the effect of mismatches is strongly position-dependent and for small numbers of sequence mismatches is correlated with the maximum length of perfectly matched probe-target duplex. Length of perfect match explained 43% of the variance in log2 signal ratios between probes with one and two mismatches. The correlation with maximum length of perfect match does not conform to expectations based on considering the effect of mismatches purely in terms of reducing the binding energy. However, it can be explained qualitatively by considering the entropic contribution to duplex stability from configurations of differing perfect match length.

Conclusion

The results of this study have implications in terms of array design and analysis. They highlight the significant effect that short sequence mismatches can have upon microarray hybridisation intensities even for long oligonucleotide probes.

All microarray data presented in this study are available from the GEO database [1], under accession number [GEO: GSE9669]
Tuberculosis vaccine strain Mycobacterium bovis BCG Russia is a natural recA mutant
Authors: Keller Peter M , Böttger Erik C , Sander Peter
Published: July 2008

Background

The current tuberculosis vaccine is a live vaccine derived from Mycobacterium bovis and attenuated by serial in vitro passaging. All vaccine substrains in use stem from one source, strain Bacille Calmette-Guérin. However, they differ in regions of genomic deletions, antigen expression levels, immunogenicity, and protective efficacy.

Results

As a RecA phenotype increases genetic stability and may contribute restricting the ongoing evolution of the various BCG substrains while maintaining their protective efficacy, we aimed to inactivate recA by allelic replacement in BCG vaccine strains representing different phylogenetic lineages (Pasteur, Frappier, Denmark, Russia). Homologous gene replacement was achieved successfully in three out of four strains. However, only illegitimate recombination was observed in BCG substrain Russia. Sequence analyses of recA revealed that a single nucleotide insertion in the 5' part of recA led to a translational frameshift with an early stop codon making BCG Russia a natural recA mutant. At the protein level BCG Russia failed to express RecA.

Conclusion

According to phylogenetic analyses BCG Russia is an ancient vaccine strain most closely related to the parental M. bovis. We hypothesize that recA inactivation in BCG Russia occurred early and is in part responsible for its high degree of genomic stability, resulting in a substrain that has less genetic alterations than other vaccine substrains with respect to M. bovis AF2122/97 wild-type.
Profiling of serum and tissue high abundance acute-phase proteins of patients with epithelial and germ line ovarian carcinoma
Authors: Chen Yeng , Lim Boon-Kiong , Peh Suat-Cheng , Abdul-Rahman Puteri Shafinaz , Hashim Onn Haji
Published: July 2008

Background

Acute-phase response involves the simultaneous altered expression of serum proteins in association to inflammation, infection, injury or malignancy. Studies of the acute-phase response usually involve determination of the levels of individual acute-phase serum proteins. In the present study, the acute-phase response of patients with epithelial (EOCa) and germ-line (GOCa) ovarian carcinoma was investigated using the gel-based proteomic approach, a technique which allowed the simultaneous assessment of the levels of the acute-phase serum high abundance proteins. Data obtained were validated using ELISA and immunostaining of biopsy samples.

Results

Enhanced expression of clusterin (CLU), α1-antitrypsin, haptoglobin and leucine rich glycoprotein was detected in all patients. However, the levels of α1-antichymotrypsin (ACT) was only enhanced in EOCa patients, while patients with GOCa were typically characterized by elevated levels of ceruloplasmin but lower levels of α2-HS glycoprotein. The enhanced expression of CLU in EOCa and GOCa patients and up-regulated expression of ACT specifically in EOCa patients were confirmed by ELISA. Immunohistochemical staining of biopsy samples of EOCa and GOCa patients demonstrated correlation of the acute-phase protein expression.

Conclusion

Patients with EOCa and GOCa demonstrated distinctive aberrant expression of serum and tissue high abundance acute-phase proteins compared to negative control women.
The influence of survivin shRNA on the cell cycle and the invasion of SW480 cells of colorectal carcinoma
Authors: Zhonghong Liu , Lianjie Lin , Changqing Zheng , Ying He , Yu Jin , Yan Lin
Published: July 2008

Background

The objective was to understand the influence of Survivin plasmid with short hairpin RNA (shRNA) on the cell cycle, invasion, and the silencing effect of Survivin gene in the SW480 cell of colorectal carcinoma.

Methods

A eukaryotic expression vector, PGCH1/Survivin shRNA, a segment sequence of Survivin as target, was created and transfected into colorectal carcinoma cell line SW480 by the non-lipid method. The influence on the Survivin protein was analyzed by Western blotting, while the cell cycle, cell apoptosis were analyzed by flow cytometry, and invasion of the cell was analyzed by Transwell's chamber method.

Results

After the transfection of PGCH1/Survivin shRNA, the expression of Survivin protein in SW480 cells was dramatically decreased by 60.68%, in which the cells were stopped at G2/M phase, even though no apoptosis was detected. The number of transmembranous cells of the experimental group, negative control group, and blank control group were 14.46 ± 2.11, 25.12 ± 8.37, and 25.86 ± 7.45, respectively (P <0.05).

Conclusion

Survivin shRNA could significantly reduce the expression of Survivin protein and invasion of SW480 cells. Changes in cell cycle were observed, but no apoptosis was induced.
Health care costs, long-term survival, and quality of life following intensive care unit admission after cardiac arrest
Authors: Graf Jürgen , Mühlhoff Cecile , Doig Gordon S , Reinartz Sebastian , Bode Kirsten , Dujardin Robert , Koch Karl-Christian , Roeb Elke , Janssens Uwe
Published: July 2008

Introduction

The purpose of this study was to investigate the costs and health status outcomes of intensive care unit (ICU) admission in patients who present after sudden cardiac arrest with in-hospital or out-of-hospital cardiopulmonary resuscitation.

Methods

Five-year survival, health-related quality of life (Medical Outcome Survey Short Form-36 questionnaire, SF-36), ICU costs, hospital costs and post-hospital health care costs per survivor, costs per life year gained, and costs per quality-adjusted life year gained of patients admitted to a single ICU were assessed.

Results

One hundred ten of 354 patients (31%) were alive 5 years after hospital discharge. The mean health status index of 5-year survivors was 0.77 (95% confidence interval 0.70 to 0.85). Women rated their health-related quality of life significantly better than men did (0.87 versus 0.74; P < 0.05). Costs per hospital discharge survivor were 49,952 €. Including the costs of post-hospital discharge health care incurred during their remaining life span, the total costs per life year gained were 10,107 €. Considering 5-year survivors only, the costs per life year gained were calculated as 9,816 € or 14,487 € per quality-adjusted life year gained. Including seven patients with severe neurological sequelae, costs per life year gained in 5-year survivors increased by 18% to 11,566 €.

Conclusion

Patients who leave the hospital following cardiac arrest without severe neurological disabilities may expect a reasonable quality of life compared with age- and gender-matched controls. Quality-adjusted costs for this patient group appear to be within ranges considered reasonable for other groups of patients.
A field study of tubular daylight guidance installations
Authors: Marwaee M Al , Carter D J
Published: July 2008

The study reports achieved conditions and user views in 14 buildings equipped with passive zenithal tubular daylight guidance systems and electric lighting and, in some cases, windows. The daylight contribution was in the order of 35% of total design workstation illuminance giving daylight factors of between 0.5 and 1.0%. User views elicited by questionnaire suggest that tubular daylight guidance systems (TDGS) were inferior to windows in delivery of both quantity and quality of daylight. Guidelines for the design of future systems are suggested.
Splice Variant-Dependent Regulation of β-Cell Sodium-Calcium Exchange by Acyl-Coenzyme As
Authors: Hamming Kevin S. C. , Riedel Michael J. , Soliman Daniel , Matemisz Laura C. , Webster Nicola J. , Searle Gavin J. , MacDonald Patrick E. , Light Peter E.
Published: July 2008

The sodium-calcium exchanger isoform 1 (NCX1) is intimately involved in the regulation of calcium (Ca2+) homeostasis in many tissues including excitation-secretion coupling in pancreatic β-cells. Our group has previously found that intracellular long-chain acyl-coenzyme As (acyl CoAs) are potent regulators of the cardiac NCX1.1 splice variant. Despite this, little is known about the biophysical properties of β-cell NCX1 splice variants and the effects of intracellular modulators on their important physiological function in health and disease. Here, we show that the forward-mode activity of β-cell NCX1 splice variants is differentially modulated by acyl-CoAs and is dependent both upon the intrinsic biophysical properties of the particular NCX1 splice variant as well as the side chain length and degree of saturation of the acyl-CoA moiety. Notably, saturated long-chain acyl-CoAs increased both peak and total NCX1 activity, whereas polyunsaturated long-chain acyl-CoAs did not show this effect. Furthermore, we have identified the exon within the alternative splicing region that bestows sensitivity to acyl-CoAs. We conclude that the physiologically relevant forward-mode activity of NCX1 splice variants expressed in the pancreatic β-cell are sensitive to acyl-CoAs of different saturation and alterations in intracellular acyl-CoA levels may ultimately lead to defects in Ca2+-mediated exocytosis and insulin secretion.
Defining a Role for Novel Biomarkers in Acute Coronary Syndromes
Authors: Bonaca Marc P , Morrow David A
Published: July 2008

Background: Biomarkers play a pivotal role in the diagnosis and treatment of patients with cardiovascular disease. Active investigation has brought forward an increasingly large number of novel candidate markers; however, few of these markers have yet to be incorporated into routine clinical use.

Content: This review discusses biomarkers currently used in the setting of acute coronary syndromes. In this context, we assess the contemporary unmet needs for novel biomarkers in acute ischemic heart disease and the related challenges faced in developing new biomarkers to the point of integration into clinical practice. In particular, we address the impact of the availability of increasingly sensitive biomarkers of myocardial necrosis on the potential roles for novel biomarkers of inflammation, thrombosis, and ischemia.

Summary: Although active investigation has produced a growing list of candidate novel biomarkers for the care of patients with cardiovascular disease, it has become increasingly challenging to find appreciable incremental clinical benefit for their addition to existing markers, in particular newer, more analytically sensitive cardiac troponin assays. A major challenge for researchers and clinicians will be to demonstrate whether candidate novel markers are useful in improving diagnosis and guiding clinical treatment.
Competing Imperialisms and Hawaiian Authority: The Cannonading of Lāhainā in 1827
Authors: Kashay Jennifer Fish
Published: July 2008

Current historical and anthropological scholarship asserts that narratives of events are not necessarily historical “truths” but interpretations made by writers who are socially and culturally situated. This article analyzes multiple perspectives, including those of sailors, merchants, Natives, and missionaries, to gain insight into the ways in which imperial power in the Sandwich Islands was cultivated, negotiated, and redeployed. In particular, the article focuses on the 1827 firing of cannon at American missionaries in Lāhainā, Māui, by the British ship John Palmer in response to several Native Hawaiian women who boarded the ship to engage in sexual relations, and to the protest by a converted Native chief. This article argues that, although Native women's bodies had been commodified since Capt. James Cook's time, by the 1820s they served as sites of desire, contestation, and economic gain.
The Space‐Control Theory of Paramedic Scene‐Management
Authors: Campeau Anthony G.
Published: July 2008

Paramedics provide emergency service in physically hazardous and socially complex situations. These work settings present unique challenges in terms of managing resources and relationships in a multicrisis context, in order to enable the delivery of emergency patient care. Using data obtained from interviewing paramedics, this study demonstrates the usefulness of symbolic interaction theory for context analysis, by analyzing an important aspect of paramedic practice: scene management. Through grounded theory methodology, this study also presents the first interactionism‐based theory of how paramedics manage emergency scenes. This theory emphasizes the critical role of social processes in establishing social control in work spaces.
Structure, Agency, and Social Reality in Blumerian Symbolic Interactionism: The Influence of Georg Simmel
Authors: Low Jacqueline
Published: July 2008

Mead no doubt had a manifest influence on Blumer's thinking, and Blumer's acknowledgment of his indebtedness to Mead is a central feature of Blumer's writing. While I do not presume to question the importance Blumer assigns to the role played by Mead in the development of Blumerian symbolic interactionism, I argue that the perspective also owes much to the insights of Georg Simmel. In particular, a Simmelian flavor is evident in how Blumer addresses the core sociological issues of the nature of social reality, the nature of the relationship between the individual and society, and the nature of social action.
Role of transforming growth factor-β1 in gene expression and activity of estradiol and progesterone-generating enzymes in FSH-stimulated bovine granulosa cells
Authors: Zheng Xiaofeng , Price Christopher A , Tremblay Yves , Lussier Jacques G , Carrière Paul D
Published: July 2008

Survival and inhibitory factors regulate steroidogenesis and determine the fate of developing follicles. The objective of this study was to determine the role of transforming growth factor-β1 (TGFB1) in the regulation of estradiol-17β (E2) and progesterone (P4) secretion in FSH-stimulated bovine granulosa cells. Granulosa cells were obtained from 2 to 5 mm follicles and cultured in serum-free medium. FSH dose (1 and 10 ng/ml for 6 days) and time in culture (2, 4, and 6 days with 1 ng/ml FSH) increased E2 secretion and mRNA expression of E2-related enzymes cytochrome P450 aromatase (CYP19A1) and 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1), but not HSD17B7. TGFB1 in the presence of FSH (1 ng/ml) inhibited E2 secretion, and decreased mRNA expression of FSH receptor (FSHR), CYP19A1, and HSD17B1, but not HSD17B7. FSH dose did not affect P4 secretion and mRNA expression of 3β-hydroxysteroid dehydrogenase (HSD3B) and α-glutathione S-transferase (GSTA), but inhibited the amount of steroidogenic acute regulatory protein (STAR) mRNA. Conversely, P4 and mRNA expression of STAR, cytochrome P450 side-chain cleavage (CYP11A1), HSD3B, and GSTA increased with time in culture. TGFB1 inhibited P4 secretion and decreased mRNA expression of STAR, CYP11A1, HSD3B, and GSTA. TGFB1 modified the formation of granulosa cell clumps and reduced total cell protein. Finally, TGFB1 decreased conversion of androgens to E2, but did not decrease the conversion of estrone (E1) to E2 and pregnenolone to P4. Overall, these results indicate that TGFB1 counteracts stimulation of E2 and P4 synthesis in granulosa cells by inhibiting key enzymes involved in the conversion of androgens to E2 and cholesterol to P4 without shutting down HSD17B reducing activity and HSD3B activity.
Mesenchymal Stem Cells Alter Migratory Property of T and Dendritic Cells to Delay the Development of Murine Lethal Acute Graft-Versus-Host Disease
Authors: Li Hong , Guo ZiKuan , Jiang XiaoXia , Zhu Heng , Li XiuSen , Mao Ning
Published: July 2008

Due to the potent immunoregulatory capacity, mesenchymal stem cells (MSCs) have been used in clinical trials to treat acute graft-versus-host disease (aGvHD), although the detailed in vivo mechanisms remain elusive. In a murine lethal aGvHD model, MSCs delayed the development of the disease. Interestingly, we found that MSC infusion increased the number of T lymphocytes in the secondary lymphoid organs (SLOs). Since the expression of CD62L and CCR7 is prerequisite for lymphocyte migration into SLOs, the in vitro experiments revealed that in the presence of MSCs, T lymphocytes (including CD4+CD25+ regulatory T cells) preferred to take the naive-like phenotype (CD62L+/CCR7+) in mixed lymphocyte reaction and maintained the migratory activity elicited by secondary lymphoid tissue chemokine (SLC). Dendritic cells (DCs) are the initiator of immune response. CCR7 expression is pivotal for their maturation and migration into SLOs. However, CCR7 expression and SLC-driven migratory activity of DCs were remarkably suppressed by MSC coculture. The processes above were realized mainly through secretory mechanism. Consistently, MSC infusion maintained T lymphocytes to take CD62L+/CCR7+ phenotype and decreased the CCR7 expression and proportion of DCs in SLOs of aGvHD mice. In conclusion, the altered migratory properties of T cells and DCs might contribute to the immunosuppressive activity of transplanted MSCs in the setting of aGvHD.

Disclosure of potential conflicts of interest is found at the end of this article.
Stem Cell-Derived Therapeutic Myelin Repair Requires 7% Cell Replacement
Authors: Kiel Mary E. , Chen Cui P. , Sadowski Dorota , McKinnon Randall D.
Published: July 2008

Embryonic stem cells (ESCs) hold great potential for therapeutic regeneration and repair in many diseases. However, many challenges remain before this can be translated into effective therapy. A principal and significant limit for outcome evaluations of clinical trials is to define the minimal graft population necessary for functional repair. Here we used a preclinical model for quantitative analysis of stem cell grafts, with wild-type ESC grafted into myelin mutant shiverer hosts, to determine minimum graft levels for therapeutic benefit. Using a timed motor function test we identified three groups, including recipients indistinguishable from nongrafted shiverer controls (time [t] = 20.1 ± 1.1 seconds), mice with marginal improvement (t = 15.7 ± 1 seconds), and mice with substantial phenotype rescue (t = 5.7 ± 0.9 seconds). The motor function rescued chimeras also had a considerably extended life span (T50 > 128 days) relative to both shiverer (T50 = 108 days) and the nonrescued chimeras. Retrospective genotype analysis identified a strong correlation (r2 = 0.85) between motor function and ESC-derived chimerism, with > 7% chimerism required for rescue in this murine model of central nervous system myelin pathology. These results establish the minimal levels of engraftment to anticipate therapeutic repair of a cell-autonomous defect by cell transplant therapy.

Disclosure of potential conflicts of interest is found at the end of this article.
Reprogramming of Neural Progenitor Cells into Induced Pluripotent Stem Cells in the Absence of Exogenous Sox2 Expression
Authors: Eminli Sarah , Utikal Jochen , Arnold Katrin , Jaenisch Rudolf , Hochedlinger Konrad
Published: July 2008

Expression of the transcription factors Oct4, Sox2, Klf4, and c-Myc in mesodermal and endodermal derivatives, including fibroblasts, lymphocytes, liver, stomach, and β cells, generates induced pluripotent stem (iPS) cells. It remains unknown, however, whether cell types of the ectodermal lineage are equally amenable to reprogramming into iPS cells by the same combination of factors. To test this, we have isolated genetically marked neural progenitor cells (NPCs) from neonatal mouse brains and infected them with viral vectors expressing Oct4, Sox2, Klf4, and c-Myc. Infected NPCs gave rise to iPS cells that expressed markers of embryonic stem cells, showed demethylation of pluripotency genes, formed teratomas, and contributed to viable chimeras. In contrast to other somatic cell types, NPCs expressed high levels of endogenous Sox2 and thus did not require viral Sox2 expression for reprogramming into iPS cells. Our data show that in addition to mesoderm- and endoderm-derived cell types, neural progenitor cells of the ectodermal lineage can be reprogrammed into iPS cells, suggesting that in vitro reprogramming is a universal process. These results also imply that the combination of factors necessary for reprogramming is dependent on cellular context.

Disclosure of potential conflicts of interest is found at the end of this article.