bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative analysis of expression profiles of chemokines, chemokine receptors, and components of signaling pathways mediated by chemokines in eight cell types during rat liver regeneration
Authors: Chen Xiaoguang , Xu Cunshuan , Zhang Fuchun , Ma Ji
Published: August 2010

It has been documented that chemokines can positively regulate liver regeneration at the tissue level after partial hepatectomy. However, the precise mechanism of the effects of chemokines on regeneration at the cellular level remains poorly defined. In this study, 8 cell types from rat regenerating liver at 8 recovery time points after 2/3 hepatectomy were isolated and purified using Percoll density gradient centrifugation and immunomagnetic bead methods. The expression profiles of each cell type were monitored using a microarray. RT-PCR analysis was performed to validate the reliability of the microarray results. The results showed that, on the whole, the expression profiles of chemokine and receptor genes varied among different cell types; most genes involved in chemokine signaling pathways showed an increase in expression across the 8 liver cell types during liver regeneration. The implication of these genes in regeneration was analyzed by bioinformatics and systems biology methods. According to the microarray results and gene synergy, activation of chemokine signaling pathways at 24 h in biliary epithelial cells and at 2–12 h in dendritic cells may be triggered by CCL2–CCR2 and CCL7–CCR3, respectively; activation of Plc/Pkc and Pi3k/Akt pathways at 2–12 h in sinusoidal endothelial cells might be caused by CCL7–CCR1; and activation of the Src/Ptk, Src/Vav, and Plc/Pkc pathways at the priming stage may be related to the inductive effect of CCL7. These data suggest the potential relevance of the pro-inflammatory chemokines for liver regeneration at the cellular level.
Fat-1 gene modulates the fatty acid composition of femoral and vertebral phospholipids
Authors: Lau Beatrice Y.Y. , Ward Wendy E. , Kang Jing X. , Ma David W.L.
Published: August 2010

Dietary polyunsaturated fatty acid (PUFA) incorporation into bone may alter its metabolism through changes in the fatty acid composition of membrane phospholipids. Alteration of the membrane phospholipid fatty acid composition may influence bone cell signalling and, potentially, bone mineralization. The objective of this study was to use the fat-1 mouse, a transgenic model that synthesizes n-3 from n-6 PUFA, to determine if the fat-1 gene modulates the fatty acid composition of femoral and vertebral phospholipids, and if so, whether the fatty acid levels would correlate with bone mineral density (BMD) at both skeletal sites. Male and female wild-type and fat-1 mice were fed an AIN93-G diet, containing 10% safflower oil, from weaning to 12 weeks of age. The fatty acid composition of femoral and vertebral phospholipids was measured by gas liquid chromatography. At 12 weeks of age, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine fractions in the vertebrae of fat-1 mice had a significantly lower n-6/n-3 ratio than wild-type mice (p < 0.05). In fat-1 femurs, these fractions, along with phosphatidylinositol, had a lower n-6/n-3 ratio than wild-type mice (p < 0.001). Docosahexaenoic acid (DHA) was positively correlated with BMD in all fractions in the vertebrae, and in phosphatidylinositol and phosphatidylserine in the femur (p < 0.05). Overall, the fat-1 gene resulted in changes in the fatty acid composition of both femoral and vertebral phospholipids. Significant correlations between DHA and BMD may indicate a positive effect on bone mineralization.
Hypohydration and muscular fatigue of the thumb alter median nerve somatosensory evoked potentials
Authors: Montain Scott J. , Tharion William J.
Published: August 2010

The mechanisms by which dehydration impairs endurance performance remain unresolved but may involve alterations in afferent neural processing. The purpose of this study was to determine the effect of hypohydration on somatosensory evoked potentials (SEPs) at rest and during recovery from fatiguing exercise. Fourteen volunteers (12 men, 2 women) performed repetitive isometric thumb contractions (50% maximal voluntary contractions (MVC) and 100% MVC in a 5:1 ratio, each contraction separated by 5 s of rest) until exhaustion when euhydrated (EU) and when hypohydrated by 4% body mass (HY). SEPs were obtained from the median nerve. The results indicated that HY did not produce statistical differences in time to exhaustion (EU = 754 (SD 255); HY = 714 (SD 318) s; p = 0.66) or rate of muscle fatigue. However, HY was associated with greater subjective feelings of fatigue and loss of vigor after exhaustive exercise (p < 0.01). HY affected N20 latency with an interaction effect of hydration by fatigue state (EU-Rest: 18.5 (SD 1.6) ms; EU-Fatigue: 19.0 (SD 1.6) ms; HY-Rest: 18.3 (SD 1.3) ms; HY-Fatigue: 18.4 (SD 1.5) ms; p = 0.034), but N20 and N20-P22 amplitude responses were similar between HY and EU trials. We concluded that moderate water deficits appear to alter afferent signal processing within the cerebral cortex.
Lifestyle factors and other health measures in a Canadian university community
Authors: Pérusse-Lachance Émilie , Tremblay Angelo , Drapeau Vicky
Published: August 2010

With the increasing prevalence of obesity, there is a continuous search for effective obesity-prevention and health-promotion interventions. These interventions should be based on factors that have the potential to influence body weight and health. This study describes various health-related factors in a Canadian university community with the aim of developing more specific obesity interventions. A total of 3143 individuals completed an online questionnaire made up of 3 sections — on physical activity (PA), food habits, and other relevant lifestyle factors. The sampling error was ±3.3% with a 95% confidence interval. Results showed that 22.9% of students and 37.3% of staff members were either overweight or obese. Students had less desirable eating patterns than staff members in terms of fish, energy drink, and regular milk product intake, and both groups reported undesirable breakfast consumption and quality. Nevertheless, results also showed that a high percentage of individuals in both groups did not meet the recommendations for vegetable, fruit, and fish intake, or PA. Only a few gender differences were observed in eating habits. Soft drink and energy drink consumption was higher and breakfast consumption was lower in men, whereas a higher percentage of women did not meet the recommendations for vegetable, fruit, or fish consumption. Dieting behaviours, disinhibition susceptibility, and moderate-intensity (MIPA) were the 3 lifestyle factors most highly associated with overweight and obesity in both groups. Results also suggest that female students were highly preoccupied with their body weight. This study shows that overweight and obesity are problems in a university community, and that they are associated with many health-related lifestyle behaviours. Although most of the lifestyle factors and health measures examined are similar across groups and genders, some differences call for the development of health-promotion programs with specific targeting strategies.
The effect of short-term creatine loading on active range of movement
Authors: Sculthorpe Nicholas , Grace Fergal , Jones Peter , Fletcher Iain
Published: August 2010

During high-intensity exercise, intracellular creatine phosphate (PCr) is rapidly broken down to maintain adenosine triphosphate turnover. This has lead to the widespread use of creatine monohydrate as a nutritional ergogenic aid. However, the increase in intracellular PCr and the concomitant increase in intracellular water have not been investigated with regard to their effect on active range of movement (ROM). Forty male subjects (age, 24 ± 3.2 years) underwent restricted randomization into 2 equal groups, either an intervention group (CS) or a control group (C). The CS group ingested 25 g·day–1 of creatine monohydrate for 5 days, followed by 5 g·day–1 for a further 3 days. Before (24 h before starting supplementation (PRE) and after (on the 8th day of supplementation (POST)) this loading phase, both groups underwent goniometry measurement of the shoulder, elbow, hip, and ankle. Data indicated significant reductions in active ROM in 3 movements: shoulder extension (57 ±11.3° PRE vs. 48 ±11.2° POST, p < 0.01), shoulder abduction (183.4 ± 6.8° PRE vs. 180.3 ± 5.1° POST, p < 0.05), and ankle dorsiflexion (14.2 ± 4.7° PRE vs. 12.1 ± 6.4° POST, p < 0.01). There was also a significant increase in body mass for the CS group (83.6 ± 6.2 kg vs. 85.2 ± 6.3 kg, p < 0.05). The results suggest that short-term supplementation with creatine monohydrate reduces the active ROM of shoulder extension and abduction and of ankle dorsiflexion. Although the mechanism for this is not fully understood, it may be related to the asymmetrical distribution of muscle mass around those joints.
Effect of eccentric contraction velocity on muscle damage in repeated bouts of elbow flexor exercise
Authors: Barroso Renato , Roschel Hamilton , Ugrinowitsch Carlos , Araújo Rubens , Nosaka Kazunori , Tricoli Valmor
Published: August 2010

Eccentric exercise induces muscle damage, but controversy exists concerning the effect of contraction velocity on the magnitude of muscle damage, and little is known about the effect of contraction velocity on the repeated-bout effect. This study examined slow (60°·s–1) and fast (180°·s–1) velocity eccentric exercises for changes in indirect markers of muscle damage following 3 exercise bouts that were performed every 2 weeks. Fifteen young men were divided into 2 groups based on the velocity of eccentric exercise: 7 in the Ecc60 (60°·s–1) group, and 8 in the Ecc180 (180°·s–1) group. The exercise consisted of 30 maximal eccentric contractions of the elbow flexors at each velocity, in which the elbow joint was forcibly extended from 60° to 180° (full extension) on an isokinetic dynamometer. Changes in maximal voluntary isometric contraction strength, range of motion, muscle soreness, and plasma creatine kinase activity before and for 4 days after the exercise were compared in the 2 groups using a mixed-model analysis (group × bout × time). No significant differences between groups were evident for changes in any variables following exercise bouts; however, the changes were significantly smaller (p < 0.05) after the second and third bouts than after the first bout. These results indicate that the contraction velocity does not influence muscle damage or the repeated-bout effect.
Development of a new interconversion tool for hot mix asphalt (HMA) linear viscoelastic functions
Authors: Hu Sheng , Zhou Fujie
Published: August 2010

The relaxation modulus E(t), creep compliance D(t), and complex modulus E*(ω) are functions often used to characterize the linear viscoelastic (LVE) behavior of hot mix asphalt (HMA). Interconversions among these LVE functions are often required. To perform an interconversion, one of the key steps is to express both the source and target LVE functions in Prony series representations. To obtain the corresponding Prony series coefficients, the collocation method and linear least squares method were often used in the past. However, the problem encountered with these two methods is in manually assigning part of the Prony series coefficients; resulting in unrealistic or negative Prony coefficients and big discrepancies between the fitting data and the original data. To address this problem, this paper developed a new algorithm by incorporating the Levenberg–Marquardt method. This new algorithm has four unique features, it (1) allows all the Prony series coefficients to be freely adjustable, (2) guarantees all positive Prony series coefficients, (3) determines all Prony series coefficients automatically and simultaneously, and (4) ensures very accurate interconversion through the fact that the fitting curve almost completely coincides with the original curve. Furthermore, to facilitate the implementation of practical applications of this new algorithm, it was incorporated into a stand-alone, windows-based software named “LVEmaster”. The simplicity and accuracy of this new interconversion software was demonstrated through a series of interconversions among HMA LVE functions.
Damage modeling of bituminous mixtures considering mixture microstructure, viscoelasticity, and cohesive zone fracture
Authors: Kim Yong-Rak , Aragão Francisco T.S. , Allen David H. , Little Dallas N.
Published: August 2010

This paper describes the development and application of a computational modeling approach incorporated with pertinent laboratory testing that can be used to predict fracture damage performance of bituminous paving mixtures. In the model, material viscoelasticity, mixture microstructure, and cohesive zone fracture properties are implemented within a finite element method, which is intended to simulate nonlinear-inelastic microscale fracture and its propagation to complete failure in bituminous mixtures. The model is applied to different materials, and the resulting model simulations are compared to experimental results for model validation. With some limitations and technical issues to be overcome in the future, the model presented herein clearly demonstrates several advancements based on its features accounting for material viscoelasticity, heterogeneity, and cohesive zone fracture. Potentially, the model can provide significant savings in time and costs and can also be used to improve currently available design analysis tools.
Fibre-reinforced polymer composite shear reinforcement: performance evaluation in concrete beams and code prediction
Authors: Ahmed Ehab A. , El-Salakawy Ehab F. , Benmokrane Brahim
Published: August 2010

This paper evaluates the performance of carbon and glass fibre-reinforced polymer (FRP) stirrups and the accuracy of the shear design provisions incorporated in the currently available design codes and guidelines. A total of seven large-scale T-beams were constructed and tested: three reinforced with carbon fibre-reinforced polymer (CFRP) stirrups, three reinforced with glass fibre-reinforced polymer (GFRP) stirrups, and one reinforced with a steel stirrup for comparison, when applicable. The test results revealed that the design strength of the tested beams is not affected by the reduced strength of FRP stirrups at bend locations. Also, the recent CAN/CSA-S6 update is capable of adequately predicting the shear strength of the beam specimens reinforced with FRP stirrups. The software, Response-2000, which is based on the modified compression field theory (MCFT), predicted well the shear strength and the average strain in the stirrups of the tested beams; however, it overestimated the shear crack width.
Earthquake-induced hydrodynamic forces on reservoir roofs
Authors: Isaacson Michael
Published: August 2010

The present paper describes the hydrodynamic loads on the roof of a water-filled reservoir or storage tank due to earthquake-induced sloshing. Initially, the paper summarizes available solutions for the water surface elevation in a rectangular reservoir subjected to harmonic and earthquake base motions, and as well an available formulation for the force on the roof of a rectangular reservoir. With this background, a new formulation for the force on the roof is developed, and selected results based on this are presented. A recommended design procedure is thereby proposed, and an example application is provided. The potential extension of the proposed formulation to other reservoir configurations is discussed. Although a validation of the proposed formulation based on laboratory test results is needed, it is suggested that in the interim the proposed formulation is adopted for design.
Triple-ring phase representation scheme for exclusive median bus lane signals
Authors: Kim Jin-Tae
Published: August 2010

Current traffic signal operation at intersections on exclusive median bus lane (EMBL) corridors prevents concurrent activation of non-bus through and left-turn phases due to the conflict between left turns and buses, as EMBL lies along the conflict side of a non-bus left-turn lane. This has lowered the performance of traffic signal operation on EMBL corridors. Recognizing the need for exclusive bus signals, this paper proposes a triple-ring phase representation scheme to harmonize the non-bus phases and exclusive bus phases at EMBL intersections. The proposed triple-ring phase representation scheme increases the efficiency of traffic signal operation on EMBL corridors.
The first series of alkali dipyrrinato complexes
Authors: Ali Adeeb Al-Sheikh , Cipot-Wechsler Judy , Crawford Sarah M. , Selim Omar , Stoddard Rhonda L. , Cameron T. Stanley , Thompson Alison
Published: August 2010

The first series of alkali dipyrrinato complexes is reported, encompassing lithium, sodium, and potassium salts of meso-unsubstituted and meso-aryl-substituted derivatives. By varying the substituents at the meso position, the intermolecular distance between the two nitrogen atoms and thus the κ2-N,N-bidentate bite angle was altered, as confirmed by comparison of crystallographic structures of dipyrrin free-bases in the solid-state. The mode of bonding varies as the ionic radius of the metal ion increases: solid-state structures reveal lithium to be accommodated in the plane of the dipyrrinato unit, whilst sodium is accommodated out of plane. The reactivity of analogous lithium, sodium, and potassium dipyrrinato complexes increases as the ionic radius of the metal ion increases, in keeping with the concept that the complexes tend towards an increasingly ionic nature as the size of the alkali metal increases.
Concerning the conformational preferences of the 2-cyano derivatives of oxane, thiane, and selenane
Authors: Benn Michael H. , Huang Yan Yan , Johannsen Frank , O’Reilly Michael , Parvez Masood , Rauk Arvi , Sorensen Ted
Published: August 2010

This paper investigates the origin of the anomalous anomeric effect in merosinigrin, a 2-cyanothiane in which the cyano group is axial as expected for the anomeric effect, but in which bond distances are opposite to that expected from the nS→[Formula: see text] orbital interaction, which underlies the classical anomeric effect. The model compounds, 2-cyanooxane, 2-cyanothiane, and 2-cyanoselenane, were synthesized and studied both experimentally and computationally. Both the thia and selena systems displayed an even higher preference for the axial conformation than the oxa system but also exhibited the bond length anomalies found previously in merosinigren. Natural bond order (NBO) analysis of the B3LYP/6–311+G(3df,2p) wave functions of the axial and equatorial forms of the three systems confirmed a weakening of the n→σ* orbital interaction in the O, S, and Se series, and a strengthening of a σ–π*(CN) interaction that explains the bond length reversals observed in the S and Se systems. It also revealed a new mechanism, n→π*, namely, a through-space interaction between the nonbonded lone pair electrons of the heteroatom and the π* orbital of the cyano group, which selects for the axial conformation.
Serine–Ca2+versus serine–Cu2+complexes — A theoretical perspective
Authors: Lamsabhi Al Mokhtar , Mó Otilia , Yáñez Manuel
Published: August 2010

The association of Ca2+and Cu2+to serine was investigated by means of B3LYP DFT calculations. The [serine–M]2+(M = Ca, Cu) potential energy surfaces include, as does the neutral serine, a large number of conformers, in which a drastic reorganization of the electron density of the serine moiety is observed. This leads to significant changes in the number and strength of the intramolecular hydrogen bonds existing in the neutral serine tautomers. In some cases, a proton is transferred from the carboxylic OH group to the amino group and accordingly, some of the more stable [serine–M]2+complexes can be viewed as the result of the interaction of the zwiterionic form of serine with the doubly charged metal ion. Whereas the interaction between Ca2+and serine is essentially electrostatic, that between Cu2+and serine has a non-negligible covalent character, reflected in larger electron densities at the bond critical points between the metal and the base, in the negative values of the electron density between the two interacting systems, and in much larger Cu2+than Ca2+binding energies. More importantly, the interaction with Cu2+is followed by a partial oxidation of the base, which is not observed when the metal ion is Ca2+. The main consequence is that in Cu2+complexes a significant acidity enhancement of the serine moiety takes place, which strongly favors the deprotonation of the [serine–Cu]2+complexes. This is not the case for Ca2+complexes. Thus, [serine–Ca]2+complexes, like those formed by urea, thiourea, selenourea, or glycine, should be detected in the gas phase. Conversely, the complexes with Cu2+should deprotonate spontaneously and therefore only [(serine–H)–Cu]+monocations should be experimentally accessible.
A computational study of methanol-to-hydrocarbon conversion — Towards the design of a low-barrier process
Authors: Chan Bun , Radom Leo
Published: August 2010

Computational quantum chemistry has been employed to examine the production of ethylene with methanol-to-hydrocarbon (MTH) processes via a carbon pool mechanism. We find that the M05-2X functional performs well for the types of reactions that are involved. The methylation reactions of the aromatic cocatalyst are the most energy-demanding steps in the process. For the subsequent production of C2H4, we have identified a low-energy pathway that involves multiple methyl shifts, followed by concerted deprotonation and C2H4 elimination. The substitutions of the Al and Si atoms in the participating Si–OH–Al moiety of zeolite catalysts with Ga and Ge do not lead to lower barriers for the methylation reactions, nor does the use of a more electron-rich aromatic cocatalyst. However, we find that the use of two cocatalysts, a nucleophile and an aromatic carbon pool, can provide an overall low-energy pathway for the MTH process.
Phaseolus vulgaris is nodulated in northern Spain by Rhizobium leguminosarum strains harboring two nodC alleles present in American Rhizobium etli strains: biogeographical and evolutionary implications
Authors: García-Fraile Paula , Mulas-García Daniel , Peix Alvaro , Rivas Raúl , González-Andrés Fernando , Velázquez Encarna
Published: August 2010

In this study a collection of rhizobial strains were isolated from effective nodules of Phaseolus vulgaris in a wide region of northern Spain, which is the major producer region of this legume in Spain. The analysis of their core genes, rrs, atpD, and recA, and the 16S–23S intergenic spacer showed that all isolates belong to the phylogenetic group of Rhizobium leguminosarum and some of them were identical to those of strains nodulating Vicia or Trifolium . None of the isolates was identified as Rhizobium etli ; however, all of them carry the nodC alleles α and γ harboured by American strains of this species. These alleles were also found in strains nodulating P. vulgaris in southern Spain identified as R. etli. These results suggest that R. etli was carried from America to Spain with common bean seeds, but that they could have found difficulties persisting in the soils of northern Spain, probably because of the climatic conditions. The symbiotic genes of this species could have been transferred, after the arrival of P. vulgaris, to strains of R. leguminosarum already present in northern Spanish soils.
Microbiote et probiotiques : impact en santé humaine
Authors: Coudeyras Sophie , Forestier Christiane
Published: August 2010

All accessible mucous membranes of the human body are colonized by an abundant and diversified microbial flora called microbiota. Recent studies have shown that these microorganisms, long regarded as purely commensal, have essential beneficial effects on human health. Thus, numerous human ailments are linked to dysbiosis; that is, imbalances in the microflora composition. The administration of probiotic microorganisms could, in some situations, provide substantial relief from such disorders. These live microorganisms, which, according to the definition, confer a health benefit to the host when administered in adequate amounts, are often derived from human flora and belong mostly to lactic acid bacteria, in particular to the genus Lactobacillus . The constant improvement of knowledge of the role of human microbiota and the growing popularity of probiotics are now opening the door to new prophylactic and therapeutic strategies in human health.
Identification of transcripts up-regulated in asexual and sexual fruiting bodies of the Dutch elm disease pathogenOphiostoma novo-ulmi
Authors: Jacobi Volker , Dufour Josée , Bouvet Guillaume F. , Aoun Mirella , Bernier Louis
Published: August 2010

Suppression subtractive hybridization cDNA libraries were prepared from asexual synnemata (S-lib) and sexual perithecia (P-lib) fruiting bodies of the Dutch elm disease pathogen Ophiostoma novo-ulmi subsp. novo-ulmi isolate H327 (mating-type MAT1-1) consisting of 630 and 401 cDNA clones, respectively. Both libraries were differentially screened in duplicate with forward and reverse subtracted probes. Up-regulated S-lib transcripts included those with homologies to phosphoenolpyruvate carboxykinase and aquaporin. Up-regulated P-lib transcripts included those with homologies to aspartyl proteinase, DNA lyase 2, and part of a mating-type (MAT) protein containing a DNA-binding domain of the high-mobility group (HMG) type. Phylogenetic analyses of HMG domains present within the putative O. novo-ulmi MAT protein and within MAT1-1-3 and MAT1-2-1 proteins of other ascomycete fungi identified the O. novo-ulmi protein as a homologue of the MAT1-1-3 protein, which represents part of the so far uncharacterized O. novo-ulmi MAT1-1 idiomorph. Reverse transcription – quantitative real-time PCR indicated up-regulation of the MAT1-1-3 homologue in O. novo-ulmi perithecia and synnemata. The present work identifies, for the first time, proteins involved in the formation of asexual and sexual fruiting bodies in O. novo-ulmi and should be of interest to researchers concerned with reproduction, mating type, and sexuality of filamentous ascomycete fungi.
Rapid identification of Listeria species and screening for variants by melting curve and high-resolution melting curve analyses of the intergenic spacer region of the rRNA gene
Authors: Wang Jun , Yamada Shoichi , Ohashi Eiji
Published: August 2010

The presence of any Listeria species in food may be an indicator of poor hygiene in food processing facilities. The biochemical identification of Listeria species is laborious and time consuming. Therefore, the development of novel identification methods that are rapid and simple to perform would be an asset. In this study, large intergenic spacer region amplicons of 343–374 bp were generated from 207 Listeria isolates. The melting curve analysis of these amplicons specifically classified all isolates into 6 Listeria species and generated 11 high-resolution melting (HRM) curve profiles. In this study, 3 HRM profiles were found in Listeria monocytogenes and Listeria innocua , and 2 were found in Listeria seeligeri . Sequencing of the amplicons representing these profiles revealed that each profile related to a unique sequence. The smallest difference recognized in this study was 1 nt. The results represented in this study show that HRM curve analysis of Listeria intergenic spacer sequences is a simple, quick, and reproducible method of simultaneously identifying 6 Listeria species and screening for variants. In particular, the completion of both reaction and analysis in a closed tube saves time by eliminating the separate steps and lowers the risk of contamination.
Darusentan is a potent inhibitor of endothelin signaling and function in both large and small arteriesThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.
Authors: Liang Faquan , Glascock Christopher B. , Schafer Denise L. , Sandoval Jennifer , Cable LouAnn , Melvin Lawrence , Hartman J. Craig , Pitts Kelly R.
Published: August 2010

Endothelin is a potent vasoconstrictor often up-regulated in hypertension. Endothelin vasoconstriction is mediated via the G-protein coupled endothelin A (ETA) receptor present on vascular smooth muscle. Endothelin receptor antagonists (ERAs) have been shown to antagonize ET-induced vasoconstriction. We describe the primary pharmacology of darusentan, a propanoic acid based ERA currently in phase 3 clinical trials for resistant hypertension. Darusentan was tested in membrane-, cell-, and tissue-based assays to determine its biochemical and functional potency. Rat aortic vascular smooth muscle cells (RAVSMs) were characterized using flow cytometry. RAVSM membrane fractions tested in saturation experiments exhibited moderate endothelin receptor density. Receptor counting revealed that >95% of the endothelin receptors in these fractions were the ETAsubtype. (S)-Darusentan competed for radiolabeled endothelin binding in RAVSM membranes with single-site kinetics, exhibiting a Ki= 13 nmol/L. (R)-Darusentan exhibited no binding activity. In cultured RAVSMs, endothelin induced increases in inositol phosphate and Ca2+signaling, both of which were attenuated by (S)-darusentan in a concentration-dependent manner. In isolated endothelium-denuded rat aortic rings, (S)-darusentan inhibited endothelin-induced vascular contractility with a pA2= 8.1 ± 0.14 (n = 4 animals; mean ± SD). (R)-Darusentan had no effect. The vasorelaxant potency of (S)-darusentan did not change when determined in isolated denuded rat mesenteric arterioles, suggesting a similar mode of action in both conductance and resistance arteries. In vascular smooth muscle, (S)-darusentan is an ERA with high affinity for the ET receptor, which in this preparation is predominantly ETAreceptors. (S)-Darusentan inhibits endothelin-induced signaling related to pro-contractile activity and is a potent inhibitor of vasoconstriction in large and small arteries.
STRUCTURAL, ELECTRICAL AND MAGNETIC STUDIES OF Li–Zn–Ni FERRITES
Authors: SOIBAM IBETOMBI , PHANJOUBAM SUMITRA , PRAKASH CHANDRA , VERMA HARISH CHANDRA , KOTNALA R. K.
Published: August 2010

Ni substituted Li – Zn ferrites with compositional formulas Li 0.4-0.5x Zn 0.2 Ni x Fe 2.4-0.5x O 4, where x = 0.02 ≤ x ≤ 0.1 in steps of 0.02, is synthesized by a chemical method using citrate precursors. The prepared ferrites are investigated for their structural, electrical and magnetic properties. Ni substitution significantly changes the characteristic properties of Li – Zn ferrites. There is an increase in grain growth as determined from SEM measurements. An increase in the room temperature DC resistivity is observed with the addition of Ni . The room temperature initial permeability shows an overall decrease with Ni concentration, which is explained with respect to saturation magnetization and supplemented by nuclear hyperfine field obtained from Mössbauer analysis. The variation of the complex permeability with frequency is measured over the frequency range of 100 Hz–1 MHz and dispersion is found. A possible mechanism contributing to the above process is discussed.
PARABOLIC FITTING OF ISOTONIC POWER-ANGLE CURVES TO EVALUATE MOTOR DEFICITS IN PATIENTS SUBMITTED TO ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION
Authors: CORAZZA IVAN , FOSCHI ELIA , BELLI GUIDO , MARZOVILLO RAFFAELLA , LATESSA PASQUALINO MAIETTA , TENTONI CLAUDIO
Published: August 2010

Power-angle curves, describing the isotonic sub-maximal movement of the lower extremities, are better means to evaluate the effects of training protocols and to highlight functional differences between the legs. The aim of this work was to compare the morphology of power-angle curves of pathological subjects (PS) and healthy subjects (HS) and to evaluate the feasibility of this approach to discriminate between pathological and healthy legs. Isotonic evaluation with leg-extension machine was performed on 46 HS and 16 PS previously submitted to knee surgery. The healthy group comprised 33 elderly healthy subjects (EHS) (mean: 65 years) and 13 young healthy subjects (YHS) (mean: 35 years) and the influence of age on the curves was evaluated. All subjects performed a sub-maximal movement with the legs working alone and together. Each curve was interpolated with a parabolic function and the R 2 Pearson coefficient was used as a score for morphological regularity. R 2 of curves of PS obtained with legs working alone were statistically different from those of the HS group, considering both YHS and EHS (p < 0.05). Statistically significant differences between YHS and EHS (p < 0.01) show the importance of age in the modality of performing movements.
NEW CHARACTERIZATION METHODOLOGY FOR SKIN TUMORS CLASSIFICATION
Authors: MESSADI M. , BESSAID A. , TALEB-AHMED A.
Published: August 2010

Our objective in this paper is to introduce the efficacies of texture in the interpretation of color skin images. Melanoma is the most malignant skin tumor, growing in melanocytes, the cells responsible for pigmentation. This type of cancer is nowadays increasing rapidly; its related mortality rate increases by more modest and inversely proportional to the thickness of the tumor. This rate can be decreased by an earlier detection and better prevention. Using the features of skin tumors, such as color, symmetry, and border regularity, an attempt is made to determinate if the skin tumor is a melanoma or a benign tumor. In this work, we are interested by adding to form parameters such as the asymmetry (A) and the shape irregularities of skin tumors (B), the textural parameters to estimate colors in dermatoscopic images. In this case, the images are analyzed using textural parameters computed in several directions. These parameters and the form parameters are added to obtain a better classification results. A statistical analysis is performed over these ratios to select the most highly discriminating textural parameters. The method has been tested successfully on 144 images and we found significant differences between the lesions (melanoma and benign). Finally, these parameters (form and parameters of texture selected) are only use to classify the benign and malignancy of the skin lesion. A multilayer neural network is employed to differentiate between malignant tumors and benign lesions.
Vagal control of pancreatic β-cell proliferation
Authors: Lausier James , Diaz William C. , Roskens Violet , LaRock Kyla , Herzer Kristi , Fong Christopher G. , Latour Martin G. , Peshavaria Mina , Jetton Thomas L.
Published: August 2010

The physiological mechanisms that preserve pancreatic β-cell mass (BCM) are not fully understood. Although the regulation of islet function by the autonomic nervous system (ANS) is well established, its potential roles in BCM homeostasis and compensatory growth have not been adequately explored. The parasympathetic vagal branch of the ANS serves to facilitate gastrointestinal function, metabolism, and pancreatic islet regulation of glucose homeostasis, including insulin secretion. Given the functional importance of the vagus nerve and its branches to the liver, gut, and pancreas in control of digestion, motility, feeding behavior, and glucose metabolism, it may also play a role in BCM regulation. We have begun to examine the potential roles of the parasympathetic nervous system in short-term BCM maintenance by performing a selective bilateral celiac branch-vagus nerve transection (CVX) in normal Sprague-Dawley rats. CVX resulted in no detectable effects on basic metabolic parameters or food intake through 1 wk postsurgery. Although there were no differences in BCM or apoptosis in this 1-wk time frame, β-cell proliferation was reduced 50% in the CVX rats, correlating with a marked reduction in activated protein kinase B/Akt. Unexpectedly, acinar proliferation was increased 50% in these rats. These data suggest that the ANS, via the vagus nerve, contributes to the regulation of BCM maintenance at the level of cell proliferation and may also mediate the drive for enhanced growth under physiological conditions when insulin requirements have increased. Furthermore, the disparate effects of CVX on β-cell and acinar cells suggest that the endocrine and exocrine pancreas respond to different neural signals in regard to mass homeostasis.
Equal Degrees of Object Selectivity for Upper and Lower Visual Field Stimuli
Authors: Strother Lars , Aldcroft Adrian , Lavell Cheryl , Vilis Tutis
Published: August 2010

Functional MRI (fMRI) studies of the human object recognition system commonly identify object-selective cortical regions by comparing blood oxygen level–dependent (BOLD) responses to objects versus those to scrambled objects. Object selectivity distinguishes human lateral occipital cortex (LO) from earlier visual areas. Recent studies suggest that, in addition to being object selective, LO is retinotopically organized; LO represents both object and location information. Although LO responses to objects have been shown to depend on location, it is not known whether responses to scrambled objects vary similarly. This is important because it would suggest that the degree of object selectivity in LO does not vary with retinal stimulus position. We used a conventional functional localizer to identify human visual area LO by comparing BOLD responses to objects versus scrambled objects presented to either the upper (UVF) or lower (LVF) visual field. In agreement with recent findings, we found evidence of position-dependent responses to objects. However, we observed the same degree of position dependence for scrambled objects and thus object selectivity did not differ for UVF and LVF stimuli. We conclude that, in terms of BOLD response, LO discriminates objects from non-objects equally well in either visual field location, despite stronger responses to objects in the LVF.
Long-Term Outcomes for Patients with Prostate Cancer Having Intermediate and High-Risk Disease, Treated with Combination External Beam Irradiation and Brachytherapy
Authors: Dattoli Michael , Wallner Kent , True Lawrence , Bostwick David , Cash Jennifer , Sorace Richard
Published: August 2010

Background. Perception remains that brachytherapy-based regimens are inappropriate for patients having increased risk of extracapsular extension (ECE).Methods. 321 consecutive intermediate and high-risk disease patients were treated between 1/92 and 2/97 by one author (M. Dattoli) and stratified by NCCN guidelines. 157 had intermediate-risk; 164 had high-risk disease. All were treated using the combination EBRT/brachytherapy hormones. Biochemical failure was defined using PSA and nadir +2 at last followup. Nonfailing patients followup was median 10.5 years. Both biochemical data and original biopsy slides were independently rereviewed at an outside institution.Results. Overall actuarial freedom from biochemical progression at 16 years was 82% (89% intermediate, 74% high-risk) with failure predictors: Gleason score and PSA . Hormonal therapy did not affect failure rates .Conclusion. This study helps to strengthen the rationale for brachytherapy-based regimens as being both durable and desirable treatment options for such patients. Prospective studies are justified to confirm these positive results.
Lower Extremity Ulcers in Systemic Sclerosis: Features and Response to Therapy
Authors: Shanmugam Victoria K. , Price Patricia , Attinger Christopher E. , Steen Virginia D.
Published: August 2010

Nondigital lower extremity ulcers are a difficult to treat complication of scleroderma, and a significant cause of morbidity. The purpose of this study was to evaluate the prevalence of nondigital lower extremity ulcers in scleroderma and describe the associations with autoantibodies and genetic prothrombotic states. A cohort of 249 consecutive scleroderma patients seen in the Georgetown University Hosptial Division of Rheumatology was evaluated, 10 of whom had active ulcers, giving a prevalence of 4.0%. Patients with diffuse scleroderma had shorter disease duration at the time of ulcer development (mean 4.05 years±0.05) compared to those with limited disease (mean 22.83 years±5.612,Pvalue .0078). Ulcers were bilateral in 70%. In the 10 patients with ulcers, antiphospholipid antibodies were positive in 50%, and genetic prothrombotic screen was positive in 70% which is higher than expected based on prevalence reports from the general scleroderma population. Of patients with biopsy specimens available(n=5), fibrin occlusive vasculopathy was seen in 100%, and all of these patients had either positive antiphospholipid antibody screen, or positive genetic prothrombotic profile. We recommend screening scleroderma patients with lower extremity ulcers for the presence of anti-phospholipid antibodies and genetic prothrombotic states.
Genome Size Study in the Valerianaceae: First Results and New Hypotheses
Authors: Hidalgo Oriane , Mathez Joël , Garcia Sònia , Garnatje Teresa , Pellicer Jaume , Vallès Joan
Published: August 2010

The purpose of this study is to provide a new focus to contribute, from the perspective of genomic evolution, towards a better understanding of the Valerianaceae evolutionary history. Chromosome numbers were determined by Feulgen staining in 24 populations of 18 species (first count for Valerianella multidentata, 2n=2x=14–16), and DNA contents were assessed by flow cytometry in 74 populations of 35 species (first assessments in all taxa but Centranthus ruber). A molecular phylogeny based on the trnL-trnF and including 41 new sequences was established, with the first DNA sequence for Centranthus nevadensis, Valeriana rotundifolia, V. saxatilis, Valerianella multidentata, and V. turgida. This work is the first large genome size study devoted to the Valerianaceae, showing a range of DNA amounts from 2C=0.39 pg (Valerianella turgida) to 2C=8.32 pg (Valeriana officinalis). At the family level, changes in basic chromosome number and genome size coincide with or precede major shifts in the evolutionary history of the group, such as those concerning stamen number and floral symmetry.
From NPC Therapeutic Target Identification to Potential Treatment Strategy
Authors: Lan Ming-Ying , Chen Chi-Long , Lin Kuan-Ting , Lee Sheng-An , Yang Wu-Lung R. , Hsu Chun-Nan , Wu Jaw-Ching , Ho Ching-Yin , Lin Jin-Ching , Huang Chi-Ying F.
Published: August 2010

Nasopharyngeal carcinoma (NPC) is relatively rare in Western countries but is a common cancer in southern Asia. Many differentially expressed genes have been linked to NPC; however, how to prioritize therapeutic targets and potential drugs from unsorted gene lists remains largely unknown. We first collected 558 upregulated and 993 downregulated NPC genes from published microarray data and the primary literatures. We then postulated that conversion of gene signatures into the protein-protein interaction network and analyzing the network topologically could provide insight into key regulators involved in tumorigenesis of NPC. Of particular interest was the presence of cliques, called fully connected subgraphs, in the inferred NPC networks. These clique-based hubs, connecting with more than three queries and ranked higher than other nodes in the NPC protein-protein interaction network, were further narrowed down by pathway analysis to retrieve 24 upregulated and 6 downregulated bottleneck genes for predicting NPC carcinogenesis. Moreover, additional oncogenes, tumor suppressor genes, genes involved in protein complexes, and genes obtained after functional profiling were merged with the bottleneck genes to form the final gene signature of 38 upregulated and 10 downregulated genes. We used the initial and final NPC gene signatures to query the Connectivity Map, respectively, and found that target reduction through our pipeline could efficiently uncover potential drugs with cytotoxicity to NPC cancer cells. An integrative Web site (http://140.109.23.188:8080/NPC) was established to facilitate future NPC research. This in silico approach, from target prioritization to potential drugs identification, might be an effective method for various cancer researches. Mol Cancer Ther; 9(9); 2511–23. ©2010 AACR.
Urokinase Plasminogen Activator Receptor and/or Matrix Metalloproteinase-9 Inhibition Induces Apoptosis Signaling through Lipid Rafts in Glioblastoma Xenograft Cells
Authors: Chetty Chandramu , Lakka Sajani S. , Bhoopathi Praveen , Gondi Christopher S. , Veeravalli Krishna Kumar , Fassett Daniel , Klopfenstein Jeffrey D. , Dinh Dzung H. , Gujrati Meena , Rao Jasti S.
Published: August 2010

Small interfering RNA (siRNA)-mediated transcriptional knockdown of urokinase plasminogen activator receptor (uPAR) and matrix metalloproteinase-9 (MMP-9), alone or in combination, inhibits uPAR and/or MMP-9 expression and induces apoptosis in the human glioblastoma xenograft cell lines 4910 and 5310. siRNA against uPAR (pU-Si), MMP-9 (pM-Si), or both (pUM-Si) induced apoptosis and was associated with the cleavage of caspase-8, caspase-3, and poly(ADP-ribose) polymerase. Furthermore, protein levels of the Fas receptor (APO-1/CD-95) were increased following transcriptional inactivation of uPAR and/or MMP-9. In addition, Fas siRNA against the Fas death receptor blocked apoptosis induced by pU-Si, pM-Si, or pUM-Si, thereby indicating the role for Fas signaling in pU-Si–, pM-Si–, or pUM-Si–mediated apoptotic cell death of human glioma xenograft cells. Thus, transcriptional inactivation of uPAR and/or MMP-9 enhanced localization of Fas death receptor, Fas-associated death domain-containing protein, and procaspase-8 into lipid rafts. Additionally, disruption of lipid rafts with methyl β cyclodextrin prevented Fas clustering and pU-Si–, pM-Si–, or pUM-Si–induced apoptosis, which is indicative of coclustering of Fas death receptor into lipid rafts in the glioblastoma xenograft cell lines 4910 and 5310. These data indicate the crucial role of the clusters of apoptotic signaling molecule-enriched rafts in programmed cell death, acting as concentrators of death receptors and downstream signaling molecules, and as the linchpin from which a potent death signal is launched in uPAR- and/or MMP-9–downregulated cells. Mol Cancer Ther; 9(9); 2605–17. ©2010 AACR.
More than Markers: Biological Significance of Cancer Stem Cell-Defining Molecules
Authors: Keysar Stephen B. , Jimeno Antonio
Published: August 2010

Small populations within an increasing array of solid tumors, labeled cancer stem cells (CSC) or tumor-initiating cells (TIC), have the ability to differentiate, self-renew, and replicate the original tumor in vivo. To date, these cells have been distinguished from the bulk-tumor population by the expression pattern of cell-surface proteins (e.g., CD24, CD44, CD133) and cellular activities, such as the efflux of Hoechst dye or aldehyde dehydrogenase activity. Recent data have shown that these markers are inducible by exposure to anticancer agents; this finding highlights not only the potential fluidity of the CSC compartment, but also the functionality of these markers. The involvement of CD44 in invasion, adhesion, and metastasis, or the role of CD24 in modulation of src, FAK, and GLI1 are examples of these relevant roles. Instead of looking solely at the marker expression in these populations, we hope to clarify the biologically significant roles these markers and activities play in tumor progression, metastases, and as possible targets for therapy. Mol Cancer Ther; 9(9); 2450–7. ©2010 AACR.