bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct Sites on the Sindbis Virus RNA-Dependent RNA Polymerase for Binding to the Promoters for the Synthesis of Genomic and Subgenomic RNA
Authors: Li Mei-Ling , Stollar Victor
Published: February 2007

Sindbis virus-infected cells make two positive-strand RNAs, a genomic (G) RNA and a subgenomic (SG) RNA. Here we report the amino acid sequence in nonstructural protein 4 (nsP4), the viral RNA-dependent RNA polymerase, that binds to the promoter for the synthesis of G RNA. In addition, using a cell-free system that makes both G and SG RNA, we show that specific amino acid changes in nsP4 that abolish the synthesis of SG RNA have no effect on the synthesis of G RNA. Our findings indicate that nsP4 has distinct sites for the recognition of the G and SG promoters.
Absolute configuration assignments by experimental and theoretical approaches of ent-labdane- and cis-ent-clerodane-type diterpenes isolated from Croton glabellus
Authors: García Abraham , Ramírez-Apan Teresa , Cogordan J Antonio , Delgado Guillermo
Published: February 2007

The bioassay-guided fractionation of the moderately cytotoxic extract from Croton glabellus resulted in the isolation of bioactive compounds, which were characterized as austroinulin (2), 6-O-acetylaustroinulin (3), the acetonide artifact of 2 (4), and 3-O-methylkaempferol (9). In addition, a new natural cis-ent-clerodane lactone diterpene named marrubiagenin (1), trans-dehydrocrotonin (6), the epimeric mixture of cajucarinolide (7/8), and 5,7,3′,4′-tetrahydroxy-3-methoxyflavonoid (10) were also characterized and identified as nonbioactive compounds. The structures of all compounds were determined by analyses of their physical and spectroscopic data and by comparison with those reported in the literature. The absolute configuration assignment of 3 was carried out by means of the modified Mosher method and by the experimental and theoretical circular dichroism method establishing that 3 belongs to the ent-labdane diterpene series. Furthermore, the absolute configuration of 1 was established by analysis of its chiroptical properties concluding that 1 belongs to the cis-ent-clerodane diterpene series.Key words: Croton glabellus, ent-labdane-type diterpenes, cis-ent-clerodane-type diterpenes, circular dichroism, TD-DFT.
Reactions of α-isobutyl-α-(methylthio)methylene Meldrum's acid with primary amines in aqueous DMSO
Authors: Biswas Supriya , Ali Mahammad , Rappoport Zvi , Salim Hatim
Published: February 2007

The aminolysis of α-isobutyl-α-(methylthio)methylene Meldrum's acid 7 with primary amines, namely, n-butylamine, glycinamide, and methoxyethylamine in DMSO–H2O (50:50, v/v) at 20 °C is overall second-order but first-order in both 7 and amines. The reaction with aminoacetonitrile (AA) is overall third-order, first-order in substrate, and second-order in amine at low amine concentration, while at high amine concentration and high pH the dependence on amine is first-order. A general three-step mechanism has been proposed for all these reactions. For the former group of amines, the first step is a rate-limiting attack of the amine to form the tetrahedral intermediate (TA±), followed by a fast acid–base equilibrium and a fast RNH3+- or H2O-assisted leaving group expulsion. For AA, general base catalysis was confirmed from the dependence of kA on [AA]f and on [OH–]. For all four amines, a good Brønsted plot of log k1 vs. pKaAH in DMSO–H2O (50:50, v/v) with βnuc = 0.34 ± 0.02 was observed. These observations are consistent with the suggested mechanism.Key words: nucleophilic vinylic substitution reactions, primary amines, α-isobutyl-α-(methylthio)methylene Meldrum's acid, three-step mechanism.
The absolute configuration of a nitroxide spin labeled derivative of podophyllotoxin determined by the crystal structure
Authors: Zhou Baohan , Yin Guodong , Meng Xianggao , Li Yitao , Wu Anxin
Published: February 2007

The crystal structure of the nitroxide spin labeled derivative of podophyllotoxin was first reported. X-ray analysis demonstrated that four contiguous chiral centers in the molecule, C1, C2, C3, and C4, adopt cis- (1:2), trans- (2:3), and cis- (3:4) arrangement.Key words: crystal structure, synthesis, nitroxyl radical, podophyllotoxin.
Dynamic NMR spectroscopy of 2,2′-dimethyl-1-picrylhydrazine in various solvents
Authors: Brown K C , El-Bermani M , Upadrashta Y , Weil J A
Published: February 2007

We have studied the 1H NMR spectra of 2,2′-dimethyl-1-(2,4,6-trinitrophenyl)hydrazine at 300 and 500 MHz in seven liquid solvents, with a view to learning details of the internal conformational changes taking place as a function of temperature and of the solvent. These molecules in liquid solution occur as interconverting enantiomorphic pairs (atropisomers). Advanced techniques for obtaining the correct activation energies and pseudo-thermodynamic parameters have been utilized, and these parameters are listed and discussed. Our results point to a transformation between the pair of atropisomers that is not quite as complicated as one might have encountered in that the solvent does not affect ΔG in any major fashion. Molecular orbital calculations clarified some of the chemical shifts observed for both 1H and 13C. One goal of this study was to enable a detailed comparison with similar results available for 2,2′-diphenyl-1-(2,4,6-trinitrophenyl)hydrazine.Key words: dynamic NMR, dimethylpicrylhydrazine, hindered rotation, atropisomers, activation parameters.
Regioselective synthesis of biologically interesting pentacyclic polyheterocycles by sequential thio-Claisen and AlCl3 catalyzed oxy-Claisen rearrangement of 4-(4′-aryloxybut-2′-ynylthio)-1-phenyl-1,8-naphthyridin-2(1H)-one
Authors: Majumdar K C , Islam R
Published: February 2007

A number of 4-aryloxymethyl-6-phenyl-2H-thiopyrano[3,2-c][1,8]naphthyridin-5(6H)-ones were regio selectively synthesized in 82%–95% yields by the thermal Claisen rearrangement of 4-(4′-aryloxybut-2′-ynylthio)-1-phenyl-[1,8]naphthyridin-2(1H)-ones. These products were then subjected to a second Claisen rearrangement in the presence of a Lewis acid catalyst, anhyd. AlCl3, to give hitherto unreported pentacyclic heterocycles in 75%–90% yields. The same final products were also obtained in low yield upon refluxing 4-aryloxymethyl-6-phenyl-2H-thio pyrano-[3,2-c][1,8]naphthyridin-5(6H)-ones in N,N-diethyl aniline for 12–14 h. This method was found to be more effective than thermal Claisen rearrangement.Key words: [3,3] sigmatropic rearrangement, regioselective synthesis, phase transfer catalysis, sequential Claisen rearrangement, Lewis acid catalyzed Claisen rearrangement, single crystal X-ray.
DISTRIBUTED SOURCE BOUNDARY POINT METHOD-BASED NEARFIELD ACOUSTIC HOLOGRAPHY FOR RECONSTRUCTING THE ACOUSTIC RADIATION FROM ARBITRARILY SHAPED OBJECTS
Authors: BI C. X. , CHEN X. Z. , CHEN J.
Published: February 2007

Nearfield acoustic holography (NAH) is an indirect technique for identifying noise sources and visualizing acoustic field. Recently, several different methods, such as the spatial Fourier transform method, the boundary element method (BEM) and the Helmholtz equation-least squares (HELS) method, have been used to realize the NAH successfully. In the paper, a novel numerical method, the distributed source boundary point method (DSBPM), is proposed to realize the NAH. In the method, the transfer matrices from the reconstructed surface to the hologram surface are constructed indirectly by a set of particular solution sources located inside the vibrating structure, and their inverses are carried out by singular value decomposition (SVD) technique. Additionally, considering the high sensitivity of the reconstructed solution to measurement errors, the Tikhonov regularization method is implemented to stabilize the reconstruction procedure and the regularization parameter is determined by L-curve criterion. Compared with the BEM-based NAH, the variable interpolation, the numerical quadrature, and the treatments of singular integral and nonuniqueness of solution are all avoided in the proposed method. Two numerical examples and an experiment are investigated to validate the feasibility and correctness of the proposed method.
Cellular trafficking of phospholamban and formation of functional sarcoplasmic reticulum during myocyte differentiation
Authors: Stenoien David L. , Knyushko Tatyana V. , Londono Monica P. , Opresko Lee K. , Mayer M. Uljana , Brady Scott T. , Squier Thomas C. , Bigelow Diana J.
Published: February 2007

Phospholamban (PLB) associates with the Ca2+-ATPase in sarcoplasmic reticulum (SR) membranes to permit the modulation of contraction in response to β-adrenergic signaling. To understand how coordinated changes in the abundance and intracellular trafficking of PLB and the Ca2+-ATPase contribute to the maturation of functional muscle, we measured changes in abundance, location, and turnover of endogenous and tagged proteins in myoblasts and during their differentiation. We found that PLB is constitutively expressed in both myoblasts and differentiated myotubes, whereas abundance increases of the Ca2+-ATPase coincide with the formation of differentiated myotubes. We observed that PLB is primarily present in highly mobile vesicular structures outside the endoplasmic reticulum, irrespective of the expression of the Ca2+-ATPase, indicating that PLB targeting is regulated through vesicle trafficking. Moreover, using pulse-chase methods, we observed that in myoblasts, PLB is trafficked through directed transport through the Golgi to the plasma membrane before endosome-mediated internalization. The observed trafficking of PLB to the plasma membrane suggests an important role for PLB during muscle differentiation, which is distinct from its previously recognized role in the regulation of the Ca2+-ATPase.
Spinal glutamatergic NMDA-dependent pelvic nerve-to-external urethra sphincter reflex potentiation caused by a mechanical stimulation in anesthetized rats
Authors: Liao Jiuan-Miaw , Huang Pei-Chen , Pan Shwu-Fen , Chen Mei-Jung , Tung Kwong-Chung , Peng Hsien-Yu , Shyu Jyh-Cherng , Liou Ying-Ming , Chen Gin-Den , Lin Tzer-Bin
Published: February 2007

The current study investigates whether the spinal pelvic nerve-to-external urethra sphincter (EUS) reflex potentiation can be induced by a mechanical stimulation and whether the glutamatergic mechanism is involved in yielding such a reflex potentiation. The external urethra sphincter electromyogram (EUSE) activity, evoked by a single or by repetitive pelvic nerve stimulation, in 30 anesthetized rats was recorded with/without bladder saline distension. Without saline distension (0 cmH2O), a single pulse nerve stimulation evoked a single action potential in the reflex activity, whereas repetitive pelvic stimulation and saline distension (6∼20 cmH2O) both elicited a long-lasting reflex potentiation (20.05 ± 3.21 and 75.01 ± 9.87 spikes/stimulation, respectively). The saline distension-induced pelvic nerve-to-EUS reflex potentiation was abolished by d-2-amino-5-phosphonovalerate [APV; a glutamatergic N -methyl-d-aspartic acid (NMDA) receptor antagonist; 100 μM, 10 μl, 1.72 ± 0.31 spikes/stimulation] and attenuated by 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline [NBQX; a glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA) receptor antagonist; 100 μM, 10 μl, 26.16 ± 7.27 spikes/stimulation], but was not affected by bicuculline (a GABAergic antagonist; 100 μM, 10 μl, 53.62 ± 15.54 spikes/stimulation). Intrathecal administration of glutamate (31.12 ± 8.25 spikes/stimulation, 100 μM, 10 μl) and NMDA (26.25 ± 4.12 spikes/stimulation, 100 μM, 10 μl) both induced a long-lasting pelvic nerve-to-EUS reflex potentiation without saline distension, which was similar to the findings observed from saline distension only. The duration of the contraction wave of the urethra was elongated by the saline distension-induced pelvic nerve-to-EUS reflex potentiation, whereas the peak pressure of the contraction wave was not affected. Our findings suggest that saline distension in the bladder elicits a pelvic nerve-to-EUS reflex potentiation and the glutamatergic mechanism contributes to the presence of such a reflex potentiation.
Inorganic mercury interacts with cysteine residues (C451 and C474) of hOCT2 to reduce its transport activity
Authors: Pelis Ryan M. , Dangprapai Yodying , Wunz Theresa M. , Wright Stephen H.
Published: February 2007

Human organic cation transporter 2 (hOCT2) is essential for the renal tubular secretion of many toxic organic cations. Previously, of the cysteines (C437, C451, C470, and C474) that occur within transmembrane helices that comprise the hydrophilic cleft (proposed site of substrate binding), only C474 was accessible to maleimide-PEO2-biotin (hydrophilic thiol-reactive reagent), and covalent modification of this residue caused lower transport rates (Pelis RM, Zhang X, Dangprapai Y, Wright SH, J Biol Chem 281: 35272–35280, 2006). Thus it was hypothesized that the environmental contaminant Hg2+(as HgCl2) would interact with C474 to reduce hOCT2-mediated transport. Uptake of [3H]tetraethylammonium (TEA) into Chinese hamster ovary cells stably expressing hOCT2 was reduced in a concentration-dependent manner by HgCl2, with an IC50of 3.9 ± 0.11 μM. Treatment with 10 μM HgCl2caused a sixfold reduction in the maximal rate of TEA transport but did not alter the affinity of hOCT2 for TEA. To determine which cysteines interact with Hg2+, a mutant with all four cleft cysteines converted to alanines (quadruple mutant), and four variants of this mutant, each with an individual cysteine restored, were created. The quadruple mutant was less sensitive to HgCl2than wild-type, whereas the C451- and C474-containing mutants were more sensitive than the quadruple mutant. Consistent with the HgCl2effect on transport, MTSEA-biotin only interacted with C451 and C474. These data indicate that C451 and C474 of hOCT2 reside in the aqueous milieu of the cleft and that interaction of Hg2+with these residues causes reduced TEA transport activity.
Visual and Auditory Alertness: Modality-Specific and Supramodal Neural Mechanisms and Their Modulation by Nicotine
Authors: Thiel Christiane M. , Fink Gereon R.
Published: February 2007

Alertness is a nonselective attention component that refers to a state of general readiness that improves stimulus processing and response initiation. We used functional magnetic resonance imaging (fMRI) to identify neural correlates of visual and auditory alertness. A further aim was to investigate the modulatory effects of the cholinergic agonist nicotine. Nonsmoking participants were given either placebo or nicotine (NICORETTE gum, 2 mg) and performed a target-detection task with warned and unwarned trials in the visual and auditory modality. Our results provide evidence for modality-specific correlates of visual and auditory alertness in respective higher-level sensory cortices and in posterior parietal and frontal brain areas. The only region commonly involved in visual and auditory alertness was the right superior temporal gyrus. A connectivity analysis showed that this supramodal region exhibited modality-dependent coupling with respective higher sensory cortices. Nicotine was found to mainly decrease visual and auditory alertness-related activity in several brain regions, which was evident as a significant interaction of nicotine-induced decreases in BOLD signal in warned trials and increases in unwarned trials. The cholinergic drug also affected alerting-dependent activity in the supramodal right superior temporal gyrus; here the effect was the result of a significant increase of neural activity in unwarned trials. We conclude that the role of the right superior temporal gyrus is to induce an “alert” state in response to warning cues and thereby optimize stimulus processing and responding. We speculate that nicotine increases brain mechanisms of alertness specifically in conditions where no extrinsic warning is provided.
Noncommutative Updating of Perceived Self-Orientation in Three Dimensions
Authors: Glasauer Stefan , Brandt Thomas
Published: February 2007

After whole body rotations around an earth-vertical axis in darkness, subjects can indicate their orientation in space with respect to their initial orientation reasonably well. This is possible because the brain is able to mathematically integrate self-velocity information provided by the vestibular system to obtain self-orientation, a process called path integration. For rotations around multiple axes, however, computations are more demanding to accurately update self-orientation with respect to space. In such a case, simple integration is no longer sufficient because of the noncommutativity of rotations. We investigated whether such updating is possible after three-dimensional whole body rotations and whether the noncommutativity of three-dimensional rotations is taken into account. The ability of ten subjects to indicate their spatial orientation in the earth-horizontal plane was tested after different rotational paths from upright to supine positions. Initial and final orientations of the subjects were the same in all cases, but the paths taken were different, and so were the angular velocities sensed by the vestibular system. The results show that seven of the ten subjects could consistently indicate their final orientation within the earth-horizontal plane. Thus perceived final orientation was independent of the path taken, i.e., the noncommutativity of rotations was taken into account.
Signaling Mechanisms of Angiotensin II–Induced Attenuation of GABAergic Input to Hypothalamic Presympathetic Neurons
Authors: Chen Qian , Pan Hui-Lin
Published: February 2007

The hypothalamic paraventricular nucleus (PVN) is an important site for the regulation of sympathetic outflow. Angiotensin II (Ang II) can activate AT1receptors to stimulate PVN presympathetic neurons through inhibition of GABAergic input. However, little is known about the downstream pathway involved in this presynaptic action of Ang II in the PVN. In this study, using whole cell recording from retrogradely labeled PVN neurons in rat brain slices, we determined the signaling mechanisms responsible for the effect of Ang II on synaptic GABA release to spinally projecting PVN neurons. Bath application of Ang II reproducibly decreased the frequency of GABAergic miniature postsynaptic inhibitory currents (mIPSCs) in fluorescence-labeled PVN neurons. Ang II failed to change the frequency of mIPSCs in labeled PVN neurons treated with pertussis toxin. However, Ang II–induced inhibition of mIPSCs persisted in the presence of either CdCl2, a voltage-gated Ca2+channel blocker, or 4-aminopyridine, a blocker of voltage-gated K+channels. Interestingly, inhibition of superoxide with superoxide dismutase or Mn(III) tetrakis (4-benzoic acid) prophyrin completely blocked Ang II–induced decrease in mIPSCs. By contrast, inhibition of hydroxyl radical formation with the ion chelator deferoxamine did not significantly alter the effect of Ang II. These findings suggest that the presynaptic action of Ang II on synaptic GABA release in the PVN is mediated by the pertussis toxin–sensitive Gi/oproteins but not by voltage-gated Ca2+and K+channels. Ang II attenuates GABAergic input to PVN presympathetic neurons through reactive oxygen species, especially superoxide anions.
A Phase 1 Escalating Single-Dose and Weekly Fixed-Dose Study of Cetuximab: Pharmacokinetic and Pharmacodynamic Rationale for Dosing
Authors: Fracasso Paula M. , Burris Howard , Arquette Matthew A. , Govindan Ramaswamy , Gao Feng , Wright Lisa P. , Goodner Sherry A. , Greco F. Anthony , Jones Suzanne F. , Willcut Noel , Chodkiewicz Catherine , Pathak Amit , Springett Gregory M. , Simon George R. , Sullivan Daniel M. , Marcelpoil Raphaël , Mayfield Shelley D. , Mauro David , Garrett Christopher R.
Published: February 2007

Purpose: This phase 1 study evaluated the pharmacokinetic and pharmacodynamic effects of cetuximab on patients with epithelial malignancies.

Experimental Design: Following a skin and tumor biopsy, patients with advanced epithelial malignancies were randomized to receive a single dose of cetuximab at 50, 100, 250, 400, or 500 mg/m2 i.v. Repeat skin (days 2, 8, 15, and 22) and tumor (day 8) biopsies were obtained. Immunohistochemical expression of epidermal growth factor receptor (EGFR) and its pathway members was done on biopsies. Blood samples were obtained over 22 days for pharmacokinetic analyses. After day 22, all patients received weekly 250 mg/m2 cetuximab until disease progression or unacceptable toxicity.

Results: Thirty-nine patients enrolled. Rash was noted in 26 (67%) patients. Three patients (two with colon cancer and one with laryngeal cancer) achieved a partial response and 13 patients had stable disease. Pharmacokinetic data revealed mean maximum observed cetuximab concentrations and mean area under the concentration-time curve from time zero to infinity increased in a dose-dependent manner up to 400 mg/m2 cetuximab. Mean clearance was similar at cetuximab doses ≥100 mg/m2, supporting saturation of EGFR binding at 250 mg/m2. Pharmacodynamic evaluation revealed that patients with partial response/stable disease had a higher-grade rash and higher cetuximab trough levels than those with progressive disease (P = 0.032 and 0.002, respectively). Administration of single doses (250-500 mg/m2) of cetuximab resulted in a dose-dependent decrease in EGFR protein expression levels in skin over time, supporting a minimal dose of cetuximab at 250 mg/m2 for a pharmacodynamic effect.

Conclusion: This study provides a pharmacokinetic and pharmacodynamic rationale for the dosing of cetuximab.
Nitric Oxide and Its Gatekeeper Thrombospondin-1 in Tumor Angiogenesis
Authors: Roberts David D. , Isenberg Jeffery S. , Ridnour Lisa A. , Wink David A.
Published: February 2007

Nitric oxide (NO) plays a central role in angiogenesis as a mediator of signaling by vascular endothelial growth factor and other angiogenic factors. Low concentrations of NO produced in response to angiogenic factors stimulate angiogenesis, whereas higher concentrations typical of inflammatory responses inhibit angiogenesis. The proangiogenic activity of NO is mediated by activation of soluble guanylyl cyclase, leading to cyclic guanosine 3′,5′-monophosphate accumulation and activation of its target kinases and ion channels. The four angiogenesis inhibitors currently approved for clinical use target components of the signaling cascade upstream of NO. New research has identified components downstream of NO as the primary target of the endogenous angiogenesis inhibitor thrombospondin-1 and has shown that circulating levels of thrombospondin-1 are sufficient to limit angiogenic responses by antagonizing NO signaling. This provides new insights into the significance of the widespread loss of thrombospondin-1 expression during malignant progression. Although clinical trials suggest that blocking NO signaling can inhibit tumor angiogenesis, this approach also inactivates inhibitory signaling from thrombospondin-1. We discuss the implications of the balance between these pathways for applying thrombospondin-1 mimetics and redox modifiers as cancer therapeutics.
CpG Island Methylator Phenotype Association with Elevated Serum α-Fetoprotein Level in Hepatocellular Carcinoma
Authors: Zhang Changsong , Li Zhengyou , Cheng Yue , Jia Fengqi , Li Rong , Wu Mengchao , Li Ke , Wei Lixin
Published: February 2007

Purpose: CpG island methylator phenotype (CIMP) involves hypermethylation targeted toward the promoters of multiple genes. To gain insight into the role of epigenetic aberration of tumor-related genes in hepatocarcinogenesis, we determined a hypermethylation profile in hepatocellular carcinoma (HCC).

Experimental Design: We examined the promoter methylation status of nine genes in 50 HCCs, 50 paired nontumor tissues, and 6 normal liver tissues by methylation-specific PCR. CIMP+ was defined as having five genes that are concordantly methylated.

Results: The frequency of promoter methylation of nine genes in 50 HCCs varied from 10% in P53 to 94% in c-Myc. The methylation status of P14, P15, P16, ER, RASSF1A, WT1, and c-Myc was significantly correlated with HCC and nontumor tissues (P < 0.05). Hypermethylation of one or more genes was found in 96% of HCC. CIMP was more frequent in HCC than in nontumor tissues (70% and 12%, P < 0.001). There is a significant association between CIMP and methylation of P14, P15, P16, ER, RSAAF1A, and WT1 (P < 0.05) and serum α-fetoprotein (AFP) level (P = 0.017). CIMP+ was more frequent in HCC with AFP ≥ 30 μg/L than those with AFP < 30 μg/L (P = 0.005). In addition, the promoter hypermethylation of P15 and P16 was associated with elevated serum AFP levels in 35 HCC samples with CIMP+ (P < 0.05).

Conclusions: Positive correlation of CIMP and AFP levels in HCC suggests that CIMP can serve as a molecular marker of late-stage HCC development.
Radiation-Induced Hepatitis B Virus Reactivation in Liver Mediated by the Bystander Effect from Irradiated Endothelial Cells
Authors: Chou Chia Hung , Chen Pei-Jer , Lee Po-Huang , Cheng Ann-Lii , Hsu Hui-Chen , Cheng Jason Chia-Hsien
Published: February 2007

Purpose: Hepatitis B virus (HBV) reactivation is one unique pathogenesis in Asian carriers with liver toxicity after radiotherapy for hepatobiliary malignancies. This study attempts to delineate the biological mechanism of radiation-induced HBV reactivation.

Experimental Design: Primary cultures of hepatocytes (PCC) were prepared from the noncancerous liver tissue removed perioperatively from 12 HBV carriers with hepatocellular carcinoma (HCC). The conditioned medium of irradiated PCCs, HCC, and endothelial cells from patients was transferred to PCCs or HepG2.2.15 cells (a human hepatoblastoma cell line transfected with HBV DNA) before subsequent irradiation. Forty-eight hours after irradiation, HBV DNA was measured by real-time quantitative PCR. Specific cytokines were determined by cytokine array and ELISA analysis. Preradiotherapy and postradiotherapy sera from 10 HBV carriers and 16 non-HBV carriers were analyzed for viral loads and cytokine activities.

Results: Radiation induced HBV DNA replication in (a) irradiated PCCs cultured with the conditioned medium from irradiated PCCs (2.74-fold; P = 0.004) and endothelial cells (9.50-fold; P = 3.1 × 10−10), but not from HCCs (1.07-fold), and in (b) irradiated HepG2.2.15 cells (17.7-fold) cocultured with human umbilical vascular endothelial cells. Cytokine assay revealed increased expression of interleukin-6 (IL-6) in conditioned medium from irradiated human umbilical vascular endothelial cells. All 16 patients with liver irradiated had the increased serum IL-6 compared with 3 of 10 patients with irradiation excluding liver (P < 0.001). All nine HBV carriers with liver irradiated had postradiotherapy increases in both HBV DNA and IL-6.

Conclusions: Radiation-induced liver toxicity with HBV reactivation is from a bystander effect on irradiated endothelial cells releasing cytokines, including IL-6.
Impact of Patient and Target-Vessel Characteristics on Arterial and Venous Bypass Graft Patency
Authors: Desai Nimesh D. , Naylor C. David , Kiss Alexander , Cohen Eric A. , Feder-Elituv Randi , Miwa Senri , Radhakrishnan Sam , Dubbin James , Schwartz Leonard , Fremes Stephen E.
Published: February 2007

Background—

The purpose of this investigation was to determine optimal patient and target-vessel characteristics to maximize arterial and venous graft patency on the basis of data from a large clinical trial.

Methods and Results—

Angiographic data on 440 radial artery grafts and 440 saphenous vein grafts were analyzed with methodology to account for within-patient clustering. Multivariable models that incorporated patient demographic, operative, anatomic, and postdischarge medical management were constructed to determine predictors of graft occlusion. Radial artery use was strongly protective against graft occlusion at 1 year after adjustment for all covariates, with a larger protective effect seen in women (
P
=0.05 for a subgroup-by-treatment interaction). Among all grafts, diabetes and small target-vessel diameter were associated with an increased risk of graft occlusion, and grafting to a target vessel with more severe proximal stenosis was associated with a decreased risk of graft occlusion. With regard to gender, radial artery graft occlusion at 1 year occurred in similar proportions of men (8.6%) and women (5.3%,
P
=0.6), whereas, for saphenous vein grafts the comparable occlusion rates were 12.0% and 23.3% respectively (
P
=0.02). A history of peripheral vascular disease was associated with an elevated risk of radial artery occlusion but was not associated with early vein graft occlusion (
P
=0.02 for a subgroup-by-treatment interaction).

Conclusions—

Patients benefit from radial artery–coronary artery bypass conduits as opposed to saphenous vein conduits, and this effect is especially strong in women. Small target-vessel size adversely affected graft patency, and grafting to a target vessel with more severe proximal stenosis improved graft patency.
Consistently Stable or Decreased Body Mass Index in Young Adulthood and Longitudinal Changes in Metabolic Syndrome Components
Authors: Lloyd-Jones Donald M. , Liu Kiang , Colangelo Laura A. , Yan Lijing L. , Klein Liviu , Loria Catherine M. , Lewis Cora E. , Savage Peter
Published: February 2007

Background—

Data are sparse regarding the association of stable body mass index (BMI) over the long term with metabolic syndrome components in young adults.

Methods and Results—

Participants in the Coronary Artery Risk Development in Young Adults Study, including white and black adults 18 to 30 years of age at the initial examination in 1985 to 1986, were stratified into groups by baseline BMI and change in BMI (stable/decreased, increased >2 kg/m
2
, or fluctuating) across all 6 examinations between years 0 and 15 of the study. Changes in metabolic syndrome components were compared between groups. Among 1358 men and 1321 women, 16.3% maintained a stable BMI, 73.9% had an increased BMI, and 9.8% had a fluctuating BMI. Over 15 years, participants with stable BMI had essentially unchanged levels of metabolic syndrome components, regardless of baseline BMI, whereas those with increased BMI had progressively worsening levels. For example, men with a baseline BMI of 20.0 to 24.9 kg/m
2
and stable BMI during follow-up had a mean increase of only 15 mg/dL in fasting triglycerides over 15 years compared with 65 mg/dL (
P
<0.001) in those whose BMI increased. Incidence of metabolic syndrome at year 15 was lower in the stable BMI group (2.2%) compared with the increased BMI group (18.8%;
P
<0.001).

Conclusions—

Adverse progression of metabolic syndrome components with advancing age may not be inevitable. Young adults who maintained stable BMI over time had minimal progression of risk factors and lower incidence of metabolic syndrome regardless of baseline BMI. Greater public health efforts should be aimed at long-term weight stabilization.
Regenerative Potential of Cardiosphere-Derived Cells Expanded From Percutaneous Endomyocardial Biopsy Specimens
Authors: Smith Rachel Ruckdeschel , Barile Lucio , Cho Hee Cheol , Leppo Michelle K. , Hare Joshua M. , Messina Elisa , Giacomello Alessandro , Abraham M. Roselle , Marbán Eduardo
Published: February 2007

Background—

Ex vivo expansion of resident cardiac stem cells, followed by delivery to the heart, may favor regeneration and functional improvement.

Methods and Results—

Percutaneous endomyocardial biopsy specimens grown in primary culture developed multicellular clusters known as cardiospheres, which were plated to yield cardiosphere-derived cells (CDCs). CDCs from human biopsy specimens and from comparable porcine samples were examined in vitro for biophysical and cytochemical evidence of cardiogenic differentiation. In addition, human CDCs were injected into the border zone of acute myocardial infarcts in immunodeficient mice. Biopsy specimens from 69 of 70 patients yielded cardiosphere-forming cells. Cardiospheres and CDCs expressed antigenic characteristics of stem cells at each stage of processing, as well as proteins vital for cardiac contractile and electrical function. Human and porcine CDCs cocultured with neonatal rat ventricular myocytes exhibited biophysical signatures characteristic of myocytes, including calcium transients synchronous with those of neighboring myocytes. Human CDCs injected into the border zone of myocardial infarcts engrafted and migrated into the infarct zone. After 20 days, the percentage of viable myocardium within the infarct zone was greater in the CDC-treated group than in the fibroblast-treated control group; likewise, left ventricular ejection fraction was higher in the CDC-treated group.

Conclusions—

A method is presented for the isolation of adult human stem cells from endomyocardial biopsy specimens. CDCs are cardiogenic in vitro; they promote cardiac regeneration and improve heart function in a mouse infarct model, which provides motivation for further development for therapeutic applications in patients.
Women and the Dura-Europos Synagogue Paintings
Authors: Steinberg Faith
Published: February 2007

Between 1928 and 1937, during excavations at a site in Mesopotamia, archaeologists uncovered an ancient city, Dura-Europos, on the Euphrates River. Among their many findings, which included numerous pagan temples, were a Christian house and a synagogue. A room in the house had been converted into a baptistery with frescoes. In a large assembly room of the synagogue, murals depicting biblical narratives were painted in three registers on all four walls. The Second Commandment forbids the use of imagery, and the finding, the earliest and only one of such magnitude to date, caused a stir and has generated an extensive literature. Many scholars attribute this phenomenon to the rise of Christianity. But there is an aspect of the paintings that has not been investigated. In the most visually accessible and most holy area of the room, the Torah shrine, heroic Jewish women of the Bible were depicted. In light of the patriarchal nature of historical Judaism, this paper examines the murals and the architectural and archeological findings in an effort to understand this anomaly.
Tomb Stone of the Sons of Attes from Myrmekion
Authors: Tokhtasiev Sergei
Published: February 2007

The author publishes a tomb stone of the 1st half of the 4th century BC discovered at the necropolis of the Bosporan city of Myrmekion (on the territory of Kerch). The name of the second buried person Kυαιανιζ should be probably read as Kυλιανιζ. The latter is known from a 4th century epitaph CIRB 162 and is often to be found on the ceramic stamps of Sinope as the name factory-owners. The name seems to be Paphlagonian, derived from the Hittito-Luvian anthroponymic stem Kul(a)-. Anatolian name of the father "Aττηζ known on the Bosporus from some other inscriptions of the 4th century BC, is attested in Myrmekion in CIRB 178. The author gives other examples from Bosporan epigraphy of how immigrant families from Asia Minor preserved their traditional names. The epigraphic data make it possible to speak about a mass migration of super ficially Hellenized barbarians (often with their families) from the northern parts of Asia Minor to the Bosporus in the 5th and 4th centuries BC.
On the Dating of one Group of Chian Amphoras (Based on Finds from the Pichvnari Greek Necropolis of the 5th Century BC)
Authors: Khalvashi Merab , Kakhidze Amiran
Published: February 2007

On the basis of the evidence of the Pichvnari Greek Necropolis of the 5th century BC, the present publication offers a new dating of the late period Chian amphoras with swollen necks. It is obvious that the manufacture of this kind of amphoras ceased in the mid-5th century BC. From the second quarter of the 5th century BC a new variety of pottery emerged, which can be regarded as a transitional form between Chian amphoras with swollen necks and amphoras with straight necks.
Epitaph of Onesimos the Son of Kallisthenes
Authors: Azarnert Leonid
Published: February 2007

This note analyses one of the Bosporan sepulchral inscriptions. The analysis suggests that the epitaph of Onesimos the son of Kallisthenes is a metric epigram cast in two iambic trimesters and not a prose inscription as has been previously believed.
Towards a European Union of Post-Security?
Authors: Joenniemi Pertti
Published: February 2007

Several new ways of security-speak are about to enter the European scene. The article seeks to identity these by investigating the use and unfolding of the security argument in the context of the European Union’s (EU) new security doctrine and the devising of an explicit neighbourhood policy. In addition to tracing the way the plot structure underpinning the EU is changing, alternative options are sought by tapping into the potential offered by the way security works in the case of the Nordic constellation. Juxtaposing of the EU and the Nordic entity is also there in order to challenge the increasingly closed and non-negotiable European configuration and to open it up for critical scrutiny.
Farmers and Farmworkers
Authors: Kingsolver Ann E.
Published: February 2007

Strategic alterity is defined here as a process of shifting between different assertions of devalued group identity in order to valorize free-trading citizens of the market and to mask the labor of those making that free market participation possible (by moralizing the devalorization). The examples provided here - based on ethnographic, oral history, and archival research in an eastern Kentucky, US community - focus on the ways that different markers of identity have characterized the farmworkers providing the low-wage or non-wage labor in tobacco over the past two centuries that has made it possible for those whose crops they work in to see themselves as independent, family farmers. Tobacco is viewed, here, as having always been a global crop produced by a ‘globalized’ labor force. The ideological arguments, most recently neoliberal, justifying the differential power (and ‘market citizenship’) of farmers and farm-workers are examined within a US context, with suggestions for comparative and historical approaches to interpreting current strategies of inclusion and exclusion related to neoliberal capitalist globalization.
Development of Long Glass Fiber Reinforced Polypropylene Composites: Mechanical and Morphological Characteristics
Authors: Kumar K. Senthil , Bhatnagar Naresh , Ghosh Anup K.
Published: February 2007

Innovative polymers and composites are broadening the range of applications and commercial production of thermoplastics. Long fiber-reinforced thermoplastic (LFRT) composite contains glass fiber, which has an aspect ratio greater than 100. This study describes the development of long fiber-reinforced polypropylene (LFRP) composites and the effect of fiber length, fiber content, and compatibilizer content on mechanical and morphological properties. LFRP pellets of different sizes were prepared by extrusion process using a specially designed impregnation die and these pellets were injection molded to develop LFRP composites. Maleic-anhydride grafted polypropylene (MA-g-PP) was chosen as a compatibilizer and its content was optimized. The addition of MA-g-PP enhanced the mechanical properties of LFRP composites, particularly the impact strength. Interfacial shear strength between glass fiber and polypropylene with and without the addition of compatibilizer was also studied. Tensile, flexural, and impact properties improved with increase in fiber length and fiber content. Morphological studies were also carried out to find the fiber length distribution in the injection molded specimens. Average fiber length in the injection-molded sample from 9 mm long pellets remained comparatively higher than that in case of samples from 3, 6, and 12 mm long pellets. The study shows that in a standard injection-molding machine, 9 mm long pellets provide improved performance properties.
Development of Rubber Pressure Molding Technique using Butyl Rubber to Fabricate Fiber Reinforced Plastic Components based on Glass Fiber and Polyester Resin
Authors: Kar Kamal K. , Sharma S. D. , Sah Tinku K. , Kumar Prashant
Published: February 2007

A new technique called rubber pressure molding (RPM), has been developed to fabricate fiber reinforced plastic (FRP) products from glass fiber/polyester resin. The technique is based on the matching die set, where the die is made from mild steel and the punch from a flexible rubber-like material, i.e., butyl rubber, to apply hydrostatic pressure on the various surfaces of a complex shaped product. A split steel die and rubber punch are designed and fabricated to prepare the FRP product. The same split die is also used to cast the rubber punch. Using this new technique, an FRP product called a flanged cone is made from glass fiber. Burn test, coin test, scanning electron microscopy (SEM), and mechanical tests like interlaminar fracture toughness, interlaminar shear test, tension test, etc. were carried out to ascertain the fiber content, void content, presence of delamination, bonding between fiber and resin, microstructure, and mechanical properties. These properties were also compared with FRP components made by the conventional technique to evaluate its performance in the structural applications. It is found that the interlaminar fracture toughness of the specimens made by RPM is 10% higher than the specimens made by the conventional method. The tensile strength of the specimen made by RPM technique is 27% more than the specimen made by the conventional method, whereas tensile modulus and Poisson’s ratio are in agreement. Furthermore, the interlaminar shear strength of the specimen made by RPM technique is 33% higher than the specimens made by the conventional method.
Developing Spiritual Lifemaps as a Culture-Centered Pictorial Instrument for Spiritual Assessments with Native American Clients
Authors: Limb Gordon E. , Hodge David R.
Published: February 2007

This study represents an initial step at giving social work practitioners an important assessment tool as they seek to provide culturally competent services to Native American clients. For the current study, a spiritual lifemap assessment tool was modified by the authors for a Native American cultural context. To determine the relevancy and consistency of utilizing the modified assessment tool with Native American clients, 50 Native American experts reviewed, rated, and gave feedback on its use. Results showed that spiritual lifemaps were generally consistent with Native American culture and, if used properly, could be very beneficial in working with Native Americans.
Cloninger’s Temperament Dimensions, Socio-economic and Lifestyle Factors and Metabolic Syndrome Markers at Age 31 Years in the Northern Finland Birth Cohort 1966
Authors: Sovio Ulla , King Vanessa , Miettunen Jouko , Ek Ellen , Laitinen Jaana , Joukamaa Matti , Veijola Juha , Järvelin Marjo-Riitta
Published: February 2007

The aim of this study was to assess the association between temperament and metabolic syndrome markers. Cloninger’s Temperament and Character Inventory and clinical examination were carried out in 1997 in the Northern Finland Birth Cohort 1966 ( N = 4364 respondents). Novelty seeking was positively associated with waist circumference in both genders. Systolic blood pressure was highest in men with high harm avoidance and low persistence scores and lowest in women with high reward dependence and high persistence scores. Childhood socio-economic status did not confound these associations. Smoking and alcohol consumption were associated with higher novelty seeking. Our results suggest that temperament is associated with metabolic syndrome markers and this association may be partly mediated by lifestyle factors and socio-economic status in adulthood.
Who’s Cueing Whom?
Authors: Steenbergen Marco R. , Edwards Erica E. , de Vries Catherine E.
Published: February 2007

The 2005 French and Dutch referendum campaigns were characterized by an alleged disconnect between pro-European political elites and Eurosceptic masses. Past evidence regarding elite-mass linkages in the context of European integration has been conflicting. Whereas some scholars argue that political elites respond to the changing preferences of their electorates, others suggest that party elites cue the mass public through a process of information and persuasion. We contend that these conflicting results stem from the reciprocal nature of elite-mass linkages and estimate a series of dynamic simultaneous equations models to account for this reverse causation. Using Euro-barometer and expert survey data from 1984-2002, we find evidence of a dual-process model, whereby party elites both respond to and shape the views of their supporters. We also find that the strength of these results is contingent on several factors, including the type of electoral system, intra-party dissent and voter characteristics.
Euroscepticism as Anti-Centralization
Authors: Hix Simon
Published: February 2007

From a rational choice institutionalist perspective, Euroscepticism is little more than a set of preferences by citizens, parties and interest groups about institutional design in Europe. If actors’ expect policy outcomes to move closer to their ideal positions as a result of European integration, they will be Euro-enthusiastic (as many centrists are). But, if they feel that policies will move further away from their ideal positions, they will be Eurosceptic (as many extremists are). This simple idea has broad historical and geographical relevance, relating to how actors view the design of multilevel polities, and how these institutional preferences change in response to policy outcomes of the central institutions.
SCaFoS: a tool for Selection, Concatenation and Fusion of Sequences for phylogenomics
Authors: Roure Béatrice , Rodriguez-Ezpeleta Naiara , Philippe Hervé
Published: February 2007

Background

Phylogenetic analyses based on datasets rich in both genes and species (phylogenomics) are becoming a standard approach to resolve evolutionary questions. However, several difficulties are associated with the assembly of large datasets, such as multiple copies of a gene per species (paralogous or xenologous genes), lack of some genes for a given species, or partial sequences. The use of undetected paralogous or xenologous genes in phylogenetic inference can lead to inaccurate results, and the use of partial sequences to a lack of resolution. A tool that selects sequences, species, and genes, while dealing with these issues, is needed in a phylogenomics context.

Results

Here, we present SCaFoS, a tool that quickly assembles phylogenomic datasets containing maximal phylogenetic information while adjusting the amount of missing data in the selection of species, sequences and genes. Starting from individual sequence alignments, and using monophyletic groups defined by the user, SCaFoS creates chimeras with partial sequences, or selects, among multiple sequences, the orthologous and/or slowest evolving sequences. Once sequences representing each predefined monophyletic group have been selected, SCaFos retains genes according to the user's allowed level of missing data and generates files for super-matrix and super-tree analyses in several formats compatible with standard phylogenetic inference software. Because no clear-cut criteria exist for the sequence selection, a semi-automatic mode is available to accommodate user's expertise.

Conclusion

SCaFos is able to deal with datasets of hundreds of species and genes, both at the amino acid or nucleotide level. It has a graphical interface and can be integrated in an automatic workflow. Moreover, SCaFoS is the first tool that integrates user's knowledge to select orthologous sequences, creates chimerical sequences to reduce missing data and selects genes according to their level of missing data. Finally, applying SCaFoS to different datasets, we show that the judicious selection of genes, species and sequences reduces tree reconstruction artefacts, especially if the dataset includes fast evolving species.