bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Sesquiterpenes from Ligularia virgaurea spp. oligocephala
Authors: Liu Xia , Wu Quan‐Xiang , Wei Xiao‐Ning , Shi Yan‐Ping
Published: September 2007

Two novel sesquiterpene dimers, ligularin A (1) and ligulolide D (2), and one new sesquiterpenoid, 1β,10α‐dihydroxy‐6β‐[(2‐methylpropyl)oxy]furanoeremophil‐9‐one (3), as well as two known sesquiterpenoids, 6β‐[(2‐methylpropyl)oxy]‐furanoeremophil‐1(10)‐en‐9‐one (4) and 1‐hydroxy‐3,7‐dimethyl‐2‐(pent‐3‐enyl)benzofuran (5), were isolated from the petroleum‐ether fraction from an alcoholic extract of the whole plant of Ligularia virgaurea spp. oligocephala. Their structures were elucidated by 1D and 2D‐NMR spectroscopy together with HR‐ESI‐MS analysis, and comparison of the spectroscopic data with those reported for structurally related compounds. In addition, the cytotoxicities against human gastric cancer SGC‐7910 cell were measured in vitro, the results demonstrated that these sesquiterpenes have no cytotoxicity against the selected tumor cell (all IC50 values >200 μM).
Chemical Constituents of the Endophytic Fungal Strain Phomopsis sp. NXZ‐05 of Camptotheca acuminata
Authors: Tan Qifang , Yan Xuefen , Lin Xiang , Huang Yaojian , Zheng Zhonghui , Song Siyang , Lu Chunhua , Shen Yuemao
Published: September 2007

From the endophytic fungal strain Phomopsis sp. NXZ‐05 of Camptotheca acuminata Decne. (Nyssaceae), six new compounds were isolated, including the ten‐membered macrolides 1–4 and their (known) parent compound multiplolide A (7), as well as a new unsaturated fatty acid, (4E)‐6,7,9‐trihydroxydec‐4‐enoic acid (5) and its methyl ester 6. Their structures were elucidated by spectroscopic and mass‐spectrometric analyses, including 1D‐ and 2D‐NMR experiments and HR‐ESI‐MS, and their biological activities were elucidated.
Synthesis and Conformational Analysis of 1′‐ and 3′‐Substituted 2‐Deoxy‐2‐fluoro‐D‐ribofuranosyl Nucleosides
Authors: Sivets Grigorii G. , Kalinichenko Elena N. , Mikhailopulo Igor A.
Published: September 2007

Convergent syntheses of the 9‐(3‐X‐2,3‐dideoxy‐2‐fluoro‐β‐D‐ribofuranosyl)adenines 5 (X=N3) and 7 (X=NH2), as well as of their respective α‐anomers 6 and 8, are described, using methyl 2‐azido‐5‐O‐benzoyl‐2,3‐dideoxy‐2‐fluoro‐β‐D‐ribofuranoside (4) as glycosylating agent. Methyl 5‐O‐benzoyl‐2,3‐dideoxy‐2,3‐difluoro‐β‐D‐ribofuranoside (12) was prepared starting from two precursors, and coupled with silylated N6‐benzoyladenine to afford, after deprotection, 2′,3′‐dideoxy‐2′,3′‐difluoroadenosine (13). Condensation of 1‐O‐acetyl‐3,5‐di‐O‐benzoyl‐2‐deoxy‐2‐fluoro‐β‐D‐ribofuranose (14) with silylated N2‐palmitoylguanine gave, after chromatographic separation and deacylation, the N7‐β‐anomer 17 as the main product, along with 2′‐deoxy‐2′‐fluoroguanosine (15) and its N9‐α‐anomer 16 in a ratio of ca. 42 : 24 : 10. An in‐depth conformational analysis of a number of 2,3‐dideoxy‐2‐fluoro‐3‐X‐D‐ribofuranosides (X=F, N3, NH2, H) as well as of purine and pyrimidine 2‐deoxy‐2‐fluoro‐D‐ribofuranosyl nucleosides was performed using the PSEUROT (version 6.3) software in combination with NMR studies.
Bismuth‐Containing SBA‐15 Mesoporous Silica Catalysts for Solvent‐Free Liquid‐Phase Oxidation of Cyclohexane by Molecular Oxygen
Authors: Wang Huan‐Ling , Li Rong , Zheng Yun‐Feng , Chen Hang‐Ning , Jin Jun , Wang Fu‐Shan , Ma Jian‐Tai
Published: September 2007

Bismuth (Bi)‐containing SBA‐15 mesoporous silica catalysts, Bi/SBA‐15, with different Bi loadings were synthesized by a direct hydrothermal method. The materials were characterized in detail by various techniques. Powder‐X‐ray‐diffraction (PXRD), N2‐adsorption/desorption, and transmission‐electron‐microscopic (TEM) analyses revealed that the well‐ordered hexagonal structure of SBA‐15 is maintained after Bi incorporation. Diffuse‐reflectance UV/VIS, Raman, and X‐ray photoelectron spectroscopy (XPS) showed that the incorporated Bi‐atoms are highly dispersed, most of them entering the internal surface of SBA‐15. The new, very stable catalysts were found to be highly efficient for the oxidation of cyclohexane in a solvent‐free system, molecular oxygen (O2) being used as oxidant.
The neuropsychology of ecstasy (MDMA) use: a quantitative review
Authors: Zakzanis Konstantine K. , Campbell Zachariah , Jovanovski Diana
Published: September 2007

A growing number of empirical studies have found varying neuropsychological impairments associated with use of 3,4‐methylenedioxymethamphetamine (MDMA) use. We set out to determine to what extent neuropsychological abilities are impaired in MDMA users. To do so, meta‐analytical methods were used to determine the magnitude of neuropsychological impairment in MDMA users across pre‐specified cognitive domains. We found that cognitive impairment secondary to recreational drug use may result in what might be described as small‐to‐medium effects across all cognitive domains with learning and memory being most impaired. We also found that total lifetime ingestion of MDMA appears to be negatively associated with performance on tasks ranging from attention and concentration to learning and memory. Implications and limitations of these findings are discussed. Copyright © 2007 John Wiley & Sons, Ltd.
An analytical method of analysing the oscillatory pressure head measured at any depth in a well casing
Authors: Chen Chia‐Shyun
Published: September 2007

When a slug test is conducted in a highly permeable aquifer, a shallow pressure transducer in the well casing produces an oscillatory pressure head that is representative of the water level fluctuation, whereas a deep pressure transducer in the well casing yields an oscillatory pressure head that is different from the water level change. Although the solutions for shallow and deep pressure head are different, it is found that the ratios of the subsequent extremity displacements are in an identical relationship (an extremity can be a maximum or a minimum in the oscillatory pressure head). Based on this relationship, an analytical data analysis method for the determination of the hydraulic conductivity is developed for both shallow and deep pressure transducer data. This analytical method is applied to the pressure head measured at different depths in the well casing of a well partially penetrating an unconfined coarse sand aquifer. Satisfactory results are obtained, validating the applicability of this analytical method for pressure transducer data at any depth in a well casing. Copyright © 2007 John Wiley & Sons, Ltd.
Understanding of hydraulic properties from configurations of stochastically distributed fracture networks
Authors: Wang Mingyu , Kulatilake P. H. S. W.
Published: September 2007

A systematic investigation of the effect of configurations of stochastically distributed fracture networks on hydraulic behaviour for fractured rock masses could provide either quantitative or qualitative correlation between the structural configuration of the fracture network and its corresponding hydraulic behaviour, and enhance our understanding of appropriate application of groundwater flow and contaminant transport modelling in fractured rock masses. In this study, the effect of block sizes, intersection angles of fracture sets, standard deviations of fracture orientation, and fracture densities on directional block hydraulic conductivity and representative elementary volume is systematically investigated in two dimensions by implementing a numerical discrete fracture fluid flow model and incorporating stochastically distributed fracture configurations. It is shown from this investigation that the configuration of a stochastically distributed fracture network has a significant quantitative or qualitative effect on the hydraulic behaviour of fractured rock masses. Compared with the deterministic fracture configurations that have been extensively dealt with in a previous study, this investigation is expected to be more practical and adequate, since fracture geometry parameters are inherently stochastically distributed in the field. Moreover, the methodology and approach presented in this study may be generally applied to any fracture system in investigating the hydraulic behaviours from configurations of the fracture system while establishing a ‘bridge’ from the discrete fracture network flow modelling to equivalent continuum modelling in fractured rock masses. Copyright © 2007 John Wiley & Sons, Ltd.
The effect of conservation tillage on runoff erosivity and soil erodibility during concentrated flow
Authors: Knapen A. , Poesen J. , Govers G. , De Baets S.
Published: September 2007

Crop residues in conservation tillage systems are known to cause both a reduction in the erosive runoff power and an increase in the topsoil erosion resistance. In this study, the relative importance of both mechanisms in reducing soil loss by concentrated flow erosion is examined. Therefore, a method to calculate the effective flow shear stress responsible for soil detachment in the presence of a residue cover is applied. The determination of effective flow shear stress is based on the recalculation of the hydraulic radius for residue treatments. The method was tested in a laboratory flume by comparing soil detachment rates of identical pairs of soil samples that only differ in the presence or absence of crop residues. This shear stress partitioning approach and a soil detachment correction were then applied to a dataset of soil detachment measurements on undisturbed topsoil samples from a no‐till field plot on a loess‐derived soil, sampled during one growing season. Results indicate that only a small fraction (10% on average) of the difference in soil detachment rate between conventional and conservation tillage can be attributed to the dissipation of shear forces on the residues. The remaining decrease in soil detachment during concentrated runoff after a two‐year application of conservation tillage can be explained by the increased dry bulk density and root and crop residue content in the topsoil that reduces soil erodibility. After correcting for the presence of residues, the temporal variability in soil detachment rates (Dr) during concentrated flow for a given flow shear stress (τ) for both treatments can be predicted fairly well (R2 = 0·87) from dry soil bulk density (DBD, representing consolidation effects), soil moisture content (SMC, representing antecedent rainfall conditions), the dry mass of organic material (OM, representing root growth and residue decomposition) and saturated soil shear strength σs, sat using an equation of the form:

This study is the first to show that the effect of conservation tillage on soil detachment rates is a result of soil property modifications affecting soil erodibility, rather than a result of the surface residue decreasing flow erosivity. Copyright © 2007 John Wiley & Sons, Ltd.
Identification of uncertainty in low flow frequency analysis using Bayesian MCMC method
Authors: Lee Kil Seong , Kim Sang Ug
Published: September 2007

This study employs the Bayesian Markov Chain Monte Carlo (MCMC) method with the Metropolis–Hastings algorithm and maximum likelihood estimation (MLE) using a quadratic approximation of the likelihood function for the evaluation of uncertainties in low flow frequency analysis using a two‐parameter Weibull distribution. The two types of prior distributions, a non‐data‐based distribution and a data‐based distribution using regional information collected from neighbouring stations, are used to establish a posterior distribution. Eight case studies using the synthetic data with a sample size of 100, generated from two‐parameter Weibull distribution, are performed to compare with results of analysis using MLE and Bayesian MCMC. Also, Bayesian MCMC and MLE are applied to 36 years of gauged data to validate the efficiency of the developed scheme. These examples illustrate the advantages of Bayesian MCMC and the limitations of MLE based on a quadratic approximation. From the point of view of uncertainty analysis, Bayesian MCMC is more effective than MLE using a quadratic approximation when the sample size is small. In particular, Bayesian MCMC method is more attractive than MLE based on a quadratic approximation because the sample size of low flow at the site of interest is mostly not enough to perform the low flow frequency analysis. Copyright © 2007 John Wiley & Sons, Ltd.
Modelling the impact of afforestation on average annual streamflow in the Loess Plateau, China
Authors: Zhang Xiao Ping , Zhang Lu , McVicar Tim R. , Van Niel Tom G. , Li Ling Tao , Li Rui , Yang QinKe , Wei Liang
Published: September 2007

To prevent severe soil erosion and to ensure sustainable development, the Chinese Central Government mandated in 1999 that forest cover would be significantly increased in the Loess Plateau, China. It is important to assess the subsequent impact on streamflow and its spatial distribution in the region. The water balance model of et al. (2001)Zhang et al. (2001) was used in this study, and the results showed that the model was able to accurately simulate average annual evapotranspiration (ET), but not average annual streamflow when compared with streamflow measurements from 38 hydrologic stations in the coarse sandy hilly catchments (CSHC) in the Loess Plateau. The model was then calibrated using the measured streamflow, and the index of agreement increased from 0·21 to 0·63, the relative error and root mean square error decreased from 42·7 and 17·2 to 18·0% and 7·9 mm, respectively. Hierarchical cluster analysis and stepwise regression were employed to regionalize the optimized model parameter and relate it to the dryness index and forest cover. Once calibrated, the water balance model was used to assess the impacts of two plantation scenarios on streamflow. The two plantation scenarios assume nearly 5·8 and 10·1% of the study area can be planted with trees. It was predicted that streamflow from the region will decrease by 5·5 and 9·2% under the two plantation scenarios. The rate of streamflow reduction decreased from southeast to northwest mainly due to decreasing precipitation. Copyright © 2007 John Wiley & Sons, Ltd.
Estimation of tree water stress from stem and soil water monitoring with time‐domain reflectometry in two small forested basins in Spain
Authors: Hernández‐Santana Virginia , Martínez‐Fernández José , Morán Carlos
Published: September 2007

Soil‐tree water relationships were studied using time domain reflectometry (TDR) in two small forested basins in Spain. The stem water content of two Mediterranean Quercus species (Quercus pyrenaica and Quercus rotundifolia) was measured using previously constructed species‐specific equations. To monitor soil moisture, a TDR station network was used in both cases. Sixteen Q. pyrenaica and six Q. rotundifolia individuals were selected to install two TDR probes in their trunks (at 20 and 120 cm above the ground) to monitor stem water content. Stem and soil water contents were measured fortnightly. The stem water content of both species showed a similar temporal trend for the period studied. A spring maximum (0·654 cm3 cm−3 for Q. pyrenaica and 0·568 cm3 cm−3 for Q. rotundifolia) was found to be associated with high transpiration and no soil moisture deficit, and a late‐summer minimum (0·520 cm3 cm−3 for Q. pyrenaica and 0·426 cm3 cm−3 for Q. rotundifolia) was associated with the end of the dry season. This drop in stem water content occurs when the available water in the soil decreases. This seasonal difference presumably reflects water withdrawn from stem storage to support the transpirational demands of the tree. Since plant water stress results in reduced stem water content and since this drop can be measured by TDR, it may be concluded that this technology offers a suitable tool for detecting plant water stress. Copyright © 2007 John Wiley & Sons, Ltd.
Hortonian overland flow from Japanese forest plantations—an aberration, the real thing, or something in between?
Authors: Sidle Roy C. , Hirano Tomonori , Gomi Takashi , Terajima Tomomi
Published: September 2007

There is a growing opinion that poorly managed plantation forests in Japan are contributing to increased storm runoff and erosion. Here we present evidence to the contrary from runoff plots at two scales (hillslope and 0·5 × 2 m plots) for several forest conditions in the Mie and Nariki catchments. Runoff coefficients from small plots in untended hinoki forests were variable but typically higher than from better managed or deciduous forests during small storms at Nariki; at Mie, runoff during small events was highly variable from all small plots but runoff coefficients were similar for hinoki plots with and without understory vegetation, while the deciduous plot had lower runoff coefficients. Storm runoff was less at the hillslope scale than the plot scale in Mie; these results were more evident at sites with better ground cover. During the largest storms at both sites, differences in runoff due to forest condition were not evident regardless of scale. Dynamic soil moisture tension measurements at Nariki indicated that during a large storm, flow in the upper organic‐rich and root‐permeated soil horizons was 3·2 times higher than measured overland runoff from a small hinoki plot with poor ground cover and 8·3 times higher than runoff from a deciduous forest plot. On the basis of field observations during storms, at least a portion of the monitored ‘Hortonian overland flow’ was actually occurring in this near‐surface ‘biomat’. Therefore our field measurements in both small and large plots potentially included biomat flow in addition to short‐lived Hortonian runoff. Because overland flow decreased with increasing scale, rill erosion did not occur on hillslopes. Additionally, runoff coefficients were not significantly different among cover conditions during large storms; thus, the ‘degraded’ forest conditions appear not to greatly enhance peak flows or erosion potential at larger scales, especially when biomat flow is significant. Copyright © 2007 John Wiley & Sons, Ltd.
Theoretical dynamic studies on the reactions of CH3C(O)CH3−nCln (n = 0–3) with the chlorine atom
Authors: Ji Yue‐meng , Zhao Xiao‐lei , Liu Jing‐yao , Wang Ying , Li Ze‐sheng
Published: September 2007

The theoretical investigations were performed on the reaction mechanisms for the title reactions CH3C(O)CH3 + Cl → products (R1), CH3C(O)CH2Cl + Cl → products (R2), CH3C(O)CHCl2 + Cl → products (R3), and CH3C(O)CCl3 + Cl → products (R4) by ab initio direct dynamics approach. Two different reaction channels have been found: abstract of the H atom from methyl (CH3) group or chloromethyl (CH3−nCln) group of chloroacetone and addition of a Cl atom to the carbon atom of the carbonyl group of chloroacetone followed by methyl or chloromethyl eliminations. Because of the higher potential energy barrier, the contribution of addition–elimination reaction pathway to the total rate constants is very small and thus this pathway is insignificant in atmospheric conditions. The rate constants for the H‐abstraction reaction channels are evaluated by using canonical variational transition state theory incorporating with the small‐curvature tunneling correction. Theoretical overall rate constants are in good agreement with the available experimental values and decrease in the order of k1 > k2 > k3 > k4. The results indicate that for halogenated acetones the substitution of halogen atom (F or Cl) leads to the decrease in the CH bond reactivity and more decrease of reactivity is caused by F‐substitution. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Accelerating molecular modeling applications with graphics processors
Authors: Stone John E. , Phillips James C. , Freddolino Lydia , Hardy David J. , Trabuco Leonardo G. , Schulten Klaus
Published: September 2007

Molecular mechanics simulations offer a computational approach to study the behavior of biomolecules at atomic detail, but such simulations are limited in size and timescale by the available computing resources. State‐of‐the‐art graphics processing units (GPUs) can perform over 500 billion arithmetic operations per second, a tremendous computational resource that can now be utilized for general purpose computing as a result of recent advances in GPU hardware and software architecture. In this article, an overview of recent advances in programmable GPUs is presented, with an emphasis on their application to molecular mechanics simulations and the programming techniques required to obtain optimal performance in these cases. We demonstrate the use of GPUs for the calculation of long‐range electrostatics and nonbonded forces for molecular dynamics simulations, where GPU‐based calculations are typically 10–100 times faster than heavily optimized CPU‐based implementations. The application of GPU acceleration to biomolecular simulation is also demonstrated through the use of GPU‐accelerated Coulomb‐based ion placement and calculation of time‐averaged potentials from molecular dynamics trajectories. A novel approximation to Coulomb potential calculation, the multilevel summation method, is introduced and compared with direct Coulomb summation. In light of the performance obtained for this set of calculations, future applications of graphics processors to molecular dynamics simulations are discussed. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
The role of the EGFR signaling in tumor microenvironment
Authors: De Luca Antonella , Carotenuto Adele , Rachiglio Annamaria , Gallo Marianna , Maiello Monica R. , Aldinucci Donatella , Pinto Antonio , Normanno Nicola
Published: September 2007

The epidermal growth factor receptor (EGFR) family comprehends four different tyrosine kinases (EGFR, ErbB‐2, ErbB‐3, and ErbB‐4) that are activated following binding to epidermal growth factor (EGF)‐like growth factors. It has been long established that the EGFR system is involved in tumorigenesis. These proteins are frequently expressed in human carcinomas and support proliferation and survival of cancer cells. However, activation of the EGFR in non‐malignant cell populations of the neoplastic microenvironment might also play an important role in cancer progression. EGFR signaling regulates in tumor cells the synthesis and secretion of several different angiogenic growth factors, including vascular endothelial growth factor (VEGF), interleukin‐8 (IL‐8), and basic fibroblast growth factor (bFGF). Overexpression of ErbB‐2 also leads to increased expression of angiogenic growth factors, whereas treatment with anti‐EGFR or anti‐ErbB‐2 agents produces a significant reduction of the synthesis of these proteins by cancer cells. EGFR expression and function in tumor‐associated endothelial cells has also been described. Therefore, EGFR signaling might regulate angiogenesis both directly and indirectly. In addition, activation of EGFR is involved in the pathogenesis of bone metastases. Within the bone marrow microenvironment, cancer cells stimulate the synthesis of osteoclastogenic factors by residing stromal cells, a phenomenon that leads to bone destruction. It has been shown that EGFR signaling regulates the ability of bone marrow stromal cells to produce osteoclastogenic factors and to sustain osteoclast activation. Taken together, these findings suggest that the EGFR system is an important mediator, within the tumor microenvironment, of autocrine and paracrine circuits that result in enhanced tumor growth. J. Cell. Physiol. 214: 559–567, 2008. © 2007 Wiley‐Liss, Inc.
Gab2 requires membrane targeting and the met binding motif to promote lamellipodia, cell scatter, and epithelial morphogenesis downstream from the met receptor
Authors: Frigault Melanie M. , Naujokas Monica A. , Park Morag
Published: September 2007

Gab1 and Gab2 are conserved scaffolding proteins that amplify and integrate signals stimulated by many growth factor receptors including the Met receptor. Gab1 acts to diversify the signal downstream from Met through the recruitment of multiple signaling proteins, and is essential for epithelial morphogenesis. However, whereas Gab1 and Gab2 are both expressed in epithelial cells, Gab2 fails to support a morphogenic response. We demonstrate that Gab1 and Gab2 are divergent in their function whereby Gab1, but not Gab2, promotes lamellipodia formation, and is localized to the membrane of lamellipodia upon Met activation. We have identified activation of ERK1/2 as a requirement for lamellipodia formation. Moreover, activated ERK1/2 are localized to lamellipodia in Gab1 expressing cells but not in cells that overexpress Gab2. By structure–function studies, we identify that enhanced membrane localization conferred through the addition of a myristoylation signal, together with the addition of the direct Met binding motif (MBM) from Gab1, are required to promote lamellipodia and confer a morphogenic signaling response to Gab2. Moreover, the morphogenesis competent myristoylated Gab2MBM promotes localization of activated ERK1/2 to the leading edge of lamellipodia in a similar manner to Gab1. Hence, subcellular localization of the Gab scaffold, as well as the ability of Gab to interact directly with the Met receptor, are both essential components of the morphogenic signaling response which involves lamellipodia formation and the localization of ERK1/2 activation in membrane ruffles. J. Cell. Physiol. 214: 694–705, 2008. © 2007 Wiley‐Liss, Inc.
Functional interleukin‐7/interleukin‐7Rα, and SDF‐1α/CXCR4 are expressed by human periodontal ligament derived mesenchymal stem cells
Authors: Trubiani Oriana , Isgro Antonella , Zini Nicoletta , Antonucci Ivana , Aiuti Fernando , Di Primio Roberto , Nanci Antonio , Caputi Sergio , Paganelli Roberto
Published: September 2007

Hematopoiesis in the bone marrow (BM) is maintained by specific interactions between both hematopoietic and non‐hematopoietic stromal cells, which are mesenchymal stem cells (MSCs) capable of giving rise to several cell types. The human periodontal ligament (PDL), a tissue of ectomesenchymal origin, has been shown to also be a source of MSCs. We have investigated whether MSCs expanded from the PDL of healthy volunteers express characteristics similar to BM‐derived stem cells using structural, immunocytochemical and molecular approaches. Their ability to support the growth of hematopoietic progenitors was also analyzed. The PDL‐MSCs exhibited a fibroblast‐like morphology and their chromatin was dispersed, indicating active gene transcription. The mesenchymal‐related antigens CD90, CD29, CD166, CD105, and CD44 were homogeneously detected by cytofluorimetric analysis, whereas membrane CXCR4 was expressed only by a minority of cells. The PDL‐MSCs differentiated in vitro into osteogenic and adipogenic cells. Immunolocalization of IL‐7, IL‐7Rα, SDF‐1α, and CXCR4 resulted in a diffuse but specific labeling. RT‐PCR analysis confirmed the expression of the above‐mentioned transcripts. The cells spontaneously produced high levels of IL‐7 and SDF‐1α and were able to support the development and long‐term maintenance of BM precursor cells more efficiently than murine stromal cells and similarly to normal BM human stromal cells. We examined IL‐7 and SDF‐1α secretion pathway during adipogenic and osteogenic differentiation. IL‐7 increased during osteogenic and adipogenic differentiation, while the SDF‐1α secretion was downregulated during osteogenic differentiation but increased during adipogenic induction. Our study provides evidence that in human PDL there is an accessible niche of MSCs showing the features of BM‐derived MSCs. J. Cell. Physiol. 214: 706–713, 2008. © 2007 Wiley‐Liss, Inc.
EGF upregulates Na+/H+ exchanger NHE1 by post‐translational regulation that is important for cervical cancer cell invasiveness
Authors: Chiang Yihan , Chou Cheng‐Yang , Hsu Keng‐Fu , Huang Yu‐Fang , Shen Meng‐Ru
Published: September 2007

Na+/H+ exchanger 1 (NHE1) is involved in cell migration but little is known about the signal pathways that regulate NHE1 activity and that are associated with tumor cell invasiveness. This study is to investigate the mechanisms by which epidermal growth factor (EGF) regulates NHE1 expression to promote cervical cancer cell invasiveness and the clinical significance in early‐stage cervical cancer. NHE1 protein was scanty in normal or noncancerous cervical tissues of all surgical specimens examined (n = 92). Tumor tissues clearly expressed NHE1 protein with different amounts. The differential expression level of NHE1 is associated with the clinical outcome. NHE1 protein was also differentially expressed between normal cervical epithelial cells and two cervical cancer cell lines. Cervical cancer cells benefit some enhanced cellular functions from NHE1 abundance, such as cell volume regulation, migration, and invasion. Interestingly, NHE1 colocalized with EGF in cervical cancer tissues. Studies in cell culture systems indicated that EGF‐stimulated NHE1 abundance in a time‐dependent manner by post‐translational regulation. This implies a likely autocrine or paracrine EGF stimulation of NHE1 production in vivo. In addition, the phosphoinositide 3‐kinase pathway is the dominant signal controlling EGF‐stimulated NHE1 abundance. Pharmacological inhibition of NHE1 activity markedly inhibited the basal and EGF‐stimulated cervical cancer cell migration. Image studies and immunoprecipitaion experiments suggest that EGF‐induced NHE1 translocation to the leading‐edge lamellipodia, where NHE1 interacted with actin‐associated protein Ezrin, thereby remodeling cytoskeleton and stimulating cervical cancer cell migration. In conclusion, EGF upregulates NHE1 by post‐translational regulation that is important for cervical cancer cell invasiveness. J. Cell. Physiol. 214: 810–819, 2008. © 2007 Wiley‐Liss, Inc.
Ultraviolet light exposure triggers nuclear accumulation of p21WAF1 and accelerated senescence in human normal and nucleotide excision repair‐deficient fibroblast strains
Authors: Mirzayans Razmik , Scott April , Andrais Bonnie , Pollock Scott , Murray David
Published: September 2007

Induction of the p21WAF1 protein (hereafter called p21) following genotoxic stress is known to inhibit proliferating cell nuclear antigen (PCNA)‐dependent DNA repair, downregulate apoptosis, and trigger a sustained growth‐arrested phenotype called accelerated senescence. Studies with immortalized human and murine cell lines have revealed that exposure to ultraviolet light (UVC; 254 nm) results in the degradation of p21 to facilitate DNA repair and promote cell survival, or may lead to apoptotic cell death. The objective of the present study was to determine whether exposure of non‐transformed human fibroblast strains to relatively low fluences of UVC (i.e., fluences typically used in the clonogenic survival assay) might induce sustained nuclear accumulation of p21, leading to accelerated senescence. We have evaluated the responses of normal human fibroblast (NHF) strains and nucleotide excision repair (NER)‐deficient fibroblast strains representing xeroderma pigmentosum (XP) complementation groups A and G and Cockayne syndrome (CS) complementation groups A and B. We report that exposure of NHFs to ≤15 J/m2 of UVC, and NER‐deficient fibroblasts to ≤5 J/m2 of UVC, results in sustained nuclear accumulation of p21 and growth arrest through accelerated senescence. With each fibroblast strain examined, exposure to UVC fluences that resulted in ∼90% loss of clonogenic potential triggered significant (>60%) accelerated senescence, but only marginal (<5%) apoptosis. We conclude that nuclear accumulation of p21 accompanied by accelerated senescence may be an integral component of the response of human fibroblasts to UVC‐induced DNA damage, irrespective of their DNA repair capabilities. J. Cell. Physiol. 215: 55–67, 2008. © 2007 Wiley‐Liss, Inc.
Future directions for in‐situ product removal (ISPR)
Authors: Woodley John M , Bisschops Marc , Straathof Adrie J J , Ottens Marcel
Published: September 2007

This paper summarizes the main findings of a round‐table discussion held to examine the key bottlenecks in the further application and industrial implementation of in‐situ product removal (ISPR) techniques.** It is well established that ISPR can yield great benefits for processes limited by inhibitory or toxic products, as well as unstable products or reactions that are thermodynamically unfavorable. However, several issues for industrial implementation were revealed in the discussion. Most notably implementation will be dependent on (1) research into the appropriate process structure, (2) methods to achieve process robustness, (3) systematic selection methods for separation operations and (4) the nature of the product market. Here, these four issues will be discussed as a basis for future work in this area. Copyright © 2007 Society of Chemical Industry
Synthesis of isotopically labelled compounds at Schering‐Plough, an historical perspective
Authors: Hesk D. , McNamara P.
Published: September 2007

The use of isotopically labelled compounds at Schering‐Plough (S‐P) has substantially increased over the past 30 years. Since the formation of the S‐P Radiochemistry section in the early 1970s, the group has expanded its role from supplying 14C‐ and 3H‐labelled compounds for ADME studies for compounds in development, to providing 3H‐labelled compounds for drug discovery and also to provide stable isotope‐labelled compounds that are used as LC/MS internal standards. Other isotopes used by the group have included 125I and 35S, which have been used to label both small molecules and proteins. Copyright © 2007 John Wiley & Sons, Ltd.
Isotope incorporation via organoboranes
Authors: Kabalka George W.
Published: September 2007

Organoboranes can be used as precursors to a wide variety of functionally substituted, isotopically labeled compounds. Straightforward boron‐based methods for incorporating short‐lived and stable isotopes of carbon, nitrogen, oxygen, and the halogens have been developed over a period of 20 years. Application of these methods to biology, agriculture, and medicine has been slowed by the limited availability of boronated precursors containing functional groups appropriate to those fields. The situation has changed markedly with the advent of metal catalyzed boron‐based reactions, which now produce a variety of important boronated materials readily available in the laboratory and from commercial sources. This is especially important in the medical and pharmaceutical communities where short‐lived isotopes of carbon, nitrogen, and the halogens are demonstrating great value in positron and single photon emission tomographic procedures. Copyright © 2007 John Wiley & Sons, Ltd.
Amersham radiochemistry to GE Healthcare
Authors: Kitson Sean L.
Published: September 2007

I was invited by Professor John R. Jones (University of Surrey) to write a paper to celebrate 50 years of the Journal of Labelled Compounds and Radiopharmaceuticals. The aim of this paper is to outline briefly the history of radiochemistry from The Radiochemical Centre at Amersham in the 1940s to the acquisition by General Electric in 2004 and the formation of GE Healthcare. Copyright © 2007 John Wiley & Sons, Ltd.
Carbon‐14 labelling of acarbose – a challenge over more than 20 years
Authors: Seidel D. , Wehlmann H. , Lenz J.
Published: September 2007

Acarbose is a potent α‐glucosidase inhibitor which is used successfully as a drug for the treatment of type II diabetes. The compound prevents enzymes of the α‐glucosidase group from cleaving carbohydrates. For the investigation of pharmacokinetics and drug metabolism a first carbon‐14 labelling synthesis was performed in 1981. According to the pharmaceutical production process, the radiosynthesis was performed by fermentation. Due to limited radiolytic stability, repeated radiosyntheses were necessary. Finally, carbon‐14 labelling was optimized to prepare [14C]acarbose on a gram scale with a significant increase of the radiochemical yield. The aspects of the fermentation over a period of about 20 years are described focussing the attention on the optimized radiosynthesis. Copyright © 2007 John Wiley & Sons, Ltd.
The imaging continuum: bench to biomarkers to diagnostics
Authors: Frank Richard A. , Långström Bengt , Antoni Gunnar , Montalto Michael C. , Agdeppa Eric D. , Mendizabal Marivi , Wilson Ian A. , Vanderheyden Jean‐Luc
Published: September 2007

Innovation in basic and applied science has brought radiotracers to fruition as diagnostics. Non‐invasive, longitudinal, and quantifiable molecular imaging is the key to diagnosing and monitoring numerous illnesses, with more to come from characterization of the clinical relevance of findings from genomics research. Radiotracers enable real‐time in vivo studies of the effects of drug candidates on receptors, pathways, pharmacodynamics, and clinically relevant endpoints, thereby providing both early detection of pathophysiology to enable early intervention, and then monitoring of treatment responses to enable individualization of treatment regimens. We review developments which have translated imaging from ‘bench to bedside’, or ‘biomarkers to diagnostics’. Notable developments include (1) synthesis methods for rapid 11C labeling of biomolecules to high specific radioactivity; (2) ligand‐binding assays for screening molecular imaging agents rather than drugs; (3) in vivo imaging of radiotracers in animals; (4) discovering the imaging advantages of 99mTc, 11C, and 18F; (5) co‐registration and automated quantitative assessment of high spatial resolution CT and MR images with molecular images from PET for longitudinal studies of treatment effect. Copyright © 2007 John Wiley & Sons, Ltd.
Solid‐phase reactions as approach to the synthesis of organic compounds labelled with tritium
Authors: Myasoedov Nikolay F.
Published: September 2007

The solid‐phase method for hydrogenolysis, hydrogenation and isotope exchange reactions is described. Its potential for tritium labelling of organic compounds including lipids, nucleotides, amino acids, peptides and pharmaceuticals is demonstrated. The influence of the reaction conditions on the yield and specific radioactivity of the labelled compounds is considered. It is shown that results can be interpreted by the dependence of tritium spillover reactions on the nature of the initial compound and other factors. Copyright © 2007 John Wiley & Sons, Ltd.
Proton MR spectroscopic imaging of the medulla and cervical spinal cord
Authors: Edden Richard A.E. , Bonekamp David , Smith Mari A. , Dubey Prachi , Barker Peter B.
Published: September 2007

Purpose

To demonstrate the feasibility of quantitative, one‐dimensional proton MR spectroscopic imaging (1D‐MRSI) of the upper cervical spine and medulla at 3.0 Tesla.

Materials and Methods

A method was developed for 1D‐point‐resolved spectroscopy sequence (PRESS)‐MRSI, exciting signal in five voxels extending from the pontomedullary junction to the level of the C3 vertebra, and performed in 10 healthy volunteers to generate control data.

Results

High‐resolution 1D‐MRSI data were obtained from all 10 subjects. Upper cervical spine concentrations of choline, creatine, and N‐acetyl aspartate were estimated to be 2.8 ± 0.5, 8.8 ± 1.8, and 10.9 ± 2.7 mM, respectively, while in the medulla they were 2.6 ± 0.5, 9.1 ± 1.7, and 10.8 ± 0.9 mM.

Conclusion

Quantitative 1D‐MRSI of the upper cervical spine has been shown to be feasible at 3.0 Tesla. J. Magn. Reson. Imaging 2007;26:1101–1105. © 2007 Wiley‐Liss, Inc.
Temporal evolution of spinal cord infarction in an in vivo experimental study of canine models characterized by diffusion‐weighted imaging
Authors: Zhang Jin Song , Huan Yi , Sun Li Jun , Ge Ya Li , Zhang Xue Xin , Chang Ying Juan
Published: September 2007

Purpose

To determine the temporal evolution of diffusion abnormalities of in vivo experimental spinal cord infarction.

Materials and Methods

Guided by a digital subtract angiography (DSA) monitor, an agent of 1:1 match of lipiodol and diatrizoate meglumine was injected into bilateral T9‐11 intercostal arteries of six dogs to embolize the spinal branches of intercostal arteries and establish the canine spinal cord infarction models. The progression of experimental spinal cord infarction was followed by dynamic MRI, including diffusion‐weighted imaging (DWI) on a 1.5 Tesla MR system from one hour to 168 hours postembolization. Apparent diffusion coefficient (ADC) values were calculated and analyzed. At the end of the MRI experiments, the spinal cords of the animals were fixed for histology.

Results

A total of six experimental models were successfully established. In all cases, DWI images showed slight hyperintensity within one hour postembolization, whereas only four cases presented slight hyperintensity on T2‐weighted images. ADC values of spinal cord infarction lesions decreased rapidly at early stage (several hours to 24 hours) and then increased gradually.

Conclusion

The temporal evolution of diffusion abnormality of experimental spinal cord infarction may help us better understand various DWI signals in the process of spinal cord infarction. J. Magn. Reson. Imaging 2007;26:848–854. © 2007 Wiley‐Liss, Inc.
Quantification of rodent cerebral blood flow (CBF) in normal and high flow states using pulsed arterial spin labeling magnetic resonance imaging
Authors: Wegener Susanne , Wu Wen‐Chau , Perthen Joanna E. , Wong Eric C.
Published: September 2007

Purpose

To implement a pulsed arterial spin labeling (ASL) technique in rats that accounts for cerebral blood flow (CBF) quantification errors due to arterial transit times (dt)—the time that tagged blood takes to reach the imaging slice—and outflow of the tag.

Materials and Methods

Wistar rats were subjected to air or 5% CO2, and flow‐sensitive alternating inversion‐recovery (FAIR) perfusion images were acquired. For CBF calculation, we applied the double‐subtraction strategy (Buxton et al., Magn Reson Med 1998;40:383–396), in which data collected at two inversion times (TIs) are combined.

Results

The ASL signal fell off more rapidly than expected from TI = one second onward, due to outflow effects. Inversion times for CBF calculation were therefore chosen to be larger than the longest transit times, but short enough to avoid systematic errors caused by outflow of tagged blood. Using our method, we observed a marked regional variability in CBF and dt, and a region dependent response to hypercapnia.

Conclusion

Even when flow is accelerated, CBF can be accurately determined using pulsed ASL, as long as dt and outflow of the tag are accounted for. J. Magn. Reson. Imaging 2007;26:855–862. © 2007 Wiley‐Liss, Inc.
Interleaved water and fat imaging and applications to lipid quantitation using the gradient reversal technique
Authors: Tang Haiying , Wu Ed X. , Kennan Richard , Liu Haiying , Williams Donald S.
Published: September 2007

Purpose

To implement and evaluate the gradient reversal‐based chemical shift imaging technique to obtain qualitative and quantitative spatially‐registered fat and water images with high imaging efficiency at very high field.

Materials and Methods

A multiecho gradient reversal‐based sequence allowing interleaved water–fat imaging during a single acquisition and quantitation of fat/water content is presented. The sequence was optimized and implemented at 11.7T. The quantitation was verified with water–fat phantoms and applied to lipid measurement in an in vivo mouse model.

Results

Results from phantoms, in vivo lipid measurement in mouse liver and hind limb muscle, and ex vivo rat knee imaging experiments demonstrated the robustness and high selectivity of this technique for interleaved and quantitative water and fat imaging at very high field.

Conclusion

The proposed MRI technique permits interleaved water and fat imaging, with which spectrally well‐separated water and fat images at the identical slice locations could be obtained in a single acquisition without increasing scan time. The technique could be used for in vivo quantitative mapping of lipid content and applied to investigations using small animal experiment models. J. Magn. Reson. Imaging 2007;26:1064–1070. © 2007 Wiley‐Liss, Inc.
Whole‐body diffusion‐weighted imaging: Technical improvement and preliminary results
Authors: Li Shuo , Sun Fei , Jin Zheng‐yu , Xue Hua‐dan , Li Ming‐li
Published: September 2007

Purpose

To optimize the free‐breathing whole‐body diffusion‐weighted imaging (WB‐DWI) protocol by using the short TI inversion‐recovery diffusion‐weighted echo‐planar imaging (STIR‐DWEPI) sequence and the built‐in body coil. Additionally, to evaluate the feasibility of tumor screening using high‐resolution three‐dimensional (3D) maximum intensity projection (MIP) images.

Materials and Methods

The prescan procedure of STIR‐DWEPI was modified using the data from 30 volunteers. During each exam, an optimized center frequency (CF) was used to minimize the slice offsets in consecutive scan stations. Prescan time was reduced from 50 seconds to 20 seconds with improved station profile. Total scan time was 30 minutes for five stations and 1.2 m coverage. A total of 30 patients with histologically‐proven malignant disease were scanned under the final protocol using a built‐in body coil. The image quality and the degree of background body signal suppression were assessed.

Results

Free‐breathing WB‐DWI was 100% successfully performed in all patients, without slice misregistration, fat contamination, significant distortion, or nonuniformity. The reconstructed 3D‐MIP images were adequate to depict malignant lesions in all 30 patients. The results of WB‐DWI were found to be comparable to those of single‐photon emission computed tomography (SPECT) and positron emission tomography (PET).

Conclusion

Stable and high‐resolution WB‐DWI is feasible using the technical improvements described in this study. WB‐DWI might have important clinical value for the detection of primary and metastatic malignancies within the whole body. The potential for diagnosis and therapeutic assessment of tumors should be further assessed in a larger patient cohort. J. Magn. Reson. Imaging 2007;26:1139–1144. © 2007 Wiley‐Liss, Inc.
Time course of diffusion imaging in acute brainstem infarcts
Authors: Axer Hubertus , Gräβel David , Brämer Dirk , Fitzek Sabine , Kaiser Werner A. , Witte Otto W. , Fitzek Clemens
Published: September 2007

Purpose

To study the time course of diffusion imaging at the lesion site in brainstem infarcts.

Materials and Methods

Sequential MR scans were acquired from 24 patients with brainstem infarcts. Diffusion‐weighted images (DWI), T2‐weighted images (T2w), maps of apparent diffusion coefficient, and maps of fractional anisotropy were generated from each MR scan. A trend function was fitted to these measurements to model an objective, general time course of the studied parameters.

Results

Apparent diffusion coefficient (ADC) continuously decreased over time until a transition time around 45 hours; afterwards a continuous increase took place. After the 14th day ADC reached values similar to the ADC of the intact contralateral side (pseudonormalization) and then further increased. Fractional anisotropy (FA) decreased continuously over 3 to 6 months.

Conclusion

Times of transition and pseudonormalization of ADC were longer than described for territorial hemispheric infarcts and describe the acute to subacute phase of brainstem ischemia. In contrast, the continuous decline of FA over 3 to 6 months indicates a chronic process of change of histological structures in brainstem ischemia, and may be regarded as an indicator of the chronic phase. J. Magn. Reson. Imaging 2007;26:905–912. © 2007 Wiley‐Liss, Inc.