bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pan‐HER biologics (Hermodulins) for the treatment of cancer
Authors: Maneval Daniel C. , Jin Pei , Shepard H. Michael 
Published: December 2008

AbstractThe four members of the human epidermal growth factor receptor (HER) family and their cognate ligands combine in a complex network to play key roles in normal growth and development. Abnormal expression, mutation, or altered signaling of HER proteins has been linked to the pathogenesis of multiple human malignancies. Clinical benefit for patients with solid tumors of the breast, colon, lung, pancreas, or head and neck has been proven for targeted antagonists directed at a single receptor in the HER family (e.g., trastuzumab, cetuximab, erlotinib). Although effective, tumor resistance to these single‐targeted drugs frequently develops, and efficacy is not as broad as was initially predicted. Redundant signaling of other HER family members provides a likely mechanism for diminished drug activity. An alternative approach to inhibit HER‐mediated tumor growth is to sequester stimulating EGF‐like growth factors with a “ligand‐trap” strategy. Hermodulins are fusion proteins that link the extracellular ligand binding domains of HER family members to the Fc region of human IgG. Data with RB200, a first‐generation Hermodulin, demonstrate effective binding of EGFR and HER3 ligands (e.g., EGF, TGF‐α, NRG1‐β1) and show anti‐tumor activity in preclinical models. An optimized molecule, RB242, has been designed that combines single amino acid changes in the extracellular domains of the EGFR and HER3 domains. Preclinical studies with RB242 are ongoing to enable testing of the pan‐HER ligand‐trap hypothesis in Phase I investigation. Drug Dev Res 69:472–479, 2008. © 2008 Wiley‐Liss, Inc.
Biomimetic Modelling of Copper Enzymes: Synthesis, Characterization, EPR Analysis and Enantioselective Catalytic Oxidations by a New Chiral Trinuclear Copper(II) Complex
Authors: Mutti Francesco G. , Zoppellaro Giorgio , Gullotti Michele , Santagostini Laura , Pagliarin Roberto , Andersson K. Kristoffer , Casella Luigi 
Published: December 2008

AbstractThe new octadentate ligand (R)‐(+)‐N,N′‐dimethyl‐N,N′‐bis{‐2‐[bis(1‐methyl‐2‐benzimidazolylmethyl)]‐2‐methylaminoethyl}‐1,1′‐binaphthyl‐2,2′diamine [(R)‐(+)‐DABN‐L‐Ala‐Bz4; L] was employed for the synthesis of dinuclear and trinuclear copper(II) complexes. The ligand design is based on the insertion of chiral residues derived from L‐alanine between the diaminobinaphthyl (R)‐(+)‐DABN spacer and the aminobis(benzimidazole) metal binding units. The chiroptical properties of the ligand and the complexes are described. EPR experiments were performed on [Cu2L]4+ and [Cu3L]6+ at low temperatures. In the case of [Cu2L]4+, a weak dipolar interaction between the two spin centres was found. A similar weak spin interaction occurred in the trinuclear copper cluster, which could be treated likewise as a weakly coupled three‐spin system. The analysis was substantiated by studying the complex EPR temperature behaviour, where population of the quartet state occurred only at high temperature (77 K), whereas at cryogenic temperatures (4 K) the system adopted a doublet state as a ground‐state spin configuration. Titration with sodium azide of [Cu2L]4+ was consistent with terminal binding of one N3– molecule to each copper ion. Furthermore, dipolar interactions between spin centres were strongly suppressed in this case. For [Cu3L]6+, the adduct formed by the interaction with two azido molecules induced formation of a μ‐azido bridges among the three Cu2+ ions and led to population of the quartet state even at cryogenic temperatures. This bridged configuration was, however, lost upon further addition of azido molecules. The copper(II) complexes were tested as catalysts in the oxidation of biogenic catechols and flavonoids by dioxygen to give the corresponding quinones, which were trapped as adducts with MBTH. The dinuclear complex [Cu2L]4+ displays poor substrate enantiodifferentiating ability, even though it exhibits catalytic activity comparable to that of [Cu3L]6+. The trinuclear complex [Cu3L]6+ exhibits significant enantioselectivity in the oxidations of the catecholamines L‐/D‐dopa methyl ester and L‐/D‐norepinephrine. The origin of this enantioselectivity must be associated with the mode of substrate binding, as it depends almost entirely on KM.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Study of the Effects of Nonlinear Potential Sweeps on Voltammetry
Authors: Ogurtsov Vladimir I. , Beni Valerio , Strutwolf Jörg , Arrigan Damien W. M. 
Published: December 2008

AbstractVoltammetric methods use a constant sweep rate during the course of a scan. This paper reports a study of the influence of a nonconstant sweep rate on the voltammetric response. In this approach, either continuously increasing or continuously decreasing potential scan rates can be employed, unlike presently available methods which rely on a constant sweep rate. The voltammetric response of potassium ferrocyanide at a glassy carbon electrode was used as a model system to test the new method. The responses obtained using traditional staircase voltammetry (linear staircase voltammetry) and the new approach (nonlinear staircase voltammetry) were compared by experiment and by simulation. The new approach offers capability for signal enhancement, whereby enhanced current or enhanced peak shape can be obtained by choice of appropriate waveform parameters.
Micellar electrokinetic chromatography: Methodological and instrumental advances focused on practical aspects
Authors: Silva Manuel 
Published: December 2008

AbstractThis article reviews the latest methodological and instrumental improvements for enhancing sensitivity and resolution in MEKC‐based determinations. On‐line sample concentration (stacking, sweeping and combination of two protocols) and other on‐capillary approaches such as in‐capillary derivatization and the coupling of flow‐injection systems with MEKC are the most relevant methodological approaches discussed for improving sensitivity. At the same time, changes in the BGE through the use of organic modifiers, ionic liquids, cations, CDs, non‐ionic and zwitterionic surfactants, mixed micelles, vesicles and carbon nanostructures as well as 2‐D CE and chemometric techniques for enhancing resolution are also considered in detail. Two instrumental approaches such as MS and LIF are also discussed, covering the proposals for overcoming the difficulties arising from the direct coupling of MEKC with MS and the excellent detection sensitivity achieved by LIF using the typical argon‐ion laser and recent growth in the use of diode lasers as excitation sources. Some thoughts on potential future directions are also expressed.
Urinary levels of oxidative DNA and RNA damage among workers exposed to polycyclic aromatic hydrocarbons in silicon production: Comparison with 1‐hydroxypyrene
Authors: Marie Caroline , Ravanat Jean‐Luc , Badouard Carine , Marques Marie , Balducci Franck , Maître Anne 
Published: December 2008

AbstractPolycyclic aromatic hydrocarbons (PAH) are ubiquitous occupational and environmental pollutants and the urinary excretion of 1‐hydroxypyrene (1‐OHP) is classically measured for the determination of PAH exposure internal dose. Some of PAH are tumorigenic due to their metabolites ability to generate DNA adducts and oxidative DNA damage through the production of reactive oxygen species during metabolism. 8‐hydroxy‐7,8‐dihydro‐2′‐deoxyguanosine (8‐OHdGuo) is one of the major oxidative DNA lesions and its use as a potential biomarker of genotoxic PAH occupational exposure should be evaluated. Indeed conflicting results are frequently reported in occupational studies in terms of correlation between 8‐OHdGuo urinary levels and PAH exposure. The aim of our study was therefore to determine the potential for PAH occupational exposure to increase urinary oxidative DNA damage. The population consisted of 68 male workers employed in silicon production. The urinary concentrations of 8‐OHdGuo and its homologue in RNA, 8‐hydroxy‐7,8‐dihydroguanosine (8‐OHGuo) were determined using high performance liquid chromatography (HPLC) coupled to tandem mass spectrometry, whereas those of 1‐OHP were measured using HPLC with fluorescence detection. Individual variation rates were calculated on a working day and a working week. The results indicated that, while 1‐OHP levels strongly increased on a working day and even more on a working week, 8‐OHdGuo and 8‐OHGuo urinary levels did not show similar significant increases. Moreover, no correlation between 1‐OHP and oxidative DNA and RNA lesions was found. Consequently, urinary 8‐OHdGuo and 8‐OHGuo did not seem to be relevant biomarkers of genotoxic PAH exposure in the case of the silicon plant studied. Environ. Mol. Mutagen., 2009. © 2008 Wiley‐Liss, Inc.
Cigarette smoke extract induces expression of cell adhesion molecules in HUVEC via actin filament reorganization
Authors: Chen Haw‐Wen , Lii Chong‐Kuei , Ku Hua‐Jung , Wang Tsu‐Shing 
Published: December 2008

AbstractEpidemiologic studies have shown a strong association between cigarette smoking and cardiovascular diseases. Various oxidative species and free radicals are produced during cigarette smoking and these lead to endothelial dysfunction and inflammation. Expression of adhesion molecules, such as intercellular adhesion molecule‐1 (ICAM‐1), E‐selectin, and vascular cell adhesion molecule‐1, and adhesion of leukocytes are present in atherosclerosis. We showed previously that a nonfractionated cigarette smoke extract (CSE) induces surface expression of ICAM‐1 and E‐selectin in human umbilical vein endothelial cells (HUVEC). We then investigated the role of the MAPKs (ERK1/2, JNK, and p38) and AP‐1 and the role of actin cytoskeleton reorganization in the CSE‐induced expression of ICAM‐1 and E‐selectin. Western blot analysis showed that CSE treatment rapidly and significantly caused phosphorylation of JNK and ERK1/2 but not of p38. Cytochalasin D (an actin filament disruptor) partially inhibited CSE‐induced ICAM‐1 and E‐selectin surface expression. However, inhibitors of ERK1/2 (PD98059) and JNK (SP600125) did not attenuate the CSE‐induced ICAM‐1 and E‐selectin surface expression. The results of electrophoretic mobility shift assay showed that CSE enhanced AP‐1 binding activity. Therefore, CSE activated AP‐1 and upregulated ICAM‐1 and E‐selectin surface expression in HUVEC seem to be via an MAPK‐independent pathway. Moreover, the dynamic reorganization of the actin cytoskeleton seems to be required for the CSE‐induced surface expression of ICAM‐1 and E‐selectin. Environ. Mol. Mutagen., 2009. © 2008 Wiley‐Liss, Inc.
A note on the Hertz contact model with nonlinear damping for pounding simulation
Authors: Ye Kun , Li Li , Zhu Hongping 
Published: December 2008

AbstractStructural pounding during earthquakes has been recently investigated extensively by using different models of impact force. In this paper, reexamination of the Hertz contact model with nonlinear damping is made. Based on this reexamination, the formula used to determine the damping constant in terms of the spring stiffness, the coefficient of restitution and relative approaching velocity of two colliding bodies is found to be incorrect for pounding simulation in structural engineering. In order to correct this problem, a more accurate approximating formula for the damping constant is theoretically derived. The correctness of the derived analytical formula has been confirmed through numerical simulations. Copyright © 2008 John Wiley & Sons, Ltd.
Complex multiple cosmogenic nuclide concentration and histories in the arid Rio Lluta catchment, northern Chile
Authors: Kober F. , Ivy‐Ochs S. , Zeilinger G. , Schlunegger F. , Kubik P. W. , Baur H. , Wieler R. 
Published: December 2008

AbstractTerrestrial cosmogenic nuclide (TCN) concentrations measured in river sediments can be used to estimate catchment‐wide denudation rates. By investigating multiple TCN the steadiness of sediment generation, transport and depositional processes can be tested. Measurements of 10Be, 21Ne and 26Al from the hyper‐ to semi‐arid Rio Lluta catchment, northern Chile, yield average single denudation rates ranging from 12 to 75 m Myr–1 throughout the catchment. Paired nuclide analysis reveals complex exposure histories for most of the samples and thus the single nuclide estimates do not exclusively represent catchment‐wide denudation rates. The lower range of single nuclide denudation rates (12–17 m Myr–1), established with the noble gas 21Ne, is in accordance with palaeodenudation rates derived from 21Ne/10Be and 26Al/10Be ratio analysis. Since this denudation rate range is measured throughout the system, it is suggested that a headwater signal is transported downstream but modulated by a complex admixture of sediment that has been stored and buried at proximal hillslope or terrace deposits, which are released during high discharge events. That is best evidenced by the stable nuclide 21Ne, which preserves the nuclide concentration even during storage intervals.The catchment‐wide single 21Ne denudation rates and the palaeodenuation rates contrast with previous TCN‐derived erosion rates from bedrock exposures at hillslope interfluves by being at least one order of magnitude higher, especially in the lower river course. These results support earlier studies that identified a coupling of erosional processes in the Western Cordillera contrasting with decoupled processes in the Western Escarpment and in the Coastal Cordillera. Copyright © 2008 John Wiley & Sons, Ltd.
Probabilistic sinkhole modelling for hazard assessment
Authors: Galve J. P. , Gutiérrez F. , Lucha P. , Guerrero J. , Bonachea J. , Remondo J. , Cendrero A. 
Published: December 2008

AbstractA method for quantitatively assessing sinkhole susceptibility (spatial probability) and hazard (spatio‐temporal probability) has been developed and independently tested in a 50 km2 sector of the Ebro Valley evaporite karst. Three genetic types of sinkholes have been mapped in the floodplain and a terrace surface: 947 small cover‐collapse sinkholes (type 1, terrace), large collapse sinkholes (type 2, floodplain) and large subsidence depressions (type 3, floodplain). The type 1 sinkhole inventory includes two temporal populations: 447 sinkholes formed before 24 November 2005, and 500 between that date and 2 November 2006. Sinkhole susceptibility models have been elaborated analysing the statistical relationships between the sinkholes of the 2005 inventory and a set of potential conditioning factors. The independent evaluation (validation) of the susceptibility models by means of several strategies (random, sequentially excluded, and temporal) has allowed us to select the most significant variables for each sinkhole type and assess quantitatively the quality of models; which are reasonable for the three sinkhole types. Validation has also provided information on the contribution of specific variables and the effect of changing their accuracy to the prediction capability of models. Susceptibility models for type 3 sinkholes have been validated satisfactorily with the 2006 sinkhole inventory (temporal validation). The best susceptibility model has been transformed into a hazard map considering the frequency of sinkholes that occurred in each susceptibility class between 2005 and 2006, as well as their average size. The susceptibility and hazard models obtained could be used as an objective basis for the application of mitigation measures, either of preventive or corrective nature. Copyright © 2008 John Wiley & Sons, Ltd.
A higher‐order accuracy lattice Boltzmann model for the wave equation
Authors: Zhang Jianying , Yan Guangwu , Dong Yinfeng 
Published: December 2008

AbstractA lattice Boltzmann model with higher‐order accuracy for the wave motion is proposed. The new model is based on the technique of the higher‐order moment of equilibrium distribution functions and a series of lattice Boltzmann equations in different time scales. The forms of moments are derived from the binary wave equation by designing the higher‐order dissipation and dispersion terms. The numerical results agree well with classical ones. Copyright © 2008 John Wiley & Sons, Ltd.
Linearity of the fMRI response in category‐selective regions of human visual cortex
Authors: Horner Aidan J. , Andrews Timothy J. 
Published: December 2008

AbstractThe goal of this study was to determine the linearity of the blood oxygen level‐dependent (BOLD) response, as measured by functional magnetic resonance imaging (fMRI), in category‐selective regions of human visual cortex. We defined regions of the temporal lobe that were selective to faces (fusiform face area, FFA) and places (parahippocampal place area, PPA). We then determined the linearity of the BOLD response in these regions to their preferred and nonpreferred stimuli. First, we tested the principle of scaling. As we increased the visibility of the stimulus, there was a corresponding linear increase in the fMRI signal in the FFA and PPA to their preferred stimulus (face and place, respectively). In contrast, responses in the FFA and PPA to the nonpreferred stimulus did not conform to the principle of scaling. Next, we asked whether the fMRI response in these regions of visual cortex conformed to the principle of additivity. To assess this, we determined whether the response to a long stimulus block could be predicted by adding the response to multiple shorter duration blocks. Although the fMRI response in the FFA and PPA was generally linear to the preferred stimulus, a more nonlinear response was apparent to the nonpreferred stimulus. In conclusion, the linearity of the BOLD response in the human ventral visual pathway varied across cortical region and stimulus category. This suggests that measures of linearity may provide a useful indication of neural selectivity in the brain. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
Model driven EEG/fMRI fusion of brain oscillations
Authors: Valdes‐Sosa Pedro A. , Sanchez‐Bornot Jose Miguel , Sotero Roberto Carlos , Iturria‐Medina Yasser , Aleman‐Gomez Yasser , Bosch‐Bayard Jorge , Carbonell Felix , Ozaki Tohru 
Published: December 2008

AbstractThis article reviews progress and challenges in model driven EEG/fMRI fusion with a focus on brain oscillations. Fusion is the combination of both imaging modalities based on a cascade of forward models from ensemble of post‐synaptic potentials (ePSP) to net primary current densities (nPCD) to EEG; and from ePSP to vasomotor feed forward signal (VFFSS) to BOLD. In absence of a model, data driven fusion creates maps of correlations between EEG and BOLD or between estimates of nPCD and VFFS. A consistent finding has been that of positive correlations between EEG alpha power and BOLD in both frontal cortices and thalamus and of negative ones for the occipital region. For model driven fusion we formulate a neural mass EEG/fMRI model coupled to a metabolic hemodynamic model. For exploratory simulations we show that the Local Linearization (LL) method for integrating stochastic differential equations is appropriate for highly nonlinear dynamics. It has been successfully applied to small and medium sized networks, reproducing the described EEG/BOLD correlations. A new LL‐algebraic method allows simulations with hundreds of thousands of neural populations, with connectivities and conduction delays estimated from diffusion weighted MRI. For parameter and state estimation, Kalman filtering combined with the LL method estimates the innovations or prediction errors. From these the likelihood of models given data are obtained. The LL‐innovation estimation method has been already applied to small and medium scale models. With improved Bayesian computations the practical estimation of very large scale EEG/fMRI models shall soon be possible. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
Phase III randomized study: Oral pilocarpine versus submandibular salivary gland transfer protocol for the management of radiation‐induced xerostomia
Authors: Jha Naresh , Seikaly Hadi , Harris Jeffrey , Williams David , Sultanem Khalil , Hier Michael , Ghosh Sunita , Black Martin , Butler James , Sutherland Donna , Kerr Paul , Barnaby Pam 
Published: December 2008

AbstractBackground.Xerostomia is a serious morbidity of radiation treatment in head and neck cancer.Methods.We conducted a prospective phase III multicenter randomized study comparing submandibular salivary gland transfer (SGT) procedure with pilocarpine during and for 3 months after XRT. Salivary flow (baseline, stimulated) and University of Washington Quality of Life Questionnaire (U of W QOL) scores were measured.Results.An interim intent to treat analysis (120 patients) at 6 months shows superior results in SGT arm: median baseline salivary flow for SGT (0.04 mL/minute) versus pilocarpine (0.01 mL/minute), p = .001; median stimulated salivary flow (0.18 mL/minute) for SGT versus (0.05 mL/minute) for pilocarpine, p = .003. Scores (U of W QOL) for amount (p = .017) and consistency of saliva (p = .005) in favor of SGT leading to premature closure of study.Conclusions.Submandibular SGT procedure is superior to pilocarpine in management of radiation‐induced xerostomia. © 2008 Wiley Periodicals, Inc. Head Neck, 2009
Effect of induction chemotherapy on speech and swallowing function in patients with oral tongue cancer
Authors: Barringer Denise A. , Hutcheson Katherine A. , Sturgis Erich M. , Kies Merrill S. , Lewin Jan S. 
Published: December 2008

AbstractBackground.Swallowing physiology, diet, and patient‐reported outcomes were evaluated after induction chemotherapy for oral tongue cancer.Methods.Fifteen of 23 patients enrolled in a phase II clinical trial of induction chemotherapy followed by surgical resection for oral tongue cancer underwent instrumental and perceptual analysis of speech and swallowing. Oropharyngeal swallow efficiency (OPSE) was calculated. Patient‐reported outcomes were collected. We compared pre‐ and postchemotherapy results.Results.OPSE scores were not significantly different (p > .05) after induction chemotherapy; however, patient‐reported swallowing and diet levels were significantly higher (p < .001 and p = .015, respectively). Diet levels improved from soft‐chewable to full diet in most patients. Speech intelligibility did not change (p = .328).Conclusion.It appears that induction chemotherapy has a negligible effect on speech and swallowing physiology but may provide symptomatic improvement of pain and swallowing after treatment. Further investigations are needed to corroborate these findings. © 2008 Wiley Periodicals, Inc. Head Neck, 2009