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Selected AbstractsComparative hepatic activity of xenobiotic-metabolizing enzymes and concentrations of organohalogens and their hydroxylated analogues in captive greenland sledge dogs (Canis familiaris),ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2009Jonathan Verreault Abstract A captive study was performed with Greenland sledge dogs (Canis familiaris) fed a naturally organohalogen-contaminated diet (Greenland minke whale [Balaenoptera acutorostrata] blubber; exposed group) or a control diet (pork fat; control group). The catalytic activity of major xenobiotic-metabolizing phase I and II hepatic microsomal enzymes was assessed. Relative to control dogs, ethoxyresorufin- O -deethylase (EROD) activity in exposed dogs was twofold higher (p = 0.001). Testosterone hydroxylation yielded 6,- and 16,-hydroxy (OH) testosterone and androstenedione, with higher rates of production (23,27%; p , 0.03) in the exposed individuals. In the exposed dogs, epoxide hydrolase (EH) activity was 31% higher (p = 0.02) relative to the control dogs, whereas uridine diphosphoglucuronosyl transferase (UDPGT) activity was not different (p = 0.62). When the exposed and control dogs were combined, the summed (,) plasma concentrations of OH-polychlorinated biphenyl (PCB) congeners were predicted by plasma ,PCB concentrations and EROD activity (p , 0.04), whereas testosterone hydroxylase, EH, and UDPGT activities were not significant predictors of these concentrations. Consistent results were found for individual OH-PCB congeners and their theoretical precursor PCBs (e.g., 4-OH-CB-187 and CB-183, and 4-OH-CB-146 and CB-146) and for EROD activity. No association was found between ,OH,polybrominated diphenyl ether (PBDE) and ,PBDE plasma concentrations, or between potential precursor-metabolite pairs, and the enzyme activities. The present results suggest that liver microsomal EROD activity and plasma PCB concentrations have a greater (e.g., relative to EH activity) predictive power for the occurrence of plasma OH-PCB residues in sledge dogs. These results also suggest that plasma OH-PBDEs likely are not products of cytochrome P450-mediated transformation but, rather, are accumulated via the diet. [source] Intralesional bovine papillomavirus DNA loads reflect severity of equine sarcoid diseaseEQUINE VETERINARY JOURNAL, Issue 4 2010R. HARALAMBUS Summary Reasons for performing study: Sarcoids are nonmetastasising, yet locally aggressive skin tumours that constitute the most frequent neoplasm in equids. Infection by bovine papillomaviruses types 1 and 2 (BPV-1, BPV-2) has been recognised as major causative factor in sarcoid pathogenesis, but a possible correlation of intralesional virus load with disease severity has not been established thus far. Hypothesis: Given the pathogenic role of BPV-1 and BPV-2 in sarcoid disease, we suggest that intralesional viral DNA concentration may reflect the degree of affection. Methods: Severity of disease was addressed by recording the tumour growth kinetics, lesion number and tumour type for 37 sarcoid-bearing horses and one donkey. Viral load was estimated via quantitative real-time PCR (qPCR) of the E2, E5, L1 and L2 genes from the BPV-1/-2 genome for one randomly selected lesion per horse and correlated with disease severity. Results: Quantitative PCR against E2 identified viral DNA concentrations ranging from 0,556 copies/tumour cell. Of 16 horses affected by quiescent, slowly growing single tumours or multiple mild-type lesions, 15 showed a viral load up to 1.4 copies per cell. In stark contrast, all equids (22/22) bearing rapidly growing and/or multiple aggressive sarcoids had a viral load between 3 and 569 copies per cell. Consistent results were obtained with qPCR against E5, L1 and L2. Conclusions: While tumours of the same clinical type carried variable virus load, confirming that viral titre does not determine clinical appearance, we identified a highly significant correlation between intralesional viral load and disease severity. Potential relevance: The rapid determination of BPV viral load will give a reliable marker for disease severity and may also be considered when establishing a therapeutic strategy. [source] Zircon U,Pb age and Hf isotope evidence for contrasting origin of bimodal protoliths for ultrahigh-pressure metamorphic rocks from the Chinese Continental Scientific Drilling projectJOURNAL OF METAMORPHIC GEOLOGY, Issue 8 2007R.-X. CHEN Abstract A combined study of zircon morphology, U,Pb ages and Hf isotopes as well as whole-rock major and trace elements was carried out for ultrahigh-pressure (UHP) eclogite and felsic gneiss from the main hole (MH) of the Chinese Continental Scientific Drilling (CCSD) project in the Sulu orogen. The results show contrasting Hf isotope compositions for bimodal UHP metaigneous rocks, pointing to contrasting origins for their protoliths (thus dual-bimodal compositions). The samples of interest were from two continuous core segments from CCSD MH at depths of 734.21,737.16 m (I) and 929.67,932.86 m (II) respectively. Zircon U,Pb dating for four samples from the two core segments yields two groups of ages at 784 ± 17 and 222 ± 3 Ma, respectively, corresponding to protolith formation during supercontinental rifting and metamorphic growth during continental collision. Although the Triassic UHP metamorphism significantly reset the zircon U,Pb system of UHP rocks, the Hf isotope compositions of igneous zircon can be used to trace their protolith origin. Contrasting types of initial Hf isotope ratios are, respectively, correlated with segments I and II, regardless of their lithochemistry. The first type shows positive ,Hf(t) values of 7.8 ± 3.1 to 6.0 ± 3.0, with young Hf model age of 1.03 and 1.11 Ga. The second type exhibits negative ,Hf(t) values of ,6.9 ± 1.6 to ,9.1 ± 1.1, with old Hf model ages of 2.11 and 2.25 Ga. It appears that the UHP rocks from the two segments have protoliths of contrasting origin. Consistent results are also obtained from their trace element compositions suggesting that mid-Neoproterozoic protoliths of bimodal UHP metaigneous rocks formed during supercontinental rifting at the northern margin of the South China Block. Thus, the first type of bimodal magmatism formed by rapid reworking of juvenile crust, whereas the second type of bimodal magmatism was principally generated by rift anatexis of Paleoproterozoic crust. Melting of orogenic lithosphere has potential to bring about bimodal magmatism with contrasting origins. Because arc,continent collision zones are the best place to accumulate both juvenile and ancient crusts, the contrasting types of bimodal magmatism are proposed to occur in an arc,continent collision orogen during the supercontinental rifting, in response to the attempted breakup of the supercontinent Rodinia at c. 780 Ma. [source] Luminous red galaxy clustering at z, 0.7 , first results using AAOmegaMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 3 2008Nicholas P. Ross ABSTRACT We report on the AAT-AAOmega LRG Pilot observing run to establish the feasibility of a large spectroscopic survey using the new AAOmega instrument. We have selected luminous red galaxies (LRGs) using single epoch SDSS riz -photometry to i < 20.5 and z < 20.2. We have observed in three fields including the COSMOS field and the COMBO-17 S11 field, obtaining a sample of ,600 redshift z, 0.5 LRGs. Exposure times varied from 1,4 h to determine the minimum exposure for AAOmega to make an essentially complete LRG redshift survey in average conditions. We show that LRG redshifts to i < 20.5 can be measured in ,1.5 h exposures and present comparisons with 2SLAQ and COMBO-17 (photo)redshifts. Crucially, the riz selection coupled with the three to four times improved AAOmega throughput is shown to extend the LRG mean redshift from z= 0.55 for 2SLAQ to z= 0.681 ± 0.005 for riz -selected LRGs. This extended range is vital for maximizing the signal-to-noise ratio for the detection of the baryon acoustic oscillations (BAOs). Furthermore, we show that the amplitude of LRG clustering is s0= 9.9 ± 0.7h,1 Mpc, as high as that seen in the 2SLAQ LRG Survey. Consistent results for this clustering amplitude are found from the projected and semi-projected correlation functions. This high amplitude is consistent with a long-lived population whose bias evolves as predicted by a simple ,high-peak' model. We conclude that a redshift survey of 360 000 LRGs over 3000 deg2, with an effective volume some four times bigger than previously used to detect BAO with LRGs, is possible with AAOmega in 170 nights. [source] Populating dark matter haloes with galaxies: comparing the 2dFGRS with mock galaxy redshift surveysMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 4 2004Xiaohu Yang ABSTRACT In two recent papers, we developed a powerful technique to link the distribution of galaxies to that of dark matter haloes by considering halo occupation numbers as a function of galaxy luminosity and type. In this paper we use these distribution functions to populate dark matter haloes in high-resolution N -body simulations of the standard ,CDM cosmology with ,m= 0.3, ,,= 0.7 and ,8= 0.9. Stacking simulation boxes of 100 h,1 Mpc and 300 h,1 Mpc with 5123 particles each we construct mock galaxy redshift surveys out to a redshift of z= 0.2 with a numerical resolution that guarantees completeness down to 0.01L*. We use these mock surveys to investigate various clustering statistics. The predicted two-dimensional correlation function ,(rp, ,) reveals clear signatures of redshift space distortions. The projected correlation functions for galaxies with different luminosities and types, derived from ,(rp, ,), match the observations well on scales larger than ,3 h,1 Mpc. On smaller scales, however, the model overpredicts the clustering power by about a factor two. Modelling the ,finger-of-God' effect on small scales reveals that the standard ,CDM model predicts pairwise velocity dispersions (PVD) that are ,400 km s,1 too high at projected pair separations of ,1 h,1 Mpc. A strong velocity bias in massive haloes, with bvel,,gal/,dm, 0.6 (where ,gal and ,dm are the velocity dispersions of galaxies and dark matter particles, respectively) can reduce the predicted PVD to the observed level, but does not help to resolve the overprediction of clustering power on small scales. Consistent results can be obtained within the standard ,CDM model only when the average mass-to-light ratio of clusters is of the order of 1000 (M/L), in the B -band. Alternatively, as we show by a simple approximation, a ,CDM model with ,8, 0.75 may also reproduce the observational results. We discuss our results in light of the recent WMAP results and the constraints on ,8 obtained independently from other observations. [source] Influence of nonspecific brain and plasma binding on CNS exposure: implications for rational drug discoveryBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 8 2002J. Cory Kalvass Abstract Relative plasma, brain and cerebrospinal fluid (CSF) exposures and unbound fractions in plasma and brain were examined for 18 proprietary compounds in rats. The relationship between in vivo brain-to-plasma ratio and in vitro plasma-to-brain unbound fraction (fu) was examined. In addition, plasma fu and brain fu were examined for their relationship to in vivo CSF-to-plasma and CSF-to-brain ratios, respectively. Findings were delineated based on the presence or absence of active efflux. Finally, the same comparisons were examined in FVB vs. MDR 1a/1b knockout mice for a selected P-glycoprotein (Pgp) substrate. For the nine compounds without indications of active efflux, predictive correlations were observed between ratios of brain-to-plasma exposure and plasma-to-brain fu (r2 = 0.98), CSF-to-brain exposure vs. brain fu (r2 = 0.72), and CSF-to-plasma exposure vs. plasma fu (r2 = 0.82). For the nine compounds with indications of active efflux, nonspecific binding data tended to over predict the brain-to-plasma and CSF-to-plasma exposure ratios. Interestingly, CSF-to-brain exposure ratio was consistently under predicted by brain fu for this set. Using a select Pgp substrate, it was demonstrated that the brain-to-plasma exposure ratio was identical to that predicted by plasma-to-brain fu ratio in MDR 1a/1b knockout mice. In FVB mice, plasma-to-brain fu over predicted brain-to-plasma exposure ratio to the same degree as the difference in brain-to-plasma exposure ratio between MDR 1a/1b and FVB mice. Consistent results were obtained in rats, suggesting a similar kinetic behavior between species. These data illustrate how an understanding of relative tissue binding (plasma, brain) can allow for a quantitative examination of active processes that determine CNS exposure. The general applicability of this approach offers advantages over species- and mechanism-specific approaches. Copyright © 2002 John Wiley & Sons, Ltd. [source] A Comparison of the Effects of Olopatadine and Ketotifen on Model MembranesACTA OPHTHALMOLOGICA, Issue 2000Howard Brockman ABSTRACT. Olopatadine is a human conjunctival mast cell stabilizer with anti-histaminic activity. Ketotifen is an older molecule that possesses antihistaminic activity and is reported to have additional pharmacological properties. The interactions of these two compounds with model membranes (i.e., monolayers of 1-stearoyl-2-oleoyl-sn-glycerophosphocholine at the argon-buffer interface), and natural (i.e., erythrocyte) membranes were compared in an effort to understand the differences in their biological activities. Drug-lipid interaction with monolayers was determined by monitoring the surface pressure as a function of the drug concentration in the aqueous phase supporting the monolayer. Drug interaction with erythrocyte membranes was determined by monitoring changes in the permeability of the membranes to hemoglobin and 6-carboxyfluorescein as a function of drug concentration in the medium. Olopatadine and ketotifen are both intrinsically surface active and both interact with phospholipid monolayers. However, in both the presence and absence of lipid monolayers, the changes in surface pressure induced by olopatadine are lower than those caused by ketotifen. The effects of these two drugs on cell membranes were dramatically different. Exposure of bovine erythrocytes to increasing concentrations of ketotifen (1,10 mM) resulted in complete hemolysis of the cells, whereas olopatadine (1,10 mM) caused only minimal hemolysis (<8%). Consistent results were obtained in experiments measuring the leakage of 6-carboxyfluorescein from erythrocyte ghosts as a more sensitive marker of membrane perturbation. Olopatadine treatment (0.1,10 mM) minimally perturbed the cell membrane while ketotifen (1,10 mM) caused a concentration dependent release of the fluorescent marker. These data demonstrate fundamental differences between the two drugs in their effects on cell membranes. Moreover, the differences are consistent with the surface activities of the two compounds measured in monolayers and with reported differences in their pharmacological activities. These findings offer an explanation for the biphasic non-specific cytotoxic effect of ketotifen on histamine release from mast cells and may account for the non-lytic mast cell stabilizing activity of olopatadine. [source] Study of conformational and optical rotation for the alaninamideINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 4 2007Shulei Zhao Abstract Six stationary points of alaninamide have been located on the potential surface energy (PES) at the B3LYP/6-311++G(2d,2p) level of theory both in the gas phase and in aqueous solution. In the aqueous solution, to take the water solvent effect into account, the polarizable continuum model (PCM) method has been used. Accurate geometric structures and their relative stabilities have been investigated. The results show that the intramolecular hydrogen bond plays a very important role in stabilizing the global minimum of the alaninamide. Moreover, the consistent result in relative energy using high-level computations, including the MP2 and MP3 methods with the same basis set [6-311++G(2d,2p)], indicates that the B3LYP/6-311++G(d,p) level may be applied to the analogue system. More importantly, the optical rotation of the optimized conformers (both in the gas phase and in aqueous solution) of alaninamide have been calculated using the density functional theory (DFT) and Hartree,Fock (HF) method at various basis sets (6-31+G*, 6-311++G(d,p), 6-311++G(2d,2p) and aug-cc-pvdz). The results show that the selection of the computation method and the basis set in calculation has great influence on the results of the optical rotations. The reliability of the HF method is less than that of DFT, and selecting the basis set of 6-311++G(2d,2p) and aug-cc-pvDZ produces relative reliable results. Analysis of the computational results of the structure parameters and the optical rotations yields the conclusion that just the helixes in molecules caused the chiral molecules to be optical active. The Boltzmann equilibrium distributions for the six conformers (both in the gas phase and in the aqueous solution) are also carried out. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007 [source] Pits and Fissures: Etch Resistance in Prismless Enamel WallsAUSTRALIAN DENTAL JOURNAL, Issue 4 2001MF Burrow Background: In a previous study to examine the nature of etching on the walls of fissures, there was a consistent result of resistance to deep etching on parts of the walls and a zone of lesser etching on part of the walls as evidenced by the uptake of stain. The staining had been used to examine the nature of the etch pattern. The aims of this study were to define the nature of this etch resistant area. Methods: A sample of 55 teeth, both molars and premolars, were divided into three groups. In the first group the wetting of fissures by the etchant was examined; the second group tested for the effects of pellicle-cuticle-debris or air entrapment on the etching process. The final group looked at alternative mechanical treatments of the fissure prior to etching. Results: The specimens split along the fissures showed clearly that the etch resistant zone was not due to lack of contact with the etchant or the presence of a pellicle-cuticle-debris covering, but to the presence of a prismless enamel structure. This study showed that this zone inhibited tag development on the fissure walls. Conclusions: The mechanical removal of this prismless layer of enamel within the fissure system should result in an improved bonding of a fissure sealant through better tag development, in turn leading to a reduction in the failure rate of a sealant used to prevent caries. [source] Adventures in multivalency, the Harry S. Fischer memorial lecture CMR 2005; Evian, FranceCONTRAST MEDIA & MOLECULAR IMAGING, Issue 1 2006Michael F. Tweedle Abstract This review discusses multivalency in the context of drug discovery, specifically the discovery of new diagnostic imaging and related agents. The aim is to draw attention to the powerful role that multivalency plays throughout research involving molecular biology, in general, and much of biochemically targeted contrast agent research, in particular. Two examples from the author's laboratory are described. We created small (,5,kDa) peptide ,dimers' composed of two different, chemically linked peptides. The monomer peptides both bound to the same target protein with Kd,,,100,s,nM, while the heterodimers had sub-nM Kd values. Biological activity was evident in the heterodimers where none or very little existed in homodimers, monomers or monomer mixtures. Two different tyrosine kinases (KDR and C-Met) and four peptide families produced consistent results: multivalent heterodimers were uniquely different. The second example begins with making two micron ultrasound bubbles coated with the peptide, TKPPR (a Tuftsin antagonist) as a negative control for bubbles targeted with angiogenesis target-binding peptides. Unexpected binding of a ,negative' control, (TKPPR)-targeted bubble to endothelial cells expressing angiogenesis targets, led to the surprising result that TKPPR, only when multimerized, binds avidly, specifically and actively to neuropilin-1, a VEGF co-receptor. VEGF is the primary stimulator of angiogenesis. Tuftsin is a small peptide (TKPR) derived from IgG that binds to macrophages during inflammation, and has been studied for over 30 years. The receptor has never been cloned. The results led to new conclusions about Tuftsin, neuropilin-1 and the purpose, up to now unknown, of exon 8 in VEGF. Multivalency can be used rationally to solve practical problems in drug discovery. When targeting larger structures, multivalency is frequently unavoidable, and can lead to unpredictable and useful biochemical information, as well as to new drug candidates. Copyright © 2006 John Wiley & Sons, Ltd. [source] Mailed treatment to augment primary care for alcohol disorders: A randomised controlled trialDRUG AND ALCOHOL REVIEW, Issue 1 2009DAVID KAVANAGH Abstract Introduction and Aims. Remote delivery of interventions is needed to address large numbers of people with alcohol use disorders who are spread over large areas. Previous correspondence trials typically examined its effects as stand-alone treatment. This study aimed to test whether adding postal treatment to general practitioner (GP) support would lower alcohol use more than GP intervention alone. Design and Methods. A single-blind, randomised controlled trial with a crossover design was conducted over 12 months on 204 people with alcohol use disorders. Participants in an immediate correspondence condition received treatment over the first 3 months; those receiving delayed treatment received it in months 3,6. Results. Few participants were referred from GPs, and little intervention was offered by them. At 3 months, 78% of participants remained in the study. Those in immediate treatment showed greater reductions in alcohol per week, drinking days, anxiety, depression and distress than those in the delayed condition. However, post-treatment and follow-up outcomes still showed elevated alcohol use, depression, anxiety and distress. Greater baseline anxiety predicted better alcohol outcomes, although more mental distress at baseline predicted dropout. Discussion and Conclusions. The study gave consistent results with those from previous research on correspondence treatments, and showed that high levels of participant engagement over 3 months can be obtained. Substantial reductions in alcohol use are seen, with indications that they are well maintained. However, many participants continue to show high-risk alcohol use and psychological distress.[Kavanagh D, Connolly JM. Mailed treatment to augment primary care for alcohol disorders: A randomised controlled trial. Drug Alcohol Rev 2009;28:73,80] [source] Aggression in imported fire ants: an explanation for shifts in their spatial distributions in Southern United States?ECOLOGICAL ENTOMOLOGY, Issue 4 2009HENRY Y. FADAMIRO Abstract 1.,The imported fire ants, Solenopsis invicta Buren (red), S. richteri Forel (black), and their hybrids (S. invicta × S. richteri) are sympatric congeners with overlapping but shifting spatial distributions in northern Alabama and Mississippi, United States. 2.,The abilities of workers of the three ant forms (or species) to recognise non-nestmate conspecifics and heterospecifics were compared in separate aggression bioassays using three group sizes of competitor numbers (battles): 1-1, 5-1, and 5-5 resident,intruder battles. 3.,Workers of all three forms showed significant aggression toward non-nestmate conspecifics and heterospecifics. The results of the intra-specific aggression bioassays showed that S. invicta had the lowest aggression threshold, whereas S. richteri was the least aggressive. Survival rates 1 day after intra-specific encounters were higher for S. richteri than for S. invicta or hybrids, consistent with its lower aggressiveness. 4.,In inter-specific interactions, S. invicta workers showed the greatest aggression and were more aggressive towards S. richteri than to hybrids. Furthermore, survival 1 day after inter-specific encounters was highest for S. invicta workers, whether they were the intruders or residents. The hybrid form was intermediate between both parental forms in aggression and post-aggression survival. 5.,The live 1-1 and 5-5 battles produced similar and consistent results, but differences were amplified in the 5-5 battles, suggesting an effect of group size on aggression. These results may explain the observed shifts in the spatial distributions of the three forms and range restriction of S. richteri in southern United States. [source] An Investigation of Alternative Methods for Item Mapping in the National Assessment of Educational ProgressEDUCATIONAL MEASUREMENT: ISSUES AND PRACTICE, Issue 2 2001Rebecca Zwick What is item mapping and how does it aid test score interpretation? Which item mapping technique produces the most consistent results and most closely matches expert opinion? [source] Dynamics of marine bacterial and phytoplankton populations using multiplex liquid bead array technologyENVIRONMENTAL MICROBIOLOGY, Issue 4 2010Xavier Mayali Summary Heterotrophic bacteria and phytoplankton dominate the biomass and play major roles in the biogeochemical cycles of the surface ocean. Here, we designed and tested a fast, high-throughput and multiplexed hybridization-based assay to detect populations of marine heterotrophic bacteria and phytoplankton based on their small subunit ribosomal DNA sequences. The assay is based on established liquid bead array technology, an approach that is gaining acceptance in biomedical research but remains underutilized in ecology. End-labelled PCR products are hybridized to taxon-specific oligonucleotide probes attached to fluorescently coded beads followed by flow cytometric detection. We used ribosomal DNA environmental clone libraries (a total of 450 clones) and cultured isolates to design and test 26 bacterial and 10 eukaryotic probes specific to various ribotypes and genera of heterotrophic bacteria and eukaryotic phytoplankton. Pure environmental clones or cultures were used as controls and demonstrated specificity of the probes to their target taxa. The quantitative nature of the assay was demonstrated by a significant relationship between the number of target molecules and fluorescence signal. Clone library sequencing and bead array fluorescence from the same sample provided consistent results. We then applied the assay to a 37-day time series of coastal surface seawater samples from the Southern California Bight to examine the temporal dynamics of microbial communities on the scale of days to weeks. As expected, several bacterial phylotypes were positively correlated with total bacterial abundances and chlorophyll a concentrations, but others were negatively correlated. Bacterial taxa belonging to the same broad taxonomic groups did not necessarily correlate with one another, confirming recent results suggesting that inferring ecological role from broad taxonomic identity may not always be accurate. [source] Redox properties of the couple compound I/native enzyme of myeloperoxidase and eosinophil peroxidaseFEBS JOURNAL, Issue 19 2001Jürgen Arnhold The standard reduction potential of the redox couple compound I/native enzyme has been determined for human myeloperoxidase (MPO) and eosinophil peroxidase (EPO) at pH 7.0 and 25 °C. This was achieved by rapid mixing of peroxidases with either hydrogen peroxide or hypochlorous acid and measuring spectrophotometrically concentrations of the reacting species and products at equilibrium. By using hydrogen peroxide, the standard reduction potential at pH 7.0 and 25 °C was 1.16 ± 0.01 V for MPO and 1.10 ± 0.01 V for EPO, independently of the concentration of hydrogen peroxide and peroxidases. In the case of hypochlorous acid, standard reduction potentials were dependent on the hypochlorous acid concentration used. They ranged from 1.16 V at low hypochlorous acid to 1.09 V at higher hypochlorous acid for MPO and from 1.10 V to 1.03 V for EPO. Thus, consistent results for the standard reduction potentials of redox couple compound I/native enzyme of both peroxidases were obtained with all hydrogen peroxide and at low hypochlorous acid concentrations: possible reasons for the deviation at higher concentrations of hypochlorous acid are discussed. They include instability of hypochlorous acid, reactions of hypochlorous acid with different amino-acid side chains in peroxidases as well as the appearance of a compound I,chloride complex. [source] Upper mantle stratification by P and S receiver functionsGEOPHYSICAL JOURNAL INTERNATIONAL, Issue 3 2000Véronique Farra Summary Seismic stratification of the upper mantle is investigated by applying two complementary techniques to the records of the Graefenberg array in southern Germany. The anisotropic P receiver function technique (Kosarev et al. 1984; Vinnik & Montagner 1996) is modified by using summary seismic events instead of individual events and different weighting functions instead of the same function for the harmonic angular analysis of the SV and T components of the Pds phases. The summary events provide better separation of the second azimuthal harmonic than the individual events. The parameters of the second harmonics of SV and T thus evaluated should be similar if they reflect the effects of azimuthal anisotropy. This can be used as a criterion to identify the anisotropy. To detect the Sdp phases and their azimuthal variations caused by azimuthal anisotropy we have developed a stacking technique, which can be termed the S receiver function technique It includes axis rotation to separate interfering P and S arrivals, determination of the principal (M) component of the S -wave motion, deconvolution of the P components of many recordings by their respective M components and stacking of the deconvolved P components with weights depending on the level of noise and the angle between the M direction and the backazimuth of the event. Both techniques yield consistent results for the Graefenberg array. As indicated by the P receiver functions, the upper layer of the mantle between the Moho and 80 km depth is anisotropic with dVs/Vs around 0.03 and the fast direction close to 20° clockwise from north. The fast direction of anisotropy below this layer is around 110°, The boundary between the upper and the lower anisotropic layers is manifested by the detectable Pds and Sdp converted phases. Shear wave splitting in SKS is strongly dominated by azimuthal anisotropy in the lower layer (asthenosphere). [source] Electropolymerized Self-Assembled Monolayers of a 3,4-Ethylenedioxythiophene-Thiophene Hybrid System,ADVANCED FUNCTIONAL MATERIALS, Issue 15 2008Maiténa Oçafrain Abstract Self-assembled monolayers (SAMs) of a conjugated bithiophenic system connected to an alkanethiol chain have been deposited on gold surface. The electroactive bithiophenic system involves a 3,4-ethylenedioxythiophene (EDOT) unit and a thiophene ring on which an alkanethiol is attached at the internal , -position via a sulfide linkage. The analysis of the structure of the SAMs by IR spectroscopy, ellipsometry, contact angle measurement and X-ray photoelectron spectroscopy (XPS) provides consistent results indicating compact monolayers in which the alkyl linkers are arranged in an almost vertical fashion while the bithiophenic-conjugated systems are essentially parallel to the surface. Cyclic voltammetry shows that application of a few potential scans to SAMs immersed in a medium containing only a supporting electrolyte leads to the typical electropolymerization curves while the CV of the electrooxized monolayer exhibits a reversible cyclic voltammogram characteristic of a stable electroactive extended conjugated system. The characterization of the electropolymerized monolayers by IR spectroscopy, ellipsometry, contact angle measurement, and XPS indicates compact monolayers. The analysis of the current voltage characteristics of the monolayers by conducting AFM before and after electrooxidation shows that the enhancement of the effective conjugation resulting from electropolymerization leads to a significant increase of the transport properties. [source] Chromosomal anomalies on 6p25 in iris hypoplasia and Axenfeld-Rieger syndrome patients defined on a purpose-built genomic microarray,HUMAN MUTATION, Issue 1 2004Rosemary Ekong Abstract In many inherited diseases, the same phenotype can be produced both by single-base changes and by large deletions, or in some cases by duplications. Routine high-throughput sequencing can now detect small mutations relatively easily in a diagnostic setting, but deletions and duplications in the 50,500-kb region remain a more difficult problem. We have explored the application of array-CGH to the detection of such changes on a set of 20 samples consisting of patients with eye diseases associated with changes on chromosome 6p25 together with unaffected individuals, as well as two samples from tuberous sclerosis 2 (TSC2)-affected patients. We developed a microarray consisting of degenerate oligonucleotide primer (DOP)-PCR products from 260 human genomic clones, including BACs, PACs, and cosmids. In a masked study, chromosome changes in patients with iris hypoplasia (duplication) and Axenfeld-Rieger syndrome (deletion) were unequivocally distinguished from controls. Of the 20 6p25 samples analyzed, 19 were analyzed correctly (10 duplication cases, two deletions, and seven normals), while one individual failed to give a result because of poor hybridization. The extent of the duplication or deletion estimated was similar to that obtained by independent and much more time-consuming FISH experiments. On the other hand, deletions in the two TSC2 -affected samples, previously mapped by DNA molecular combing, were not detected on the array, possibly due to the repeat content of that region. Excluding the 16p13 cosmids, consistent results were obtained from all other cosmid clones; the potential for producing affordable disease-specific diagnostic microarray as an adjunct to diagnosis is discussed. Hum Mutat 24:76,85, 2004. © 2004 Wiley-Liss, Inc. [source] Parameter identification for leaky aquifers using global optimization methodsHYDROLOGICAL PROCESSES, Issue 7 2007Hund-Der Yeh Abstract In the past, graphical or computer methods were usually employed to determine the aquifer parameters of the observed data obtained from field pumping tests. Since we employed the computer methods to determine the aquifer parameters, an analytical aquifer model was required to estimate the predicted drawdown. Following this, the gradient-type approach was used to solve the nonlinear least-squares equations to obtain the aquifer parameters. This paper proposes a novel approach based on a drawdown model and a global optimization method of simulated annealing (SA) or a genetic algorithm (GA) to determine the best-fit aquifer parameters for leaky aquifer systems. The aquifer parameters obtained from SA and the GA almost agree with those obtained from the extended Kalman filter and gradient-type method. Moreover, all results indicate that the SA and GA are robust and yield consistent results when dealing with the parameter identification problems. Copyright © 2006 John Wiley & Sons, Ltd. [source] Medical management of left-sided ulcerative colitis and ulcerative proctitis: Critical evaluation of therapeutic trialsINFLAMMATORY BOWEL DISEASES, Issue 10 2006Miguel Regueiro MD Abstract Background: The goal of this work was to critically evaluate the published studies on the treatment of ulcerative proctitis (UP) and left-sided ulcerative colitis (L-UC). The results of this review provided the content for the accompanying treatment guidelines, Clinical Guidelines for the Medical Management of Left-sided Ulcerative Colitis and Ulcerative Proctitis: Summary Statement. Methods: All English language articles published between 1995 and September 2005 were identified through a comprehensive literature search using OVID and PubMed. The quality of the data supporting or rejecting the use of specific therapies was categorized by a data quality grading scale. An "A+" grade was assigned to treatment supported by multiple high-quality randomized controlled trials with consistent results, whereas a "D" grade was given to therapy supported only by expert opinion. The therapeutic efficacy of a treatment was defined by its success in treating UP and L-UC compared with placebo. A medication was ranked as "excellent" if it was specifically studied for UP and L-UC and had consistently positive results compared with placebo or another agent. Quality and efficacy scores were agreed on by author consensus. Results: For the acute treatment of UP or L-UC, the rectally administered corticosteroids and mesalazine (5-ASA), either alone or in combination with oral 5-ASAs, are the most effective therapy: evidence quality, A+; efficacy, excellent. Only rectally administered 5-ASA received an A+/excellent rating for maintenance of remission. Infliximab received an A+ grade for induction and maintenance of remission but only a "good" rating because the studies were performed in all UC, not specifically UP or L-UC. Conclusions: This critical evaluation of treatment provides a "report card" on medications available for the management of patients with UP and L-UC. The guidelines should provide a useful reference and supplement for physicians treating UC patients. [source] Critical evaluation of CFD codes for interfacial simulation of bubble-train flow in a narrow channelINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS, Issue 6 2007Furkan Özkan Abstract Computational fluid dynamics (CFD) codes that are able to describe in detail the dynamic evolution of the deformable interface in gas,liquid or liquid,liquid flows may be a valuable tool to explore the potential of multi-fluid flow in narrow channels for process intensification. In the present paper, a computational exercise for co-current bubble-train flow in a square vertical mini-channel is performed to investigate the performance of well-known CFD codes for this type of flows. The computations are based on the volume-of-fluid method (VOF) where the transport equation for the liquid volumetric fraction is solved either by the methods involving a geometrical reconstruction of the interface or by the methods that use higher-order difference schemes instead. The codes contributing to the present code-to-code comparison are an in-house code and the commercial CFD packages CFX, FLUENT and STAR-CD. Results are presented for two basic cases. In the first one, the flow is driven by buoyancy only, while in the second case the flow is additionally forced by an external pressure gradient. The results of the code-to-code comparison show that only the VOF method with interface reconstruction leads to physically sound and consistent results, whereas the use of difference schemes for the volume fraction equation shows some deficiencies. Copyright © 2007 John Wiley & Sons, Ltd. [source] Statistical downscaling model based on canonical correlation analysis for winter extreme precipitation events in the Emilia-Romagna regionINTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 4 2008A. Busuioc Abstract Optimum statistical downscaling models for three winter precipitation indices in the Emilia-Romagna region, especially related to extreme events, were investigated. For this purpose, the indices referring to the number of events exceeding the long-term 90 percentile of rainy days, simple daily intensity and maximum number of consecutive dry days were calculated as spatial averages over homogeneous sub-regions identified by the cluster analysis. The statistical downscaling model (SDM) based on the canonical correlation analysis (CCA) was used as downscaling procedure. The CCA was also used to understand the large-/regional-scale mechanisms controlling precipitation variability across the analysed area, especially with respect to extreme events. The dynamic (mean sea-level pressure-SLP) and thermodynamic (potential instability-,Q and specific humidity-SH) variables were considered as predictors (either individually or together). The large-scale SLP can be considered a good predictor for all sub-regions in the dry index case and for two sub-regions in the case of the other two indices, showing the importance of dynamical forcing in these cases. Potential instability is the best predictor for the highest mountain region in the case of heavy rainfall frequency, when it can be considered as a single predictor. The combination of dynamic and thermodynamic predictors improves the SDM's skill for all sub-regions in the dry index case and for some sub-regions in the simple daily intensity index case. The selected SDMs are stable in time only in terms of correlation coefficient for all sub-regions for which they are skilful and only for some sub-regions in terms of explained variance. The reasons are linked to the changes in the atmospheric circulation patterns influencing the local rainfall variability in Emilia-Romagna as well as the differences in temporal variability over some sub-regions and sub-intervals. It was concluded that the average skill over an ensemble of the most skilful and stable SDMs for each region/sub-interval gives more consistent results. Copyright © 2007 Royal Meteorological Society [source] In vitro degradation of articular cartilage: does trypsin treatment produce consistent results?JOURNAL OF ANATOMY, Issue 2 2006H. R. Moody Abstract It is common practice in laboratories to create models of degraded articular cartilage in vitro and use these to study the effects of degeneration on cartilage responses to external stimuli such as mechanical loading. However, there are inconsistencies in the reported action of trypsin, and there is no guide on the concentration of trypsin or the time to which a given sample can be treated so that a specific level of proteoglycan depletion is achieved. This paper argues that before any level of confidence can be established in comparative analysis it is necessary to first obtain samples with similar properties. Consequently, we examine the consistency of the outcome of the artificial modification of cartilage relative to the effects of the common enzyme, trypsin, used in the process of in vitro proteoglycan depletion. The results demonstrate that for a given time and enzyme concentration, the action of trypsin on proteoglycans is highly variable and is dependent on the initial distribution and concentration of proteoglycans at different depths, the intrinsic sample depth, the location in the joint space and the medium type, thereby sounding a note of caution to researchers attempting to model a proteoglycan-based degeneration of articular cartilage in their experimental studies. [source] The wolves of Isle Royale display scale-invariant satiation and ratio-dependent predation on mooseJOURNAL OF ANIMAL ECOLOGY, Issue 5 2005CHRISTIAN JOST Summary 1The importance of two features of the predator functional response (satiation and predator dependence) is investigated in the wolf,moose interaction on Isle Royale National Park (Michigan, USA). This is done by fitting and comparing nine different functional response models to the observed kill rates. 2Three different observational scales (the whole island, the wolf packs, or a ,mixed' scale) are used to assess the sensitivity of the detected properties with respect to these spatial scales. 3Independently of the observational scale and of statistical assumptions on data structure, strong predator dependence and satiation of the wolf functional response are found. The ,mixed' scale gives the most consistent results, suggesting that predation should be measured for each pack, but that packs share all moose on the island. On this scale, the functional response is clearly ratio-dependent. [source] Popliteal lymph node assay: facts and perspectivesJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2005Guillaume Ravel Abstract The popliteal lymph node assay (PLNA) derives from the hypothesis that some supposedly immunemediated adverse effects induced by certain pharmaceuticals involve a mechanism resembling a graft-versus-host reaction. The injection of many but not all of these compounds into the footpad of mice or rats produces an increase in the weight and/or cellularity of the popliteal lymph node in the treated limb (direct PLNA). Some of the compounds known to cause these adverse effects in humans, however, failed to induce a positive PLNA response, leading to refinements of the technique to include pretreatment with enzyme inducers, depletion of CD4+ T cells or additional endpoints such as histological examination, lymphocyte subset analysis and cytokine fingerprinting. Alternative approaches have been used to improve further the predictability of the assay. In the secondary PLNA, the test compound is injected twice in order to illicit a greater secondary response, thus suggesting a memory-specific T cell response. In the adoptive PLNA, popliteal lymph node cells from treated mice are injected into the footpad of naive mice; a marked response to a subsequent footpad challenge demonstrates the involvement of T cells. Finally, the reporter antigens TNP-Ficoll and TNP-ovalbumin are used to differentiate compounds that induce responses involving neo-antigen help or co-stimulatory signals (modified PLNA). The PLNA is increasingly considered as a tool for detection of the potential to induce both sensitization and autoimmune reactions. A major current limitation is validation. A small inter-laboratory validation study of the direct PLNA found consistent results. No such study has been performed using an alternative protocol. Other issues include selection of the optimal protocol for an improved prediction of sensitization vs autoimmunity, and the elimination of false-positive responses due to primary irritation. Finally, a better understanding of underlying mechanisms is essential to determine the most relevant endpoints. The confusion resulting from use of the PLNA to predict autoimmune-like reactions as well as sensitization should be clarified. Interestingly, most drugs that were positive in the direct PLNA are also known to cause drug hypersensitivity syndrome in treated patients. This observation is expected to open new avenues of research. Copyright © 2005 John Wiley & Sons, Ltd. [source] Performance of DFT in modeling electronic and structural properties of cobalaminsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 12 2006Jadwiga Kuta Abstract Computational modeling of the enzymatic activity of B12 -dependent enzymes requires a detailed understanding of the factors that influence the strength of the CoC bond and the limits associated with a particular level of theory. To address this issue, a systematic analysis of the electronic and structural properties of coenzyme B12 models has been performed to establish the performance of three different functionals including B3LYP, BP86, and revPBE. In particular the cobalt,carbon bond dissociation energies, axial bond lengths, and selected stretching frequencies have been analyzed in detail. Current analysis shows that widely used B3LYP functional significantly underestimates the strength of the CoC bond while the nonhybrid BP86 functional produces very consistent results in comparison to experimental data. To explain such different performance of these functionals molecular orbital analysis associated with axial bonds has been performed to show differences in axial bonding provided by hybrid and nonhybrid functionals. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1429,1437, 2006 [source] Glacial refugia of temperate trees in Europe: insights from species distribution modellingJOURNAL OF ECOLOGY, Issue 6 2008Jens-Christian Svenning Summary 1The Pleistocene is an important period for assessing the impact of climate change on biodiversity. During the Last Glacial Maximum (LGM; 21 000 years ago), large glaciers and permafrost reached far south in Europe. Trees are traditionally thought to have survived only in scattered Mediterranean refugia (southern refugia hypothesis), but a recent proposal suggests that trees may have been much more widely and northerly distributed (northern refugia hypothesis). 2In this study, the southern vs. northern refugia hypotheses were investigated by estimating the potential LGM distributions of 7 boreal and 15 nemoral widespread European tree species using species distribution modelling. The models were calibrated using data for modern species distributions and climate and projected onto two LGM climate simulations for Europe. Five modelling variants were implemented. 3Models with moderate to good predictive ability for current species range limits and species richness patterns were developed. 4Broadly consistent results were obtained irrespective of the climate simulation and modelling variant used. Our results indicate that LGM climatic conditions suitable for boreal species existed across Central and Eastern Europe and into the Russian Plain. In contrast, suitable climatic conditions for nemoral tree species were largely restricted to the Mediterranean and Black Sea regions. Large proportions of these northern and southern regions would have been suitable for a number of boreal or boreal plus nemoral tree species, respectively. 5These findings are consistent with recent palaeoecological and phylogeographic data regarding LGM distributions of trees and other boreal and nemoral taxa. 6Synthesis. It is clear that the view of the LGM landscape in Europe as largely treeless, especially north of the Alps, needs to be revised. Trees were probably much more widespread during the LGM than hitherto thought, although patchily distributed at low densities due to low atmospheric CO2 concentrations and high wind-speeds. The findings presented here help explain the occurrence of mammal assemblages with mixtures of forest, tundra and steppe species at many localities in southern Central and Eastern Europe during the LGM, as well as the phylogeographic evidence for the extra-Mediterranean persistence of many boreal species. [source] Qualification and Quantification of Fish Protein in Prepared Surimi CrabstickJOURNAL OF FOOD SCIENCE, Issue 5 2008Z.H. Reed ABSTRACT:, Species identification and protein quantification in surimi crabstick were achieved using sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). When the Lowry and Kjeldahl protein determination methods were compared, the former showed more consistent results. Densitometric scanning of the gels was used for quantification of total fish protein as well as total egg white protein. The lower molecular weight proteins, 30 kDa and lower, proved to be the most useful in fish species identification as well as egg white protein addition. Using a combination of the myosin heavy chain band and the species-specific myosin light chain (Alaska pollock: 22.5 kDa; Pacific whiting: 24.4 kDa) proved the most accurate in calculating fish protein content of the crabstick sample, while for those samples that contained egg white, quantification was accomplished from the densitometric analysis of the overlapping bands of actin (45 kDa) from fish and ovalbumin from egg white. Lysozyme (14.3 kDa) proved to be a unique protein band in determining the presence of egg white when the content of dried egg white was equal to or exceeded 0.5% of the total weight of the final crabstick. [source] DNA Extraction from Olive Oil and PCR Amplification of Microsatellite MarkersJOURNAL OF FOOD SCIENCE, Issue 1 2005Raffaele Testolin And ABSTRACT: DNA was extracted from single-cultivar of cold-pressed (virgin) unfiltered and cotton-filtered olive oils that were stored at 4 °C for up to a year using different DNA extraction kits and protocols. DNA was amplified using original and nested primers designed on 6 microsatellites loci of the UDO series. The most consistent results in terms of successful single sequence repeat amplifications were achieved using the Qiagen QIAamp DNA stool extraction kit, slightly modified and applied to oil sample amounts as small as 200 ,L without any pretreatment. The kit allowed getting polymerase chain reaction (PCR) amplicons visible on gel and scorable peaks at the automatic sequencer for all 6 markers analyzed. Less consistent results were achieved with other kits, such as the Promega Wizard Magnetic DNA Purification System for Food, the LB Link-Biotech ExtMan 50,100 Evolution, the Qiagen Plant Mini kit, and the standard cetyltrimethyl-ammonium bromide-based DNA extraction protocol. The integration in the protocols of further tools, such as the hexane-based phase separation, the addition of water or NaCl solutions to the oil, the precipitation and the use of the pellet, and others, did not result in any substantial use. PCR amplifications that gave low DNA yields were improved by adopting the nested PCR technique, which uses the product of the 1st PCR as a template for a 2nd PCR carried out by means of internal primers. Conclusions are drawn as to the applicability of the method to trace the identity of single-cultivar virgin olive oils. Further work is required to check the sensitivity of the method in determining the varietal composition of blended oils, especially in detecting alleles from cultivars present in only small amounts. [source] A Review of Psychometric Properties of Feeding Assessment Tools Used in NeonatesJOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 3 2008Tsu-Hsin Howe ABSTRACT Objective:, To appraise the psychometric properties of clinical feeding assessment tools used in a neonatal population. Data sources:, PubMed, OvidMedline, CINHAL, and PsycINFO databases from 1980 to 2007. Reference lists of all identified articles were also reviewed. Study selection:, Research reports written in English that utilized or validated clinical feeding assessment tools. Data extraction:, In total, 941 articles were reviewed. Seven neonatal clinical feeding assessment tools were identified and categorized into three groups: tools used for assessing either bottle-feeding or breastfeeding behaviors, tools used only for assessing bottle-feeding behaviors, and tools used only for assessing breastfeeding behaviors. Results:, The psychometric properties of none of the seven assessment tools identified were satisfactory, and the limited representativeness of the samples of the psychometric research was noted in all assessment tools identified. The Neonatal Oral-Motor Assessment Scale appeared to have been examined more thoroughly and showed more consistent results in psychometric properties than the others, despite its own limitations. Conclusions:, A psychometrically sound neonate feeding assessment tool has not yet been empirically validated. Clinicians who use these tools for clinical and research purposes should take into account this lack of evidence of psychometric soundness and interpret results of assessment with precautions. Well-designed research is needed to study the scientific integrity of these instruments for program evaluations in neonatal care. [source] |