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GBS
Terms modified by GBS Selected AbstractsAn update on the role of glutamate in the pathophysiology of depressionACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2010N. D. Mitchell Mitchell ND, Baker GB. An update on the role of glutamate in the pathophysiology of depression. Objective:, To review the literature on the involvement of glutamate (Glu), including its interactions with other neurochemical systems, in the pathophysiology of depression. Method:, A MEDLINE search using the terms glutamate, depression and major depressive disorder, was performed. Results:, Alterations in proteins involved in glutamatergic signalling are implicated in variations in behaviour in animal models of depression. Drugs acting at Glu receptors appear to have antidepressant-like effects in these models, and traditional antidepressant pharmacotherapies act on the glutamatergic system. Recent evidence from genetic studies and in vivo spectroscopy also correlate glutamatergic dysfunction with depression. Trials of N -methyl- d -aspartate receptor antagonists in humans have provided mixed results. Conclusion:, A growing body of evidence indicates that the glutamatergic system is involved in the pathophysiology of depression, and may represent a target for intervention. [source] Frequency and clinical correlates of adult separation anxiety in a sample of 508 outpatients with mood and anxiety disordersACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2010S. Pini Pini S, Abelli M, Shear KM, Cardini A, Lari L, Gesi C, Muti M, Calugi S, Galderisi S, Troisi A, Bertolino A, Cassano GB. Frequency and clinical correlates of adult separation anxiety in a sample of 508 outpatients with mood and anxiety disorders. Objective:, To evaluate the frequency and clinical correlates of adult separation anxiety disorder in a large cohort of patients with mood and anxiety disorders. Method:, Overall, 508 outpatients with anxiety and mood disorders were assessed by the structured clinical interview for diagnostic and statistical manual (IV edition) axis I disorders for principal diagnosis and comorbidity and by other appropriate instruments for separation anxiety into adulthood or childhood. Results:, Overall, 105 subjects (20.7%) were assessed as having adult separation anxiety disorder without a history of childhood separation anxiety and 110 (21.7%) had adult separation anxiety disorder with a history of childhood separation anxiety. Adult separation anxiety was associated with severe role impairment in work and social relationships after controlling for potential confounding effect of anxiety comorbidity. Conclusion:, Adult separation anxiety disorder is likely to be much more common in adults than previously recognized. Research is needed to better understand the relationships of this condition with other co-occurring affective disorders. [source] Which parts of GB are vulnerable to the credit crunch?ECONOMIC OUTLOOK, Issue 3 2008Article first published online: 28 JUL 200 First page of article [source] Unraveling Deterministic Mesoscopic Polarization Switching Mechanisms: Spatially Resolved Studies of a Tilt Grain Boundary in Bismuth FerriteADVANCED FUNCTIONAL MATERIALS, Issue 13 2009Brian J. Rodriguez Abstract The deterministic mesoscopic mechanism of ferroelectric domain nucleation is probed at a single atomically-defined model defect: an artificially fabricated bicrystal grain boundary (GB) in an epitaxial bismuth ferrite film. Switching spectroscopy piezoresponse force microscopy (SS-PFM) is used to map the variation of local hysteresis loops at the GB and in its immediate vicinity. It is found that the the influence of the GB on nucleation results in a slight shift of the negative nucleation bias to larger voltages. The mesoscopic mechanisms of domain nucleation in the bulk and at the GB are studied in detail using phase-field modeling, elucidating the complex mechanisms governed by the interplay between ferroelectric and ferroelastic wall energies, depolarization fields, and interface charge. The combination of phase-field modeling and SS-PFM allows quantitative analysis of the mesoscopic mechanisms for polarization switching, and hence suggests a route for unraveling the mechanisms of polarization switching at a single defect level and ultimately optimizing materials properties through microstructure engineering. [source] Lichen planopilaris [cicatricial (scarring) alopecia] in a childINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2001FNASC, FRAS (Lond.), Virendra N. Sehgal MD A mother of a 12-year-old boy, 2 years ago, noticed that he showed patchy loss of hair on the vertex of the scalp. It was asymptomatic and progressive. Subsequently, similar patches appeared elsewhere on the scalp. Some of these patches joined to form a large bald patch. This was accompanied by dusky blue eruptions over the left upper lip and eyebrows. Later, there was localized loss of hair. A family history of a similar ailment was absent. Examination of the scalp revealed plaques of alopecia with mild to moderate erythema. The skin was smooth, shiny, and atrophic (Fig. 1). Atrophy was apparent by the presence of wrinkles in places, and by holding the skin between the thumb and the index finger. The periphery of the lesions was well demarcated and was occupied by erythematous, scaly, follicular papules. Lesions were also located on the patches of alopecia. In addition, flat-topped, dusky blue, papules/plaques were present over the upper lip. Figure 1. Lichen planopilaris: plaques of alopecia showing smooth, shiny, atrophic skin with erythema A study of hematoxylin and eosin-stained microsections prepared from the upper lip and vertex of the scalp was undertaken. The former revealed hyperkeratosis, hypergranulosis, sawtooth irregular acanthosis, and destruction of the basal cell layer which, in turn, was embraced by a lymphohistiocytic infiltrate disposed in a band-like fashion. A few cells were seen invading the epidermis. Pigment-laden histiocytes were found intermingled with the infiltrate. In the scalp skin, on the other hand, atrophy of the epidermis with punctuation of keratin plugs, together with fibrosis of the dermis, was prominent. The walls of the hair follicles were hyperkeratotic, while their lumina were conspicuous by their dilatation and contained keratotic plugs (Fig. 2a,b). Sebaceous and sweat glands were absent. Figure 2. Lichen planopilaris showing atrophy of the epidermis, fibrosis of the dermis, dilatation of the hair follicle lumina containing keratotic plug(s), and hyperkeratosis of the wall of the follicle (hematoxylin and eosin: a , ×,40; b , ×,100) Response to treatment, comprising ultramicronized griseofulvin (Gris O.D.) 375 mg/day (Sehgal VN, Abraham GJS, Malik GB. Griseofulvin therapy in lichen planus ,- a double blind controlled trial. Br J Dermatol 1972; 86: 383,385; Sehgal VN, Bikhchandani R, Koranne RV et al. Histopathological evaluation of griseofulvin therapy in lichen planus. A double blind controlled study. Dermatologica 1980; 161: 22,27) and prednisolone 20 mg/day for 6 months, was excellent (Fig. 3). Topical betamethasone dipropionate (Diprovate) lotion was used as a supplement. Figure 3. Perceptible decline in band-like lymphohistiocytic inflammatory infiltrate (hematoxylin and eosin, a, × 40; b, ×,100) [source] Potential of peanut skin phenolic extract as antioxidative and antibacterial agent in cooked and raw ground beefINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 7 2010Jianmei Yu Summary This study investigated the potential of peanut skin extract (PSE) as inhibitor of lipid oxidation in cooked and raw ground beef (GB) and as antimicrobial agent in raw GB. Results show that addition of PSE to raw GB before cooking significantly inhibited the formation of peroxides and TBARS in cooked GB during the refrigerated storage. PSE at concentration ,0.06% was as effective as BHA/BHT at 0.02% in inhibiting lipid oxidation. PSE also inhibited the oxidation of meat pigments thereby preserving the fresh redness of treated meat when used at 0.02,0.10%. Microplate assay showed complete inhibition of test bacteria (Bacillus subtilis, Salmonella typhimurium, Staphylococcus aureus, Streptococcus faecalis and Escherichia coli) in the presence of PSE at 0.4% or higher. However, the antimicrobial effect of PSE in GB was less potent. Hence, PSE can primarily serve the dual purposes of preserving the colour of raw GB and preventing lipid oxidation in cooked products. [source] A review of the road safety strategy in hong kongJOURNAL OF ADVANCED TRANSPORTATION, Issue 1 2007Becky P. Y. Loo Abstract Since the mid-1990s, the effectiveness of road safety measures in Hong Kong has been weakening. Six administrations in Australia, California, Great Britain (GB), Japan, New Zealand and Sweden are selected to help review the road safety activities in Hong Kong. Nine main components of the road safety strategy, including vision, objectives, targets, action plan, evaluation and monitoring, research and development, quantitative modeling, institutional framework and funding are summarized from the road safety strategies of these overseas administrations and compared to that of Hong Kong. It is found that Hong Kong's road safety activities have to be restructured to make significant improvement. In the future, a new approach structured by the nine different road safety components is recommended. The lessons learnt can be generalized to smooth the progress of other administrations at the Intermediate Stage towards the Advanced Stage of road safety development by using the short-, medium- and long-term approaches. [source] DROUGHT STRESS: Comparative Time Course Action of the Foliar Applied Glycinebetaine, Salicylic Acid, Nitrous Oxide, Brassinosteroids and Spermine in Improving Drought Resistance of RiceJOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 5 2010M. Farooq Abstract Worldwide rice productivity is being threatened by increased endeavours of drought stress. Among the visible symptoms of drought stress, hampered water relations and disrupted cellular membrane functions are the most important. Exogenous use of polyamines (PAs), salicylic acid (SA), brassinosteroids (BRs), glycinebetaine (GB) and nitrous oxide (NO) can induce abiotic stresses tolerance in many crops. In this time course study, we appraised the comparative role of all these substances to improve the drought tolerance in rice (Oryza sativa L.) cultivar Super-Basmati. Plants were subjected to drought stress at four leaf stage (4 weeks after emergence) by maintaining soil moisture at 50 % of field capacity. Pre-optimized concentrations of GB (150 mg l,1), SA (100 mg l,1), NO (100 ,mol l,1 sodium nitroprusside as NO donor), BR (0.01 ,m 24-epibrassinolide) and spermine (Spm; 10 ,m) were foliar sprayed at five-leaf stage (5 weeks after emergence). There were two controls both receiving no foliar spray, viz. well watered (CK1) and drought stressed (CK2). There was substantial reduction in allometric response of rice, gas exchange and water relation attributes by drought stress. While drought stress enhanced the H2O2, malondialdehyde (MDA) and relative membrane permeability, foliar spray of all the chemicals improved growth possibly because of the improved carbon assimilation, enhanced synthesis of metabolites and maintenance of tissue water status. Simultaneous reduction in H2O2 and MDA production was also noted in the plants treated with these substances. Drought tolerance was sturdily associated with the greater tissue water potential, increased synthesis of metabolites and enhanced capacity of antioxidant system. Of all the chemicals, foliar spray with Spm was the most effective followed by BR. [source] Exogenous Glycinebetaine and Salicylic Acid Application Improves Water Relations, Allometry and Quality of Hybrid Sunflower under Water Deficit ConditionsJOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 2 2009M. Hussain Abstract Limited water availability hampers the sustainability of crop production. Exogenous application of glycinebetaine (GB) and salicylic acid (SA) has been found very effective in reducing the adverse effects of water scarcity. This study was conducted to examine the possible role of exogenous GB and SA application in improving the growth and water relations of hybrid sunflower (Helianthus annuus L.) under different irrigation regimes. There were three levels of irrigation, viz. control (normal irrigations), water stress at budding stage (irrigation missing at budding stage) and water stress at flowering stage (FS) (irrigation missing at FS). GB and SA were applied exogenously at 100 and 0.724 mm respectively, each at the budding and FS. Control plants did not receive application of GB and SA. Water stress reduced the leaf area index (LAI), leaf area duration (LAD), crop growth rate (CGR), leaf relative water contents, water potential, osmotic potential, turgor pressure, achene yield and water use efficiency. Nevertheless, exogenous GB and SA application appreciably improved these attributes under water stress. However, exogenous GB application at the FS was more effective than other treatments. Net assimilation rate was not affected by water stress as well as application of GB and SA. The protein contents were considerably increased by water stress at different growth stages, but were reduced by exogenous GB and SA application. The effects of water stress and foliar application of GB were more pronounced when applied at FS than at the budding stage. Moreover, exogenous GB application was only advantageous under stress conditions. [source] Improving Drought Tolerance by Exogenous Application of Glycinebetaine and Salicylic Acid in SunflowerJOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 3 2008M. Hussain Abstract Water shortage is a severe threat to the sustainability of crop production. Exogenous application of glycinebetaine (GB) and salicylic acid (SA) has been found very effective in reducing the adverse affects of drought stress. This study was conducted to examine the possible role of exogenous GB and SA application in improving the yield of hybrid sunflower (Helianthus annuus L.) under different irrigation regimes. There were three levels of irrigation, viz. control (normal irrigations), water stress at vegetative stage (irrigation missing at vegetative stage) and water stress at flowering stage (irrigation missing at flowering stage). GB and SA were applied exogenously at 100 and 0.724 mm, respectively, each at the vegetative and at the flowering stage. Control plants did not receive application of GB and SA. Water stress reduced the head diameter, number of achene, 1000-achene weight, achene yield and oil yield. Nevertheless, exogenous GB and SA application significantly improved these attributes under water stress. However, drought stress increased the free leaf proline and GB, and were further increased by exogenous application of GB and SA. However, exogenous GB application at the flowering stage was more effective than other treatments. Oil contents were also reduced under water stress; however, GB and SA application could not ameliorate the negative effect of water stress on achene oil contents. The effects of water stress and foliar application of GB were more pronounced when applied at the flowering stage than at the vegetative stage. Moreover, exogenous GB application was only beneficial under stress conditions. [source] Use of a systematic review to assist the development of Campylobacter control strategies in broilersJOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2006A. Adkin Abstract Aims:, Produce an evidence-based ranking of the major contributing factors and sources of Campylobacter occurrence in broilers produced in England, Scotland and Wales , Great Britain (GB). Method and Results:, Relevant data were extracted from 159 research papers and findings were grouped into 14 sources of on-farm contamination and 37 contributing factors. A relevancy score was developed to take into account various measures from each study of applicability to GB broilers and strength of findings. Results indicate that major sources of Campylobacter include a depopulation event, another house on-farm, on-farm staff, and other animals on farm. The depopulation schedule (staggered slaughter) and multiple houses on-farm were identified as contributing factors associated with increasing the risk, and those decreasing the risk were use of a hygiene barrier, parent company and certain seasons of rearing. Conclusions:, Although the review was more resource intensive compared to narrative studies, the system allows an increased level of transparency and the ability to investigate patterns and trends. Significance and Impact of the Study:, This paper provides the first evidence-based ranking of the major sources and contributing factors for Campylobacter presence in broilers in GB using a systematic review. [source] Screening for soluble methane monooxygenase in methanotrophic bacteria using combined molecular and biochemical methods for hydroxylase detectionJOURNAL OF BASIC MICROBIOLOGY, Issue 1 2003Stephan Grosse Dr. Three well known methanotrophic bacteria (Methylosinus trichosporium OB3b, Methylocystis sp. WI 14, and Methylocystis sp. GB 25) and three newly isolated methanotrophic bacteria (Methylocystis sp. WI 11, Methylocystis sp. X, and FI-9) were screened for sMMO considering the existence of hydroxylase (component A) genes as well as its gene expression. For these purposes monoclonal antibodies that specifically recognize each subunit of the hydroxylase of Methylocystis sp. WI 14 (, -subunit [9E5/F2], , -subunit [4E2/G11], , -subunit [10G3/D7]) were produced. PCR amplification using well known primers showed that the hydroxylase encoding genes appear to be only present in M. trichosporium OB3b, Methylocystis sp. WI 11 and WI 14, and in the isolate FI-9. Western and ELISA analysis using the monoclonal antibodies revealed that all subunits of hydroxylase were present. However, in FI-9, only the , -subunit of the hydroxylase might be expressed. Surprisingly, in Methylocystis sp. GB 25, where no sMMO activity and no amplification with sMMO specific primers was obtained, the antibody 4E2/G11 recognized a protein band with exactly the same molecular mass as the , -subunit of the hydroxylase. Methylocystis sp. X showed no positive reaction in any of the tests. In combination with the detection methods currently used, the described antibodies provide a powerful tool for detecting even partially expressed hydroxylase genes. [source] Effect of octanol:water partition coefficients of organophosphorus compounds on biodistribution and percutaneous toxicity,,JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 5 2006Steven E. Czerwinski Abstract Knowledge of partition coefficient (log P) data can play a critical role in understanding the pharmacokinetic and pharmacodistributive properties of toxic organophosphorus (OP) compounds. Using a recently published gas chromatographic method, the octanol:water log P values for the compounds tabun (GA), sarin (GB), cyclosarin (GF), and O -ethyl- S -(2-diisopropylaminoethyl) methylphosphonothiolate (VX) were determined to be 0.384 ± 0.033, 0.299 ± 0.016, 1.038 ± 0.055, and 0.675 ± 0.070, respectively. Based on these data, the log P value of the fluorophosphonate fragment, common to GB, soman (GD), and GF, was determined to be ,2.256 ± 0.273. The predictive value for absorption and distribution of the determined log P values was compared to measured values. The time to onset of local fasciculations (47.3, 29.0, 8.8, 8.5, and 6.3 min, respectively) in guinea pigs exposed percutaneously to equilethal doses of GA, VX, GF, GB, or GD was used as an indicator of dermal penetration. There was a good correlation (r = 0.95) between the measured log P value and the rate of onset of local fasciculations. Assuming a direct correspondence, equilibrium tissue:blood log P may be estimated from octanol:water log P. Comparison of the estimated and directly measured tissue:blood log P revealed a correlation of 0.8 for GD in liver, muscle, and adipose tissue. Our results demonstrate the use of log P data to both predict absorption and determine the distribution of OP compounds in tissues. This facilitates further estimates of in vivo OP effects from in vitro experiments. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:241,246, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20140 [source] Bonding characteristics of newly developed all-in-one adhesivesJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2007S. K. Sidhu Abstract This study evaluated the microtensile bond strength and the interfacial morphology of newer adhesives. The occlusal surfaces of extracted teeth were ground flat for random allocation to four equal groups. Resin composite was bonded to each surface using either Clearfil SE Bond [SEB], Clearfil Protect Bond [PB], G-Bond [GB], or an experimental adhesive, SSB-200 [SSB]. After storage for 24 h in water at 37°C, they were sectioned into beams (cross-sectional area 1 mm2) for microtensile bond strength testing (,TBS) at a crosshead speed of 1 mm/min. The load at failure of each was recorded; the data were analyzed by one-way ANOVA and Games Howell tests. The surfaces of the fractured specimens were observed using SEM. For the ultra-morphology of the interface, the occlusal surfaces of four more teeth were prepared as before and a thin layer of flowable resin composite was bonded to each surface using one of the four adhesives. The mean ,TBS ranged from 39.68 MPa (GB) to 64.97 MPa (SEB). There were no statistical differences between SEB and SSB, or between PB and GB (p > 0.05). The ,TBS of SEB and SSB were significantly greater than that of PB and GB (p < 0.05). SEMs of the fractured surfaces revealed a mixed (cohesive/interfacial) failure. TEM examination highlighted differences in the hybrid layer; SEB had a thicker layer than the others. In conclusion, the newer all-in-one adhesives produced a thin hybrid layer but varied in their bond strengths. The 2-step self-etching adhesives do not necessarily produce higher bond strengths than that of the all-in-one systems. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007 [source] A Prospective Pediatric Clinical Trial of Digital Music Players: Do They Interfere with Pacemakers?JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2009CHRISTINE C. CHIU M.Sc. Background: There has been recent concern in the media about iPodÔ interference with pacemakers. We systematically tested two types of digital music players (DMP) on pacemaker or ICD function in children. Methods/Results: Patients were monitored by a 6-lead ECG and programmer telemetry. The pacemaker was tested in bipolar and unipolar sensing at normal and maximal sensitivities. The order of DMP tested was randomized. Each DMP was placed on top of the pacemaker pocket, put into "play" mode three times (5 seconds each), with and without programmer wand placed one cm adjacent to DMP. Pacemaker interference was defined as: pacing inhibition, inappropriate pacing, oversensing, or detection of high-rate episodes associated with the use of DMP. Of the 67 patients (mean age 12 ± 5 years), 62 had pacemakers and five had ICDs; 39 endocardial and 28 epicardial systems. Patients were tested with SansaÔ (67), iPodÔ 30 GB (51), and other DMPs (43). There was no evidence of interference with pacemaker function by any DMP under any of the study conditions (each performed in triplicate). Reproducible programmer telemetry interference was shown in 11 cases (Medtronic 6/47, St. Jude Medical 5/18, Guidant 0/2) related to use of iPodÔ (6), SansaÔ (1), or others (4). None of these were associated with any evidence of pacemaker malfunction. Conclusion: Interference with pacemaker function could not be shown with iPodÔ or MP3 players. No additional precaution beyond standard is necessary for patients with pacemakers when they are using these players. [source] Evaluation of preoperative sonography in acute cholecystitis to predict technical difficulties during laparoscopic cholecystectomyJOURNAL OF CLINICAL ULTRASOUND, Issue 3 2004Kyung Soo Cho MD Abstract Purpose The aim of this study was to evaluate the role of preoperative sonography in predicting technical difficulties during laparoscopic cholecystectomy in patients with acute cholecystitis. Methods Sonographic assessment of 14 parameters was performed in 55 patients during a 9-month period: volume of gallbladder (GB), thickness of GB wall, pattern of GB wall thickening, size of largest gallstone, gallstone mobility, adhesion of GB to its bed, fat plane between GB and hepatoduodenal ligament, free fluid in GB fossa, common bile duct (CBD) dilatation, CBD stone(s), color and power Doppler signals in GB wall, and increased color and power Doppler signals in adjacent liver. Each of the 5 operative steps of laparoscopic cholecystectomy was scored as being difficult (1) or not (0). The scores for each step were added to obtain the overall difficulty score (0,5). We evaluated prospectively whether there were significant associations among the preoperative sonographic findings and the overall difficulty score, scores for each of the 5 operative steps, and operation time. Results The overall difficulty score was significantly associated with a GB volume of 50 cm3 or more, GB wall thickness of 3 mm or more, and presence of color Doppler signals in the GB wall. Increased GB volume also made dissection of adhesions from the GB and dissection of Calot's triangle more difficult. Extraction of the GB from the abdomen was more difficult with a thickened GB wall or adhesion of the GB to its bed. The presence of a CBD stone, dilatation of the CBD (, 8 mm), color Doppler signals in the GB wall, and increased power Doppler signals in the adjacent liver were significantly associated with increased operation time. Conclusions Based on our experience, preoperative determination of GB volume, GB wall thickness, and presence of color Doppler signals in the GB wall in patients with acute cholecystitis helps predict technical difficulties during laparoscopic cholecystectomy. © 2004 Wiley Periodicals, Inc. J Clin Ultrasound 32:115,122, 2004 [source] Accurate prediction of protonation state as a prerequisite for reliable MM-PB(GB)SA binding free energy calculations of HIV-1 protease inhibitorsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 5 2008Kitiyaporn Wittayanarakul Abstract Binding free energies were calculated for the inhibitors lopinavir, ritonavir, saquinavir, indinavir, amprenavir, and nelfinavir bound to HIV-1 protease. An MMPB/SA-type analysis was applied to conformational samples from 3 ns explicit solvent molecular dynamics simulations of the enzyme-inhibitor complexes. Binding affinities and the sampled conformations of the inhibitor and enzyme were compared between different HIV-1 protease protonation states to find the most likely protonation state of the enzyme in the complex with each of the inhibitors. The resulting set of protonation states leads to good agreement between calculated and experimental binding affinities. Results from the MMPB/SA analysis are compared with an explicit/implicit hybrid scheme and with MMGB/SA methods. It is found that the inclusion of explicit water molecules may offer a slight advantage in reproducing absolute binding free energies while the use of the Generalized Born approximation significantly affects the accuracy of the calculated binding affinities. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008 [source] Prediction of pKa shifts in proteins using a combination of molecular mechanical and continuum solvent calculationsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 15 2004Bernd Kuhn Abstract The prediction of pKa shifts of ionizable groups in proteins is of great relevance for a number of important biological phenomena. We present an implementation of the MM-GBSA approach, which combines molecular mechanical (MM) and generalized Born (GB) continuum solvent energy terms, to the calculation of pKa values of a panel of nine proteins, including 69 individual comparisons with experiment. While applied so far mainly to the calculation of biomolecular binding free energies, we show that this method can also be used for the estimation of protein pKa shifts, with an accuracy around 1 pKa unit, even for strongly shifted residues. Our analysis reveals that the nonelectrostatic terms that are part of the MM-GBSA free energy expression are important contributors to improved prediction accuracy. This suggests that most of the previous approaches that focus only on electrostatic interactions could be improved by adding other nonpolar energy terms to their free energy expression. Interestingly, our method yields best accuracy at protein dielectric constants of ,int = 2,4, which is in contrast to previous approaches that peak at higher ,int , 8. An important component of our procedure is an intermediate minimization step of each protonation state involving different rotamers and tautomers as a way to explicitly model protein relaxation upon (de)protonation. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1865,1872, 2004 [source] Converging free energy estimates: MM-PB(GB)SA studies on the protein,protein complex Ras,RafJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 2 2004Holger Gohlke Abstract Estimating protein,protein interaction energies is a very challenging task for current simulation protocols. Here, absolute binding free energies are reported for the complex H-Ras/C-Raf1 using the MM-PB(GB)SA approach, testing the internal consistency and model dependence of the results. Averaging gas-phase energies (MM), solvation free energies as determined by Generalized Born models (GB/SA), and entropic contributions calculated by normal mode analysis for snapshots obtained from 10 ns explicit-solvent molecular dynamics in general results in an overestimation of the binding affinity when a solvent-accessible surface area-dependent model is used to estimate the nonpolar solvation contribution. Applying the sum of a cavity solvation free energy and explicitly modeled solute,solvent van der Waals interaction energies instead provides less negative estimates for the nonpolar solvation contribution. When the polar contribution to the solvation free energy is determined by solving the Poisson,Boltzmann equation (PB) instead, the calculated binding affinity strongly depends on the atomic radii set chosen. For three GB models investigated, different absolute deviations from PB energies were found for the unbound proteins and the complex. As an alternative to normal-mode calculations, quasiharmonic analyses have been performed to estimate entropic contributions due to changes of solute flexibility upon binding. However, such entropy estimates do not converge after 10 ns of simulation time, indicating that sampling issues may limit the applicability of this approach. Finally, binding free energies estimated from snapshots of the unbound proteins extracted from the complex trajectory result in an underestimate of binding affinity. This points to the need to exercise caution in applying the computationally cheaper "one-trajectory-alternative" to systems where there may be significant changes in flexibility and structure due to binding. The best estimate for the binding free energy of Ras,Raf obtained in this study of ,8.3 kcal mol,1 is in good agreement with the experimental result of ,9.6 kcal mol,1, however, further probing the transferability of the applied protocol that led to this result is necessary. © 2003 Wiley Periodicals, Inc. J Comput Chem 2: 238,250, 2003 [source] New analytic approximation to the standard molecular volume definition and its application to generalized Born calculationsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 11 2003Michael S. Lee Abstract In a recent article (Lee, M. S.; Salsbury, F. R. Jr.; Brooks, C. L., III. J Chem Phys 2002, 116, 10606), we demonstrated that generalized Born (GB) theory provides a good approximation to Poisson electrostatic solvation energy calculations if one uses the same definitions of molecular volume for each. In this work, we present a new and improved analytic method for reproducing the Lee,Richards molecular volume, which is the most common volume definition for Poisson calculations. Overall, 1% errors are achieved for absolute solvation energies of a large set of proteins and relative solvation energies of protein conformations. We also introduce an accurate SASA approximation that uses the same machinery employed by our GB method and requires a small addition of computational cost. The combined methodology is shown to yield an efficient and accurate implicit solvent representation for simulations of biopolymers. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 1348,1356, 2003 [source] The treatment of solvation by a generalized Born model and a self-consistent charge-density functional theory-based tight-binding methodJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 15 2002Li Xie Abstract We present a model to calculate the free energies of solvation of small organic compounds as well as large biomolecules. This model is based on a generalized Born (GB) model and a self-consistent charge-density functional theory-based tight-binding (SCC-DFTB) method with the nonelectrostatic contributions to the free energy of solvation modeled in terms of solvent-accessible surface areas (SA). The parametrization of the SCC-DFTB/GBSA model has been based on 60 neutral and six ionic molecules composed of H, C, N, O, and S, and spanning a wide range of chemical groups. Effective atomic radii as parameters have been obtained through Monte Carlo Simulated Annealing optimization in the parameter space to minimize the differences between the calculated and experimental free energies of solvation. The standard error in the free energies of solvation calculated by the final model is 1.11 kcal mol,1. We also calculated the free energies of solvation for these molecules using a conductor-like screening model (COSMO) in combination with different levels of theory (AM1, SCC-DFTB, and B3LYP/6-31G*) and compared the results with SCC-DFTB/GBSA. To assess the efficiency of our model for large biomolecules, we calculated the free energy of solvation for a HIV protease-inhibitor complex containing 3204 atoms using the SCC-DFTB/GBSA and the SCC-DFTB/COSMO models, separately. The computed relative free energies of solvation are comparable, while the SCC-DFTB/GBSA model is three to four times more efficient, in terms of computational cost. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1404,1415, 2002 [source] Application of the frozen atom approximation to the GB/SA continuum model for solvation free energyJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 2 2002Olgun Guvench Abstract The generalized Born/surface area (GB/SA) continuum model for solvation free energy is a fast and accurate alternative to using discrete water molecules in molecular simulations of solvated systems. However, computational studies of large solvated molecular systems such as enzyme,ligand complexes can still be computationally expensive even with continuum solvation methods simply because of the large number of atoms in the solute molecules. Because in such systems often only a relatively small portion of the system such as the ligand binding site is under study, it becomes less attractive to calculate energies and derivatives for all atoms in the system. To curtail computation while still maintaining high energetic accuracy, atoms distant from the site of interest are often frozen; that is, their coordinates are made invariant. Such frozen atoms do not require energetic and derivative updates during the course of a simulation. Herein we describe methodology and results for applying the frozen atom approach to both the generalized Born (GB) and the solvent accessible surface area (SASA) parts of the GB/SA continuum model for solvation free energy. For strictly pairwise energetic terms, such as the Coulombic and van-der-Waals energies, contributions from pairs of frozen atoms can be ignored. This leaves energetic differences unaffected for conformations that vary only in the positions of nonfrozen atoms. Due to the nonlocal nature of the GB analytical form, however, excluding such pairs from a GB calculation leads to unacceptable inaccuracies. To apply a frozen-atom scheme to GB calculations, a buffer region within the frozen-atom zone is generated based on a user-definable cutoff distance from the nonfrozen atoms. Certain pairwise interactions between frozen atoms in the buffer region are retained in the GB computation. This allows high accuracy in conformational GB comparisons to be maintained while achieving significant savings in computational time compared to the full (nonfrozen) calculation. A similar approach for using a buffer region of frozen atoms is taken for the SASA calculation. The SASA calculation is local in nature, and thus exact SASA energies are maintained. With a buffer region of 8 Å for the frozen-atom cases, excellent agreement in differences in energies for three different conformations of cytochrome P450 with a bound camphor ligand are obtained with respect to the nonfrozen cases. For various minimization protocols, simulations run 2 to 10.5 times faster and memory usage is reduced by a factor of 1.5 to 5. Application of the frozen atom method for GB/SA calculations thus can render computationally tractable biologically and medically important simulations such as those used to study ligand,receptor binding conformations and energies in a solvated environment. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 214,221, 2002 [source] Preclinical study of endoscopic ultrasonography with electronic radial scanning echoendoscopeJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2003KATSUSHI NIWA Background: To evaluate the imaging possibility of a newly designed electronic radial scanning echoendoscope (ER-ES). Methods: In the in vivo study of swine, we obtained B-mode endoscopic ultrasonography (EUS) images of the gastric and gallbladder (GB) walls and checked the ability to detect Doppler signals using ER-ES and electronic linear array echoendoscope (EL-ES). Furthermore, in the ex vivo study of swine, B-mode EUS images of fixed gastric and GB wall specimens were obtained using ER-ES, EL-ES and mechanical radial scanning echoendoscope (MR-ES). In the study of resected human specimens, we obtained B-mode EUS images of five resected GB specimens (three normal GB, one cholecystitis and one cancerous) using the three types of echoendoscope. Results: In the in vivo study of swine, ER-ES and EL-ES depicted the gastric walls as five-layered, and the GB walls as single-layered structures. The ability to detect Doppler signals was equal between ER-ES and EL-ES. In the ex vivo study of swine, ER-ES, MR-ES and EL-ES equally delineated the gastric walls as five-layered and GB walls as three-layered structures. In the study of resected human specimens, results demonstrated the normal GB walls as three-layered, the cholecystitis as a combination of outer high-echoic and inner low-echoic layers, and the cancer as a protruded tumor. Conclusions: We conclude that ER-ES has faculties for making B-mode images as well as EL-ES and MR-ES. In addition, in the in vivo study, ER-ES can analyze blood flow information as well as EL-ES. © 2003 Blackwell Publishing Asia Pty Ltd [source] Radiosynthesis of 3-[18F]fluoropropyl and 4-[18F]fluorobenzyl triarylphosphonium ionsJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 8 2004Hayden T. Ravert Abstract 3-[18F]Fluoropropyl-, 4-[18F]fluorobenzyl-triphenylphosphonium and 4-[18F]fluorobenzyltris-4-dimethylaminophenylphosphonium cations were synthesized in multi-step reactions from no carrier added (nca) [18F]fluoride. The time for synthesis, purification, and formulation was 56, 82, and 79 min with an average radiochemical yield of 12, 6 and 15%, respectively (not corrected for decay). The average specific radioactivity for the three radiolabeled compounds was 14.9 GB q/µmole (403 mCi/µmole) at end of synthesis (EOS). Copyright © 2004 John Wiley & Sons, Ltd. [source] Effect of buffer cations and of H3O+ on the charge states of native proteins.JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 6 2003Significance to determinations of stability constants of protein complexes Abstract The progressive reduction of charge in charge states of non-denatured proteins (lysozyme, ubiquitin, and cytochrome c), observed with nanospray in the positive ion mode, when the buffer salt ammonium acetate is replaced by ethylammonium acetates (EtNH3Ac, Et2NH2Ac and Et3NHAc) is rationalized on the basis of the charge residue model (CRM). The charge states of the multiply protonated protein are shown to be controlled by the increasing gas-phase basicities, GB(B), of the bases(B) NH3, EtNH2, Et2NH and Et3N. Charge states derived from evaluated apparent gas-phase basicities GBapp of the basic side-chains of the protein and the known GB(B) of the above bases are found to be in agreement with the experimentally observed charge states. This is a requirement of the CRM, because in this model the small positive ions (the buffer cations in the present case) at the surface of the electrospray droplets are the excess ions that provide the charge of the final small droplet that contains the protein molecule and on evaporation of the solvent transfer the charge to the protein. The observed charge states in the absence of buffer salts, i.e. pure water, are attributed to excess H3O+ ions produced by the electrolysis process that attends electrospray. A proposed extended mechanism provides predictions of factors that determine the sensitivity for detection of the multiply protonated proteins. Consideration of restraints imposed by the CRM lead to some simple predictions for conditions that should be present to obtain accurate determinations by electrospray and nanospray of stability constants for the protein,complex equilibrium in aqueous solution. Copyright © 2003 John Wiley & Sons, Ltd. [source] Feasibility of the spontaneous gas-phase proton transfer equilibria between neutral Brønsted acids and Brønsted basesJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 7-8 2008Peeter Burk Abstract The computational investigation of interactions of different acid,base pairs regarding the nature and extent of spontaneous proton transfer was carried out at B3LYP/6-311,+,G** level. The selected acid,base pairs include the interactions of strong base (K2O) with acids of different strength (HClO4, HCl, and HF), and strong acid (HClO4) with bases ranging from K2O (GB,=,322.8,kcal/mol) to H2O (GB,=,157.6,kcal/mol). It was shown that spontaneus, unassisted proton transfer can take place in the gas-phase reactions of strong neutral Brønsted acids and bases. The reaction might be barrierless as in case of interactions between strong acids and bases, for example perchloric acid and alkali metal oxides or potassium oxide and halogen hydrides, or involve the encounter complex (hydrogen bonded acid,base cluster), which is separated from ion-pair by the transition state. Copyright © 2008 John Wiley & Sons, Ltd. [source] Phase Evolution in Heat-Treated Si3N4 with Additions of Yb2O3JOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 2 2008Gang Feng Guo The heat treatment of silicon nitride (Si3N4) ceramics with additions of 8, 12, and 16 wt% Yb2O3 was carried out at different temperatures and the evolution of grain boundary (GB) phase was investigated systematically by X-ray diffraction (XRD) as well as scanning electron and transmission electron microscopic analyses. XRD results reveal that the extent and the ease of GB crystallization increase with increasing the Yb2O3 content, and that high heat-treatment temperatures in general favor crystallization of the quaternary compounds such as the Yb4Si2O7N2 phase. These results provide an insight into the GB phase evolution in the Yb-system Si3N4 ceramics subjected to a postsintering heat treatment. [source] The Effect of Frequency of Input-Enhancements on Word Learning and Text ComprehensionLANGUAGE LEARNING, Issue 2 2007Susanne Rott Research on second language lexical development during reading has found positive effects for word frequency, the provision of glosses, and elaborative word processing. However, findings have been inconclusive regarding the effect of such intervention tasks on long-term retention. Likewise, few studies have looked at the cumulative effect of interventions on word learning or text comprehension. This investigation sought to assess the effect of increased frequency of target words (TWs) comparing lexical gain of words that occurred once (F1) or four times (F4) in the input passage. The study further investigated the combined effect of frequency (F4) and semantic or visual enhancements. It compared the following reading conditions: (a) TWs were glossed four times in the text (four-gloss: 4G); (b) TWs were first glossed, then retrieved in the first language, and bolded twice (gloss-retrieval: GR); and (c) TWs were first glossed and then bolded three times (gloss-bolding: GB). In addition, the study assessed the effect of these interventions on long-term retention (4,6 weeks) of lexical knowledge and on text comprehension. Findings revealed that the GR and 4G reading conditions resulted in more productive word gain than the GB condition or when readers encountered a TW only once. Repeated visual enhancements seemed to have no effect on strengthening word encoding. The comprehension of main ideas was highest when the TW was glossed four times followed by the gloss-bolding reading condition and the gloss-retrieval task. [source] A New Technique for Preparing a Filled Type of Polymeric Gradient MaterialMACROMOLECULAR MATERIALS & ENGINEERING, Issue 11 2006Yong-Bin Zhu Abstract Summary: So-called functionally gradient materials have received increased attention as a new type of composite whose microelements, including composition and structure, change spatially to optimize the gradient properties for a specific application. In this study, a new technique for continuously preparing a filled type of PGM was investigated through co-extrusion/gradient distribution/2-dimensional mixing with conventional polymeric material processing facilities. The processing line from co-extrusion, gradient distribution to 2-dimensional mixing was fulfilled by two extruders, a gradient distribution unit and 2-dimensional mixing units. The gradient distribution unit and 2-dimensional mixing units were designed separately in our group. As an example, a PE/GB PGM was prepared by using this new technique. The gradient variation of composition along the sample thickness direction was studied by TG and SEM. The TG results indicated that a gradient variation of the content of GB was formed along the thickness of the sample. The direct gradient distribution of GB came from SEM observation, which showed an increased stacking density of GB along the sample thickness. Experimental results indicated that the processing method with co-extrusion/gradient distribution/2-dimensional mixing can serve as a new way to produce a filled type of PGM and is worthy of further investigation. The prepared polyethylene/glass bead PGM; the graph illustrates the glass bead concentration gradient across the sample thickness. [source] Effects of antibodies against a fusion protein consisting of parts of cell surface protein antigen and glucosyltransferase of Streptococcus sobrinus on cell adhesion of mutans streptococciMOLECULAR ORAL MICROBIOLOGY, Issue 1 2008T. Kawato Background/aims:, The cell surface protein antigen (PAg) and glucosyltransferases (GTFs) produced by Streptococcus sobrinus are considered to be major colonization factors of the organism. Methods:, We constructed a fusion gene encoding a protein composed of the alanine-rich region of PAg (PAgA) and the glucan-binding domain (GB) of GTF-I, which catalyzes the synthesis of water-insoluble glucan in S. sobrinus. The fusion protein PAgA-GB was purified from cell extracts of Escherichia coli harboring the fusion gene, and antibodies against the fusion protein were prepared in rabbits. Results:, In the presence of sucrose, the antibody against PAgA-GB significantly inhibited the adhesion of both S. sobrinus MT8145 and Streptococcus mutans Xc to saliva-coated hydroxyapatite beads, and the inhibitory effect on S. sobrinus was stronger than that on S. mutans. In the absence of sucrose, the antibody against PAgA-GB significantly inhibited the adhesion of both S. sobrinus and S. mutans, however the inhibitory effect on S. sobrinus was unexpectedly weaker than that on S. mutans. A similar result was observed with the antibody against the intact recombinant PAg protein (rPAg), while the same antibody reacted more strongly against S. sobrinus than against S. mutans cells. Conclusion:, Taken together, these results show that the antibody against S. sobrinus GTF-I may be useful for effective inhibition of the sucrose-dependent adhesion of S. sobrinus. However, PAg of S. sobrinus may not function primarily as a receptor for acquired pellicles, and other cell surface proteins may be involved in the sucrose-independent adhesion of S. sobrinus. [source] | ||||||||||||||||||||||||||||||||||||||||||||||