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GAFFlipid: a General Amber Force Field for the accurate molecular dynamics simulation of phospholipid

Callum J. Dickson, Lula Rosso, Robin M. Betz, Ross C. Walker, Ian R. Gould
2012 Soft Matter  
Previous attempts to simulate phospholipid bilayers using the General Amber Force Field (GAFF) yielded many bilayer characteristics in agreement with experiment, however when using a tensionless NPT ensemble the bilayer is seen to compress to an undesirable extent resulting in low areas per lipid and high order parameters in comparison to experiment. In this work, the GAFF Lennard-Jones parameters for the simulation of acyl chains are corrected to allow the accurate and stable simulation of
more » ... lipid bilayers. Lipid bilayers comprised of six phospholipid types were simulated for timescales approaching a quarter of a microsecond under tensionless constant pressure conditions using Graphics Processing Units. Structural properties including area per lipid, volume per lipid, bilayer thickness, order parameter and headgroup hydration show favourable agreement with available experimental values. Expanding the system size from 72 to 288 lipids and a more experimentally realistic 2 Â 288 lipid bilayer stack induces little change in the observed properties. This preliminary work is intended for combination with the new AMBER Lipid11 modular force field as part of on-going attempts to create a modular phospholipid AMBER force field allowing tensionless NPT simulations of complex lipid bilayers.
doi:10.1039/c2sm26007g fatcat:vqs2r6l7enhmljju4whp6hppoa

On the use of the adiabatic molecular dynamics technique in the calculation of free energy profiles

Lula Rosso, Peter Mináry, Zhongwei Zhu, Mark E. Tuckerman
2002 Journal of Chemical Physics  
., Vol. 116, No. 11, 15 March 2002 Rosso et al.  ... 
doi:10.1063/1.1448491 fatcat:k6h343eftbh4xdomyzjjbllhxe

Evaluation of limited blood sampling population input approaches for kinetic quantification of [18F]fluorothymidine PET data

Kaiyumars B Contractor, Laura M Kenny, Charles R Coombes, Federico E Turkheimer, Eric O Aboagye, Lula Rosso
2012 EJNMMI Research  
Quantification of kinetic parameters of positron emission tomography (PET) imaging agents normally requires collecting arterial blood samples which is inconvenient for patients and difficult to implement in routine clinical practice. The aim of this study was to investigate whether a population-based input function (POP-IF) reliant on only a few individual discrete samples allows accurate estimates of tumour proliferation using [ 18 F] fluorothymidine (FLT). Methods: Thirty-six historical
more » ... T data with concurrent arterial sampling were available for this study. A population average of baseline scans blood data was constructed using leave-one-out cross-validation for each scan and used in conjunction with individual blood samples. Three limited sampling protocols were investigated including, respectively, only seven (POP-IF7), five (POP-IF5) and three (POP-IF3) discrete samples of the historical dataset. Additionally, using the three-point protocol, we derived a POP-IF3M, the only input function which was not corrected for the fraction of radiolabelled metabolites present in blood. The kinetic parameter for net FLT retention at steady state, K i , was derived using the modified Patlak plot and compared with the original full arterial set for validation. Results: Small percentage differences in the area under the curve between all the POP-IFs and full arterial sampling IF was found over 60 min (4.2%-5.7%), while there were, as expected, larger differences in the peak position and peak height. A high correlation between K i values calculated using the original arterial input function and all the populationderived IFs was observed (R 2 = 0.85-0.98). The population-based input showed good intra-subject reproducibility of K i values (R 2 = 0.81-0.94) and good correlation (R 2 = 0.60-0.85) with Ki-67. Conclusions: Input functions generated using these simplified protocols over scan duration of 60 min estimate net PET-FLT retention with reasonable accuracy.
doi:10.1186/2191-219x-2-11 pmid:22444834 pmcid:PMC3340309 fatcat:nvsoaddr5vewbedtihsa75n7ny

Acute induction of anxiety in humans by delta-9-tetrahydrocannabinol related to amygdalar cannabinoid-1 (CB1) receptors

Sagnik Bhattacharyya, Alice Egerton, Euitae Kim, Lula Rosso, Daniela Riano Barros, Alexander Hammers, Michael Brammer, Federico E. Turkheimer, Oliver D. Howes, Philip McGuire
2017 Scientific Reports  
Use of Cannabis, the most widely used illicit drug worldwide, is associated with acute anxiety, and anxiety disorders following regular use. The precise neural and receptor basis of these effects have not been tested in man. Employing a combination of functional MRI (fMRI) and positron emission tomography (PET), we investigated whether the effects of delta-9-tetrahydrocannabinol (delta-9-THC), the main psychoactive ingredient of cannabis, on anxiety and on amygdala response while processing
more » ... ful stimuli were related to local availability of its main central molecular target, cannabinoid-1 (CB1) receptors in man. Fourteen healthy males were studied with fMRI twice, one month apart, following an oral dose of either delta-9-THC (10 mg) or placebo, while they performed a fear-processing task. Baseline availability of the CB1 receptor was studied using PET with [ 11 C]MePPEP, a CB1 inverse agonist radioligand. Relative to the placebo condition, delta-9-THC induced anxiety and modulated right amygdala activation while processing fear. Both these effects were positively correlated with CB1 receptor availability in the right amygdala. These results suggest that the acute effects of cannabis on anxiety in males are mediated by the modulation of amygdalar function by delta-9-THC and the extent of these effects are related to local availability of CB1 receptors. Cannabis is the world's most commonly used illicit substance 1 . Although most recreational users smoke cannabis for its relaxing effects, the drug has a range of adverse effects including the induction of acute anxiety 2-5 and, development of anxiety disorders in regular users 6 . While these effects of cannabis are mediated by its main psychoactive constituent, delta-9-tetrahydrocannabinol (delta-9-THC) 3 , the extract of the cannabis plant has many other ingredients, some of which e.g. Cannabidiol may have anxiolytic effects 3 . Consistent with this, and evidence that many of the behavioural effects of exogenous cannabinoids can be linked to their effects on the endocannabinoid system 7 , a large body of preclinical evidence has accumulated implicating different components of the endocannabinoid system in emotional processing and anxiety 8 . Preclinical studies suggest that contradictory evidence regarding the precise effect of exogenous cannabinoids on anxiety, in terms of an anxiolytic or anxiogenic response, may be linked to dose of the cannabinoid 7 as well as its site of action 9 , while there is less mechanistic Published: xx xx xxxx OPEN 2 Scientific RepoRts | 7: 15025 |
doi:10.1038/s41598-017-14203-4 pmid:29101333 pmcid:PMC5670208 fatcat:q2pmiwmtx5ea7pavnjx6fb5oaa

Test–retest reproducibility of cannabinoid-receptor type 1 availability quantified with the PET ligand [11C]MePPEP

Daniela A. Riaño Barros, Colm J. McGinnity, Lula Rosso, Rolf A. Heckemann, Oliver D. Howes, David J. Brooks, John S. Duncan, Federico E. Turkheimer, Matthias J. Koepp, Alexander Hammers
2014 NeuroImage  
Endocannabinoids are involved in normal cognition, and dysfunction in cannabinoid-receptormediated neurotransmission has been suggested in a variety of neurological and psychiatric pathologies. The type 1 cannabinoid receptor (CB 1 ) is widely expressed in the human central nervous system. The objective of this study was to quantify the test-retest reproducibility of measures of the PET ligand [ 11 C]MePPEP in order to assess the stability of CB 1 -receptor quantification in humans in vivo.
more » ... ods: Fifteen healthy subjects (eight females; median age 32 years, range 25 to 65 years) had a 90-minute PET scan on two occasions after injection of a median dose of [ 11 C]MePPEP of 364 MBq. Metabolite-corrected arterial plasma input functions were obtained for all scans. Eight ROIs, reflecting different levels of receptor densities/concentrations, were defined automatically: hippocampus, anterior cingulate gyrus, inferior frontal gyrus, caudate nucleus, globus pallidus, nucleus accumbens, thalamus, and pons. We used seven quantification methods: reversible compartmental models with one and two tissue classes, two and four rate constants, and a variable blood volume term (2kbv; 4kbv); model-free (spectral) analyses with and without regularisation, including one with voxel-wise quantification; the simplified reference tissue model (SRTM) with pons as a pseudoreference region; and modified standard uptake values (mSUVs) calculated for the period of~30-60 min after injection. Percentage test-retest change and between-subject variability were both assessed, and test-retest reliability was quantified by the intraclass correlation coefficient (ICC). The ratio of binding estimates pallidum: pons served as an indicator of a method's ability to reflect binding heterogeneity. Results: Neither the SRTM nor the 4kbv model produced reliable measures, with ICCs around zero. Very good (N0.75) or excellent (N 0.80) ICCs were obtained with the other methods. The most reliable were spectral analysis parametric maps (average across regions ± standard deviation 0.83 ± 0.03), rank shaping regularised spectral analysis (0.82 ± 0.05), and the 2kbv model (0.82 ± 0.09), but mSUVs were also reliable for most regions (0.79 ± 0.13). Mean test-retest changes among the five well-performing methods ranged from 12 ± 10% for mSUVs to 16% for 2kbv. Intersubject variability was high, with mean between-subject coefficients of variation ranging from 32 ± 13% for mSUVs to 45% for 2kbv. The highest pallidum:pons ratios of binding estimates were achieved by mSUV (4.2), spectral analysis-derived parametric maps (3.6), and 2kbv (3.6). Conclusion: Quantification of CB 1 receptor availability using [ 11 C]MePPEP shows good to excellent reproducibility with several kinetic models and model-free analyses, whether applied on a region-of-interest or voxelwise basis. Simple mSUV measures were also reliable for most regions, but do not allow fully quantitative interpretation. [ 11 C] MePPEP PET is well placed as a tool to investigate CB 1 -receptor mediated neurotransmission in health and disease. Crown
doi:10.1016/j.neuroimage.2014.04.020 pmid:24736184 pmcid:PMC4283194 fatcat:l6xyzwuxlnghda7bocmiraaxom

Test-retest reproducibility of quantitative binding measures of [ 11 C]Ro15-4513, a PET ligand for GABA A receptors containing alpha5 subunits

Colm J. McGinnity, Daniela A. Riaño Barros, Lula Rosso, Mattia Veronese, Gaia Rizzo, Alessandra Bertoldo, Rainer Hinz, Federico E. Turkheimer, Matthias J. Koepp, Alexander Hammers
2017 NeuroImage  
Alteration of γ-aminobutyric acid "A" (GABAA) receptor-mediated neurotransmission has been associated with various neurological and psychiatric disorders. [11C]Ro15-4513 is a PET ligand with high affinity for α5-subunit-containing GABAA receptors, which are highly expressed in limbic regions of the human brain (Sur et al., 1998). We quantified the test-retest reproducibility of measures of [11C]Ro15-4513 binding derived from six different quantification methods (12 variants).
doi:10.1016/j.neuroimage.2016.12.038 pmid:28292717 pmcid:PMC5440177 fatcat:2dmkhunborfibd2cfdewfbtgpu

Characterisation of the Contribution of the GABA-Benzodiazepine α1 Receptor Subtype to [11C]Ro15-4513 PET Images

James FM Myers, Lula Rosso, Ben J Watson, Sue J Wilson, Nicola J Kalk, Nicoletta Clementi, David J Brooks, David J Nutt, Federico E Turkheimer, Anne R Lingford-Hughes
2012 Journal of Cerebral Blood Flow and Metabolism  
This positron emission tomography (PET) study aimed to further define selectivity of [ 11 C]Ro15-4513 binding to the GABARa5 relative to the GABARa1 benzodiazepine receptor subtype. The impact of zolpidem, a GABARa1-selective agonist, on [ 11 C]Ro15-4513, which shows selectivity for GABARa5, and the nonselective benzodiazepine ligand [ 11 C]flumazenil binding was assessed in humans. Compartmental modelling of the kinetics of [ 11 C]Ro15-4513 time-activity curves was used to describe
more » ... volume (V T ) differences in regions populated by different GABA receptor subtypes. Those with low a5 were best fitted by one-tissue compartment models; and those with high a5 required a more complex model. The heterogeneity between brain regions suggested spectral analysis as a more appropriate method to quantify binding as it does not a priori specify compartments. Spectral analysis revealed that zolpidem caused a significant V T decrease (B10%) in [ 11 C]flumazenil, but no decrease in [ 11 C]Ro15-4513 binding. Further analysis of [ 11 C]Ro15-4513 kinetics revealed additional frequency components present in regions containing both a1 and a5 subtypes compared with those containing only a1. Zolpidem reduced one component (mean ± s.d.: 71%±41%), presumed to reflect a1-subtype binding, but not another (13%±22%), presumed to reflect a5. The proposed method for [ 11 C]Ro15-4513 analysis may allow more accurate selective binding assays and estimation of drug occupancy for other nonselective ligands.
doi:10.1038/jcbfm.2011.177 pmid:22214903 pmcid:PMC3318150 fatcat:2qjocmug3fccji6mg3ojqdjjca

Using [ 11 C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism

Anne Lingford-Hughes, James Myers, Ben Watson, Alastair G. Reid, Nicola Kalk, Adrian Feeney, Alexander Hammers, Daniela A. Riaño-Barros, Colm J. McGinnity, Lindsay G. Taylor, Lula Rosso, David J. Brooks (+2 others)
2016 NeuroImage  
The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised in addiction. Using the α1/α5 benzodiazepine receptor PET radioligand [ 11 C]Ro15 4513, we previously showed reduced binding in the nucleus accumbens and hippocampus in abstinent alcohol dependence. We proposed that reduced [ 11 C]Ro15 4513 binding in the nucleus accumbens was a marker of addiction whilst the reduction in hippocampus and positive relationship with memory was a consequence of
more » ... hronic alcohol abuse. To examine this further we assessed [ 11 C]Ro15 4513 binding in another addiction, opiate dependence, and used spectral analysis to estimate contributions of α1 and α5 subtypes to [ 11 C]Ro15 4513 binding in opiate and previously acquired alcohol-dependent groups. Opiate substitute maintained opiate-dependent men (n = 12) underwent an [ 11 C]Ro15 4513 PET scan and compared with matched healthy controls (n = 13). We found a significant reduction in [ 11 C]Ro15 4513 binding in the nucleus accumbens in the opiate-dependent compared with the healthy control group. There was no relationship between [ 11 C]Ro15 4513 binding in the hippocampus with memory. We found that reduced [ 11 C]Ro15 4513 binding was associated with reduced α5 but not α1 subtypes in the opiate-dependent group. This was also seen in an alcohol-dependent group where an association between memory performance and [ 11 C]Ro15 4513 binding was primarily driven by α5 and not α1 subtype. We suggest that reduced α5 levels in the nucleus accumbens are associated with addiction since we have now shown this in dependence to two pharmacologically different substances, alcohol and opiates.
doi:10.1016/j.neuroimage.2016.02.005 pmid:26876472 pmcid:PMC4862962 fatcat:vqk3huk4ibe3joe2qbjcanr5fu

Imaging of cellular proliferation in liver metastasis by [18F]fluorothymidine positron emission tomography: effect of therapy

Kaiyumars Contractor, Amarnath Challapalli, Giampaolo Tomasi, Lula Rosso, Harpreet Wasan, Justin Stebbing, Laura Kenny, Stephen Mangar, Pippa Riddle, Carlo Palmieri, Adil Al-Nahhas, Rohini Sharma (+3 others)
2012 Physics in Medicine and Biology  
We explore the possibility that the G2 gas cloud falling in toward SgrA * is the mass-loss envelope of a young T Tauri star. As the star plunges to smaller radius at 1000-6000 km s −1 , a strong bow shock forms where the stellar wind is impacted by the hot X-ray emitting gas in the vicinity of SgrA * . For a stellar mass-loss rate of 4 × 10 −8 M yr −1 and wind velocity 100 km s −1 , the bow shock will have an emission measure (EM = n 2 vol) at a distance ∼10 16 cm, similar to that inferred from
more » ... the IR emission lines. The ionization of the dense bow shock gas is potentially provided by collisional ionization at the shock front and cooling radiation (X-ray and UV) from the post shock gas. The former would predict a constant line flux as a function of distance from SgrA * , while the latter will have increasing emission at lesser distances. In this model, the star and its mass-loss wind should survive pericenter passage since the wind is likely launched at 0.2 AU and this is much less than the Roche radius at pericenter (∼3 AU for a stellar mass of 2 M ). In this model, the emission cloud will probably survive pericenter passage, discriminating this scenario from others.
doi:10.1088/0031-9155/57/11/3419 pmid:22572708 fatcat:hrfo7cclxna5neel65i2rymwzq

Quantification of Ligand PET Studies using a Reference Region with a Displaceable Fraction: Application to Occupancy Studies with [11C]-DASB as an Example

Federico E Turkheimer, Sudhakar Selvaraj, Rainer Hinz, Venkatesha Murthy, Zubin Bhagwagar, Paul Grasby, Oliver Howes, Lula Rosso, Subrata K Bose
2011 Journal of Cerebral Blood Flow and Metabolism  
In the case of BP ND , the nondisplaceable fraction depends largely on the binding of the ligand to the cellular lipid bilayer (Rosso et al, 2008) , which can be usually assumed constant throughout an  ... 
doi:10.1038/jcbfm.2011.108 pmid:21811290 pmcid:PMC3323353 fatcat:o2l62m3ejbgx5pordalxc7qgwm

Revisione degli Scotonomus della Sardegna e descrizione di dodici specie nuove (Coleoptera Staphylinidae)

Arnaldo Bordoni, Luca Fancello, Piero Leo
2012 Bollettino della Società Entomologica Italiana  
, Lula, prés entrée Gr. de capsa", "Holotype" (a stampa su cartellino rosso), "Scotonomus troglophilus coiff., H. coiffait det. 1969" (MnHnP); paratipo [con il cartellino rosso "Paratype" (a stampa) e  ...  Lula, leg. ? iii.1961, 1 ex.; stessi dati, X.1961, 2 exx. (MHnG); oniferi (nuoro), M. curti leg. 6.iii.1979, 1 ex.  ...  .), A. dodero 5.Xi.1909", "Holotype" (a stampa su cartellino rosso), "Scotonomus doderoi coiff., H. coiffait det. 1970" (MHnP).  ... 
doi:10.4081/bollettinosei.2012.51 fatcat:ptpd5mzqcfehfiolev2ibe2yxy

Page 105 of Acta Vitaminologica et Enzymologica Vol. 3, Issue 3 [page]

1949 Acta Vitaminologica et Enzymologica  
risulta dall’esame microscopico. 2) I polmoni, aperto il torace, collassano e sullo sfondo di colorito rosso spiccano vaste zone emorra- giche rosso-scure a margini irregolari, pil numerose nei lobi inferiori  ...  In questo si riscontra: 1) Tutti gli organi si presentano infarciti di sangue per ripienezza soprattutto dei capillari pid fini ed anche per infiltrazione di globuli rossi fra cellula e cel- lula, come  ... 

As centrais sindicais e o fenômeno do transformismo no governo Lula

José de Lima Soares
2013 Sociedade e Estado  
analisar as cinco principais centrais sindicais brasileiras, no contexto do fenômeno do transformismo e das políticas de reestruturação produtiva e de precarização do trabalho levadas a cabo no governo Lula  ...  O vertiginoso surgimento de centrais sindicais após o ano 2000 fornece força cabal ao argumento da fragmentação(Dal Rosso, 2013: 39). Lutas (Conlutas).  ...  O que reforça, por si só, a tese do sindicalismo de Estado. 2 A propósito desta questão, Dal Rosso (2013) tem chamado a atenção para um aspecto relevante do problema que diz respeito à "fragmentação sindical  ... 
doi:10.1590/s0102-69922013000300005 fatcat:6hiddlxby5fl3i3s6sivtb4h7i

P.1.e.004 Brain serotonin neurotransmission and affect regulation in humans: a positron emission tomography study

S. Selvaraj, F. Turkheimer, P. Faulkner, E. Mouchlianitis, J.P. Roiser, P. McGuire, P.J. Cowen, O. Howes
2012 European Neuropsychopharmacology  
Rosso 1 , Prof Philip J Cowen 3 , Dr Jonathan P Roiser 3 , Dr Oliver Howes 1,2 1 Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London ; 2 Institute of Psychiatry, King's College  ...  activate the amygdala on a separate day This study was funded by Medical Research Council UK Fig 1 Dr Sudhakar Selvaraj 1,2 , Dr Elias Mouchlianitis 1 , Mr Paul Faulkner 3 , Dr Federico Turkheimer 1 , Dr Lula  ... 
doi:10.1016/s0924-977x(12)70279-1 fatcat:bmtacvuhkbawrnhqipfzmjyseq

Sul bromuro di titanio

A. W. Hofmann, R. Piria
1856 Il Nuovo Cimento  
La rcazionc si-Ol)('ra al calor rosso, e (tit l)cr prodotto un liquido brun% il quale ralfi'eddandosi si solidifi(~a nel rccipicn~ in una massa cristallina.  ...  In consegtwnza I'acido titanico, chc finora 6 stato riguardato corn(, un biossido, si dovrcbbc csprimerc c,)lla fi)rl|lula Ti 0 z analoga a quella delracido silicico. l,'equiwdentc del titanio, invcc~,  ... 
doi:10.1007/bf02727328 fatcat:ttb73vvsqvhtvdqqpbgltanwii
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