bluuebunny/crossref_metadata_2025 huggingface dataset:
Municipal waste incinerator fly ash: supercritical fluid extraction of metals
Authors: Kersch Christof , Kraan Martijn van der , Woerlee Geert F , Witkamp Geert J
Published: September 2002

The amount of residues such as fly ash from municipal waste incinerators and coal‐fired power plants is growing. Fly ash is usually contaminated with toxic heavy metals that leach out on contact with water and pollute the groundwater. Therefore, isolated and expensive disposal of the ash is required. Reuse of ash as a filler for cement or pavements only allows minimum leachability of metals and maximum leaching values of various metals from reused fly ash are prescribed by national legislation. Supercritical‐fluid extraction (SFE) offers a method to reduce the metal content so that leachability is reduced and the demands of legislation are observed. This paper presents results of metal extraction from municipal waste incinerator ash using supercritical CO2. Initial experiments with a 12 dm3 rotating extraction vessel and constant solvent flow showed extraction efficiencies of between 10% and 52%. The influences of complexing‐agent concentration and process time are studied on divalent metals such as Zn2+, Pb2+, Cu2+, Sb2+, Ni2+, and Cd2+.

© 2002 Society of Chemical Industry
Loss on ignition and carbon content in pulverized fuel ashes (PFA): two crucial parameters for quality control
Authors: Payá J , Monzó J , Borrachero M V , Amahjour F , Peris‐Mora E
Published: September 2002

Loss on ignition (LOI) is one of the selected chemical parameters for characterizing the quality of pulverized fuel ashes (PFA). However, this parameter does not represent the unburned carbon in ashes because of the presence of several other compounds which also decompose on heating. In order to evaluate the carbon content in PFA, several thermal analysis methods have been proposed. Thermogravimetric experiments using active/inert atmospheres, high resolution thermogravimetric procedures, and single differential thermal analysis experiments are proposed as new tools for evaluating the presence of unburned carbon and other materials that are also present in PFA, such as calcium carbonate and calcium hydroxide.

© 2002 Society of Chemical Industry
Factory‐scale proving trials using combined mixtures of three by‐product wastes (including incinerated sewage sludge ash) in clay building bricks
Authors: Anderson Michael , Elliott Mark , Hickson Celia
Published: September 2002

This paper reports the results of a series of factory trials which has been recently completed involving Staffordshire University, a major United Kingdom water company and a commercial brick manufacturer, which demonstrate the practical possibilities of incorporating three by‐product wastes, waterworks sludge, incinerated sewage sludge ash and carpet yarn, into the commercial brick‐manufacturing process as a sustainable alternative to their current disposal route of landfill. An initial laboratory development programme primarily involving waterworks sludge or water treatment residue (WTR) confirmed the technical feasibility of its use in brick‐making as an alternative disposal route. However, owing to the very high water content of this waste when freshly produced, ranging between 85 and 70% depending on individual sources, its introduction into the commercial brick‐making processes was identified as likely to present practical difficulties. Consequently, to overcome this problem the reported work describes a successful way in which the handling of WTR was improved by pre‐mixing it with the two other by‐products that jointly possess water‐absorbing properties and the ability of improving the unfired strength of the experimental products. This investigation then progressed from the laboratory to full‐scale brickworks trials encompassing the manufacture of >300 000 experimental bricks. This work programme also included emission monitoring during the firing process, together with full physical testing of the experimental products for direct comparison with the standard commercial products manufactured at the collaborating brick factory.

© 2002 Society of Chemical Industry
Application of zeolitic material synthesised from fly ash to the decontamination of waste water and flue gas
Authors: Querol X , Moreno N , Umaña J C , Juan R , Hernández S , Fernandez‐Pereira C , Ayora C , Janssen M , García‐Martínez J , Linares‐Solano A , Cazorla‐Amoros D
Published: September 2002

Zeolitic material was synthesised from fly ash using two different conversion methodologies. The two conversion products obtained were: (a) impure zeolitic material obtained by direct conversion from different Spanish fly ashes, and (b) a high purity 4A–X zeolite blend synthesised from the silica extracts obtained from the Meirama fly ash (NW Spain). The zeolitic material was tested for potential application as an ion exchanger to decontaminate waters containing high concentrations of ammonium and heavy metals. Preliminary results show high cation uptake efficiencies (up to 4.7 meq g−1) which allowed fast decontamination of different types of industrial or acidic mine waste waters. The CO2, SO2 and NH3 sorption capacity of several zeolitic products was also determined and very promising results were obtained for the A4–X blend. Sorption capacity values of up to 74, 297, and 111 mg g−1 for CO2, SO2 and NH3 respectively were obtained for the zeolitic material synthesised from silica extracts from fly ash and a high‐aluminate waste water.

© 2002 Society of Chemical Industry
Zeolite synthesis from coal fly ash by hydrothermal reaction using various alkali sources
Authors: Murayama Norihiro , Yamamoto Hideki , Shibata Junji
Published: September 2002

The main objective of this study was to investigate the reaction mechanism of zeolitization from coal fly ash by alkali hydrothermal treatment. The hydrothermal synthesis of zeolites was carried out using various alkali sources. The changes in the various properties, such as crystal structure, surface texture and cation exchange capacity, of the products and the amounts of Si4+ and Al3+ dissolved in the alkaline solution were investigated during the hydrothermal reaction. The mechanism of zeolite crystallization and the role of various alkali sources on the synthesis reaction were considered.

© 2002 Society of Chemical Industry
Operating and scale‐up factors for the electrolytic removal of algae from eutrophied lakewater
Authors: Alfafara Catalino G , Nakano Kazunori , Nomura Nakao , Igarashi Takeshi , Matsumura Masatoshi
Published: September 2002

Electrolytic removal of algae was conducted in batch and continuous reactors to investigate operating factors affecting removal efficiency and to explore engineering relationships which could be useful for operation and scale‐up. The system integrated both electro‐flocculation and electro‐flotation mechanisms by using polyvalent metal anodes and inert metal cathodes. Batch reactor studies confirmed that high electrical input power or higher electrical current achieved higher and faster removal efficiencies. Natural liquid circulation was observed during electrolytic operation and increased with higher electrical power. However, a small degree of external mixing may be useful at lower electrical power input. Electro‐flotation alone could not achieve complete algae removal (maximum efficiency 40–50%), and showed the importance of algal floc formation for the complete removal of algae. In continuous electrolysis experiments, the ratio of the volumetric current intensity (amperes dm−3) and the chlorophyll a loading (mg dm−3 h−1) was found to be a useful operating and scale‐up factor to balance high algal removal efficiency with minimum release of excess aluminum. This ratio was eventually found to be just the charge dose or the amount of coulombs required to remove a unit mass of chlorophyll a. The optimum charge dose was determined and used to relate the operating current and electrolysis time of a continuous process.

© 2002 Society of Chemical Industry
Extraction separation of Ir(III) and Rh(III) with Cyanex 923 from chloride media: a possible recovery from spent autocatalysts
Authors: Chavan Devendra V , Dhadke Purushottam M
Published: September 2002

Liquid–liquid extraction of Ir(III) and Rh(III) with Cyanex 923 from aqueous hydrochloric acid media has been studied. Quantitative extraction of Ir(III) was observed in the range of 5.0–8.0 mol dm−3 HCl with 0.1 mol dm−3 Cyanex 923, while Rh(III) was extracted quantitatively in the range of 1.0–2.0 mol dm−3 HCl with 0.05 mol dm−3 Cyanex 923 in toluene along with 0.2 mol dm−3 SnCl2. The Ir(III) was back extracted with 4.0 mol dm−3 HNO3 quantitatively from the organic phase while Rh(III) was stripped with 3.0 mol dm−3 HNO3. The extraction of Rh(III) with Cyanex 923 was not quantitative without use of SnCl2. However in the extraction of Ir(III) a negative trend was observed in the presence of SnCl2. Varying the temperature of extraction showed that the extraction reactions of both the metal ions are exothermic in nature, and the stoichiometric ratio of Ir(III)/Rh(III) to Cyanex 923 in organic phase was found to be 1:3. The methods developed were applied to the recovery of these metal ions from a synthetic solution of similar composition to that from leaching of spent autocatalysts in 6.0 mol dm−3 HCl.

© 2002 Society of Chemical Industry
Anaerobic degradation: the effect of the combined treatment of substrates on the refractory fraction
Authors: Fueyo Gema , Gutierrez Antonio , Berrueta José
Published: September 2002

The anaerobic digestion of landfill leachates mixed with domestic sewage was studied using a batch reactor at laboratory scale. Batch assays were carried out with different proportions of leachate in the feed: 100, 70, 50 and 30% by volume, with and without adjustment of pH, in order to determine the percentage of acidification and methanization, COD removal, anaerobic biodegradability and biomass growth yield. The main effect of the mixing with sewage was a synergistic improvement of the anaerobic treatment of leachates, but in different ways; the greatest improvement in COD removal was obtained when the proportion of leachate in the feed was 70%, but the highest degree of anaerobic biodegradability was obtained with 30% of leachate in the feed. The kinetics of these assays was studied and the experimental data were fitted to a modification of the equation of Chen and Hashimoto. A new concept of ‘non‐biodegradable fraction’ is proposed.

© 2002 Society of Chemical Industry
Unstructured model for seed cultures without pH control of Lactobacillus helveticus growing on supplemented whey permeate
Authors: Amrane Abdeltif , Couriol Catherine
Published: September 2002

In cultures of Lactobacillus helveticus with pH controlled at 5.9, growth and lactic acid production were under the control of nutritional limitations (carbon and nitrogen). In the absence of pH control, as was the case for seed cultures, an inhibitory effect on growth of both pH and the undissociated lactic acid concentration were evident before nutritional limitations. The variations of the specific growth rate with the undissociated lactic acid concentration followed exponential decay. Then, the inhibitory effect of pH was also taken into account through the Henderson–Hasselbach equation. The specific growth rate history has been previously found to follow sigmoidal variation. Integration of these relationships gave the theoretical biomass and lactic acid production kinetics. The model fitted experimental kinetic data well and allowed fine analysis of the various growth phases, since the growth‐associated, the deceleration and the stationary states can be characterized by means of the model parameters.

© 2002 Society of Chemical Industry
Optimization of the production of β‐carotene from molasses by Blakeslea trispora: a statistical approach
Authors: Goksungur Y , Mantzouridou F , Roukas T
Published: September 2002

The effect of pretreatment of molasses, nitrogen sources, natural oils, fatty acids, antioxidant, precursors, and mixtures of the above substances on β‐carotene production by Blakeslea trispora in shake flask culture was investigated. Also, a central composite design was employed to determine the maximum β‐carotene concentration at optimum values for the process variables (linoleic acid, kerosene, antioxidant). The highest concentration of the carotenoid pigment was obtained in molasses solution treated with invertase. Corn steep liquor and yeast extract at concentrations of 5.0% and 0.5% (w/v), respectively, increased slightly the concentration of β‐carotene, while the natural oils, fatty acids, and precursors (except kerosene) did not improve the production of pigment when they were added separately to the medium. On the other hand, the mixture of linoleic acid, kerosene and antioxidant increased significantly the concentration of β‐carotene. The fit of the model was found to be good. Linoleic acid, kerosene and antioxidant had a strong linear effect on β‐carotene concentration. The concentration of β‐carotene was significantly affected by linoleic acid–antioxidant and kerosene–antioxidant interactions as well as by the negative quadratic effects of these variables. The interaction between linoleic acid–kerosene had no significant linear effect. Maximum β‐carotene concentration (790.0 mg dm−3) was obtained in culture grown in molasses solution supplemented with linoleic acid (30.74 g dm−3), kerosene (27.79 g dm−3) and antioxidant (10.22 g dm−3).

© 2002 Society of Chemical Industry
Evaluation of a porcine model for pulmonary gene transfer using a novel synthetic vector
Authors: Cunningham Steven , Meng Qing‐Hai , Klein Nigel , McAnulty Robin J. , Hart Stephen L.
Published: September 2002

Background

The pig lung, given its gross anatomical, histological and physiological similarities to the human lung, may be useful as a large animal model, in addition to rodents, in which to assess the potential of vectors for pulmonary airway gene transfer. The aim of this study was to assess the utility of the pig lung as a model of gene transfer to the human lung with a synthetic vector system.

Methods

The LID vector system consists of a complex of lipofectin (L), integrin‐binding peptide (I) and plasmid DNA (D). LID complexes containing a β‐galactosidase reporter gene under a CMV promoter or a control plasmid at1 mg/3 ml PBS, or 3 ml buffer, was administered to the right lower lobe ofthe pig lung through a bronchoscope. Pigs were culled at 48 h and lung sections prepared for immunohistochemical and histological analysis. Bronchoalveolar lavage fluid was collected and analysed for TNF‐α by ELISA.

Results

Immunohistochemical staining for the β‐galactosidase reporter gene indicated high efficiency of gene transfer by the LID vector to pig bronchial epithelium with 46% of large bronchi staining positively. There was no evidence for vector‐specific inflammation assessed by leukocytosis and cytokine production.

Conclusions

This study demonstrates the use of the pig for studies of gene transfer in the lung and confirms in a second species the potential of the LID vector for gene therapy of pulmonary diseases such as cystic fibrosis. Copyright © 2002 John Wiley & Sons, Ltd.
Cyanide bystander effect of the linamarase/linamarin killer‐suicide gene therapy system
Authors: Luisa Cortés Maria , García‐Escudero Vega , Hughes Monica , Izquierdo Marta
Published: September 2002

Background

The killer‐suicide system linamarase/linamarin (lis/lin) uses the plant gene linamarase (β‐glucosidase) to convert the cyanogenic glucoside substrate, linamarin, into glucose and cyanide. We have studied the bystander effect associated with this new system mediated by the production of the cyanide ion that diffuses freely across membranes.

Methods

Immunofluorescent staining of cells treated with an anti‐linamarase antibody allowed us to localize the enzyme within the cells. Flow cytometry was used to determine the sensitivity of different mixtures of cells, C6lis and C6gfp (green), to linamarin as a percentage of cell survival.

Results

We demonstrate here that rat glioblastoma C6 cells carrying the linamarase gene (lis), mixed with naive C6 cells and exposed to linamarin, induce generalized cell death. Cells expressing lis efficiently export linamarase, whereas linamarin enters cells poorly by endocytosis; as a result most of the cyanide is produced outside the cells. The study was facilitated by the presence of the green fluorescent protein (gfp) gene in the bystander population. As few as 10% C6lis‐positive cells are sufficient to eliminate the entire cell culture in 96 h.

Conclusions

This bystander mechanism does not preferentially kill toxic metabolite producer cells compared with bystander cells, thus allowing production of sufficient cyanide to cause tumor regression. In this report we confirm the potential of the lis/lin gene therapy system as a powerful tool to eliminate tumors in vivo. Copyright © 2002 John Wiley & Sons, Ltd.
Genetic retargeting of adenovirus vectors: functionality of targeting ligands and their influence on virus viability
Authors: Magnusson Maria K. , See Hong Saw , Henning Petra , Boulanger Pierre , Lindholm Leif
Published: September 2002

Background

We studied the ability of adenovirus type 5 (Ad5) to encapsidate new cellular ligands carried by their fibers to yield functional retargeted vectors for gene therapy. Recombinant Ad5 fibers containing shaft repeats 1 to 7 and an extrinsic trimerization motif, and terminated by its native knob or amino acid motifs containing RGD, have been rescued into infectious virions.

Methods

Polypeptide ligands of cell surface molecules, including single‐chain antibodies or epidermal growth factor, were cloned into recombinant fibers. Phenotypic analysis of fiber constructs and rescuing into the Ad5 genome were performed. Recombinant viruses were characterized with reference to fiber content, growth rate and infectivity.

Results

A major limiting factor for recovering viable recombinant Ad5 carrying fiber‐fused polypeptide ligands was apparently the ability of the ligand to fold correctly within the cellular cytoplasm. This constraint has previously not been systematically evaluated in the literature. Phenotypic analysis of the fiber‐ligand fusions showed that their degree of cytoplasmic solubility correlated with their ability to yield viable Ad5 vectors. Our results suggested that the fiber manipulations diminish virus growth rate, probably through different, opposing effects: (i) the reduced shaft length increases fiber solubility in the absence of the knob but (ii) diminishes virus entry, and (iii) the absence of the knob alters the overall protein composition of the virion and decreases its fiber copy number.

Conclusions

Based on our findings, cytoplasmic solubility and cytoplasmic ligand reactivity of fiber‐ligand fusion proteins are the best prediction criterion for viability and recovery of genetically retargeted Ad vectors. Copyright © 2002 John Wiley & Sons, Ltd.
Antisense MBD2 gene therapy inhibits tumorigenesis
Authors: Slack Andrew , Bovenzi Veronica , Bigey Pascal , Ivanov M. A. , Ramchandani Shyam , Bhattacharya Sanjoy , tenOever Benjamin , Lamrihi B. , Scherman Daniel , Szyf Moshe
Published: September 2002

Background

Aberration in the pattern of DNA methylation is one of the hallmarks of cancer. We present data suggesting that dysregulation of MBD2, a recently characterized member of a novel family of methylated DNA binding proteins, is involved in tumorigenesis. Two functions were ascribed to MBD2, DNA demethylase activity and repression of methylated genes.

Methods

Multiple antisense expression and delivery systems, transfection, electrotransfer and adenoviral were employed to demonstrate that MBD2 is essential in tumorigenesis, both ex vivo and in vivo.

Results

Inhibition of MBD2 by antisense expression resulted in inhibition of anchorage‐independent growth of antisense transfected cancer cells or cells infected with an adenoviral vector expressing MBD2 antisense. Xenograft tumors treated with an adenoviral vector expressing MBD2 antisense or xenografts treated with electrotransferred plasmids expressing MBD2 antisense showed reduced growth.

Conclusions

These results support the hypothesis that one or both of the functions described for MBD2 are critical in tumorigenesis and that MBD2 is a potential anticancer target. Copyright © 2002 John Wiley & Sons, Ltd.
Development and characterization of a minimal inducible packaging cell line for simian immunodeficiency virus‐based lentiviral vectors
Authors: Kuate Seraphin , Wagner Ralf , Überla Klaus
Published: September 2002

Background

Lentiviral vectors allow gene transfer into non‐dividing cells. Further development of these vector systems requires stable packaging cell lines that enable adequate safety testing.

Methods

To generate a packaging cell line for vectors based on simian immunodeficiency virus (SIV), expression plasmids were constructed that contain the codon‐optimized gag‐pol gene of SIV and the gene for the G protein of vesicular stomatitis virus (VSV‐G) under the control of an ponasterone‐inducible promoter. Stable cell lines expressing these packaging constructs were established and characterized.

Results

The RT activity and vector titers of cell clones stably transfected with the inducible gag‐pol expession plasmid could be induced by ponasterone by more than a factor of 1000. One of these clones was subsequently transfected with the ponasterone‐inducible VSV‐G expression plasmid to generate packaging cells. Clones of the packaging cells were screened for vector production by infection with an SIV vector and subsequent induction by ponasterone. In the supernatant of selected ponasterone‐induced producer clones vector titers of more than 1×105 transducing units/ml were obtained. Producer cell clones were stable for at least five months, as tested by vector production.

Conclusions

The packaging cells described should be suitable for most preclinical applications of SIV‐based vectors. By avoiding regions of high homology between the vector and the packaging constructs, the design of the SIV packaging cell line should reduce the risk of transfer of packaging genes to target cells and at the same time provide flexibility with respect to the SIV vector constructs that can be packaged. Copyright © 2002 John Wiley & Sons, Ltd.
Constructing representations of Karl Spencer Lashley
Authors: Dewsbury Donald A.
Published: September 2002

I compare, contrast, and analyze two published constructions, a straightforward approach and a social constructivist perspective, of the life and work of psychobiologist Karl S. Lashley (1890–1958). Although it is clear at a general level that scientific endeavors are affected by extrascientific factors, particular concern is directed at the issues involved in demonstrating that the scientific work of an individual, in this case Lashley, is affected by specific extrascientific influences. There is insufficient evidence to conclude that Lashley's work was driven predominantly by racial and genetic determinist positions and that he was something other than the scientist he represented himself as being. I then discuss an unpublished personality theory approach to Lashley that suggests the influence of some personality characteristics on his work and helps to provide balance and perspective in constructing representations of Lashley. © 2002 Wiley Periodicals, Inc.
Friedrich Albert Lange on neo‐Kantianism, socialist Darwinism, and a psychology without a soul
Authors: Teo Thomas
Published: September 2002

Friedrich Albert Lange was a German philosopher, political theorist, educator, and psychologist who outlined an objective psychology in the 1860s. This article shows how some of the most important worldviews of the nineteenth century (Kantianism, Marxism, and Darwinism) were combined creatively in his thought system. He was crucial in the development of neo‐Kantianism and incorporated psycho‐physiological research on sensation and perception in order to defend Kant's epistemological idealism. Based on a critique of phrenology and philosophical psychology of his time, Lange developed a program of a psychology without a soul. He suggested that only those phenomena that can be observed and controlled should be studied, that psychology should focus on actions and speech, and that for each psychological event the corresponding physical or physiological processes should be identified. Lange opposed introspection and subjective accounts and promoted experiments and statistics. He also promoted Darwinism for psychology while developing a socialist progressive‐democratic reading of Darwin in his social theory. The implications of socialist Darwinism on Lange's conceptualization of race are discussed and his prominence in nineteenth century philosophy and psychology is summarized. © 2002 Wiley Periodicals, Inc.
The role of evidence in interpretations of the scientific work of Karl Lashley
Authors: Dewsbury Donald A.
Published: September 2002

I discuss some of the issues underlying the different perspectives of Nadine Weidman and myself on the scientific oeuvre of Karl Lashley. I emphasize that our disagreements concern the kind of evidence needed to support specific claims more than any differences in our models of science. © 2002 Wiley Periodicals, Inc.
Exports, domestic policy and world markets: a panel study
Authors: Love J. , Turner E.
Published: September 2002

This paper analyses how export growth rates in sub‐Saharan Africa are determined by both domestic and external market conditions. We highlight the problems of measuring trade orientation given the various domestically‐determined factors which influence the conditions faced by exporters. Focusing on the impact of trade policy is not a good measure of trade orientation since additional domestic policies can have an important influence on the trade orientation of a country. Hence, we select an index which incorporates the effect of trade and other policies. Then we construct an index which provides a more appropriate measure of conditions faced by exporters in the world market than previously cited measures. We find that, contrary to the recent literature, external market conditions are still critical in explaining export growth rates in sub‐Saharan Africa and should be taken into account when engaging in policy decisions. Copyright © 2001 John Wiley & Sons, Ltd.
Stabex versus IMF compensatory financing: impact on fiscal policy
Authors: Brun Jean‐Francois , Chambas Gérard , Laporte Bertrand
Published: September 2002

The supply of external financing to developing countries generally tends to increase in periods when export earnings are booming and thus, in periods of increasing government revenues. Conversely, Stabex and IMF Compensatory Financing transfers are primarily designed to take place in response to a fall in export earnings, and thus, in periods when government revenues are decreasing. However, these transfers occur in an unsteady way with respect to the cycle of government revenues. When occurring in periods of decreasing government revenues, only Stabex transfers are used to finance additional primary expenditures (i.e. expenditures other than interest on public debt). This effect contrasts with the effects usually reported for other instruments of external financing. In periods of increasing government revenues, Stabex and Compensatory Financing transfers have no impact on fiscal deficit. Copyright © 2001 John Wiley & Sons, Ltd.
Women and war: the role Kuwaiti women played during the Iraqi occupation
Authors: Juliá Maria , Ridha Hadi
Published: September 2002

In many societies, women face a gender bias rooted in feudal socio‐economic relations and religious institutions that justify female subordination (Youseff,1972). Yet, aided by the experience of human rights movements, women have made progress in the past few decades in overcoming a cultural tradition of male domination and superiority. Circumstances of war have also empowered women, allowing them to become active agents in their own development and liberation (Cagan and Juliá,1998). However, movement toward equality or democratization during these conflicts indicate that ‘women's success might be ephemeral, a product of crisis mobilization’ (Jaquetteet. al.,1994. 2). Once the armed conflict is over and peace returns, women's choices, rights, and lives once again tend to become circumscribed by tradition, religion, and male prerogative.

There is a vital need for information about what happens to women during and following periods of war—their survival strategies, the metamorphosis of gender relations, the retention of positive changes, the identification of their needs, and the support required to meet those needs (Wallace and March,1991). Attempting to answer such questions, the purpose of this paper is to explore the experiences of Kuwaiti women during and after the Iraqi invasion and occupation of 1990. The authors' contention is that, in terms of gender empowerment, Kuwaiti women's experience during this period was and is no differnt than the experiences of women during and after wartime crises elsewhere. In an attempt to take into account variations of context and historical specificities the impact of Islamic beliefs and practices and their compatibility or incompatibility with women's rights are examined alongside social development/status variables. Copyright © 2001 John Wiley & Sons, Ltd.
Precursor synthesis and radiolabelling of [11C]ADAM: a potential radioligand for the serotonin transporter exploration by PET
Authors: VERCOUILLIE Johnny , TARKIAINEN Jari , HALLDIN Christer , EMOND Patrick , CHALON Sylvie , SANDELL Johan , LANGER Oliver , GUILLOTEAU Denis
Published: September 2002

The serotoninergic system is involved in a variety of neurological and psychiatric disorders. Exploration of the serotonin transporters (5‐HTT) in living human brain by PET would be of great value for better understanding, diagnosis and therapeutic follow up of these diseases. In order to obtain a selective radioligand to explore the 5‐HTT by PET we report the synthesis of [11C]N,N‐dimethyl‐2‐(2‐amino‐4‐iodophenylthio)‐benzylamine ([11C]ADAM). The precursor for labelling N‐demethyl ADAM, was obtained in five steps using 2,5‐dibromonitrobenzene and 2‐thio‐N‐methylbenzamide as starting material. [11C]ADAM was synthesised by N‐alkylation of the precursor using [11C]methyl iodide in DMF. The incorporation yield of [11C]methyl iodide was in the range of 50 to 70%. Finally [11C]ADAM was obtained in 30 minutes synthesis time including HPLC and with a radiochemical purity better than 99%. Copyright © 2001 John Wiley & Sons, Ltd.
Synthesis of fluorine‐18 labeled sulfonureas as β‐cell imaging agents
Authors: Shiue Grace G. , Schirrmacher Ralf , Shiue Chyng‐Yann , Alavi Abass A.
Published: September 2002

Tolbutamide (1) and glyburide (7) are hypoglycemic drugs used to stimulate insulin secretion in type 2 diabetic patients. We have synthesized their fluorine‐18 labeled analogs, 1‐[(4‐[18F]fluorobenzenesulfonyl)]‐3‐butyl]urea (p‐[18F]fluorotolbutamide, 3a) and N‐{4‐[β‐(2‐[18F]fluoroethoxybenzene carboxamido)ethyl]benzenesulfonyl}‐N′‐cyclohexylurea (2‐[18F]fluoroethoxyglyburide, 6a) as β‐cell imaging agents. Compound 3a was synthesized via two approaches: One‐step synthesis via nucleophilic substitution of p‐nitrotolbutamide (2) with K[18F]/Kryptofix 2.2.2 in either CH3CN or DMSO gave a complicated mixture; a two‐step synthesis via preparation and reaction of 4‐[18F]fluorobenzenesulfonamide with butyl isocyanate in the presence of either copper (I) chloride or borontrifluoride etherate complex in CH3CN followed by HPLC purification yielded compound 3a in an overall yield of 1–2% with a synthesis time of 120 minutes from EOB. Compound 6a was synthesized by alkylation of the corresponding hydroxy precursor (5) with [18F]fluoroethyl tosylate in DMSO at 120°C for 20 minutes followed by HPLC purification in an overall yield of 5–10 % with a synthesis time of 100 minutes from Copyright © 2001 John Wiley & Sons, Ltd.
Highly efficient synthesis of [11C]S12968 and [11C]S12967, for the in vivo imaging of the cardiac calcium channels using PET
Authors: Dolle Frédéric , Valette Héric , Hinnen Françoise , Demphel Stéphane , Bramoulle Yann , Peglion Jean‐Louis , Crouzel Christian
Published: September 2002

The dihydrophyridines S12968 ((−)‐S11568, absolute configuration S) and S12967 ((+)‐S11568, absolute configuration R), 3‐ethyl 5‐methyl (−/+)‐2‐[(2‐(2‐aminoethoxy)ethoxy)methyl]‐4‐(2,3‐dichlorophenyl)‐6‐methyl‐1,4‐dihydropyridine‐3,5‐dicarboxylate, have both an in vitro profile of high potency and of high selectivity for the low‐voltage‐dependent L‐type calcium channel. In this paper, the radiosynthesis of both enantiomers, S12968 and S12967, with carbon‐11, a positron‐emitting isotope (half‐life : 20.4 min) was investigated and oriented towards the preparation of multi milliCuries of radiotracer. Typically, 130–250 mCi (4.81–9.25 GBq) of [11C]S12968 and [11C]S12967 were obtained within 30 min of radiosynthesis (HPLC purification included) with specific radioactivities ranging from 500 to 1000 mCi/μmol (18.5–37.0 GBq/μmol) using no‐carrier‐added [11C]methyl triflate as the alkylating agent and the appropriate, enantiomerically pure carboxylic acid precursor at 100°C for 1 min. Based on preliminary PET experiments, only the levo enantiomer S12968 ((−)‐[11C]‐1) appears to be suitable for myocardial PET imaging as demonstrated in vivo in beagle dogs: with S12968, 85% of the uptake of [11C]S12968 could be inhibited in pretreatment experiments and up to 70% of [11C]S12968 could be displaced. Further investigations are currently underway in order to provide an absolute quantification of ventricular calcium channels with PET. Copyright © 2001 John Wiley & Sons, Ltd.
Labeling of human C‐peptide by conjugation with N‐succinimidyl‐4‐[18F]fluorobenzoate
Authors: Fredriksson Anna , Johnström Peter , Stone‐Elander Sharon , Jonasson Per , Nygren Per‐Åke , Ekberg Karin , Johansson Bo‐Lennart , Wahren John
Published: September 2002

We have labeled proinsulin connecting peptide (C‐peptide) with fluorine‐18 (t½=109.7 min) in order to perform in vivo biodistribution and pharmacokinetic studies with position emission tomography (PET). This study reports the optimization of the conjugation labeling in the N‐terminal with N‐succinimidyl‐4‐[18F]fluorobenzoate ([18F]SFB). In preparative runs N‐4‐[18F]fluorobenzoyl‐C‐peptide ([18F]FB‐C‐peptide) was produced in 8–12% decay‐corrected yields, counted from resolubilized [18F]F−, in less than 5 h. The specific radioactivity of [18F]FB‐C‐peptide, determined using ELISA for one of the preparations, was around 70 GBq/μmol at end of synthesis. Copyright © 2001 John Wiley & Sons, Ltd.
Exchange radioiodination produces inversion at C‐4 of 1‐(4‐deoxy‐4‐iodo‐β‐D‐xylopyranosyl)‐2‐nitroimidazole
Authors: Schneider R.F. , Price W.A. , Chapman J.D.
Published: September 2002

The title compound, 3a, when exchange labeled with 125I results in three new labeled products. The major labeled product (84.1%) is 1‐(4‐deoxy‐4‐iodo‐β‐L‐arabinopyranosyl)‐2‐nitroimidazole, 3b, that could result from inversion of configuration at C‐4. Exchange labeling carried out under conditions of kinetic control yielded dramatically different product ratios than thermodynamic equilibrium reactions. Confirmation of these results was established by extensive 1HNMR spectral analyses. A possible mechanism is presented. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of 3‐[[4‐(4‐[18F] fluorophenyl)piperazin‐1‐yl]methyl]‐1H‐pyrrolo[2,3‐b]pyridine
Authors: Eskola Olli , Bergman Jörgen , Lehikoinen Pertti , Haaparanta Merja , Grönroos Tove , Forsback Sarita , Solin Olof
Published: September 2002

3‐[[4hyphen;(4‐[18F]fluorophenyl)piperazin‐1‐yl] methyl] ‐1H‐pyrrolo[2,3‐b]pyridine, acandidate to image dopamine D4 receptors, was synthesised via electrophilic fluorination of a trimethylstannyl precursor with high specific radioactivity [18F]F2. The precursor was obtained by a facile four‐step synthetic approach; the trimethylstannyl leaving group was introduced by displacement of iodine utilising palladium catalysis and hexamethyldistannane in an inert solvent. The total radiosynthesis time was 50 min, including purification and formulation for injection. Decay corrected radiochemical yield was <1% as calculated from the amount of [18F]F− produced. Specific radioactivity at the end of synthesis was 12.8–16.4 GBq/μmol. Radiochemical purity was 88–92%. Ex vivo studies in rats showed homogeneous distribution of radioactivity within rat brain. Copyright © 2002 John Wiley & Sons, Ltd.
Magnetic resonance microscopy at 17.6‐Tesla on chicken embryos in vitro
Authors: Hogers Bianca , Gross Dieter , Lehmann Volker , de Groot Huub J.M. , de Roos Albert , Gittenberger‐de Groot Adriana C. , Poelmann Robert E.
Published: September 2002

The non‐destructive nature and the rapid acquisition of a three‐dimensional image makes magnetic resonance microscopy (MRM) very attractive and suitable for functional imaging investigations. We explored the use of an ultra high magnetic field for MRM to increase image quality per image acquisition time. Improved image quality was characterized by a better signal‐to‐noise ratio (SNR), better image contrast, and higher resolution compared to images obtained at lower magnetic field strengths. Fixed chicken embryos at several stages of development were imaged at 7.0‐T (300 MHz) and at 17.6‐T (750 MHz). Maximum intensity projection resulted in three‐dimensional vascular images with ample detail of the embryonic vasculature. We showed that at 750 MHz frequency, an image with approximately three times better SNR can be obtained by T1‐weighting using a standard gadolinium contrast agent, compared to the same measurement at 300 MHz. The image contrast improved by around 20 percent and the contrast‐to‐noise ratio improved by almost a factor of 3.5. Smaller blood vessels of the vascular system were identified at the high field, which indicates a better image resolution. Thus, ultra high field is beneficial for MRM and opens new areas for functional imaging research, in particular when SNR, resolution, and contrast are limited by acquisition time. J. Magn. Reson. Imaging 2001;14:83–86. © 2001 Wiley‐Liss, Inc.
Analysis of alcohols, as dimethylglycine esters, by electrospray ionization tandem mass spectrometry
Authors: Johnson David W.
Published: September 2002

Dimethylglycine (DMG) esters are new derivatives for the rapid, sensitive and selective analysis of primary and secondary alcohols, in complex mixtures, by electrospray ionization tandem mass spectrometry (ESI‐MS/MS). Their development was inspired by the use of the complementary dimethylaminoethyl esters for the trace, rapid analysis of fatty acids. DMG esters are simply prepared by heating a dichloromethane solution of the imidazolide of dimethylglycine, containing triethylamine, and an alcohol. DMG esters of long‐chain fatty alcohols, isoprenoidal alcohols and hydroxy‐acids are analysed by electrospray ionization tandem mass spectrometry with a precursor ion of m/z 104 scan. Diols, glyceryl esters, glyceryl ethers and some sterols are analysed by a neutral loss of 103 Da scan. Trimethylglycine (TMG) ester iodides, prepared by alkylation of DMG esters with methyl iodide, are more sensitive derivatives for molecules containing secondary alcohol groups, such as cholesterol and gibberellic acid. They are analysed by a precursor ion of m/z 118 scan. DMG or TMG derivatives were shown to be at least comparable and sometimes an order of magnitude more sensitive than N‐methylpyridyl ether derivatives for ESI‐MS/MS analysis of the different classes of alcohols. Applications of these derivatives for the diagnosis of inherited disorders and the analysis of natural products are presented. Copyright © 2001 John Wiley & Sons, Ltd.
Characterization of the vulcanization products of squalene by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry: model studies on the vulcanization of natural rubber
Authors: Gros M. , Borrós S. , Amabilino D.B. , Veciana J. , Folch I.
Published: September 2002

A method for the characterization of the vulcanization reaction products of squalene using matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) was developed. Squalene was chosen as a model molecule for natural rubber. Different matrix–solvent pairs were evaluated with the spectrometer functioning in the linear mode, working with positive/negative high voltages and different laser powers. The study led to the following important conclusions. The identification of squalene requires a cationizing agent whereas the identification of the two families of curing systems used, a sulfenamide and a thiuram, requires only the use of a matrix (dithranol and dihydroxybenzoic acid, respectively). For the first time, the intermediate compounds such as squalene derivatives with pendant sulfur‐containing groups and interacting with zinc as well as cross‐linked squalene were identified. Only a matrix is required and the solvent acetonitrile leads to better spectra than THF (which oligomerizes during sample preparation). Adequate sample treatment is critical to the success of the method. Suitable conditions were found for the characterization of the vulcanization reaction. MALDI‐TOFMS appears to be an important tool for the analysis and deconvolution of the mechanisms of the vulcanization of natural rubber. Copyright © 2001 John Wiley & Sons, Ltd.
Quantitative detection of N7‐(2‐hydroxyethyl)guanine adducts in DNA using high‐performance liquid chromatography/electrospray ionization tandem mass spectrometry
Authors: Liao Pao‐Chi , Li Ching‐Ming , Hung Chien‐Wen , Chen Shu‐Hui
Published: September 2002

High‐performance liquid chromatography (HPLC) was combined with electrospray ionization tandem mass spectrometry (ESI‐MS/MS) to develop a sensitive and selective method for the quantitative measurement of N7‐(2‐hydroxyethyl)guanine (N7‐HEG) adducts in DNA obtained from ethylene oxide‐exposed biological samples. Selected reaction monitoring (SRM) was used as the detection mode while the fragmentation product ion at m/z 152 generated from the precursor protonated N7‐HEG (m/z 196) was monitored. The detection limits for N7‐HEG were estimated by twofold serial dilution and determined to be 4 fmol in neat standard solution and 16 fmol when a matrix effect is considered. When the mass spectrometer was operated in the selected ion monitoring mode using only the first quadrupole (without MS/MS function), the detection limits increased to 128 fmol and 1 pmol (when matrix effect is considered), respectively. A good linear correlation (R2 = 0.999) was observed for signal intensities obtained by injecting 16 fmol–33 pmol of N7‐HEG into the HPLC/ESI‐MS/MS system. Hep G2 cells were incubated for 8 h with medium containing various concentrations of ethylene oxide (ranging from 0.05 to 5.0 mM). A dose–response relationship was established, indicating that the adduct formation increases with the exposure level. The method shows potential, although the detection limit needs to be lowered for practical applications, for use in monitoring N7‐HEG formation in other biological systems. Copyright © 2001 John Wiley & Sons, Ltd.
Density functional computations of proton affinity and gas‐phase basicity of proline
Authors: Marino T. , Russo N. , Tocci E. , Toscano M.
Published: September 2002

An Erratum has been published for this article in Journal of Mass Spectrometry 37(2) 2002, 232.

The proton affinity and gas‐phase basicity of proline were evaluated by using density functional theory coupling the B3‐LYP hybrid functional with the extended 6–311++G** basis set. Cis and trans conformations of the carboxyl moiety for both exo and endo ring structures were considered for the neutral proline. The results show that the most stable structure of proline has the endo ring conformation with the carboxyl group in the cis position. The structure at the global minimum is stabilized by an intramolecular hydrogen bond. The nitrogen of the ring in the exo form is the preferred protonation site. The calculated proton affinity (924.3 kJ mol−1) and gas‐phase basicity (894.4 kJ mol−1) are in very good agreement with the experimental counterparts. Copyright © 2001 John Wiley & Sons, Ltd.
Spontaneous N → O acyl shift in the [M + H]+ ions of [MeBmt1]‐cyclosporins in an ion trap
Authors: Jegorov Alexandr , Havlíček Vladimír
Published: September 2002

In an ion trap the protonated molecules of the cyclic undecapeptides cyclosporins having 3‐hydroxy‐4‐methyl‐2‐methylamino‐6‐octenoic acid (MeBmt) in their backbone undergo an N → O peptidyl shift into the corresponding [M + H]+ ions of isocyclosporins. This rearrangement does not take place in cyclosporins [Bmt1]Cs and [3′‐deoxy‐MeBmt1]Cs. In cyclosporin [Thr2]Cs having two threonines in the molecule, only one of them participates in the N,O‐acyl transfer. It can be concluded that the presence of the basic N‐methylamino group of MeBmt, which can serve as the primary site of protonation, is necessary for isocyclosporin formation. A dominating ion series originating from the primary cleavage between MeBmt (first position in the cyclosporin ring) and amino acid residue at the neighbouring eleventh position is then observed in collision‐induced dissociation spectra of protonated molecules of cyclosporins. This ‘isocyclosporin’ ion series can effectively be used for easy and complete cyclosporin sequencing using a tandem mass spectrometric (MS3) experiment in an ion trap. The paper further introduces an improved Gross mass spectral nomenclature for cyclic peptide sequencing and several techniques for the generation of protonated molecules of cyclosporins. Their preparation represents the fundamental requirement for smooth sequencing of cyclosporins by tandem mass spectral techniques. Copyright © 2001 John Wiley & Sons, Ltd.
Liquid chromatography/mass spectrometry in anabolic steroid analysis—optimization and comparison of three ionization techniques: electrospray ionization, atmospheric pressure chemical ionization and atmospheric pressure photoionization
Authors: Leinonen Antti , Kuuranne Tiia , Kostiainen Risto
Published: September 2002

The applicability of liquid chromatography/tandem mass spectrometry (LC/MS/MS) for the detection of the free anabolic steroid fraction in human urine was examined. Electrospray ionization (ESI), atmospheric pressure chemical ionization and atmospheric pressure photoionization methods were optimized regarding eluent composition, ion source parameters and fragmentation. The methods were compared with respect to specificity and detection limit. Although all methods proved suitable, LC/ESI‐MS/MS with a methanol–water gradient including 5 mM ammonium acetate and 0.01% acetic acid was found best for the purpose. Multiple reaction monitoring allowed the determination of steroids in urine at low nanogram per milliliter levels. LC/MS/MS exhibited high sensitivity and specificity for the detection of free steroids and may be a suitable technique for screening for the abuse of anabolic steroids in sports. Copyright © 2002 John Wiley & Sons, Ltd.