bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Approximate Formulation of the Koutecky Function
Authors: Ruiz Morales Juan Carlos , Placeres Jesús César Rodríguez , Barrera Niebla Manuel , Trujillo Jacinto del Castillo Juan José , Germá Luis Rodríguez
Published: March 2003

A new approximate formulation of the Koutecky function is proposed, with two new equations; one for the approximate calculation of the Koutecky function F(χ) in terms of its argument χ and the inverse χ=f [F(χ)]. Both use only two adjustable parameters, substantially more precise than the Smith‐McCord‐Hung and Oldham‐Parry formulations. The dependence χ=f [F(χ)] permits a more accurate general equation for polarographic waves to be deducted.
Characteristics of Cl‐ and Au‐Containing Nanocomplex and Its Effect on the Following Electrodeposition of Polypyrrole
Authors: Liu Yu‐Chuan , Liang Yu‐Sheng
Published: March 2003

In this study, polypyrrole (PPy) films were electrochemically deposited on gold substrates roughened by a triangular‐wave oxidation‐reduction cycle (ORC) with different anodic and cathodic vertexes in an aqueous solution containing 0.1 N NaCl. In ORC treatment, the Cl‐ and Au‐containing nanocomplex was formed on the surface of gold. The results indicate that the crystalline orientation and diameter of Au are significantly different before and after ORC treatment. Also the redox behavior in ORC, surface morphology formed and depth profile of Cl in the nanocomplex are influenced by the anodic and cathodic vertexes used in roughening Au. The roughened Au demonstrates an electrocatalytic activity for pyrrole polymerization. Correspondingly, the characteristics of PPy films electrodeposited on these roughened Au substrates are notable. They include the surface‐enhanced Raman scattering (SERS) effect shown, a higher conductivity obtained and an increase in oxidation level demonstrated.
A Study on the Electrochemical and Electrochemiluminescent Behavior of Homogentisic Acid at Carbon Electrodes
Authors: Chi Yuwu , Duan Jianping , Feng Zhao Zheng , Chen Hongqinq , Chen Guonan
Published: March 2003

The electrochemical oxidation and electrochemiluminescent behavior of homogentisic acid (HGA) has been studied in aqueous solutions over a wide pH range by linear sweep voltammetry, cyclic voltammetry, chronocoulometry at a glassy carbon electrode, by controlled potential electrolysis at a large area spectroscopic graphite electrode, and by spectroelectrochemistry at an optically transparent drilled holes graphite (DHG) electrode in a thin‐layer cell. The studies reveal that the electrochemical oxidation of HGA at carbon electrodes is a reversible process involving two‐electron, two‐proton transfer. In addition to the electrochemical oxidation, the chemical oxidation of HGA by dissolved oxygen was investigated by spectroscopic method combined with voltammetry. It was revealed that HGA is fairly stable in strongly acidic media but readily oxidized by dissolved oxygen in alkaline media giving rise to 1,4‐benzoquinone‐2‐acetic acid, the same product as that of electrooxidation of HGA. This oxidation product is stable in acidic, neutral and weakly alkaline media, but can further degrade in strongly alkaline media yielding oxalate as the final product. The electrochemiluminescent mechanism of HGA in the presence of Ru(bpy)32+ at a glassy carbon electrode was also investigated in detail, based on which a sensitive ECL method for determination of HGA was developed, and the detection limit was 3.0×10−8 mol L−1.
An Amperometric Biosensor Based on the Coimmobilization of Horseradish Peroxidase and Methylene Blue on a Carbon Nanotubes Modified Electrode
Authors: Xu Jin‐Zhong , Zhu Jun‐Jie , Wu Qiang , Hu Zheng , Chen Hong‐Yuan
Published: March 2003

A novel hydrogen peroxide biosensor has been constructed based on the characteristics of the carbon nanotube. The multiwall carbon nanotube (MWNT) was used as a coimmobilization matrix to incorporate horseradish peroxidase (HRP) and electron transfer mediator methylene blue (MB) onto a glassy carbon electrode surface. Cyclic voltammetry and amperometric measurements were employed to demonstrate the feasibility of methylene blue as an electron carrier between the immobilized peroxidase and the surface of glassy carbon electrode. The amperometric response of this resulting biosensor to H2O2 shows a linear relation in the range from 4 μM to 2 mM. The detection limit was 1 μM when the signal to noise ratio is 3. The presence of dopamine and ascorbic acid hardly affects the sensitive determination of H2O2. This biosensor also possesses very good stability and reproducibility.
Electrochemical Evaluation of the Interaction between Avidin and Biotin at Biotinylated Polypyrrole Electrode Using a Redox Marker
Authors: Kuramitz Hideki , Matsuda Mari , Sugawara Kazuharu , Tanaka Shunitz
Published: March 2003

The interaction between avidin and biotin was evaluated electrochemically by monitoring the change in the electrode response of redox markers. Biotin was immobilized on the electrode surface by means of the electrochemical polymerization of biotinylated pyrrole and pyrrole. When avidin was introduced onto the biotinylated polypyrrole electrode surface, the large change in the electrode response of the redox marker was detected. The fact that the change in the electrode response of a marker ion could be attributed to the electrostatic interaction between avidin on the electrode surface and the redox marker ion present in a solution was verified by replacing avidin with NutrAvidin. At a pH lower than the isoelectric point of avidin, the electrode response of ferrocyanide as an anionic marker ion increased linearly within the range of 5.0×10−9 −3.0×10−8 M avidin. The relative standard deviation at 1.5×10−8 M avidin was about 5.4% (n=5). The detection of biotin was also performed using a competitive reaction between biotin in solution and biotin that had been immobilized on the electrode surface in the form of the biotinylated polypyrrole.
Voltammetric Oxidation of Ambroxol and Application to Its Determination in Pharmaceuticals and in Drug Dissolution Studies
Authors: Demircigil B. Tolga , Uslu Bengi , Özkan Yalçin , Özkan Sibel A. , Sentürk Zühre
Published: March 2003

A detailed study of the electrochemistry of ambroxol at a glassy carbon electrode was carried out in the pH range 1.8–11.0 in aqueous solution using cyclic and differential pulse voltammetry. The compound was oxidized irreversibly at high positive potentials resulting in the formation of a chemical product at less positive potentials, which was more readily oxidized than the parent compound. In addition, a differential pulse voltammetric method was proposed for the determination of the drug in different pharmaceutical formulations, and in drug dissolution studies.
Study of a Catalytic Mechanism in Additive Differential Pulse Techniques
Authors: Molina Angela , Moreno Marién M. , Serna Carmen , Martínez‐Ortiz Francisco
Published: March 2003

The new electrochemical double pulse technique, known as additive differential normal pulse voltammetry (ADNPV) when there is no restriction on the duration of both pulses, and additive differential pulse voltammetry (ADPV) when t2≪t1, has been applied to a pseudo‐first‐order catalytic mechanism. The expressions obtained here are applicable to planar and spherical electrodes, of any radius. This is of great interest since the size of the electrode plays an important role in the preponderating of diffusive and kinetics processes. The signal obtained with this technique presents the same morphological characteristics as the triple pulse technique, double differential pulse voltammetry (DDPV) and is more advantageous than DDPV and than the double pulse one, differential pulse voltammetry (DPV).
Electrocatalytic Oxidation of Methanol at Lower Potentials on Glassy Carbon Electrode Modified by Platinum and Platinum Alloys Incorporated in Poly(o‐Aminophenol) Film
Authors: Golabi S. M. , Nozad A.
Published: March 2003

The electrocatalytic oxidation of methanol at a glassy carbon electrode modified by a thin film of poly(o‐aminophenol) (PoAP) containing Pt, Pt‐Ru and Pt‐Sn microparticles has been investigated using cyclic voltammetry as analytical technique and 0.10 M perchloric acid as supporting electrolyte. It has been shown that the presence of PoAP film increases considerably the efficiency of deposited Pt microparticles toward the oxidation of methanol. The catalytic activity of Pt particles is further enhanced when Ru or specially Sn is co‐deposited in the polymer film. The effects of various parameters such as the thickness of polymer film, concentration of methanol, medium temperature as well as the long term stability of modified electrodes have also been investigated.
Adsorption of Tri‐n‐Butyl Phosphate (TBP) from NaClO4 Aqueous Solution on Hg Electrode
Authors: Dogić R. , Krznarić D.
Published: March 2003

The adsorption of TBP on Hg electrode from aqueous NaClO4 media has been studied using differential capacity and chronocoulometric measurements. TBP adsorbs in two steps, the first corresponding to a flat and second to a perpendicular orientation. Both orientations were observed in the entire investigated potential range. The maximal measured surface concentration (Γmax) of TBP reaches a value of 1.55×10−10 mol cm−2, which corresponds to the theoretical value for densely packed molecules in perpendicular orientation. Γ value of the first isotherm step plateau is about 7 to 15% smaller than Γmax and decreases strongly at potentials more negative than −0.9 V due to the repelling of negative charges between the electrode and the phosphate group. The standard Gibbs energy of adsorption was found to reach the value of −34 kJ mol−1.
Determination of octanol‐water partition coefficients for carbonate esters and other small organic molecules by microemulsion electrokinetic chromatography
Authors: Østergaard Jesper , Hansen Steen Honoré , Larsen Claus , Schou Christian , Heegaard Niels H. H.
Published: March 2003

Microemulsion electrokinetic chromatography (MEEKC) was assessed as a tool for determination of octanol‐water partition coefficients using 34 solutes encompassing 8 carbonate esters. It was confirmed that microemulsions containing 1.44–2.88% w/w SDS, 6.49% w/w 1‐butanol, and 0.82% w/w n‐heptane constitute a good model of octanol‐water partitioning in the pH range of 1.4–7.4. Use of the migration index concept led to improved repeatability of the MEEKC method compared to the use of retention factors. Using a dynamical coating, a high electroosmotic flow at pH 1.4 and 4.75 was achieved expanding the practical pH working range of the MEEKC system. The correlation obtained between the migration index and log P was unaffected by pH indicating that the properties of the microemulsion droplets and, thus, partitioning are independent of pH. No evidence for congeneric behavior was found for the sample set comprising solutes with different hydrogen bonding properties suggesting that simple reference compounds can be used as calibrators. Lipophilicity estimates for the series of carbonate esters were obtained. The increase in lipophilicity with chain length was smaller than expected from the Hansch substituent constant, π.
Monitoring liposome‐mediated delivery and fate of an antisense drug in cell extracts and in single cells by capillary electrophoresis with laser‐induced fluorescence
Authors: Malek Amir H. , Khaledi Morteza G.
Published: March 2003

Capillary electrophoresis with laser‐induced fluorescence (CE‐LIF) detection was used for evaluation of the effectiveness of delivery and fate of a model 25‐mer DNA‐based phosphorothiate antisense drug in cells. The antisense molecule was delivered to the cells through a simple incubation and by using a cationic liposome (Cytofectin GS 3815). The cationic lipid interacted with the negatively charged antisense to form a more positively charged complex. It was observed that uptake of the liposome‐antisense complex by the cell was dependent on concentration of lipid, duration of transfection, and the cell type. The antisense drug interacted with intracellular components such as proteins and additional steps were needed to quantify the free antisense. Proteinase‐K was able to release antisense from proteins. However, the addition of sodium dodecyl sulfate (SDS) to the sample or running buffer was more effective than Proteinase‐K to release both naked and liposome‐bound antisense from the cellular materials. Analysis of single HeLa cells for uptake of the unbound and liposome‐complexed antisense revealed averages of 8.9×10‐19 moles and 4.9×10‐18 moles, respectively. The amount of uptake, however, varied greatly among individual cells and depended on the delivery method. With liposome‐mediated delivery, the relative standard deviation (RSD) for the amount of antisense in individual cells was 130%, while the variation was much smaller (RSD = 45%) when the cells were incubated with the unbound antisense. These uptake variations agreed with those obtained from flow cytometry analysis.
Separation of capsular polysaccharide K4 and defructosylated K4 derived disaccharides by high‐performance capillary electrophoresis and high‐performance liquid chromatography
Authors: Volpi Nicola
Published: March 2003

A rapid, highly sensitive and reproducible high‐performance capillary electrophoresis (HPCE) method (electrokinetic chromatography with sodium dodecyl sulfate) is described for the determination of disaccharides present in the polysaccharide from the uropathogenic Escherichia coli K4 bacteria (05:K4:H4) and its defructosylated product. Following chondroitinase digestion of K4 and its derivative, the two disaccharides, ΔHexAFrc‐GalNAc for K4 and δHexA‐GalNAc for defructosylated K4, are separated and readily determined within 20 min on an uncoated fused‐silica capillary using normal polarity at 20 kV and detection at 230 nm. Comparison was made by separation of these two disaccharides in isocratic strong‐anion exchange HPLC. A linear relationship was found for the two unsaturated disaccharides over a wide range of concentrations, from approximately 0.5 to 5 μg for high‐performance liquid chromatography (HPLC) and from approximately 0.06 to 0.3 μg for HPCE. The HPCE separation produced a greater detection sensitivity (about 10 times greater) than HPLC. The described methods were used to evaluate the defructosylation process of K4 under drastic acid conditions. Good correspondence was found for the amount of unsaturated disaccharides for the two techniques.
Migration order of dipeptide and tripeptide enantiomers in the presence of single isomer and randomly sulfated cyclodextrins as a function of pH
Authors: Süß Falko , Sänger‐van de Griend Cari E. , Scriba Gerhard K. E.
Published: March 2003

The present study was conducted in order to evaluate the cyclodextrin (CD)‐mediated chiral separation of peptide enantiomers as uncharged analytes at pH 5.3 using randomly sulfated β‐cyclodextrin, heptakis‐6‐sulfato‐β‐CD and heptakis‐(2,3‐diacetyl‐6‐sulfato)‐β‐CD as chiral selectors. Although less effective compared to stronger acidic conditions, the CDs proved to be suitable chiral selectors for the present set of peptides at pH 5.3. The carrier ability of the negatively charged CDs upon reversal of the applied voltage may also be exploited leading to a reversal of the migration order. In addition, reversal of the enantiomer migration order upon increasing the buffer pH from 2.5 to 5.3 was also observed for Ala‐Tyr in the presence of randomly sulfated β‐CD, for Ala‐Phe, Ala‐Tyr, Phe‐Phe, Asp‐PheNH2 and Gly‐Ala‐Phe in the presence of heptakis‐6‐sulfato‐β‐CD, and for Phe‐Phe and Ala‐Leu in the presence of heptakis‐(2,3‐diacetyl‐6‐sulfato)‐β‐CD. The migration behavior could be explained on the basis of the complexation constants and the mobilities of the peptide‐CD complexes. While a change in the affinity pattern of the CDs upon increasing the pH was observed for some peptides, complex mobility was the primary factor for other peptide‐CD combinations affecting the enantiomer migration order at the two pH values studied.
Chiral separation of 3,4‐methylenedioxymeth‐ amphetamine and related compounds in clandestine tablets and urine samples by capillary electrophoresis/fluorescence spectroscopy
Authors: Huang Yu‐San , Liu Ju‐Tsung , Lin Li‐Chang , Lin Cheng‐Huang
Published: March 2003

The R‐(–)‐ and S‐(+)‐isomers of 3,4‐methylenedioxymethamphetamine (MDMA) and its metabolite 3,4‐methylenedioxyamphetamine (MDA) were prepared, identified by gas chromatography/mass spectrometry (GC/MS) and then used as standards in a series of capillary electrophoresis (CE) experiments. Using these R‐(–)‐ and S‐(+)‐isomers, the distribution of (RS)‐MDA and (RS)‐MDMA stereoisomers in clandestine tablets and suspect urine samples were identified. Several electrophoretic parameters, such as the concentration of β‐cyclodextrin used in the electrophoretic separation and the amount of organic solvents required for the separation, were optimized.
Determination of kanamycin by electrophoretically mediated microanalysis with in‐capillary derivatization and UV detection
Authors: Kaale Eliangiringa , Van Schepdael Ann , Roets Eugène , Hoogmartens Jos
Published: March 2003

An electrophoretically mediated microanalysis (EMMA) approach, used to perform on‐line chemistry between two small molecules, has been characterized and optimized. The plug‐plug type EMMA method involved electrophoretic mixing and subsequent reaction of nanoliter plugs of kanamycin‐containing samples and 1,2‐phthalic dicarboxaldehyde and mercaptoacetic acid within the confines of the capillary column, which acts as a microreactor. Analyses were performed by pressure‐injecting a plug of kanamycin sandwiched in two reagent plugs. A potential of 375 Vcm‐1 was then applied to electrophoretically mix the two reactants, and an incubation time of up to 5 min allowed the reaction to proceed prior to the application of a separation potential of 588 Vcm‐1. UV detection was at 335 nm. The background electrolyte was 30 mM sodium tetraborate at pH 10.0, containing 16% of methanol. The method was validated in terms of linearity, limits of quantitation and detection, and precision. The method allows determination of kanamycin in bulk samples as a fully automated procedure.
Open‐tubular capillary electrochromatography using a polymeric surfactant coating
Authors: Kamande Mary W. , Kapnissi Constantina P. , Zhu Xiaofeng , Akbay Cevdet , Warner Isiah M.
Published: March 2003

A stable polyelectrolyte multilayer (PEM) coating was investigated for use in open‐tubular capillary electrochromatography (o‐CEC). In this approach, the PEM consisted of the cationic polymer of a quaternary ammonium salt, poly(diallyldimethylammonium chloride) and the anionic polymeric surfactant, poly(sodium undecylenic sulfate). Both the cationic and anionic polymers were physically adsorbed to the surface of a fused‐silica capillary by use of a simple coating procedure. This procedure involved an alternate rinse of the positively and negatively charged polymers. The performance of the PEM coating as a dynamic stationary phase was evaluated by use of electrochromatographic experiments and showed good selectivity for both phenols and benzodiazepines. Reproducibility of the PEM coating was also evaluated by calculating the relative standard deviations (RSDs) of the electroosomotic flow (EOF). The run‐to‐run and capillary‐to‐capillary RSD values of the EOF were less than 1.5%. The endurance of the coating was more than 100 runs. The importance of the PEM coating was illustrated by comparing separations on a bare uncoated capillary with the coated capillary. In addition, the chromatographic performance using o‐CEC and micellar electrokinetic chromatography (MEKC) was compared for the separation of benzodiazepines.
Molecularly imprinted polymer films grafted from porous or nonporous silica: Novel affinity stationary phases in capillary electrochromatography
Authors: Quaglia Milena , De Lorenzi Ersilia , Sulitzky Claudia , Caccialanza Gabriele , Sellergren Börje
Published: March 2003

Molecularly imprinted composite materials were evaluated as chiral stationary phases in capillary electrochromatography (CEC). These consisted of spherical silica particles of different sizes and of different porosities, containing a surface‐immobilized layer of molecularly imprinted polymer (MIP) targeted to bind L‐phenylalanine anilide. Fused silica capillaries were packed over a length of 8.5 cm, using a pneumate amplification pump, and the stationary phase thus obtained was tested with respect to its electrochromatographic performance. The electroendosmotic flow (EOF) mobility was evaluated with respect to the content of grafted polymer, as well as the ionic strength and the acetonitrile content of the electrolyte. Moreover, the influence of the layer thickness and of the stationary phase porosity on the performance and on the sample load capacity was investigated. The packings exhibited different relative efficiencies for the two enantiomers. The results were discussed in terms of differencies in accessibility to the binding sites of the packings and of the mechanism of EOF generation. In the wide context of the different approaches so far proposed for MIP stationary phases in CEC, these materials can be a good alternative, worthy of further development and application, not restricted to chiral separations.
Alkyl‐modified siloxanes as pseudostationary phases for electrokinetic chromatography
Authors: Schulte Shannon , Palmer Christopher P.
Published: March 2003

Anionic siloxane polymers with novel linker arm structures have been synthesized and characterized with respect to their performance and selectivity as pseudophases for electrokinetic chromatography. The linker arm between the siloxane backbone and the sulfonate head group is shorter and does not have the tertiary amine structure found in the siloxane pseudophases studied previously. This change in the linker arm structure and chemistry has dramatic effects on the chemical selectivity of the pseudophases. Linear solvation energy relationship (LSER) studies show that the greatest contributor to the difference in selectivity is that the new polymers are not as nonpolar as those previously studied. This result indicates that siloxane polymers are not by their nature more nonpolar or hydrophobic than other pseudophases. The LSER studies also demonstrate that siloxane pseudophases have a strong tendency to accept hydrogen bonds that cannot be attributed to the presence of the tertiary amine in the linker arm.
Direct coupling of micellar electrokinetic chromatography to mass spectrometry using a volatile buffer system based on perfluorooctanoic acid and ammonia
Authors: Petersson Patrik , Jörntén‐Karlsson Magnus , Stålebro Maria
Published: March 2003

Direct coupling of micellar electrokinetic chromatography (MEKC) to mass spectrometry (MS) without employing partial filling is considered to be a challenge. One way of solving the problem would be the use of an MS‐compatible surfactant. In the present study, the applicability of a series of surfactants (sodium dodecyl sulfate (SDS), lauric acid, cholic acid and perfluorated carboxylic acids) have been investigated both in terms of separation performance and MS compatibility. It was found that a MEKC system based on perfluorooctanoic acid (PFOA) and ammonia gave excellent results. The separation performance of the suggested system is comparable to the one obtained with standard systems based on SDS and sodium borate buffer although the selectivity is different. The electrospray ionization MS signal of the analytes is not seriously suppressed even at a PFOA concentration of 100 mM. Clusters are formed but their intensities are relatively low and comparable to those obtained with acetic acid. PFOA is volatile enough to allow long‐term use, 30 h of continuous use has been recorded without any signs of decreasing performance. After use residual PFOA is easily removed from the ion‐source (no memory effects). Furthermore, quantitation of trace impurities is possible at 25 ppb level when employing selected ion monitoring.
Monitoring of Polymorphism – From Detection to Quantification
Authors: Giron D.
Published: March 2003

The polymorphic behavior of organic substances is driven by thermodynamic and kinetic factors. Therefore several solid phases may coexist. Since the properties of the solid state may be extremely relevant for the quality of medicines, the International Conference of Harmonization (ICH) requires a polymorphic study for new active ingredients. The different steps of investigations and the analytical methods which are used during the development phase in order to achieve adequately this challenging task, from detection to quantification are emphasized.
Crystallization of Pharmaceutical Compounds Polymorphs, Pseudo‐Polymorphs and Particle Formation
Authors: Beckmann W.
Published: March 2003

The crystallization of a pharmaceutical compound, of an active pharmaceutical ingredient, is governed by a set of interdependent requirements. Two of the most prominent parameters are polymorphism and crystal or particle size distribution. The requirements for these parameters are governed by regulatory issues as well as by demands arising from the formulation process and the use of the drug substance. This paper focuses on the optimal choice of the modification of the active pharmaceutical ingredient and on the controlled crystallization of the polymorph chosen. These requirements are checked against the processes used to control particle size.
Development of a New Coating Process in Pharmaceutical Industry by Crystallization
Authors: Kim J.‐W. , Ulrich J.
Published: March 2003

This study concentrates on the development of a new coating technology, which is applied via a solution crystallization process using heterogeneous seeds. Hemi‐sphere pastilles of different materials (seed particles) and isomaltulose solution are used as core materials and coating materials, respectively. The surface nucleation and the growth rate on the surface of seed particles are investigated. An effective crystalline coating, which is very compact in structure without cracking and uniform in shape, is achieved. The growth rate and the quality of coating are related to the degree of subcooling, the retention time and the surface characteristic of the used seed particles. This study focuses on how crystalline‐formed coatings are formed by a crystallization process, how an operating variable effects the quality of coatings and how a good quality of a coating can be achieved.
Polymorphism and Liquid‐Liquid Demixing in Supersaturated Drug Solution
Authors: Lafferrère L. , Hoff C. , Veesler S.
Published: March 2003

In the field of pharmaceutical compound crystallization, one of the challenging tasks is to control the nucleation and the polymorphism. With these objectives, it becomes clear that an important stage is the phase diagram determination of the considered substance. We have investigated the phase diagram of a pharmaceutical compound in a mixture of ethanol/water. We have observed and characterized, in this phase diagram, a solid‐solid (polymorphism) and a liquid‐liquid phase separation as a function of temperature and drug substance concentration.
Solubility Equilibria in Chiral Systems and Their Importance for Enantioseparation
Authors: Lorenz H. , Sapoundjiev D. , Seidel‐Morgenstern A.
Published: March 2003

Ternary solubility equilibria are studied for three chiral systems in various aqueous and nonaqueous solvents. The chosen systems were a pharmaceutical intermediate, threonine and mandelic acid. Measured solubility data are presented and the nature of the ternary solubility phase diagrams is described. On this basis possible procedures for a crystallization based enantioseparation are derived. Also, the impact of solubility equilibria on the resolution of racemates by liquid chromatography is analyzed and discussed for the systems under investigation. Finally, a hybrid approach coupling both separation techniques for an efficient chiral resolution is demonstrated by means of the fundamental solubility phase diagrams.
Micronization of Organic Materials by Crystallization with Compressed Gases
Authors: Kröber H. , Teipel U.
Published: March 2003

A pilot plant is presented, which has been built to prepare fine particles by the Precipitation with a Compressed Fluid Antisolvent (PCA process). This technique offers interesting applications for products, which are produced in small amounts, as certain pharmaceuticals or energetic materials. In this contribution the micronization of paracetamol and tartaric acid is presented. Liquid solutions of tartaric acid in acetone, ethanol and methanol/ethanol mixtures have been sprayed into supercritical carbon dioxide used as antisolvent. The mean particle size of the precipitated powder can be manipulated by changing the precipitation pressure and solvent type however the precipitation temperature has no significant influence on the particle size. Paracetamol is micronized from acetone, methanol and DMF and morphologies from needles to spheres were found depending on the solvent. The particle size was in the submicron range.
Recent Progress at Crystallization of Sugar
Authors: Bubnik Z. , Kadlec P. , Hinkova A.
Published: March 2003

This work is focused on the research and verification of new processes of sucrose crystallization in the sugar technology. A major part of the work deals with testing of different conditions at crystallization of sucrose either from sugar raw juice treated by micro‐ and ultrafiltration or from technical sugar solution extracted from continuous chromatographic separation. The equilibrium data were obtained by means of a crystallization test and the width of metastable zone was determined by the ultrasonic sensor. Juice thickening to demanded dry matter content was carried out on a climbing film evaporator under reduced pressure. Results approved possibility of sucrose crystallization from sugar juice without any previous exacting chemical procedure and thus reduce energy and environmental heftiness of sugar production.
Modeling of Sugar Crystallization through Knowledge Integration
Authors: Georgieva P. , Feyo de Azevedo S. , Gonçalves M.J. , Ho P.
Published: March 2003

This paper reports on the comparison of three modeling approaches that were applied to a fed batch evaporative sugar crystallization process. They are termed white box, black box, and grey box modeling strategies, which reflects the level of physical transparency and understanding of the model. White box models represent the traditional modeling approach, based on modeling by first principles. Black box models rely on recorded process data and knowledge collected during the normal process operation. Among various tools in this group an artificial neural networks (ANN) approach is adopted in this paper. The grey box model is obtained from a combination of first principles modeling, based on mass, energy and population balances, with an ANN to approximate three kinetic parameters ‐‐ crystal growth rate, nucleation rate and the agglomeration kernel. The results have shown that the hybrid modeling approach outperformed the other aforementioned modeling strategies.
Scaleup in Suspension Crystallization of Two Multi Compound Fatty Acid Mixtures
Authors: Lüdecke U. , Brendler L. , Ulrich J.
Published: March 2003

Every vegetable oil needs specific process parameters for separation. These have to be determined in experiments for distinct scales and process parameters. Subsequently, fractionations of a mixture of 12 and a mixture of 8 fatty acids were carried out with the objective of producing a cloud point of 8 to 5 °C in the unsaturated product fraction. The data are used to present an improved version of a separation coefficient. The process is streamlined by reducing the crystallization steps to a minimum and decreasing the yield of the higher melting fractions. The filtration step was performed in different scales of the filter units to find the limits. To optimize the separation of fatty acid mixtures further an additional sweating procedure was applied. The following study highlights the scaleup in suspension crystallization of the examined materials and varied process parameters.
Control of Polymorphs on the Crystallization of Glycine Using a WWDJ Batch Crystallizer
Authors: Igarashi K. , Sasaki Y. , Azuma M. , Noda H. , Ooshima H.
Published: March 2003

The control of crystal polymorphs was investigated using a WWDJ batch crystallizer and glycine as a model compound. The WWDJ batch crystallizer is a newly developed crystallizer, which is equipped with a slurry sprinkler named Wall Wetter fixed on the shaft of an impeller and a double‐deck jacket. When a conventional crystallizer was used, the unstable α‐form crystals were always obtained. However, when the WWDJ batch crystallizer was used, the stable γ‐form crystals were obtained. The appearance of different polymorphs depends on the cooling rate during the crystallization. The γ‐form crystals were obtained by slow cooling, while the α‐form was obtained by rapid cooling. It means that the solvent‐mediated transformation of glycine crystal polymorphs can be controlled by changing the cooling rate in the WWDJ crystallizer. These results were obtained due to the fact that the WWDJ batch crystallizer accelerates the dissolution of metastable crystals and the growth of stable crystals.
Simulation of shockwave propagation with a thermal lattice Boltzmann model
Authors: Feng ShiDe , Dong Ping , Tsutahara Michihisa , Takada Naoki
Published: March 2003

A two‐dimensional 19‐velocity (D2Q19) lattice Boltzmann model which satisfies the conservation laws governing the macroscopic and microscopic mass, momentum and energy with local equilibrium distribution order O(u4) rather than the usual O(u3) has been developed. This model is applied to simulate the reflection of shockwaves on the surface of a triangular obstacle. Good qualitative agreement between the numerical predictions and experimental measurements is obtained. As the model contains the higher‐order terms in the local equilibrium distribution, it performs much better in terms of numerical accuracy and stability than the earlier 13‐velocity models with the local equilibrium distribution accurate only up to the second order in the velocity u. Copyright © 2003 John Wiley & Sons, Ltd.
Development of an optimal hybrid finite volume/element method for viscoelastic flows
Authors: Aboubacar M. , Webster M. F.
Published: March 2003

A cell‐vertex hybrid finite volume/element method is investigated that is implemented on triangles and applied to the numerical solution of Oldroyd model fluids in contraction flows. Particular attention is paid to establishing high‐order accuracy, whilst retaining favourable stability properties. Elevated levels of elasticity are sought. The main impact of this study reveals that switching from quadratic to linear finite volume stress representation with discontinuous stress gradients, and incorporating local reduced quadrature at the re‐entrant corner, provide enhance stability properties. Solution smoothness is achieved by adopting the non‐conservative flux form with area integration, by appealing to quadratic recovered velocity‐gradients, and through consistency considerations in the treatment of the time term in the constitutive equation. In this manner, high‐order accuracy is maintained, stability is ensured, and the finer features of the flow are confirmed via mesh refinement. Lip vortices are observed for We>1, and a trailing‐edge vortex is also apparent. Loss of evolution and solution asymptotic behaviour towards the re‐entrant corner are also discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Optimal designs for estimating penetrance of rare mutations of a disease‐susceptibility gene
Authors: Gong Gail , Whittemore Alice S.
Published: March 2003

Many clinical decisions require accurate estimates of disease risks associated with mutations of known disease‐susceptibility genes. Such risk estimation is difficult when the mutations are rare. We used computer simulations to compare the performance of estimates obtained from two types of designs based on family data. In the first (clinic‐based designs), families are ascertained because they meet certain criteria concerning multiple disease occurrences among family members. In the second (population‐based designs), families are sampled through a population‐based registry of affected individuals called probands, with oversampling of probands whose families are more likely to segregate mutations. We generated family structures, genotypes, and phenotypes using models that reflect the frequencies and penetrances of mutations of the BRCA1/2 genes. We studied the effects of risk heterogeneity due to unmeasured, shared risk factors by including risk variation due to unmeasured genotypes of another gene. The simulations were chosen to mimic the ascertainment and selection processes commonly used in the two types of designs. We found that penetrance estimates from both designs are nearly unbiased in the absence of unmeasured shared risk factors, but are biased upward in the presence of such factors. The bias increases with increasing variation in risks across genotypes of the second gene. However, it is small compared to the standard error of the estimates. Standard errors from population‐based designs are roughly twice those from clinic‐based designs with the same number of families. Using the root‐mean‐square error as a measure of performance, we found that in all instances, the clinic‐based designs gave more accurate estimates than did the population‐based designs with the same numbers of families. Rough variance calculations suggest that clinic‐based designs give more accurate estimates because they include more identified mutation carriers. Genet Epidemiol 24:173–180, 2003. © 2003 Wiley‐Liss, Inc.
Removing phenotypic distribution assumptions from tests of linkage disequilibrium for quantitative traits
Authors: Alcaïs Alexandre , Abel Laurent
Published: March 2003

The transmission disequilibrium test (TDT) has become a family‐based method of reference to search for linkage disequilibrium (LD). Although it was first developed for dichotomous traits, numerous approaches have extended the TDT to quantitative phenotypes that either rely on regression or variance component techniques. Both of these approaches are based on some phenotypic distribution assumptions, the violation of which can lead to inflation of type I error rates, and derive information from phenotypic variability, so that their power is very low under some selection schemes (e.g., one‐tailed selection). We propose a new family‐based test of association for quantitative traits, denoted maximum‐likelihood‐binomial (MLB)‐QTDT, which addresses the two previous issues by incorporating a latent binary variable that captures the LD information between the marker allele and the quantitative phenotype. The method can be understood as a classical TDT for binary traits that would include pure affected and pure unaffected children, and the probability for a child to be affected or unaffected depends on his/her quantitative phenotypic value. Simulation studies under the null hypothesis show that the MLB‐QTDT provides very consistent type I errors even in small and/or selected samples. Under the alternative hypothesis, the MLB‐QTDT has good power to analyze one‐tailed selected samples, and performs as well as a classical approach in other designs. The MLB‐QTDT is a flexible distribution‐free method to test for LD with quantitative phenotypes in nuclear families, and can easily incorporate previous extensions developed in the context of family‐based association studies with binary traits. Genet Epidemiol 24:191–199, 2003. © 2003 Wiley‐Liss, Inc.
Does accounting for gene‐environment (G×E) interaction increase the power to detect the effect of a gene in a multifactorial disease?
Authors: Selinger‐Leneman Hana , Genin Emmanuelle , Norris Jill M. , Khlat Myriam
Published: March 2003

Despite tremendous efforts, few genes involved in the susceptibility for complex disorders have been identified. One explanation is that these disorders are a result of an interaction between genes and environment, and under such conditions, it may be difficult to measure the true genetic effect without accounting for the interaction. Umbach and Weinberg ([2000] Am. J. Hum. Genet. 66:251–261) proposed an association test which looks at the joint effects of genotype and environment, using case‐parent trios. In this study, we explore under which conditions accounting for G×E interaction enhances one's ability to detect the role of genetic factors in complex diseases. Using asymptotic power calculations, we investigate the power to detect the gene effect over varying exposure frequencies and different scenarios of G×E interaction. We show that for a given sample size, interaction scenario, and allele frequency, the actual gain in power while accounting for the interaction depends on the magnitude of the exposure frequency: the largest gains are seen for relatively low exposure frequencies. Moreover, a loss of power can be observed when the exposure is frequent and/or the exposure effect is strong. If we consider a gene with a disease allele frequency of 0.2, with no effect in the absence of exposure, an exposure with a 10‐fold increase risk and a G×E relative risk of 2, then when the exposure frequency is 0.1, accounting for G×E interaction increases the power to detect the gene effect in 200 trios by 10%; alternatively, when the exposure frequency is 0.9, it decreases the power by 15%. Genet Epidemiol 24:200–207, 2003. © 2003 Wiley‐Liss, Inc.
Regressive logistic and proportional hazards disease models for within‐family analyses of measured genotypes, with application to a CYP17 polymorphism and breast cancer
Authors: Cui Jisheng S. , Spurdle Amanda B. , Southey Melissa C. , Dite Gillian S. , Venter Deon J. , McCredie Margaret R.E. , Giles Graham G. , Chenevix‐Trench Georgia , Hopper John L.
Published: March 2003

Various statistical methods have been proposed to evaluate associations between measured genetic variants and disease, including some using family designs. For breast cancer and rare variants, we applied a modified segregation analysis method that uses the population cancer incidence and population‐based case families in which a mutation is known to be segregating. Here we extend the method to a common polymorphism, and use a regressive logistic approach to model familial aggregation by conditioning each individual on their mother's breast cancer history. We considered three models: 1) class A regressive logistic model; 2) age‐of‐onset regressive logistic model; and 3) proportional hazards familial model. Maximum likelihood estimates were calculated using the software MENDEL. We applied these methods to data from the Australian Breast Cancer Family Study on the CYP17 5′UTR T→C MspA1 polymorphism measured for 1,447 case probands, 787 controls, and 213 relatives of case probands found to have the CC genotype. Breast cancer data for first‐ and second‐degree relatives of case probands were used. The three methods gave consistent estimates. The best‐fitting model involved a recessive inheritance, with homozygotes being at an increased risk of 47% (95% CI, 28–68%). The cumulative risk of the disease up to age 70 years was estimated to be 10% or 22% for a CYP17 homozygote whose mother was unaffected or affected, respectively. This analytical approach is well‐suited to the data that arise from population‐based case‐control‐family studies, in which cases, controls and relatives are studied, and genotype is measured for some but not all subjects.Genet Epidemiol24:161–172, 2003. © 2003 Wiley‐Liss, Inc.
Variants of developmental genes (TGFA, TGFB3, and MSX1) and their associations with orofacial clefts: A case‐parent triad analysis
Authors: Jugessur Astanand , Lie Rolv T. , Wilcox Allen J. , Murray Jeffrey C. , Taylor Jack A. , Saugstad Ola D. , Vindenes Hallvard A. , Åbyholm Frank
Published: March 2003

We selected 262 case‐parent triads from a population‐based study of orofacial clefts in Norway, and examined variants of developmental genes TGFA, TGFB3, and MSX1 in the etiology of orofacial clefts. One hundred seventy‐four triads of cleft lip cases (CL±P) and 88 triads of cleft palate only cases (CPO) were analyzed. There was little evidence for an association of any of these genes with CL±P. The strongest association was a 1.7‐fold risk with two copies of the TGFB3‐CA variant (95% CI=0.9–3.0). Among CPO cases, there was a 3‐fold risk with two copies of the TGFA TaqI A2 allele, and no increase with one copy. Assuming this to be a recessive effect, we estimated a 3.2‐fold risk among babies homozygous for the variant (95% CI=1.1–9.2). Furthermore, there was strong evidence of gene‐gene interaction. While there was only a weak association of the MSX1‐CA variant with CPO, the risk was 9.7‐fold (95% CI=2.9–32) among children homozygous for both the MSX1‐CA A4 allele and the TGFA A2 allele. No association of CPO with the TGFA variant was seen among the other MSX1‐CA genotypes. In conclusion, no strong associations were found between CL±P and variants at these three genes. There was a possible recessive effect of the TGFA TaqI variant on the risk of CPO, with a 3‐fold risk among children homozygous for the variant. The effect of this TGFA genotype was even stronger among children homozygous for the MSX1‐CA A4 allele, raising the possibility of interaction between these two genes. Genet Epidemiol 24:230–239, 2003. © 2003 Wiley‐Liss, Inc.
A score for Bayesian genome screening
Authors: Daw E. Warwick , Wijsman Ellen M. , Thompson Elizabeth A.
Published: March 2003

Bayesian Monte Carlo Markov chain (MCMC) techniques have shown promise in dissecting complex genetic traits. The methods introduced by Heath ([1997], Am. J. Hum. Genet. 61:748–760), and implemented in the program Loki, have been able to localize genes for complex traits in both real and simulated data sets. Loki estimates the posterior probability of quantitative trait loci (QTL) at locations on a chromosome in an iterative MCMC process. Unfortunately, interpretation of the results and assessment of their significance have been difficult. Here, we introduce a score, the log of the posterior placement probability ratio (LOP), for assessing oligogenic QTL detection and localization. The LOP is the log of the posterior probability of linkage to the real chromosome divided by the posterior probability of linkage to an unlinked pseudochromosome, with marker informativeness similar to the marker data on the real chromosome. Since the LOP cannot be calculated exactly, we estimate it in simultaneous MCMC on both real and pseudochromosomes. We investigate empirically the distributional properties of the LOP in the presence and absence of trait genes. The LOP is not subject to trait model misspecification in the way a lod score may be, and we show that the LOP can detect linkage for loci of small effect when the lod score cannot. We show how, in the absence of linkage, an empirical distribution of the LOP may be estimated by simulation and used to provide an assessment of linkage detection significance. Genet Epidemiol 24:181–190, 2003. © 2003 Wiley‐Liss, Inc.