bluuebunny/crossref_metadata_2025_split huggingface dataset:
Micronization of Organic Materials by Crystallization with Compressed Gases
Authors: Kröber H. , Teipel U. 
Published: March 2003

AbstractA 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

AbstractThis 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

AbstractThis 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

AbstractEvery 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

AbstractThe 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

AbstractA 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

AbstractA 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

AbstractMany 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

AbstractThe 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

AbstractDespite 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

AbstractVarious 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

AbstractWe 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

AbstractBayesian 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.
A general class of association tests for family‐based data using weight functions
Authors: Liu Xin , Gordon Derek 
Published: March 2003

AbstractBased on the symmetry of transmitted/nontransmitted alleles from heterozygous parents under the null hypothesis of no association, the work proposed here establishes a general statistical framework for constructing association tests with data from nuclear families with multiple affected children. A class of association tests is proposed for both diallelic and multiallelic markers. The proposed test statistics reduce to the transmission disequilibrium test for trios, to Tsu by Martin et al. ([1997] Am. J. Hum. Genet. 61:439–448) for affected sib pairs, and to the pedigree disequilibrium test by Martin et al. ([2000] Am. J. Hum. Genet. 67:146–154); [2001] Am. J. Hum. Genet. 68:1065–1067) when using affected sibships only. The association test used in simulation and for real data (sitosterolemia) is the one which has the best overall power in detecting association. This association test is generally more powerful than the association tests proposed by Martin et al. ([2000] Am. J. Hum. Genet. 67:146–154); [2001] Am. J. Hum. Genet. 68:1065–1067) when using only affected sibships. For the sitosterolemia data set, the association test has its most significant result (P‐value=0.0012) for the marker locus on the same bacterial artificial chromosome as the disease locus. Genet Epidemiol 24:208–219, 2003. © 2003 Wiley‐Liss, Inc.
Kin‐cohort evaluation of relative risks of genetic variants
Authors: Saunders Catherine L. , Begg Colin B. 
Published: March 2003

AbstractThe kin‐cohort study, an embedded retrospective cohort of first‐degree relatives of probands, has been used frequently in conjunction with case‐control studies to evaluate penetrance of high‐risk genotypes. However, in principle, the kin‐cohort approach can be used in conjunction with a case‐control study in which family history data are carefully recorded to examine and validate the observed association of any candidate genotype with disease. Its utility for this purpose is governed by the relative efficiency of the kin‐cohort analysis to test hypotheses about the relevant genotype‐disease odds ratios, which in turn depends strongly on various factors, notably the magnitude of the disease incidence rate and the prevalence of the aberrant genotype. In this study, we compare the efficiencies of the two analytic approaches, case‐control vs. kin‐cohort, and illustrate the results in the context of cancer epidemiology. The kin‐cohort analysis can provide substantial, important supplementary information for relatively common cancers such as breast, lung, colorectal, and prostate, and is also relatively efficient in general for the evaluation of the stronger and more rare genetic risk factors. Genet Epidemiol 24:220–229, 2003. © 2003 Wiley‐Liss, Inc.
Microglia activation influences dye coupling and Cx43 expression of the astrocytic network
Authors: Faustmann Pedro M. , Haase Claus G. , Romberg Sabine , Hinkerohe Daniel , Szlachta Dominika , Smikalla Dirk , Krause Dorothee , Dermietzel Rolf 
Published: March 2003

AbstractUnder inflammatory conditions, activated microglia are capable of producing proinflammatory cytokines that are reported to influence cell‐to‐cell communication. The present study was performed to evaluate the influence of microglial activation on the coupling efficiency of the astroglial network. Primary astrocyte cultures of newborn rats were cocultured with either 5% (M5) or 30% (M30) microglia. Microglial activation (rounded phagocytotic phenotype) was investigated using the monoclonal anti‐ED1 antibody, and immunofluorescence with a polyclonal anti‐Cx43 antibody was used to study astroglial Cx43 expression and distribution. Functional coupling of astrocytes was evaluated by monitoring the transfer of microinjected Lucifer yellow into neighboring cells. The data obtained can be summarized as follows: astroglia/M30 cocultures contained significantly fewer resting microglia and significantly more activated microglia than the M5 cocultures; significantly reduced astroglial Cx43 staining was found in M30 cocultures concurrently with a reduced number of dye coupled astrocytes; and the positive correlation of percent activated microglia with reduced astroglial Cx43 expression was highly significant, indicating that the degree of intercellular communication in the astroglial network may be modulated by the activation of microglia under in vitro conditions. GLIA 42:101–108, 2003. © 2003 Wiley‐Liss, Inc.