bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a novel diffusion‐based method to estimate the size of the aggregated Aβ species responsible for neurotoxicity
Authors: Wang Steven S.‐S. , Becerra‐Arteaga Alejandro , Good Theresa A. 
Published: September 2002

Abstractβ‐Amyloid peptide (Aβ) is the primary protein component of senile plaques in Alzheimer's disease and is believed to be responsible for the neurodegeneration associated with the disease. Aβ is toxic only when aggregated, however, the size and structure of the aggregated species associated with toxicity is unknown. In the present study, we developed a diffusion‐based method to simultaneously separate and detect the biological activity of toxic Aβ oligomers and used the method to examine the relationship between size of aggregated protein and toxicity to SH‐SY5Y cells. From these measurements, the effective diffusivity and hydrodynamic radius of the toxic oligomeric species of Aβ could be determined. A sensitivity analysis was performed to examine the effects of model assumptions used in data analysis on the effective diffusivity calculated. The method provides a new estimate of the size of small toxic Aβ species associated with fibril formation. This work contributes to our understanding of the relationship between Aβ structure and toxicity and with further refinements may aid in our ability to design agents which alter the Aβ aggregation/dissociation processes associated with neurotoxicity. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 50–59, 2002.
Integrated reactor concepts for the enzymatic kinetic synthesis of cephalexin
Authors: Schroën C. G. P. H. , Nierstrasz V. A. , Bosma R. , Kroon P. J. , Tjeerdsma P. S. , DeVroom E. , VanderLaan J. M. , Moody H. M. , Beeftink H. H. , Janssen A. E. M. , Tramper J. 
Published: September 2002

AbstractIntegrated process concepts for enzymatic cephalexin synthesis were investigated by our group, and this article focuses on the integration of reactions and product removal during the reactions. The last step in cephalexin production is the enzymatic kinetic coupling of activated phenylglycine (phenylglycine amide or phenylglycine methyl ester) and 7‐aminodeacetoxycephalosporanic acid (7‐ADCA). The traditional production of 7‐ADCA takes place via a chemical ring expansion step and an enzymatic hydrolysis step starting from penicillin G. However, 7‐ADCA can also be produced by the enzymatic hydrolysis of adipyl‐7‐ADCA. In this work, this reaction was combined with the enzymatic synthesis reaction and performed simultaneously (i.e., one‐pot synthesis). Furthermore, in situ product removal by adsorption and complexation were investigated as means of preventing enzymatic hydrolysis of cephalexin. We found that adipyl‐7‐ADCA hydrolysis and cephalexin synthesis could be performed simultaneously. The maximum yield on conversion (reaction) of the combined process was very similar to the yield of the separate processes performed under the same reaction conditions with the enzyme concentrations adjusted correctly. This implied that the number of reaction steps in the cephalexin process could be reduced significantly. The removal of cephalexin by adsorption was not specific enough to be applied in situ. The adsorbents also bound the substrates and therewith caused lower yields. Complexation with β‐naphthol proved to be an effective removal technique; however, it also showed a drawback in that the activity of the cephalexin‐synthesizing enzyme was influenced negatively. Complexation with β‐naphthol rendered a 50% higher cephalexin yield and considerably less byproduct formation (reduction of 40%) as compared to cephalexin synthesis only. If adipyl‐7‐ADCA hydrolysis and cephalexin synthesis were performed simultaneously and in combination with complexation with β‐naphthol, higher cephalexin concentrations also were found. In conclusion, a highly integrated process (two reactions simultaneously combined with in situ product removal) was shown possible, although further optimization is necessary. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 144–155, 2002.
Simulation of algae growth in a bench‐scale bubble column reactor
Authors: Wu Xiaoxi , Merchuk Jose C. 
Published: September 2002

AbstractThe growth of the marine red microalga Porphyridium sp. in a bubble‐column photobioreactor was simulated. The proposed model constitutes a dynamic integration of the kinetics of photosynthesis and photoinhibition with the fluid dynamics of the bubble column, including the effects of shear stress on the kinetics of growth. The kinetic data used in the model were obtained in independent experiments run in a thin‐film photobioreactor with defined light/dark cycles. The maintenance term was modified to take into account the effects of liquid flow in the bioreactor on the growth rate. A hybrid method proposed for the approximate solution of the equations gave an appreciable reduction of the calculation time. Extrapolations of the model indicated the possibility of predicting the optimal diameter for an assembly of bubble column photobioreactors. Satisfactory fit was found with the experimental results of biomass growth in a 13‐liter bubble column. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 156–168, 2002.
Determination of oxygen gradients in engineered tissue using a fluorescent sensor
Authors: Kellner Karin , Liebsch Gregor , Klimant Ingo , Wolfbeis Otto S. , Blunk Torsten , Schulz Michaela B. , Göpferich Achim 
Published: September 2002

AbstractNutrient and oxygen supply of cells are crucial to tissue engineering in general. If a sufficient supply cannot be maintained, the development of the tissue will slow down or even fail completely. Previous studies on oxygen supply have focused on measurement of oxygen partial pressures (pO2) in culture media or described the use of invasive techniques with spatially limited resolution. The experimental setup described here allows for continuous, noninvasive, high‐resolution pO2 measurements over the cross‐section of cultivated tissues. Applying a recently developed technique for time‐resolved pO2 sensing using optical sensor foils, containing luminescent O2‐sensitive indicator dyes, we were able to monitor and analyze gradients in the oxygen supply in a tissue over a 3‐week culture period. Cylindrical tissue samples were immobilized on top of the sensors. By measuring the luminescence decay time, two‐dimensional pO2 distributions across the tissue section in contact with the foil surface were determined. We applied this technique to cartilage explants and to tissue‐engineered cartilage. For both tissue types, changes were detected in monotonously decreasing gradients of pO2 from the surface with high pO2 to minimum pO2 values in the center of the samples. Nearly anoxic conditions were observed in tissue constructs (∼0 Torr) but not in excised cartilage discs (∼20 Torr) after 1 day. Furthermore, the oxygen supply seemed to strongly depend on cell density and cell function. Additionally, histological analysis revealed a maximum depth of ∼1.3 mm of regular cartilage development in constructs grown under the applied culture conditions. Correlating analytical and histological analysis with the oxygen distributions, we found that pO2 values below 11 Torr might impair proper tissue development in the center. The results illustrate that the method developed is an ideal one to precisely assess the oxygen demand of cartilage cultures. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 73–83, 2002.
Yield prediction and stoichiometry of multi‐step biodegradation reactions involving oxygenation
Authors: Yuan Zhiwen , VanBriesen Jeanne M. 
Published: September 2002

AbstractMicroorganisms can initiate the degradation of organic compounds by oxygenation reactions that require the investment of energy and electrons. This diversion of energy and electrons away from synthesis reactions leads to decreased overall cell yields. A thermodynamic method was developed that improves the accuracy of cell yield prediction for compounds degraded through pathways involving oxygenation reactions. This method predicts yields and stoichiometry for each step in the biodegradation pathway, thus enabling modeling a multi‐step biodegradation process in which oxygenations occur and intermediates may persist. EDTA and benzene biodegradation are presented as examples. The method compares favorably with other yield prediction methods while providing additional information of yields for intermediates produced in the degradation pathway. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 100–113, 2002.
The potential for establishment of axial temperature profiles during solid‐state fermentation in rotating drum bioreactors
Authors: Mitchell David A. , Tongta A. , Stuart D. M. , Krieger N. 
Published: September 2002

AbstractThe mixing and heat transfer phenomena within rotating drum bioreactors (RDBs) used for solid‐state fermentation processes are poorly studied. The potential for the establishment of axial temperature gradients within the substrate bed was explored using a heat transfer model. For growth of Aspergillus oryzae on wheat bran within a 24 L RDB with air at a superficial velocity of 0.0023 m s−1 and 15% relative humidity, the model predicts an axial gradient between the air inlet and outlet of 2°C during rapid growth, compared to experimental axial temperature gradients of between 1 and 4°C. Undesirably high temperatures occur throughout the bed under these operating conditions, but the model predicts that good temperature control can be achieved using humid air (90% relative humidity) at superficial velocities of 1 m s−1 for a 204 L RDB. For a 2200 L RDB, good temperature control is predicted with superficial velocities as low as 0.4 m s−1 with the airflow being switched from 90% to 15% relative humidity whenever the temperature at the outlet end of the drum exceeds the optimal temperature for growth. This work suggests that significant axial temperature gradients can arise in those RDBs that lack provision for axial mixing. It is therefore advisable to use angled lifters within RDBs to promote axial mixing. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 114–122, 2002
Selective separation of cis‐trans geometrical isomers of β‐carotene via CO2 supercritical fluid extraction
Authors: Gamlieli‐Bonshtein Iris , Korin Eli , Cohen Smadar 
Published: September 2002

AbstractWe investigated a novel method for the selective separation of β‐carotene isomers from a freeze‐dried powder of the algae Dunaliella bardawil using supercritical fluid extraction. The separation method relies on the different dissolution rate of the 9Z and all‐E isomers of β‐carotene in SC‐CO2. At first, the equilibrium solubility of the two isomers in SC‐CO2 was determined at the extraction conditions of 44.8 MPa and 40°C. The solubility of the 9Z isomer was found to be nearly 4 times higher than that of the all‐E isomer (1.92 × 10−5 g all‐E isomer/g CO2 compared to 7.64 × 10−5 g 9Z isomer/g CO2). When supercritical fluid extraction was applied to a carotenoid concentrate from the algae (29 wt% β‐carotene) or a freeze‐dried powder of the algae (3.1% β‐carotene), a selective separation of the 9Z/all‐E isomers of β‐carotene was obtained. Thirty‐nine percent recovery of β‐carotene with 80% purity of 9Z isomer was achieved at the initial stages of extraction (40 mL CO2). The extraction rate of β‐carotene from the freeze‐dried algae powder was slower than that from the carotenoid concentrate, resulting in a reduction in the recovery and purity of the 9Z isomer. This indicates that even at the initial stage of the extraction the internal mass resistance is significant. Isomer purity and recovery could be enhanced upon grinding of the algae powder. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 169–174, 2002.
Sensitivity function‐based model reduction: A bacterial gene expression case study
Authors: Smets Ilse , Bernaerts Kristel , Sun Jun , Marchal Kathleen , Vanderleyden Jos , Van Impe Jan 
Published: September 2002

AbstractMathematical models used to predict the behavior of genetically modified organisms require 1) a (rather) large number of state variables, and 2) complicated kinetic expressions containing a large number of parameters. Since these models are hardly identifiable and of limited use in model‐based optimization and control strategies, a generic methodology based on sensitivity function analysis is presented to reduce the model complexity at the level of the kinetics, while maintaining high prediction power. As a case study to illustrate the method and results obtained, the influence of the dissolved oxygen concentration on the cytN gene expression in the bacterium Azospirillum brasilense Sp7 is modeled. As a first modeling approach, available mechanistic knowledge is incorporated into a mass balance equation model with 3 states and 14 parameters. The large differences in order of magnitude of the model parameters identified on the available experimental data indicate 1) possible structural problems in the kinetic model and, associated with this, 2) a possibly too high number of model parameters. A careful sensitivity function analysis reveals that a reduced model with only seven parameters is almost as accurate as the original model. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 195–200, 2002.
Operational intensification by direct product sequestration from cell disruptates: Application of a pellicular adsorbent in a mechanically integrated disruption‐fluidised bed adsorption process
Authors: Jahanshahi Mohsen , Sun Yan , Santos Everaldo , Pacek Andrzej , Teixera Franco Telma , Nienow Alvin , Lyddiatt Andrew 
Published: September 2002

AbstractA novel prototype adsorbent, designed for intensified fluidised bed adsorption processes, was assembled by the emulsification coating of 4% (w/v) porous agarose upon a zirconia‐silica solid core. The adsorbent, designated ZSA (particle density 1.75 g/ml, maximum pellicle depth 40 μm), was subjected to physical and biochemical comparison with the performance of two commercial adsorbents (Streamline and Macrosorb K4AX). Bed expansion qualities and hydrodynamic characteristics (N, Daxl and Bo) of ZSA demonstrated a marked robustness in the face of elevated velocities (up to 550 cm/h) and biomass loading (up to 30% (ww/v)) disrupted yeast cells. Cibracron Blue derivatives of the pellicular prototype (ZSA‐CB), evaluated in the batch and fluidised bed recovery of glyceraldehyde 3‐phosphate dehydrogenase (G3PDH) from unclarified yeast disruptates, exhibited superior capacities and adsorption/desorption performance to the commercial derivatives. These advanced physical and biochemical properties facilitated a demonstration of the direct, mechanical coupling of bead‐milling and fluidised bed adsorption in a fully integrated process for the accelerated recovery of G3PDH from yeast. The generic application of such pellicular adsorbents and integrated processes to the recovery of labile, intracellular products is discussed. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 201–212, 2002.
General O‐glycosylation of 2‐furfuryl alcohol using β‐glucuronidase
Authors: Martin Brett D. , Welsh Eric R. , Mastrangelo Jonathan C. , Aggarwal Renu 
Published: September 2002

Abstractβ‐Glucuronidase from bovine liver is able to catalyze transfer of several carbohydrates to furfuryl alcohol, an acid‐sensitive diene, with transfer yields as high as 84%. Carbohydrates that were transferred in yields of 30% or higher include gluco‐, galacto‐, xylo‐, and fucopyranose. Small variations in the configuration of the substrate hydroxyls lead to large variations in the catalytic behavior of the enzyme in terms of both the initial reaction velocities and the final ratios of transfer‐to‐hydrolysis. The high transfer yields and surprising nonspecificity towards carbohydrate suggest that the enzyme may be a versatile tool for the general O‐glycosylation of dienic alcohols. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 222–227, 2002
Separating lysozyme from bacteriophage P22 in two‐phase aqueous micellar systems
Authors: Kamei Daniel T. , King Jonathan A. , Wang Daniel I. C. , Blankschtein Daniel 
Published: September 2002

AbstractThis communication demonstrates that two‐phase aqueous mixed (nonionic/ionic) micellar systems have the potential for improving the separation of proteins from viruses. Specifically, two separation experiments were performed to show that the addition of the anionic surfactant sodium dodecyl sulfate (SDS) to the two‐phase aqueous nonionic n‐decyl tetra(ethylene oxide) (C10E4) micellar system increases the yield of a model net positively charged protein, lysozyme, in the micelle‐rich phase from 75 to 95%, while still maintaining approximately the same yield of a model net negatively charged virus, bacteriophage P22, in the micelle‐poor phase (97% vs. 98%). © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 233–236, 2002.
In vitro gene expression dissected: chemostat surgery for Mycobacterium tuberculosis
Authors: James Brian W. , Bacon Joanna , Hampshire Tobias , Morley Kim , Marsh Philip D. 
Published: September 2002

AbstractA unique approach, combining defined and reproducible in vitro models with DNA microarrays, has been developed to study environmental modulation of mycobacterial gene expression. The gene expression profiles of samples of Mycobacterium tuberculosis, from independent chemostat cultures grown under defined and reproducible conditions, were found to be highly correlated. This approach is now being used to study the effect of relevant stimuli, such as limited oxygen availability, on mycobacterial gene expression. A modification of the chemostat culture system, enabling large‐volume controlled batch culture, has been developed to study starvation survival. Cultures of M. tuberculosis have been maintained under nutrient‐starved conditions for extended periods, with 106–107 bacilli surviving in a culturable state after 100 days. The design of the culture system has made it possible to control the environment and collect multiple time‐course samples to study patterns of gene expression. These studies demonstrate that it is possible to perform long‐term studies and obtain reproducible expression data using controlled and defined in vitro models. Copyright © 2002 John Wiley & Sons, Ltd.
The use of microarray technology for the analysis of Streptococcus pneumoniae
Authors: McCluskey Jackie , Dowson Christopher G. , Mitchell Timothy J. 
Published: September 2002

AbstractStreptococcus pneumoniae is an important human pathogen associated with pneumonia, septicaemia, meningitis and otitis media. It is estimated to result in over 3 million child deaths worldwide every year and an even greater number of deaths among the elderly. Prior to the complete sequencing of the genomes of S. pneumoniae TIGR4 (serotype 4) and S. pneumoniae R6 (serotype 2), we designed a custom miniarray consisting of 497 pneumococcal genes. The overall objectives of our microarray investigations were, first, to assess the genetic diversity between different S. pneumoniae serotypes, clinical isolates and also different Streptococcus species; second, we aimed to use microarray technology to examine the mechanisms by which environmental factors influence pneumococcal gene expression, and ultimately to further the understanding of how these changes in gene expression are achieved and how they may alter the virulence of the organism. Copyright © 2002 John Wiley & Sons, Ltd.
Microarrays for public health: genomic epidemiology of tuberculosis
Authors: Shafi Jamila , Andrew Peter W. , Barer Michael R. 
Published: September 2002

AbstractIn response to a large local school‐based outbreak of tuberculosis, we have been evaluating the utility of microarray bacterial genomic analysis in outbreak management. After initial comparison of the isolate from the index case with Mycobacterium tuberculosis H37Rv, it was possible to design robust PCRs directed towards strain‐specific deletions. Rapid PCR analysis of isolates proved valuable in determining whether or not other isolates were compatible with the outbreak strain and further microarray studies revealed genetic markers that could be used to discriminate between locally circulating strains. We suggest that this approach forms the basis for developing rapid local genotyping schemes applicable to M. tuberculosis and that application to other pathogens warrants consideration. Copyright © 2002 John Wiley & Sons, Ltd.
The curse of normalization
Authors: Wolkenhauer Olaf , Möller‐Levet Carla , Sanchez‐Cabo Fatima 
Published: September 2002

AbstractDespite its enormous promise to further our understanding of cellular processes involved in the regulation of gene expression, microarray technology generates data for which statistical pre‐processing has become a necessity before any interpretation of data can begin. The process by which we distinguish (and remove) non‐biological variation from biological variation is called normalization. With a multitude of experimental designs, techniques and technologies influencing the acquisition of data, numerous approaches to normalization have been proposed in the literature. The purpose of this short review is not to add to the many suggestions that have been made, but to discuss some of the difficulties we encounter when analysing microarray data. Copyright © 2002 John Wiley & Sons, Ltd.
Haemophilus influenzae microarrays: virulence and vaccines
Authors: Ali Tahir R. , Kroll J. Simon , Langford Paul R. 
Published: September 2002

AbstractIn 1995 the genome sequence of the Haemophilus influenzae KW20 (Rd) strain was published, the first available for a free‐living organism. The genome has been invaluable in global strategies to identify certain virulence‐related genes, e.g. those involved in LPS synthesis, and also essential genes, but there is a paucity of whole‐genome transcriptome studies. We have now constructed a whole‐genome array consisting of genes from Rd, additional genes identified in other strains of H. influenzae and controls (from eukaryotic sources and other bacteria). We intend to use this array in studies aimed at understanding the bacterium's basic metabolism and its response to changing environments; deciphering global regulatory networks (by comparison of wild‐type and mutant strains); and identifying genes expressed in vivo. The use of H. influenzae DNA arrays combined with proteomic approaches will enhance our understanding of the metabolism and virulence of the organism. Additionally, the genome sequence of a non‐typable H. influenzae strain is in progress. The sequence from this isolate will be invaluable not only in identifying potential novel antibiotic targets and putative vaccine candidates but also in the design of a microarray for genome‐typing purposes. Copyright © 2002 John Wiley & Sons, Ltd.
Can replication save noisy microarray data?
Authors: Wernisch Lorenz 
Published: September 2002

AbstractMicroarray experiments are multi‐step processes. At each step — the growth of cultures, extraction of mRNA, reverse transcription, labelling, hybridization, scanning, and image analysis — variation and error cannot be completely avoided. Estimating the amount of such noise and variation is essential, not only to test for differential expression but also to suggest at which level replication is most effective.Replication and averaging are the key to the estimation as well as the reduction of variability. Here I discuss the use of ANOVA mixed models and of analysis of variance components as a rigorous way to calculate the number of replicates necessary to detect a given target fold‐change in expression levels. Procedures are available in the package YASMA (http://www.cryst.bbk.ac.uk/wernisch/yasma.html) for the statistical data analysis system R (http://www.R‐project.org). Copyright © 2002 John Wiley & Sons, Ltd.