bluuebunny/crossref_metadata_2025_split huggingface dataset:
Omphalocele‐exstrophy‐imperforate anus‐spinal defects (OEIS) in triplet pregnancy after IVF and CVS
Authors: Shanske Alan L. , Pande Sumati , Aref Karim , Vega‐Rich Carlos , Brion Luc , Reznik Sandra , Timor‐Tritsch Ilan E. 
Published: June 2003

AbstractBACKGROUNDOmphalocele‐exstrophy‐imperforate anus‐spinal defects (OEIS) complex is a rare sporadic condition.CASEWe identified an infant with major malformations resembling OEIS. He was the product of a 30‐week triplet pregnancy conceived by in vitro fertilization (IVF) and evaluated by chorionic villi sampling (CVS). In this article, we review the possible pathogenetic mechanisms in this case, including IVF, multiple gestation, trauma to the uterus or uterine vessels following CVS, and placenta accreta.CONCLUSIONSWe conclude that the cumulative effects of all or some of these factors may have resulted in uteroplacental insufficiency adequate to produce this phenotype. This case provides additional evidence for the uterine vascular pathogenesis of OEIS complex in humans. Birth Defects Research (Part A) 67467–471, 2003. © 2003 Wiley‐Liss, Inc.
Cyclophosphamide, methotrexate, and cytarabine embropathy: Is apoptosis the common pathway?
Authors: Vaux Keith K. , Kahole Nathanial C.O. , Jones Kenneth Lyons 
Published: June 2003

AbstractBACKGROUNDCyclophosphamide (CP) is an alkylating agent primarily used for the treatment of autoimmune disease and cancer. The purpose of this article is two‐fold: first, to indicate that CP is a recognized human teratogen based on the features seen in a child prenatally exposed to this agent, as well as features seen in the previously reported cases; second, to suggest a common pathway to explain the similarity in the pattern of malformation seen in infants prenatally exposed to CP, in infants prenatally exposed to methotrexate (MTX), and in infants prenatally exposed to cytosine arabinoside (CA).METHODSCase report and review of the literature of an infant prenatally exposed to CP during the first trimester with a specific pattern of malformation. Features are compared to seven previous reports.RESULTSA common pattern of malformation is delineated including growth deficiency, hypoplasia of the calvarial and facial bones, and oligodactyly.CONCLUSIONSThe finding of a similar pattern of malformation among eight infants prenatally exposed to CP suggests that CP is a human teratogen. MTX and CA produce similar patterns of malformation in prenatally exposed infants despite very different pharmocologic profiles and metabolism. We speculate that the phenotype is a consequence of apoptosis in certain cells which are susceptible to the effects of the teratogen at specific stages of development. Birth Defects Research (Part A) 67403–408, 2003. Published 2003 Wiley‐Liss, Inc.
Substrate aggregation due to aerial hyphae during discontinuously mixed solid‐state fermentation with Aspergillus oryzae: Experiments and modeling
Authors: Schutyser M. A. I. , de Pagter P. , Weber F. J. , Briels W. J. , Boom R. M. , Rinzema A. 
Published: June 2003

AbstractSolid‐state fermentation (SSF) is prone to process failure due to channeling caused by evaporative cooling and the formation of an interparticle mycelium network. Mixing is needed to break the mycelium network and to avoid such failure. This study presents the first attempt to quantify and predict the effect of mycelium bonds on particle mixing and vice versa. We developed a novel experimental set‐up to measure the tensile strength of hyphal bonds in SSF: Aspergillus oryzae was cultivated between two wheat‐dough disks and the tensile strength of the aerial mycelium was measured with a texture analyzer. Tensile strength at different incubation times was related to oxygen consumption, to allow a translation to a rotating drum with A. oryzae cultivated on wheat grain. We performed several discontinuously mixed solid‐state fermentations in the drum fermentor and measured the number and size of grain‐aggregates remaining after the first mixing action. We integrated data on mycelium tensile strength into a previously developed two‐dimensional discrete‐particle model that calculates forces acting on individual substrate particles and the resulting radial‐particle movements. The discrete‐particle model predicted the quantity and size of the aggregates remaining after mixing successfully. The results show that the first mixing event in SSF with A. oryzae is needed to break mycelium to avoid aggregate formation in the grain bed, and not to distribute water added to compensate for evaporation losses, or smooth out temperature gradients. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 503–513, 2003.
CFD‐aided design of a dynamic filter for mammalian cell separation
Authors: Castilho Leda R. , Anspach F. Birger 
Published: June 2003

AbstractIn the present work, a rotating disk filter was designed for mammalian cell separation with the aim of avoiding both cell damage and membrane fouling. Different geometric and operational variables of the rotating disk filter were studied using computational fluid dynamics (CFD) by varying rotor radius, rotor angle, membrane–rotor distance, and angular velocity. The combinations of these variables followed a statistical design, so that an analysis of the CFD results provided correlations describing the average shear stress on the membrane surface and the maximum shear stress in the whole module as a function of the variables studied. Based on these correlations, and on the shear resistance levels of Chinese hamster ovary (CHO) and baby hamster kidney (BHK) cell lines, which were investigated using a cone‐and‐plate viscosimeter, it was possible to determine the geometry and angular velocity that would minimize both cell damage and membrane fouling. After construction, the filter was tested in filtration experiments at increasing permeate fluxes. Cell viability remained >90% for the duration of the experiments (2.5 h), and no indication of fouling was observed. It was shown that the designed dynamic filter is able to effectively avoid both cell damage and membrane fouling, and thus can be used for mammalian cell harvesting and perfusion. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 514–524, 2003.
Effect of membrane morphology on system capacity during normal flow microfiltration
Authors: Zydney Andrew L. , Ho Chia‐Chi 
Published: June 2003

AbstractUnderstanding the effects of membrane fouling on system capacity is critical for the successful design and scale‐up of microfiltration systems. The underlying morphology and structure of the microfiltration membrane can have a significant effect on system capacity by altering the rate and extent of fouling. Experimental data were obtained for system capacity during protein microfiltration using several model membranes with both homogeneous and composite structures. Data were compared with predictions of a new model that can account for both pore blockage and cake formation, and also includes the effects of membrane morphology on internal flow profiles within the membrane. Membranes with highly interconnected pores have a significantly higher capacity due to the reduction in flux decline arising from the fluid flow under and around any surface blockage. The model calculations are in good agreement with the flux decline data, allowing far more accurate predictions of system capacity than for the commonly used Vmax analysis. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 537–543, 2003.
Combined use of proteomic analysis and enzyme activity assays for metabolic pathway analysis of glycerol fermentation by Klebsiella pneumoniae
Authors: Wang Wei , Sun Jibin , Hartlep Michael , Deckwer Wolf‐Dieter , Zeng An‐Ping 
Published: June 2003

AbstractThe fed‐batch fermentation of glycerol to 1,3‐propanediol by Klebsiella pneumoniae displayed an unusual dynamic behavior that can be clearly divided into four distinct phases according to cell growth and CO2 evolution rate. Metabolism changed significantly during the different phases as reflected by the varied specific rates of substrate consumption and product formation. An assay of activities of the three initial enzymes of glycerol metabolism, namely glycerol dehydratase (GDHt), glycerol dehydrogenase (GDH), and 1,3‐propanediol‐oxidoreductase (PDOR), showed apparently different patterns of expression. To understand the culture dynamics and patterns of enzyme formation at a more systemic level we analyzed the expression patterns of intracellular proteins of K. pneumoniae from different phases of the fed‐batch fermentation using two‐dimensional gel electrophoresis (2DE). Two new enzymes, namely a phosphoenolpyruvate‐dependent dihydroxyacetone kinase (DHAK II) and a hypothetical oxidoreductase (HOR), which are directly related to glycerol metabolism and 1,3‐propanediol formation, were identified among the highly expressed proteins. The changes in expression of these new enzymes and several other proteins identified from the 2DE analysis helped to understand not only the dynamic behavior of the fed‐batch fermentation reported in this work but also some previously insufficiently understood phenomena related to this fermentation process. In particular, we demonstrated the combined use of proteomic analysis and enzyme activity assay data for metabolic pathway analysis and for a better identification of targets for bioprocess improvement. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 525–536, 2003.
Isolation of monocytes from human peripheral blood using immuno‐affinity expanded‐bed adsorption
Authors: Ujam L. B. , Clemmitt R. H. , Clarke S. A. , Brooks R. A. , Rushton N. , Chase H. A. 
Published: June 2003

AbstractA novel technique for the separation of monocytes from human peripheral blood preparations has been developed. The technique is based on the use of expanded‐bed adsorption and a solid perfluorocarbon derivatized with avidin or streptavidin for the indirect positive or negative capture of cells labeled with biotinylated monoclonal antibodies. The perfluorocarbon support was prepared and characterized and the contactor design and operating conditions, that enable cells to be selectively isolated, were investigated. Experiments consisted of applying an immunolabeled pulse of 1 × 108 peripheral blood mononuclear cells (PBMCs), isolated by density gradient centrifugation, directly onto a refrigerated expanded bed. The major cell types remaining were T‐lymphocytes, B‐lymphocytes, and monocytes. Monocytes could be positively adsorbed, following labeling with anti‐CD14 mAb, with a clearance of up to 89% and a depletion factor of 7.6. They could also be “eluted” using mechanical shear, with a 77% yield of the applied cells at a purity of 90% and ≥ 65% viability. Negative isolation of monocytes, following labeling of the other cells present with anti‐CD2, CD7, CD16, CD19, and CD56 mAbs, resulted in lymphocyte depletions of up to 81% with a monocyte enrichment factor of 3.8 and purity of 71%. The monocyte viability in the flowthrough was assessed to be > 95%. This combination of expanded‐bed adsorption and fluidizable affinity supports shows significant potential for the intensification of cell separations. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 554–566, 2003.
Precipitation of RNA impurities with high salt in a plasmid DNA purification process: Use of experimental design to determine reaction conditions
Authors: Eon‐Duval Alex , Gumbs Karlene , Ellett Christopher 
Published: June 2003

AbstractThe use of high salt solution to precipitate RNA in a pharmaceutical‐grade plasmid DNA purification process was investigated. Five antichaotropic salts were tested for their potential to precipitate RNA. Calcium chloride was by far the best precipitant with high RNA removal in a very short incubation time. Calcium chloride precipitation conditions were investigated at two stages of a plasmid purification process using experimental design techniques. The effect of up to five factors on RNA precipitation and plasmid recovery was assessed by statistical modeling. Optimized conditions for calcium chloride precipitation were then introduced to the plasmid purification process resulting in the efficient removal of most impurities (RNA, chromosomal DNA, proteins, and endotoxins). © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 544–553, 2003.
A new kinetic scheme for lysozyme refolding and aggregation
Authors: Buswell A. Mark , Middelberg Anton P. J. 
Published: June 2003

AbstractThe competing first‐ and third‐order reaction scheme for lysozyme is shown to not predict fed‐batch lysozyme refolding when the model is parameterized using independent batch experiments, even when variations in chemical composition during the fed‐batch experiment are accounted for. A new kinetic scheme is proposed that involves rapid partitioning between the alternative fates of refolding and aggregation, and which allows for aggregation via a sequential mechanism. The model assumes that monomeric lysozyme in different states, including native, is able to aggregate with intermediates, accounting for recent experimental evidence that native protein can be incorporated into aggregates and explaining why native protein in the refolding buffer reduces yield. Stopped‐flow light‐scattering measurements were used to measure the association rate for the sequential aggregation mechanism, and refolding rate constants were determined in a series of batch experiments designed to be “snapshots” of the composition during a fed‐batch experiment. The new kinetic scheme gave a good a priori prediction of fed‐batch refolding performance. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 567–577, 2003.
Magnitude and kinetics of rehydration influence the viability of dehydrated E. coli K‐12
Authors: Mille Yannick , Beney Laurent , Gervais Patrick 
Published: June 2003

AbstractThe influence of rehydration conditions on the recovery of Escherichia coli K‐12 was studied. The results showed that the osmotic pressure gradient of rehydration shock realized before plating greatly affected cell viability. When rehydration occurred quickly from an hyperosmotic level of 133 MPa in glycerol solution before slow rehydration by plating on an agar surface to reach initial osmotic pressure (1.4 MPa), bacterial viability was strongly related to the intensity of the hypo‐osmotic gradient used. Rehydration to 107 MPa resulted in a survival ratio of 41%, whereas strong rehydration to 1.4 MPa resulted in only 0.7% survival. These studies also demonstrated the influence of the rehydration kinetic on cell recovery. An optimal rehydration rate of 0.136 MPa · s−1 increased cell recovery by a factor of 40 when compared with the faster and slower rates of 131.6 MPa · s−1 and 0.006 MPa · s−1, respectively. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 578–582, 2003.
Hydrodynamic characteristics of immobilized cell beads in a liquid–solid fluidized‐bed bioreactor
Authors: Wu Jane‐Yii , Chen Kuo‐Cheng , Chen Chun‐Ting , Hwang Sz‐Chwun John 
Published: June 2003

AbstractThis study examined the hydrodynamic characteristics of a liquid–solid fluidized‐bed bioreactor using elastic particles (PVA gel beads) of various diameters as carriers. The drag coefficient‐Reynolds number, velocity‐voidage, and expansion index‐Reynolds number relationships observed during fluidization of PVA gel beads in a fluidized bed in our experiments were compared with the published results. Predictions made from previous correlations were examined with our new experimental findings, revealing the inadequacy of most of these correlations. Thus, new correlations describing the above‐mentioned relationships are suggested. The drag coefficient of immobilized cell beads is larger than that of free cell ones at the same Reynolds number because the surface of the immobilized cell beads is rougher. For multiparticle systems, the correction factor, f(ϵ), is a function of the falling gel bead properties (Reynolds number) as well as the fluidized gel bead properties (Archimedes number), and depend strongly on the bed voidage (ϵ). A new simple relation was developed to predict easily the ϵ value from 0.5–0.9 at 4,986 < Ar < 40,745 or 34 < Ret < 186. For all the immobilized cell beads used in this study, the prediction error of the bed voidage was less than 5% at ϵ > 0.5. The prediction equations in this study can be further applied to analyzing the hydrodynamic characteristics of a fluidized‐bed reactor using similar entrapped elastic particles as carriers. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 583–594, 2003.
Bidirectional expression units enable streptogramin‐adjustable gene expression in mammalian cells
Authors: Fux Cornelia , Fussenegger Martin 
Published: June 2003

AbstractSerious initiatives in gene therapy and tissue engineering require a sophisticated molecular toolbox combining DNA transfer technologies, human‐compatible transcription control systems, as well as compact and robust expression configurations. We have designed several versatile bidirectional expression cassettes that enable coadjustable expression of two desired transgenes in response to clinically licensed antibiotics of the streptogramin class (pristinamycin, Pyostacin®, Synercid®). The bidirectional expression modules consist of a central operator (PIR) that is specific for the pristinamycin‐dependent transactivator (PIT). Streptogramin‐adjustable binding of PIT to PIR transactivates two divergently oriented promoters and initiates transcription of the desired transgenes. The bidirectional expression module can be equipped with different minimal promoters and configured for expression of (1) two functional effector genes, (2) one effector gene and a reporter gene, (3) PIT and an effector gene to form a highly compact one‐vector expression arrangement. We have validated the streptogramin‐adjustable bidirectional expression technology in different basic and autoregulated expression configurations in a variety of mammalian and human cell lines. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 618–625, 2003.
Fed‐batch production of recombinant β‐galactosidase using the universal stress promoters uspA and uspB in high cell density cultivations
Authors: Prytz Ingela , Sandén Anna Maria , Nyström Thomas , Farewell Anne , Wahlström Åsa , Förberg Cecilia , Pragai Zoltan , Barer Mike , Harwood Colin , Larsson Gen 
Published: June 2003

AbstractA high‐level production system using the universal stress promoters uspA and uspB in a fed‐batch cultivation based on minimal medium was designed. In development it was shown that a standard industrial fed‐batch protocol could not be used for this purpose since it failed to induce the levels of product as compared to the basal level. Instead, a batch protocol followed by a low constant feed of glucose was shown to give full induction. The levels of the product protein, β‐galactosidase, corresponded to approximately 25% of the total protein. Higher levels were found using the uspA than uspB vectors where uspA showed considerably higher basal level. The data indicate that the σ70 regulated promoter, uspA, although affected by the alarmone guanosine tetraphosphate, ppGpp, worked partly in a similar manner to constitutive promoters. An industrial high cell density fed‐batch cultivation on the basis of the suggested fed‐batch protocol and the uspA promoter gave a final β‐galatosidase concentration of 7 g/L and a final cell concentration of 65 g/L. The heterogeneity in production of the individual cell was measured by fluorescence microscopy. The data show that there is a process time independent heterogeneity in production, which is suggested to be caused by heterogeneity in the substrate uptake rate of the individual cell. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 595–603, 2003.
Effect of oxygen concentration on nitrification and denitrification in single activated sludge flocs
Authors: Satoh Hisashi , Nakamura Yoshiyuki , Ono Hideki , Okabe Satoshi 
Published: June 2003

AbstractSimultaneous nitrification and denitrification (SND) was investigated in the single aeration tank of a municipal wastewater treatment plant. Microelectrode measurements and batch experiments were performed to test for the presence of SND. Microelectrodes recorded the presence of O2 concentration gradients in individual activated sludge flocs. When the O2 concentration in the bulk liquid was <45 μM, anoxic zones were detected within flocs with a larger diameter (approximately 3000 μm). The O2 penetration depth in the floc was found to be dependent on the O2 concentration in the bulk liquid. Nitrification was restricted to the oxic zones, whereas denitrification occurred mainly in the anoxic zones. The nitrification rate of the activated sludge increased with increasing O2 concentration in the bulk liquid, up to 40 μM, and remained constant thereafter. SND was observed in the aerated activated sludge when O2 concentration was in the range of 10 to 35 μM. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 604–607, 2003.
Lipase‐mediated acidolysis of butteroil with free conjugated linoleic acid in a packed bed reactor
Authors: Sehanputri Prima S. , Hill Charles G. 
Published: June 2003

AbstractAcidolysis of butteroil with free conjugated linoleic acid (CLA) was studied in a packed bed reactor containing an immobilized Candida antarctica (fraction B) lipase. Kinetic data were used to develop quantitative reversible rate expressions of the general Michaelis–Menten form that also incorporate a term for first‐order deactivation of the enzyme. The extent of incorporation of CLA in the triacylglycerols of butteroil was characterized for reactions carried out at several temperatures (namely 45°, 50°, and 55°C) with different weight ratios of butteroil to CLA (namely 10:1 and 2:1). At the optimum operating temperature of 50°C, similar levels of incorporation of CLA (60% to 85%) were achieved at low space times (<3 h) for both 10:1 and 2:1 (w/w) ratios of butteroil to CLA. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 608–617, 2003.
Telomere length variation and maintenance in hepatocarcinogenesis
Authors: Yokota Takashi , Suda Takeshi , Igarashi Masato , Kuroiwa Takashi , Waguri Nobuo , Kawai Hirokazu , Mita Yusaku , Aoyagi Yutaka 
Published: June 2003

AbstractBACKGROUNDDespite the recent discovery of interchromosomal telomere length variation, a role for heterogeneity in telomere maintenance has yet to be established. This study investigated the significance of telomere length variation between chromosomes with respect to the association of cancer progression and telomere length regulation.METHODSTerminal restriction fragment (TRF) was evaluated in 20 surgically resected hepatocellular carcinoma specimens (HCC), corresponding noncancerous liver tissue specimens (NCL), and in 10 liver tissue specimens with chronic liver diseases devoid of cancer (DOC). Average TRF length (TRF‐A) was defined as the point of maximum intensity. Shorter and longer TRF lengths (TRF‐S and TRF‐L) were defined as the length above which 90% of TRF distribution was involved. A ratio, (TRF‐L−TRF‐S)/TRF‐A, was defined as telomere length dispersion.RESULTSThe dispersion was significantly larger in HCC than in NCL specimens (P = 0.012) and in NCL than in DOC (P = 0.048). TRF‐A and TRF‐S were significantly shorter in HCC than in NCL (P = 0.0026, P = 0.0010). In seven patients in whom HCC recurred within 1 year, TRF‐A and TRF‐S were significantly shorter than in 10 patients in whom recurrence occurred after 1 year (P = 0.018, P = 0.0097). Telomeric repeat binding factor 1 was up‐regulated in HCC with elongated TRF‐L, whereas expression of human telomerase reverse transcriptase was greater in HCC with a shorter TRF‐S.CONCLUSIONSThese results suggest that telomere length varied through chronic liver diseases by preferentially increasing shorter telomeres, whose length is a good indicator for malignant potential of HCC. Telomere length variation may be a crucial code in telomere maintenance through hepatocarcinogenesis. Cancer 2003;98:110–8. © 2003 American Cancer Society.DOI 10.1002/cncr.11428