bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rett syndrome in adolescent and adult females: Clinical and molecular genetic findings
Authors: Smeets E. , Schollen E. , Moog U. , Matthijs G. , Herbergs J. , Smeets H. , Curfs L. , Schrander‐Stumpel C. , Fryns J.P. 
Published: September 2003

AbstractRett syndrome (RTT) is a neurodevelopmental disorder which is diagnosed clinically. We report on 30 adolescent and adult females with classical or atypical RTT of whom 24 have a MECP2 mutation. In these 24 females, the clinical manifestations, degree of severity, and disorder profiles are discussed as well as the genotype phenotype correlation. After X‐chromosome inactivation (XCI) study in these cases, we found no correlation between skewing and milder phenotype. Three large deletions were found after additional Southern blot analysis in three classical RTT cases. We confirm that early truncating mutations in MECP2 are responsible for a more severe course of the disorder. Three disorder profiles related to the missense mutations R133C and R306C, and to deletions in the C terminal segment are described and are of interest for further clinical study on larger numbers of cases. The R133C genotype has a predominantly autistic presentation while the R306C genotype is associated with a slower disease progression. The phenotype of the “hotspot” deletions in the C terminal segment is predominantly characterized by rapid progressive neurogenic scoliosis. Older women with RTT are underdiagnosed: seven adults were first diagnosed as having RTT between 29 and 60 years of age, and confirmed on finding a MECP2 mutation. Knowledge of the clinical phenotype of RTT at an adult age is important for all involved in the care of these individuals. The involvement of the parent support group is very important in this matter. © 2003 Wiley‐Liss, Inc.
Association of the serotonin transporter gene with sudden infant death syndrome: A haplotype analysis
Authors: Weese‐Mayer Debra E. , Zhou Lili , Berry‐Kravis Elizabeth M. , Maher Brion S. , Silvestri Jean M. , Marazita Mary L. 
Published: September 2003

AbstractSerotonergic receptor binding in the arcuate nucleus, n. raphé obscurus, and other medullary regions is decreased in sudden infant death syndrome (SIDS) cases. Further, an insertion/deletion polymorphism in the promoter region of the serotonin transporter protein (5‐HTT) gene has recently been associated with risk of SIDS. This polymorphism differentially regulates 5‐HTT expression, with the long allele (L), the SIDS‐associated allele, being a more effective promoter than the short allele (S). To further elucidate the role of the 5‐HTT gene in SIDS, we investigated the 5‐HTT intron 2 polymorphism, which also differentially regulates 5‐HTT expression with the 12 repeat allele being the more effective promoter. In a cohort of 90 SIDS cases (44 African‐American and 46 Caucasian) and gender/ethnicity‐matched controls, significant positive associations were found between SIDS and the intron 2 genotype distribution (P‐value = 0.041) among African‐American SIDS vs. African‐American controls, specifically with the 12/12 genotype (P‐value = 0.03), and with the 12 repeat allele (P‐value=0.018). The frequency of the 12/12 genotype and 12‐repeat allele was significantly different (P < 0.001) between the African‐American and Caucasian SIDS cases. Furthermore, the promoter and intron 2 loci were in significant linkage disequilibrium, and the L‐12 haplotype was significantly associated with SIDS in the African‐American (P = 0.002) but not Caucasian (P = 0.117) subgroups. These results indicate a relationship between SIDS and the 12‐repeat allele of the intron 2 variable number tandem repeat of the 5‐HTT gene in African‐Americans, and a significant role of the haplotype containing the 12‐repeat allele and the promoter L‐allele in defining SIDS risk in African‐Americans. These data, if confirmed in larger studies, may begin to explain the differences in SIDS incidence by ethnicity, suggest a role for levels of 5‐HTT expression in generation of SIDS susceptibility, and provide an important tool for identifying at‐risk individuals and estimating the risk of recurrence. © 2003 Wiley‐Liss, Inc.
Collection and analysis of hematopoietic progenitor cells from cynomolgus macaques (Macaca fascicularis): Assessment of cross‐reacting monoclonal antibodies
Authors: Shibata Hiroaki , Hanazono Yutaka , Ageyama Naohide , Nagashima Takeyuki , Ueda Yasuji , Hasegawa Mamoru , Ozawa Keiya , Yoshikawa Yasuhiro , Terao Keiji 
Published: September 2003

AbstractPrevious studies have shown that hematopoietic progenitor cells can be isolated from human or nonhuman primate bone marrow (BM) cells. In the present study, we studied the cross‐reactivity of 13 anti‐human CD34, two anti‐human c‐Kit, and one anti‐human CD133 monoclonal antibodies (mAbs) with cynomolgus macaque (Macaca fascicularis) BM cells, using flow cytometric analysis, cell enrichment, and clonogenic assay. Among the 13 anti‐human CD34 mAbs assessed, six cross‐reacted as previously reported by other groups. However, only three of these six mAbs (clones 561, 563, and 12.8) recognized cynomolgus CD34+ cells that formed progenitor colonies when grown in methylcellulose culture. Similarly, of the two anti‐human c‐Kit mAbs (clones NU‐c‐kit and 95C3) that were previously reported to cross‐react with cynomolgus BM cells, only one (clone NU‐c‐kit) resulted in a similar outcome. The anti‐human CD133 mAb (clone AC133) also cross‐reacted with cynomolgus BM cells, although these cells did not give rise to colonies when grown in culture. These results suggest that antibodies that cross‐react with nonhuman primate cells may not identify the hematopoietic cells of interest. In addition, while the CD34 mAb (clone 561) results in the selection of hematopoietic progenitor cells of all lineages when assessed in methylcellulose culture, the c‐Kithigh fraction (NU‐c‐kit) exclusively identifies erythroid‐specific progenitor cells after growth in culture. It is important to consider these findings when selecting cross‐reacting mAbs to identify cells of hematopoietic lineages in macaque species. Am. J. Primatol. 61:3–12, 2003. © 2003 Wiley‐Liss, Inc.
Hematology of a natural population of toque macaques (Macaca sinica) at polonnaruwa, Sri Lanka
Authors: Ekanayake Dilrukshi K. , Horadagoda Neil U. , Sanjeevani G.K. Madura , Arulkanthan Appudurai , Gunatilake K.A. Sunil , Dittus Wolfgang P.J. 
Published: September 2003

AbstractHematological studies were conducted in three wild groups of toque macaques (Macaca sinica) inhabiting the Polonnaruwa Sanctuary in northeastern Sri Lanka. The macaques were temporarily trapped and anesthetized, and femoral blood was drawn from 35 males and 37 females (age range: 0.33–24.5 yr). Statistically significant (P<0.05) differences were observed by sex for total plasma proteins (PP), and by age for red blood cell (RBC) counts, hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular Hb (MCH), mean corpuscular Hb concentration (MCHC), PP, erythrocyte sedimentation rate (ESR), differential and absolute neutrophil counts, differential lymphocyte counts, and absolute eosinophil counts. In general, the results were similar to those reported for other species of colony‐bred and free‐ranging macaques. However, there also were differences. First, in contrast to earlier studies of nonhuman primates, we examined the hematology of infants. Compared to other age classes, infants (<1 yr old) had lower RBC, Hb, MCHC, and ESR values, and a higher MCV. These findings were similar to those obtained in human infants. Second, we observed variations in hematology among social groups in relation to their ecology. Two groups (IH3 and M3) had ready access to water throughout the dry season (the period of sampling), whereas the third group (J) did not. The Hb, RBC, and PP values obtained in groups IH3 and M3 were similar to those reported in other macaque species. However, these parameters in group J were significantly (P<0.01) higher, which suggests that this group (representing about 26% of the sample) had been dehydrated during the dry season. Finally, two indices indicative of injury and infection–the ESR and leukocyte counts–were higher in the wild toque macaques than has been reported for other species of macaques held in captivity, and about 15% of the toque macaques sampled had extreme outlier values for these parameters; however, none were visibly ill or died. These results suggest that wild toque macaques are subject to a wide array of physical and biological insults that are unique to natural populations. Am. J. Primatol. 61:13–28, 2003. © 2003 Wiley‐Liss, Inc.
Crocodylian forelimb musculature and its relevance to Archosauria
Authors: Meers Mason B. 
Published: September 2003

AbstractThe musculoskeletal anatomy of the crocodylian forelimb is documented to facilitate functional morphological studies of extant and extinct archosaurs. Comparative descriptions of muscles of the forelimb of several crocodylian species are presented, including attachment sites, innervation, and anatomical functions. The muscular anatomy of the crocodylian forelimb is highly conservative among the different species; however, interspecific differences do occur. Interspecific anatomical variation is interpreted functionally, and discussed in the context of the terrestrial locomotion of crocodylians as it applies to the forelimb. In addition, muscular apomorphies are identified among a phylogenetically diverse sample of extant crocodylians, providing insight into the evolution of forelimb anatomy in a clade of archosaurs possessing highly variable terrestrial locomotor behaviors. Anat Rec Part A 274A:891–916, 2003. © 2003 Wiley‐Liss, Inc.
Presystemic metabolism and intestinal absorption of antipsoriatic fumaric acid esters
Authors: Werdenberg D. , Joshi R. , Wolffram S. , Merkle H.P. , Langguth P. 
Published: September 2003

AbstractPsoriasis is a chronic inflammatory skin disease. Its treatment is based on the inhibition of proliferation of epidermal cells and interference in the inflammatory process. A new systemic antipsoriasis drug, which consists of dimethylfumarate and ethylhydrogenfumarate in the form of their calcium, magnesium and zinc salts has been introduced in Europe with successful results. In the present study, a homologous series of mono‐ and diesters of fumaric acid has been studied with respect to the sites and kinetics of presystemic ester degradation using pancreas extract, intestinal perfusate, intestinal homogenate and liver S9 fraction. In addition, intestinal permeability has been determined using isolated intestinal mucosa as well as Caco‐2 cell monolayers, in order to obtain estimates of the fraction of the dose absorbed for these compounds. Relationships between the physicochemical properties of the fumaric acid esters and their biological responses were investigated. The uncharged diester dimethylfumarate displayed a high presystemic metabolic lability in all metabolism models. It also showed the highest permeability in the Caco‐2 cell model. However, in permeation experiments with intestinal mucosa in Ussing‐type chambers, no undegraded DMF was found on the receiver side, indicating complete metabolism in the intestinal tissue. The intestinal permeability of the monoesters methyl hydrogen fumarate, ethyl hydrogen fumarate, n‐propylhydrogen fumarate and n‐pentyl hydrogen fumarate increased with an increase in their lipophilicity, however, their presystemic metabolism rates likewise increased with increasing ester chain length. It is concluded that for fumarates, an increase in intestinal permeability of the more lipophilic derivatives is counterbalanced by an increase in first‐pass extraction. Copyright © 2003 John Wiley & Sons, Ltd.
Effect of wood ash treatment on improving the fermentability of wood hydrolysate
Authors: Miyafuji Hisashi , Danner Herbert , Neureiter Markus , Thomasser Christiane , Braun Rudolf 
Published: September 2003

AbstractSoftwood hydrolysates were overlimed with wood ash to improve the fermentability of hydrolysates. It could be demonstrated in fermentation tests that wood ash treatment increases fermentability compared to the hydrolysates untreated and treated with alkaline compounds such as Ca(OH)2, NaOH, and KOH, which are commonly used for overliming. The enhanced fermentability of the hydrolysate treated with wood ash is due to the reduction of the inhibitors of the fermentation such as furan and phenolic compounds and to nutrient effects of some inorganic components from the wood ash on the fermentation. © 2003 Wiley Periodicals. Biotechnol Bioeng 84: 390–393, 2003.
An integrated approach to optimization of Escherichia coli fermentations using historical data
Authors: Coleman Matthew C. , Buck Kristan K. S. , Block David E. 
Published: September 2003

AbstractUsing a fermentation database for Escherichia coli producing green fluorescent protein (GFP), we have implemented a novel three‐step optimization method to identify the process input variables most important in modeling the fermentation, as well as the values of those critical input variables that result in an increase in the desired output. In the first step of this algorithm, we use either decision‐tree analysis (DTA) or information theoretic subset selection (ITSS) as a database mining technique to identify which process input variables best classify each of the process outputs (maximum cell concentration, maximum product concentration, and productivity) monitored in the experimental fermentations. The second step of the optimization method is to train an artificial neural network (ANN) model of the process input–output data, using the critical inputs identified in the first step. Finally, a hybrid genetic algorithm (hybrid GA), which includes both gradient and stochastic search methods, is used to identify the maximum output modeled by the ANN and the values of the input conditions that result in that maximum. The results of the database mining techniques are compared, both in terms of the inputs selected and the subsequent ANN performance. For the E. coli process used in this study, we identified 6 inputs from the original 13 that resulted in an ANN that best modeled the GFP fluorescence outputs of an independent test set. Values of the six inputs that resulted in a modeled maximum fluorescence were identified by applying a hybrid GA to the ANN model developed. When these conditions were tested in laboratory fermentors, an actual maximum fluorescence of 2.16E6 AU was obtained. The previous high value of fluorescence that was observed was 1.51E6 AU. Thus, this input condition set that was suggested by implementing the proposed optimization scheme on the available historical database increased the maximum fluorescence by 55%. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 84: 274–285, 2003.
A study of oxygen transfer in shake flasks using a non‐invasive oxygen sensor
Authors: Gupta Atul , Rao Govind 
Published: September 2003

AbstractWe describe a study of oxygen transfer in shake flasks using a non‐invasive optical sensor. This study investigates the effect of different plugs, presence of baffles, and the type of media on the dissolved oxygen profiles during Escherichia coli fermentation. We measured the volumetric mass transfer coefficient (kLa) under various conditions and also the resistances of the various plugs. Finally, we compared shake flask kLa with that from a stirred tank fermentor. By matching kLa's we were able to obtain similar growth and recombinant protein product formation kinetics in both a fermentor and a shake flask. These results provide a quantitative comparison of fermentations in a shake flask vs. a bench‐scale fermentor and should be valuable in guiding scale‐up efforts. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 84: 351–358, 2003.
Titrostat: A reliable technique for continuous cultivation of microorganisms utilizing liquid or gaseous water insoluble substrates
Authors: Mutafov S. , Angelova B. , Schmauder H.‐P. , Avramova T. , Boyadjieva L. 
Published: September 2003

AbstractWe describe a method for continuous cultivation of microorganisms utilizing liquid or gaseous water insoluble substrates as a single source of carbon and energy. The water insoluble substrate, which is also the growth‐limiting factor, enters the cultivation space as a manually adjustable single‐compound material flow. All nonlimiting nutrients (with the exception of oxygen) enter the cultivation space as ingredients of titrant solution which feed rate is reliably coupled to the rate of substrate addition by means of the system titrator.The method provides mild starting conditions appropriate for primary isolation of microorganisms utilizing substrates with growth‐inhibiting properties such as BTEX (benzene, toluene, ethylbenzene, and xylene). The sound control over the microbial specific growth rate makes it suitable for precise kinetic studies as well.We provide a detailed description of both the principles of the method and the equipment used. The dependence of the systems operative range on the concentration of titrant solution is illustrated in the case of continuous cultivation of a mixed bacterial culture on toluene. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 84: 160–169, 2003.
Fabrication of nickel and chromium nanoparticles using the protein cage of apoferritin
Authors: Okuda Mitsuhiro , Iwahori Kenji , Yamashita Ichiro , Yoshimura Hideyuki 
Published: September 2003

AbstractThe iron storage protein, apoferritin, has a cavity in which iron is oxidized and stored as a hydrated oxide core. The size of the core is about 7 nm in diameter and is regulated by the cavity size. The cavity can be utilized as a nanoreactor to grow inorganic crystals. We incubated apoferritin in nickel or chromium salt solutions to fabricate hydroxide nanoparticles in the cavity. By using a solution containing dissolved carbon dioxide and by precisely controlling the pH, we succeeded in fabricating nickel and chromium cores. During the hydroxylation process of nickel ions a large portion of the apoferritin precipitated through bulk precipitation of nickel hydroxide. Bulk precipitation was suppressed by adding ammonium ions. However, even in the presence of ammonium ions the core did not form using a degassed solution. We concluded that carbonate ions were indispensable for core formation and that the ammonium ions prevented precipitation in the bulk solution. The optimized condition for nickel core formation was 0.3 mg/mL horse spleen apoferritin and 5 mM ammonium nickel sulfate in water containing dissolved carbon dioxide. The pH was maintained at 8.65 using two buffer solutions: 150 mM HEPES (pH 7.5) and 195 mM CAPSO (pH 9.5) with 20 mM ammonium at 23°C. The pH had not changed after 48 h. After 24 h of incubation, all apoferritins remained in the supernatant and all of them had cores. Recombinant L‐ferritin showed less precipitation even above a pH of 8.65. A chromium core was formed under the following conditions: 0.1 mg/mL apoferritin, 1 mM ammonium chromium sulfate, 100 mM HEPES (pH 7.5) with a solution containing dissolved carbon dioxide. About 80% of the supernatant apoferritin (0.07 mg/mL) formed a core. In nickel and chromium core formation, carbonate ions would play an important role in accelerating the hydroxylation in the apoferritin cavity compared to the bulk solution outside. © 2003 Wiley Periodicals. Biotechnol Bioeng 84: 187–194, 2003.
Physicochemical and blood compatibility characterization of polypyrrole surface functionalized with heparin
Authors: Li Yali , Neoh Koon Gee , Cen Lian , Kang En‐Tong 
Published: September 2003

AbstractA surface modification technique was developed for the covalent immobilization of heparin onto electrically conductive polypyrrole (PPY) film. The PPY film was first graft copolymerized with poly(ethylene glycol) methacrylate (PEGMA) and then activated with cyanuric chloride (CC). Heparin was then immobilized onto the film through the reaction between the chloride groups of CC and the amine and/or hydroxyl groups of heparin. X‐ray photoelectron spectroscopy (XPS) was used to characterize the surface‐modified film after each stage. The biocompatibility of the surface‐modified PPY was evaluated using plasma recalcification time (PRT) and platelet adhesion. After surface modification, the film had improved wettability while retaining significant electrical conductivity. With immobilized heparin, platelet adhesion and platelet activation on PPY film was significantly suppressed, and the PRT was significantly prolonged. Electrical stimulation also plays a positive role in decreasing platelet adhesion and increasing PRT on pristine and surface‐modified PPY films. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 84: 305–313, 2003.
Complex catalytic colloids on the basis of firefly luciferase as optical nanosensor platform
Authors: Pastorino Laura , Disawal Sandeep , Nicolini Claudio , Lvov Yuri M. , Erokhin Victor V. 
Published: September 2003

AbstractIn the present work the layer‐by‐layer nano‐assembly technique was used for the development of complex catalytic microparticles on the basis of firefly luciferase (FL). FL films containing 1, 2, or 3 monolayers were assembled on silver electrode QCM‐resonators and on 520‐nm diameter sulfonated polystyrene latex by alternate adsorption of FL and polycations using electrostatic interactions for the interlayer interaction. The assembly process was studied with quartz crystal microbalance, UV‐vis spectroscopy, and microelectrophoresis (surface potential). Structural studies of the resulting multilayers confirmed stepwise deposition of FL and cationic poly(dimethyldiallyl ammonium chloride) with a bilayer thickness of 14 nm; a systematic shift of the surface potential from +28 mV for poly(dimethyldiallyl ammonium chloride) to –14 mV for luciferase outermost layer was established. The functionality and stability of the biocolloids were demonstrated by monitoring the intensity of the light emission. Factors influencing the light emitted upon catalytic activity of FL such as the number of luciferase layers in the film and polyion layer at the outermost layer were studied. © 2003 Wiley Periodicals. Biotechnol Bioeng 84: 286–291, 2003.
High cell density induces spontaneous bifurcations of dissolved oxygen controllers during CHO cell fermentations
Authors: Chung John D. , Chang Conway C. , Groves James Ashley 
Published: September 2003

AbstractHigh cell density cultures of CHO cells growing in a bioreactor under dissolved oxygen control were found to undergo spontaneous bifurcations and a subsequent loss of stability some time into the fermentation. This loss of stability was manifested by sustained and amplified oscillations in the bioreactor dissolved oxygen concentration and in the oxygen gas flow rate to the reactor. To identify potential biological and operational causes for the phenomenon, linear stability analysis was applied in a neighborhood of the experimentally observed bifurcation point. The analysis revealed that two steady state process gains, KP1 and KP2, regulated kla and gas phase oxygen concentration inputs, respectively, and the magnitude of KP1 was found to determine system stability about the bifurcation point. The magnitude of KP1, and hence the corresponding open‐loop steady state gain KOL1, scaled linearly with the bioreactor cell density, increasing with increasing cell density. These results allowed the generation of a fermentation stability diagram, which partitioned KC‐N operating space into stable and unstable regions separated by the loci of predicted critically stable controller constants, KC,critical, as a function of bioreactor cell density. This consistency of this operating diagram with experimentally observed changes in system stability was demonstrated. We conclude that time‐dependent increases in cell density are the cause of the observed instabilities and that cell density is the critical bifurcation parameter. The results of this study should be readily applicable to the design of a more robust controller. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 84: 224–232, 2003.