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Selected AbstractsSoil organic carbon in density fractions of tropical soils under forest , pasture , secondary forest land use changesEUROPEAN JOURNAL OF SOIL SCIENCE, Issue 2 2008S. Paul Summary Our knowledge of effects of land use changes and soil types on the storage and stability of different soil organic carbon (SOC) fractions in the tropics is limited. We analysed the effect of land use (natural forest, pasture, secondary forest) on SOC storage (depth 0,0.1 m) in density fractions of soils developed on marine Tertiary sediments and on volcanic ashes in the humid tropics of northwest Ecuador. The origin of organic carbon stored in free light (< 1.6 g cm,3) fractions, and in two light fractions (LF) occluded within aggregates of different stability, was determined by means of ,13C natural abundance. Light occluded organic matter was isolated in a first step after aggregate disruption by shaking aggregates with glass pearls (occluded I LF) and in a subsequent step by manual destruction of the most stable microaggregates that survived the first step (occluded II LF). SOC storage in LFs was greater in volcanic ash soils (7.6 ± 0.6 Mg C ha,1) than in sedimentary soils (4.3 ± 0.3 Mg C ha,1). The contribution of the LFs to SOC storage was greater in natural forest (19.2 ± 1.2%) and secondary forest (16.6 ± 1.0%) than in pasture soils (12.8 ± 1.0%), independent of soil parent material. The amount of SOC stored in the occluded I LF material increased with increasing silt + clay content (sedimentary soils, r = 0.73; volcanic ash soils, r = 0.58) and aggregation (sedimentary soils, r = 0.52; volcanic ash soils, r = 0.45). SOC associated with occluded I LF, had the smallest proportion of new, pasture-derived carbon, indicating the stabilizing effect of aggregation. Fast turnover of the occluded II LF material, which was separated from highly stable microaggregates, strongly suggested that this fraction is important in the initial process of aggregate formation. No pasture-derived carbon could be detected in any density fractions of volcanic ash soils under secondary forest, indicating fast turnover of these fractions in tropical volcanic ash soils. [source] On coupling the Reynolds-averaged Navier,Stokes equations with two-equation turbulence model equationsINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS, Issue 2 2006Seungsoo Lee Abstract Two methods for coupling the Reynolds-averaged Navier,Stokes equations with the q,, turbulence model equations on structured grid systems have been studied; namely a loosely coupled method and a strongly coupled method. The loosely coupled method first solves the Navier,Stokes equations with the turbulent viscosity fixed. In a subsequent step, the turbulence model equations are solved with all flow quantities fixed. On the other hand, the strongly coupled method solves the Reynolds-averaged Navier,Stokes equations and the turbulence model equations simultaneously. In this paper, numerical stabilities of both methods in conjunction with the approximated factorization-alternative direction implicit method are analysed. The effect of the turbulent kinetic energy terms in the governing equations on the convergence characteristics is also studied. The performance of the two methods is compared for several two- and three-dimensional problems. Copyright © 2005 John Wiley & Sons, Ltd. [source] Synthesis and characterization of zwitterionic organogels based on Schiff base chemistryJOURNAL OF APPLIED POLYMER SCIENCE, Issue 5 2010Nazia Tarannum Abstract Poly(sulfobetaine)s and poly(carboxybetaine)s have been extensively studied for their zwitterionic and biocompatible nature. The specific features that make such zwitterionic structures technologically important are their chemical structure, a straight forward synthetic route, high ionic contents with interesting dilute solution, and solid state properties. The objective of this work is to synthesize novel zwitterionic polymers having gel characteristics. Here, p- phenylene diamine/melamine react as nucleophiles with glutaraldehyde to produce poly(schiff base)s. In the subsequent step, the poly(sulfobetaine)s and poly(carboxybetaine)s were produced on treatment with 1,3-propane sultone/,-butyrolactone. Hence, a catalyst free facile approach to novel zwitterionic polymers was obtained. The polymers were characterized by elemental analyses, FTIR, XRD analyses, SEM, pH metric titrations, conductometric titrations, and thermal analyses (TGA/DTA). The polymeric samples carry the gel characteristics, showing lamellar structure with porous network. XRD pattern shows Bragg peaks indicative of superstructures. Thermal analysis indicates the Hoffman elimination of , hydrogen and subsequent release of sulfopropyl/carboxybutyl group. One of the gel polymers shows fluorescence also. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 [source] Theoretical studies on farnesyl transferase: Evidence for thioether product coordination to the active-site zinc sphereJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 7 2007Sérgio Filipe Sousa Abstract Farnesyltransferase (FTase), an interesting zinc metaloenzyme, has been the subject of great attention in anticancer research over the last decade. However, despite the major accomplishments in the field, some very pungent questions on the farnesylation mechanism still persist. In this study, the authors have analyzed a mechanistic paradox that arises from the existence of several contradicting and inconclusive experimental evidence regarding the existence of direct coordination between the active-site zinc cation and the thioether from the farnesylated peptide product, which include UV,vis spectroscopy data on a Co2+ -substituted FTase, two X-ray crystallographic structures of the FTase-product complex, and extended X-ray absorption fine structure results. Using high-level theoretical calculations on two models of different sizes, and QM/MM calculations on the full enzyme, the authors have shown that the farnesylated product is Zn coordinated, and that a subsequent step where this Zn bond is broken is coherent with the available kinetic results. Furthermore, an explanation for the contradicting experimental evidence is suggested. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007 [source] Highly Functional Poly(meth)acrylates via Cascade ReactionMACROMOLECULAR CHEMISTRY AND PHYSICS, Issue 2 2009Dragos Popescu Abstract A new route to the synthesis of highly functional and reactive polymethacrylates via cascade reactions comprising enzymatically and chemically catalyzed steps is presented. Transacylation of methyl acrylate and methyl methacrylate as substrates with different functional alcohols in the presence of Novozyme 435 leads to a mixture of functional monomers, which in a subsequent step was copolymerized via free radical polymerization, resulting in polymethacrylates with predefined functionalities. Hydrophilic, hydrophobic, as well as ionic methacrylate repeating units were assembled in a copolymer and adjusted for surface coatings. [source] Frontal polymerization of acrylic monomers for the consolidation of stonePOLYMERS FOR ADVANCED TECHNOLOGIES, Issue 4 2005Silvia Vicini Abstract Polymeric products are largely used for consolidation of stone in the field of cultural heritage. Nevertheless, the main problem of polymeric compounds is related to their macromolecular nature, it being difficult for a polymer to penetrate inside the pores which may have a very small diameter. These considerations are the starting points for in situ polymerization. According to this technique, not the pre-formed polymer, but the monomer is introduced into the stone and it is polymerized in situ in a subsequent step. Frontal polymerization (FP) is a particular technique in which the heat released by the exothermal reaction of monomer to polymer conversion is exploited to promote the formation of a hot traveling front able to propagate and self-sustain the reaction. In the present work, FP is performed inside the pores of the stone and the results lead to the conclusion that the hot front is still active in the presence of an inorganic material which dissipates partially the heat released during the polymerization. In addition some recent applications of FP are discussed in comparison with the traditional polymerization for the in situ consolidation and protection of stones. Copyright © 2005 John Wiley & Sons, Ltd. [source] An algorithm for the pharmacological treatment of depressionACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2010J. Spijker Spijker J, Nolen WA. An algorithm for the pharmacological treatment of depression. Objective:, Non-response to treatment with antidepressants (AD) is a clinical problem. Method:, The algorithm for pharmacological treatment of the Dutch multidisciplinary guideline for depression is compared with four other algorithms. Results:, The Dutch algorithm consists of five subsequent steps. Treatment is started with one out of many optional ADs (step 1); in case of non-response after 4,10 weeks, best evidence is for switching to another AD (step 2); next step is augmentation with lithium as the best option (step 3); the next step is a monoamine oxidase inhibitor (MAOI) (step 4); and finally electroconvulsive therapy (step 5). There are major differences with other algorithms regarding timing of augmentation step, best agents for augmentation and role of MAOI. Conclusion:, Algorithms for AD treatment vary according to national and local preferences. Although the evidence for most of the treatment strategies is rather meagre, an AD algorithm appears to be an useful instrument in clinical practice. [source] GATA-4 is required for sex steroidogenic cell development in the fetal mouseDEVELOPMENTAL DYNAMICS, Issue 1 2007Malgorzata Bielinska Abstract The transcription factor GATA-4 is expressed in Sertoli cells, steroidogenic Leydig cells, and other testicular somatic cells. Previous studies have established that interaction between GATA-4 and its cofactor FOG-2 is necessary for proper Sry expression and all subsequent steps in testicular organogenesis, including testis cord formation and differentiation of both Sertoli and fetal Leydig cells. Since fetal Leydig cell differentiation depends on Sertoli cell,derived factors, it has remained unclear whether GATA-4 has a cell autonomous role in Leydig cell development. We used two experimental systems to explore the role of GATA-4 in the ontogeny of testicular steroidogenic cells. First, chimeric mice were generated by injection of Gata4,/, ES cells into Rosa26 blastocysts. Analysis of the resultant chimeras showed that in developing testis Gata4,/, cells can contribute to fetal germ cells and interstitial fibroblasts but not fetal Leydig cells. Second, wild-type or Gata4,/, ES cells were injected into the flanks of intact or gonadectomized nude mice and the resultant teratomas examined for expression of steroidogenic markers. Wild-type but not Gata4,/, ES cells were capable of differentiating into gonadal-type steroidogenic lineages in teratomas grown in gonadectomized mice. In chimeric teratomas derived from mixtures of GFP-tagged Gata4+/+ ES cells and unlabeled Gata4,/, ES cells, sex steroidogenic cell differentiation was restricted to GFP-expressing cells. Collectively these data suggest that GATA-4 plays an integral role in the development of testicular steroidogenic cells. Developmental Dynamics 236:203,213, 2007. © 2006 Wiley-Liss, Inc. [source] New reproductive anomalies in fruitless -mutant Drosophila males: Extreme lengthening of mating durations and infertility correlated with defective serotonergic innervation of reproductive organsDEVELOPMENTAL NEUROBIOLOGY, Issue 2 2001Gyunghee Lee Abstract Several features of male reproductive behavior are under the neural control of fruitless (fru) in Drosophila melanogaster. This gene is known to influence courtship steps prior to mating, due to the absence of attempted copulation in the behavioral repertoire of most types of fru -mutant males. However, certain combinations of fru mutations allow for fertility. By analyzing such matings and their consequences, we uncovered two striking defects: mating times up to four times the normal average duration of copulation; and frequent infertility, regardless of the time of mating by a given transheterozygous fru -mutant male. The lengthened copulation times may be connected with fru -induced defects in the formation of a male-specific abdominal muscle. Production of sperm and certain seminal fluid proteins are normal in these fru mutants. However, analysis of postmating qualities of females that copulated with transheterozygous mutants strongly implied defects in the ability of these males to transfer sperm and seminal fluids. Such abnormalities may be associated with certain serotonergic neurons in the abdominal ganglion in which production of 5HT is regulated by fru. These cells send processes to contractile muscles of the male's internal sex organs; such projection patterns are aberrant in the semifertile fru mutants. Therefore, the reproductive functions regulated by fruitless are expanded in their scope, encompassing not only the earliest stages of courtship behavior along with almost all subsequent steps in the behavioral sequence, but also more than one component of the culminating events. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 121,149, 2001 [source] The role of the nitrate respiration element of Thermus thermophilus in the control and activity of the denitrification apparatusENVIRONMENTAL MICROBIOLOGY, Issue 2 2008Felipe Cava Summary The nitrate conjugative element (NCE) encodes the ability to respire nitrate in the facultative Thermus thermophilus NAR1 strain. This process is carried out by two heterotetrameric enzymes that catalyse the oxidation of NADH (Nrc) and the reduction of nitrate (Nar), whose expression is activated by the NCE-encoded transcription factors DnrS and DnrT. We report the presence of NCE in other facultative strains of T. thermophilus and analyse its role in subsequent steps of the denitrification pathway. We encountered that nrc mutants of denitrifying strains show a decrease in anaerobic growth rates not only with nitrate, but also with nitrite, NO and N2O, which is concomitant to their lower NADH oxidation activities in vitro. We show that nitrate, nitrite and NO are activating signals for transcription of nrc in these strains. Finally, we demonstrate that DnrS and DnrT are required for anaerobic growth not only with nitrate, but also with nitrite, NO and N2O. These data allow us to conclude that: (i) Nrc constitutes the main electron donor for the four reductases of the denitrification pathway, and (ii) the NCE controls the expression of the whole denitrification pathway and the repression of the aerobic respiration through the transcription factors DnrS and DnrT. [source] De Novo Synthesis of Racemic Spirocyclopropane-Annelated 2-Deoxyhexose DerivativesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 3 2003Armin de Meijere Abstract High-pressure-induced inverse-electron-demand hetero-Diels,Alder reactions of ethyl trans -4-ethoxy-2-oxo-3-butenoate (2a) and methyl trans -4-benzyloxy-2-oxo-3-butenoate (2b) with benzyl (cyclopropylidenemethyl) ether (1) each yielded mixtures of two separable diastereomeric esters 7a (64%) and 7b (80%) which, in three subsequent steps, led to the 3-ethylated and 3-benzylated ,- and ,-anomeric benzyl spiro[2-deoxy-(D,L)- arabino -hexopyranoside-2,1,-cyclopropanes] ,- 10a,b and ,- 10a,b, respectively. The relative configuration of ,- 10a was proved by an X-ray crystal structure analysis. Deprotection of ,- 10b was achieved by Pd-catalyzed hydrogenation in dimethylacetamide leading to spiro[2-deoxy-,/,-2-(D,L)- arabino -hexopyranoside-2,1,-cyclopropane] (4). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Subminimal cycle basis of a graph for efficient force method of frame analysisINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING, Issue 11 2005A. Kaveh Abstract A new method is presented for the formation of subminimal cycle bases of graphs corresponding to sparse flexibility matrices. In this approach, a Contraction method is used, leading to the reduction of the size of the graph at each step. This reduction facilitates the selection of the smallest cycle at subsequent steps. Copyright © 2005 John Wiley & Sons, Ltd. [source] Multiple-Well, multiple-path unimolecular reaction systems.INTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 4 2001Vibrationally excited 2-methylhexyl radicals formed by shock wave activation or by chemical activation can isomerize by multiple pathways to form any of six stable isomers, can fragment by multiple CH and CC bond fission pathways, and can be collisionally stabilized. Master equation simulations of chemical activation and of shock wave activation are used to explore the generic behavior of this complicated coupled system. Selecting the argon pressure in chemical activation systems that produce the 2-methyl-1-hexyl radical isomer (1) can control the yield of specific isomers. Shock heating of 1 also shows a highly regular sequence of isomer formation. This regular behavior is because the first isomerization steps are faster than subsequent steps. Other radical isomers, such as 2-methyl-3-hexyl (3), do not show such regular behavior, because the first isomerization step is slower than subsequent steps. Incubation and unimolecular rate-constant fall-off are observed in the shock wave simulations. The unimolecular rate-constant fall-off for the coupled system produces low-pressure limiting rate constants proportional to [M]n, where n can be greater than unity. The fact that n can be greater than unity is a natural feature of multichannel coupled unimolecular reaction systems, but detection of the effect in experiments may be very demanding. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33: 246,261, 2001 [source] Genome-wide linkage and QTL mapping in porcine F2 families generated from Pietrain, Meishan and Wild Boar crossesJOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 6 2003H. Geldermann Summary Three informative pig F2 families based on European Wild Boar (W), Meishan (M) and Pietrain (P) crosses have been used for genome-wide linkage and quantitative trait loci (QTL) analysis. Altogether 129 microsatellites, 56 type I loci and 46 trait definitions (specific to growth, fattening, fat deposition, muscling, meat quality, stress resistance and body conformation) were included in the study. In the linkage maps of M × P, W × P and W × M families, average spacing of markers were 18.4, 19.7 and 18.8 cM, the numbers of informative meioses were 582, 534 and 625, and the total lengths of autosomes measured were 27.3, 26.0 and 26.2 Morgan units, respectively. Maternal maps were on average 1.3 times longer than paternal maps. QTLs contributing more than 3% of F2 phenotypic variance could be identified at p < 0.05 chromosome-wide level. Differences in the numbers and positions of QTLs were observed between families. Genome-wide significant QTL effects were mapped for growth and fattening traits on eight chromosomes (1, 2, 4, 13, 14, 17, 18 and X), for fat deposition traits on seven chromosomes (1, 2, 3, 4, 6, 7 and X), for muscling traits on 11 chromosomes (1, 2, 3, 4, 6, 7, 8, 12, 14, 15 and X), for meat quality and stress resistance traits on seven chromosomes (2, 3, 6, 13, 16, 18 and X), and QTLs for body-conformation traits were detected on 14 chromosomes. Closely correlated traits showed similar QTL profiles within families. Major QTL effects for meat quality and stress resistance traits were found on SSC6 in the interval RYR1-A1BG in the W × P and M × P families, and could be attributed to segregation of the RYR1 allele T derived from Pietrain, whereas no effect in the corresponding SSC6 interval was found in family W × M, where Wild Boar and Meishan both contributed the RYR1 allele C. QTL positions were mostly similar in two of the three families for body conformation traits and for growth, fattening, fat deposition and muscling traits, especially on SSC4 (interval SW1073-NGFB). QTLs with large effects were also mapped on SSC7 in the major histocompatibility complex (MHC) (interval CYP21A2-S0102) and affected body length, weight of head and many other traits. The identification of DNA variants in genes causative for the QTLs requires further fine mapping of QTL intervals and a positional cloning. However, for these subsequent steps, the genome-wide QTL mapping in F2 families represents an essential starting point and is therefore significant for animal breeding. Zusammenfassung Drei informative F2 -Familien, die aus Kreuzungen von Europäischem Wildschwein (W), Meishan (M) und Pietrain (P) erstellt worden waren, wurden für eine genomweite Kopplungs- und QTL-Analyse benutzt. Insgesamt wurden 129 Mikrosatellitenloci, 56 Type-I-Loci und 46 Merkmalsdefinitionen (für Wachstum, Mastleistung, Fettansatz, Bemuskelung, Fleischqualität, Stressresistenz und Körperform) in die Untersuchungen einbezogen. In den Kopplungskarten der Familien M × P, W × P und W × M wurden durchschnittliche Markerabstände von 18.4, 19.7 bzw. 18.8 cM erreicht und 582, 534 bzw. 625 informative Meiosen beobachtet. Für die Gesamtlängen der Autosomen wurden in den drei Familien 27.3, 26.0 bzw. 26.2 Morgan-Einheiten gemessen. Die maternalen Kopplungskarten waren durchschnittlich 1.3-fach länger als die paternalen. QTLs, die mehr als 3% der phänotypischen Varianz in der F2 -Generation erklärten, konnten mit p < 0.05 chromosomenweitem Signifikanzniveau nachgewiesen werden. Zwischen den Familien wurden Differenzen in den Anzahlen und Positionen der QTLs beobachtet. Genomweit signifikante QTL-Effekte wurden für Wachstum und Fettansatz auf acht Chromosomen (1, 2, 4, 13, 14, 17, 18 und X) kartiert, für Fettansatz auf sieben Chromosomen (1, 2, 3, 4, 6, 7 und X), für Bemuskelung auf elf Chromosomen (1, 2, 3, 4, 6, 7, 8, 12, 14, 15 und X), für Fleischqualität/Stressresistenz auf sieben Chromosomen (2, 3, 6, 13, 16, 18 und X), und QTLs für die Körperform wurden auf 14 Chromosomen kartiert. Eng korrelierte Merkmale zeigten ähnliche QTL-Profile innerhalb Familien. Die bedeutsamsten QTL-Effekte wurden für Fleischqualitäts- und Stressresistenzmerkmale auf Chromosom 6, Intervall RYR1-A1BG, in den Familien W × P und M × P gefunden, während in diesem Chromosomenintervall in der Familie W × M, in der der RYR1 -Locus keine segregierenden Exon-Allele aufwies, kein QTL zu erkennen war. Mehrere der QTL-Positionen waren für die Körperform wie auch für Wachstum, Mastleistung, Fettansatz und Bemuskelung in zwei von drei Familien ähnlich. Dies galt besonders für Chromosom 4 (Intervall SW1073-NGFB). QTLs mit großen Effekten wurden auf Chromosom 7 im MHC (Intervall CYP21A2-S0102) kartiert; sie beeinflussten Körperlänge, Kopfgewicht, aber auch viele weitere Merkmale. Zur Identifizierung der DNA-Varianten, die einem QTL zugrunde liegen, ist eine Feinkartierung von QTLs und positionale Klonierung erforderlich. Für diese nachfolgenden Untersuchungsmethoden ist jedoch die genomweite QTL-Kartierung in F2 -Familien ein entscheidender Ausgangspunkt; sie ist deshalb bedeutungsvoll für die Tierzüchtung. [source] Radiofrequency Catheter Ablation of Atrial Fibrillation in Athletes Referred for Disabling Symptoms Preventing Usual Training Schedule and Sport CompetitionJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 5 2008FRANCESCO FURLANELLO M.D. Introduction: Atrial fibrillation (AF) may occasionally affect athletes by impairing their ability to compete, and leading to noneligibility at prequalification screening. The impact of catheter ablation (CA) in restoring full competitive activity of athletes affected by AF is not known. The aim of our study was to investigate the effectiveness of CA of idiopathic AF in athletes with palpitations impairing physical performance and compromising eligibility for competitive activities. Methods and Results: Twenty consecutive competitive athletes (all males; 44.4 ± 13.0 years) with disabling palpitations on the basis of idiopathic drug-refractory AF underwent 46 procedures (2.3 ± 0.4 per patient) according to a prospectively designed multiprocedural CA approach that consolidates pulmonary veins (PV) isolation through subsequent steps. Preablation, effort-induced AF could be documented in 13 patients (65%) during stress ECG and significantly reduced maximal effort capacity (176 ± 21 W), as compared with patients with no AF during effort (207 ± 43 W, P < 0.05). At the end of CA protocol, which also included ablation of atrial flutter (AFL) in 7 patients, 18 (90.0%) patients were free of AF and two (10.0%) reported short-lasting (minutes) episodes of palpitations during 36.1 ± 12.7 months follow-up. Compared with preablation, postablation maximal exercise capacity significantly improved (from 183 ± 32 to 218 ± 20 W, P < 0.02). All baseline quality of life (QoL) parameters pertinent to physical activity significantly improved (P < 0.05) at the end of CA protocol. All athletes obtained reeligibility and could effectively reinitiate sport activity. Conclusions: AF, alone or in combination with AFL, may significantly impair maximal effort capacity thereby limiting competitive performance. Multiple PV isolation proved very effective in these patients to restore full competitive activity and allow reeligibility. [source] The molecular physiology of activity-dependent bulk endocytosis of synaptic vesiclesJOURNAL OF NEUROCHEMISTRY, Issue 4 2009Emma L. Clayton Abstract Central nerve terminals release neurotransmitter in response to a wide variety of stimuli. Because maintenance of neurotransmitter release is dependent on the continual supply of synaptic vesicles (SVs), nerve terminals possess an array of endocytosis modes to retrieve and recycle SV membrane and proteins. During mild stimulation conditions, single SV retrieval modes such as clathrin-mediated endocytosis predominate. However, during increased neuronal activity, additional SV retrieval capacity is required, which is provided by activity-dependent bulk endocytosis (ADBE). ADBE is the dominant SV retrieval mechanism during elevated neuronal activity. It is a high capacity SV retrieval mode that is immediately triggered during such stimulation conditions. This review will summarize the current knowledge regarding the molecular mechanism of ADBE, including molecules required for its triggering and subsequent steps, including SV budding from bulk endosomes. The molecular relationship between ADBE and the SV reserve pool will also be discussed. It is becoming clear that an understanding of the molecular physiology of ADBE will be of critical importance in attempts to modulate both normal and abnormal synaptic function during intense neuronal activity. [source] Ultra scale-down approach to correct dispersive and retentive effects in small-scale columns when predicting larger scale elution profilesBIOTECHNOLOGY PROGRESS, Issue 4 2009N. Hutchinson Abstract Ultra scale-down approaches represent valuable methods for chromatography development work in the biopharmaceutical sector, but for them to be of value, scale-down mimics must predict large-scale process performance accurately. For example, one application of a scale-down model involves using it to predict large-scale elution profiles correctly with respect to the size of a product peak and its position in a chromatogram relative to contaminants. Predicting large-scale profiles from data generated by small laboratory columns is complicated, however, by differences in dispersion and retention volumes between the two scales of operation. Correcting for these effects would improve the accuracy of the scale-down models when predicting outputs such as eluate volumes at larger scale and thus enable the efficient design and operation of subsequent steps. This paper describes a novel ultra scale-down approach which uses empirical correlations derived from conductivity changes during operation of laboratory and pilot columns to correct chromatographic profiles for the differences in dispersion and retention. The methodology was tested by using 1 mL column data to predict elution profiles of a chimeric monoclonal antibody obtained from Protein A chromatography columns at 3 mL laboratory- and 18.3 L pilot-scale. The predictions were then verified experimentally. Results showed that the empirical corrections enabled accurate estimations of the characteristics of larger-scale elution profiles. These data then provide the justification to adjust small-scale conditions to achieve an eluate volume and product concentration which is consistent with that obtained at large-scale and which can then be used for subsequent ultra scale-down operations. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] | ||||||||||||||||||||||