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  • 1
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 41 (1995), S. 415-425 
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A 1-D model, which neglects radial variations, describes the hydrodynamics of cell-free ultrafiltration hollow-fiber bioreactors (HFBRs) and the transport of highmolecular-weight proteins trapped in the extracapillary space (ECS). The profiles of radially-averaged protein concentrations predicted by this model are identical to those obtained using a model with radial variations. The model predictions agree well with axial profiles of bovine serum albumin (BSA) and human transferrin concentrations measured in transient and steady-state experiments. The validated model explores the influence of cell culture operating conditions on HFBR protein transport. Increasing protein loading decreases BSA and transferrin polarization in HFBRs operated with unidirectional lumen flow. A relationship developed predicts the protein loading needed to ensure a nonzero steady-state protein concentration throughout the ECS. This critical protein loading depends only on the lumen pressure drop and the ECS protein osmotic pressure. Periodic reversal of the lumen flow direction also decreases protein polarization. The influence of the flow-direction switching time and membrane permeability on the ECS protein distribution is investigated.
    Additional Material: 11 Ill.
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  • 2
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 50 (1996), S. 580-586 
    ISSN: 0006-3592
    Keywords: tissue engineering ; N1E-115 neuroblastoma cells ; electrophysiological differentiation ; retinoid cytotoxicity ; teratogenesis ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The cytotoxic effects of retinoids on neuroblastoma cells at various times during electrophysiological differentiation were evaluated. We used N1E-115, a clone of the murine neuroblastoma C1300 derived from the neural crest, and three retinoids: vitamin A (retinol), all-trans retinoic acid (tretinoin), and 13-cis-retinoic acid (isotretinoin). Differentiating N1E-115 cells exposed to retinoids at an isotretinoin EC50 of 16 μM exhibited the greatest vulnerability in terms of cell death during a period (8 to 10 days) that was previously found to be the most sensitive for induction of gross malformations in rodents. This finding suggested possible similarities between the in vivo and in vitro retinoid mechanism(s) of action. The greatest period of vulnerability to retinoid cytotoxicity was also found to coincide with the rapid resting membrane potential (Vm) development period, suggesting a linkage between neuronal Vm and/or electrical excitability development and vulnerability to retinoid cytotoxicity. © 1996 John Wiley & Sons, Inc.
    Additional Material: 5 Ill.
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  • 3
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 50 (1996), S. 125-135 
    ISSN: 0006-3592
    Keywords: ultrafiltration ; proteins ; colloidal interactions ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A rigorous dynamic mathematical model for predicting the rate of ultrafiltration of proteins has been developed. The model is based on sophisticated descriptions of the protein-protein interactions within the layer close to the membrane surface which are responsible for controlling permeation rate. Electrostatic interactions are accounted for by a Wigner-Seitz cell approach, including a numerical solution of the nonlinear Poisson-Boltzmann equation. London-van der Waals forces are calculated using a computationally efficient means of approximating screened, retarded Lifshitz-Hamaker constants. Configurational entropy effects are calculated using an equation of state giving excellent agreement with molecular dynamic data. Electroviscous effects are also taken into account. These descriptions of protein-protein interactions are used to develop an a priori model, with no adjustable parameters, that allows quantitative prediction of the rate of filtration of proteins as a function of zeta potential (and hence pH), ionic strength, applied pressure, protein size, and membrane resistance. A comparison with experimental data for the filtration of bovine serum albumin (BSA) shows that the model is in excellent agreement with such data. © 1996 John Wiley & Sons, Inc.
    Additional Material: 8 Ill.
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 49 (1996), S. 130-138 
    ISSN: 0006-3592
    Keywords: recombinant baculovirus ; virus-like particles ; parvovirus B19 ; multiplicity of infection ; co-infection ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Recombinant human parvovirus B19 virus-like particles (VLPs), a candidate vaccine, were produced using the insect cell (Sf-9)-baculovirus (AcNPV) expression system. The synthesis and assembly of the particles in Sf-9 cells are directed by double infections with one recombinant virus (bacVP1) expressing the parvovirus minor viral protein VP1 and a second virus (bacVP2) expressing the major viral protein VP2. Previous animal studies demonstrated that the polypeptide composition of the VLPs strongly affects the elicitation of virus neutralizing antibodies. The key factor controlling the production of an immunologically potent product in bioreactors was identified to be the multiplicity of infection (MOI) of bacVP1 and bacVP2 used for infection. A probabilistic model, which correlates well with the experimental results, was employed to facilitate the selection of MOIs and to provide a better understanding of the baculovirus co-infection process. A novel production process based on secondary infections was developed to ensure product consistency and to simplify large-scale logistics. The effects of other critical process parameters, such as temperature, dissolved oxygen concentration, lactate concentration, cell concentration at infection, and harvest time, were also investigated. © 1996 John Wiley & Sons, Inc.
    Additional Material: 11 Ill.
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 46 (1995), S. 28-35 
    ISSN: 0006-3592
    Keywords: microfiltration ; membrane ; enzyme ; fouling ; atomic force microscopy ; photon correlation spectroscopy ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The transmission and rate of filtration of the enzyme yeast alcohol dehydrogenase (YADH) has been studied at capillary pore microfiltration membranes. Photon correlation spectroscopy (PCS) with nanometer resolution showed that the enzyme existed as discreate molecules only for a narrow range of pH and ionic strength. Under such conditions, the transmission of the enzyme was high. However, the rate of filtration still decreased continuously with time. Analyssis of the time dependence of the rate of filtration indicated that this decrease was due to in-pore enzyme deposition at low concentration (“standard blocking model”) and suface depositon at high concentration (“cake filtration model”). Use of atomic force microscopy (AFM) gave unequivocal and quantitative confirmation of these inferences. The work shows the great advantage of using advanced physical characterization techniques, both for the identification of the optimum conditions for filtration (PCS) and for the elucidation of mechanisms giving rise to inefficiencies in the filtration process (AFM). © 1995 John Wiley & Sons, Inc.
    Additional Material: 10 Ill.
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 48 (1995), S. 559-572 
    ISSN: 0006-3592
    Keywords: ion exchange ; amino acids ; microcalorimetry ; thermodynamics ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The thermodynamics and energetics of the ion exchange of four amino acids at a cellulosic ion exchanger have been studied. Experimental work included determination of ion exchange isotherms and the use of high-sensitivity titration microcalorimetry. A rigorous thermodynamic analysis of the data was developed allowing calculation of the standard free energy, the standard enthalpy, and standard entropy of exchange, and also the differential free energy, incremental enthalpy, and incremental entropy of exchange. The results show that the relative contributions of the enthalpy and entropy to the overall free energy differ markedly for the chosen amino acids. The reasons for these differences are analyzed and discussed. A knowledge of these fundamental thermodynamic properties indicates the solution conditions likely to give enhanced affinity of the ion exchanger for selected amino acids. The experimental techniques and analysis procedures developed are generally applicable to ion exchange separations of biomolecules. © 1995 John Wiley & Sons, Inc.
    Additional Material: 7 Ill.
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  • 7
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Computational Chemistry 19 (1998), S. 1370-1386 
    ISSN: 0192-8651
    Keywords: acyl halides ; MM3 ; ab initio calculations ; conformational analysis ; Chemistry ; Theoretical, Physical and Computational Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Computer Science
    Notes: A new molecular mechanics (MM3) force field has been developed based on various experimental data as well as ab initio calculations. Computer-generated molecular structures and energy values were compared with experimentally determined data. The acyl halides studied were formyl halides, acetyl halides, propionyl halides, n-butyryl halides, 2-methylpropionyl halides, and 2,2-dimethylpropionyl halides. The rms deviations were 0.005 Å and 1.06° for bond lengths and bond angles, respectively. MM3 was in good overall agreement with the available structural, conformational, and thermodynamic data.   © 1998 John Wiley & Sons, Inc.   J Comput Chem 19: 1370-1386, 1998
    Additional Material: 2 Ill.
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Computational Chemistry 16 (1995), S. 1250-1260 
    ISSN: 0192-8651
    Keywords: Computational Chemistry and Molecular Modeling ; Biochemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Computer Science
    Notes: High-level ab initio calculations have been performed on N-methyl-N-methyleneammonium and related compounds to obtain accurate rotational barriers, structures, and vibrational frequencies. The 6-31G** basis set has been utilized at the Hartree-Fock level of theory for these calculations because little experimental data are available. The MM2(91) and MM3(94) force fields have been parameterized to include these nonconjugated charged nitrogen-containing compounds. Molecular mechanics geometries and vibrational frequencies compare well with the ab initio results. © 1995 John Wiley & Sons, Inc.
    Additional Material: 3 Ill.
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Computational Chemistry 17 (1996), S. 1395-1405 
    ISSN: 0192-8651
    Keywords: Chemistry ; Theoretical, Physical and Computational Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Computer Science
    Notes: Ab initio calculations have been carried out on s-trans-N-vinylmethyleneammonium, pyridinium, and related compounds to obtain rotational barriers, structures, and vibrational frequencies. The restricted Hartree-Fock (RHF) level of theory with 6-31G** basis set was used for these calculations. In addition, the MM2(91) and MM3(94) force fields have been parameterized to calculate these positively charged nitrogen-containing compounds. A bond order term was incorporated in the force field to reproduce accurately the rotational barriers of s-trans-N-vinylmethyleneammonium and related compounds. Molecular mechanics geometries and vibrational frequencies compare well with those calculated by ab initio methods. © 1996 by John Wiley & Sons, Inc.
    Additional Material: 5 Ill.
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  • 10
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Computational Chemistry 17 (1996), S. 940-953 
    ISSN: 0192-8651
    Keywords: Chemistry ; Theoretical, Physical and Computational Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Computer Science
    Notes: The multiparameter multistep relaxation (MPMSR) method, a routine within a new suite of parameterization programs entitled parameter analysis and refinement toolkit system (PARTS), was developed to assist in the development of molecular mechanics (MM3 and MM2) force field parameters and represents an ongoing effort in our laboratories to generate more accurate force fields in shorter times. In contrast to other computerized parameterization approaches, this method simulates intuition guided trial-and-error and has been used successfully within our laboratories to develop MM2 and MM3 force fields. The primary aim of this approach is to minimize human inspection time and effort, with simultaneous improvement in the efficiency and accuracy of the parameterization process. In an effort to validate the generality of the MPMSR method, a well parameterized data set of phosphine derivatives was reexamined. With the identical set of training molecules used in the original MM3 phosphine parameterization and with minimal human intervention, MPMSR shortened the process from several months to approximately five days. Although the previous phosphine force field is well parameterized, the newly generated MPMSR set of parameters has achieved an overall better fit to the experimentally observed data and ab initio calculations. © 1996 by John Wiley & Sons, Inc.
    Additional Material: 15 Tab.
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