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  • Electronic Resource  (6)
  • 1990-1994  (6)
  • Engineering General  (3)
  • degradation  (3)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 11 (1994), S. 72-76 
    ISSN: 1573-904X
    Keywords: interleukin 11 (IL-11) ; recombinant human IL-11 ; degradation ; kinetics ; products ; aspartate–proline cleavage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Recombinant human interleukin 11 (rhIL-11) is a multispectrum cytokine that plays an important role in megakaryocytopoiesis and platelet production. Probing rhIL-11 chemical reactivity in aqueous solution is an important initial step in developing a dosage form for rhIL-11 clinical trials. This report documents rhIL-11 degradation kinetics at 50°C in solutions adjusted to pH 3.0 to 9.5. Stressed samples were analyzed by reverse-phase HPLC and degradation product peaks were isolated for structural characterization. The results show maximal stability in the region pH 6.5 to 7.0. Degradation product identification shows that the major reaction pathway in acidic solution involves peptide cleavage at aspartate133–proline134. In alkaline solution, protein disappearance proceeds via nonspecific loss to container surfaces. Degradation products at alkaline pH have not been identified.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Keywords: macrophage colony stimulating factor ; rhM-CSF ; degradation ; products ; mass spectrometry ; bioactivity ; β-elimination ; aspartate-proline cleavage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Recombinant human macrophage colony-stimulating factor (rhM-CSF) promotes macrophage proliferation and activity. rhM-CSF clinical trials are currently in progress and require a stable, pharmaceutically acceptable dosage form. This report documents pH effects on rhM-CSF degradation profiles in aqueous solution, with an emphasis on identifying degradation products. Thus, highly purified rhM-CSF was maintained at 30 to 50°C in solutions adjusted to pH 2 to 10. Stressed samples were analyzed by SDS-PAGE, reverse-phase HPLC, size exclusion HPLC, scanning microcalorimetry, and murine bone marrow activity. The results show maximal protein stability in the region pH 7 to 8. Degradation product chromatographic and electrophoretic analyses show distinctly different degradation product profiles in acidic versus alkaline solution. For samples stressed in acidic solution, degradation products were isolated chromatographically and electrophoretically. These degradation products were characterized by N-terminal amino acid sequencing, fast-atom bombardment mass spectrometry, and peptide mapping. The results show that the major degradation pathway in acidic solution involves peptide cleavage at two sites: aspartate169-proline170 and aspartate213-proline214. A third potential cleavage site (aspartate45-proline46) remains intact under conditions that cleave Asp169-Pro170 and Asp213-Pro214. In alkaline solution, degradation proceeds via parallel cleavage and intramolecular cross-linking reactions. A β-elimination mechanism is proposed to account for the degradation in alkaline solution. Consistent with literature observations, the rhM-CSF N-terminal cleavage products retain biological activity.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 9 (1992), S. 939-944 
    ISSN: 1573-904X
    Keywords: calorimetry ; microcalorimetry ; stability ; kinetics, solid state ; degradation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A new technique has been developed to calculate rapidly the solid-state room-temperature degradation rate of drugs and drug candidates. The technique utilizes measurements of the initial rate of heat output at several elevated temperatures by isothermal calorimetry and the degradation rate of the compound determined at a single elevated temperature by chromatography. The activation energies and degradation rates at 25°C calculated by conventional methods and by isothermal calorimetry are compared and discussed. The compounds studied were phenytoin, triamterene, digoxin, tetracycline, theophylline, diltiazem, and several proprietary ICI compounds.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    International Journal for Numerical Methods in Fluids 12 (1991), S. 911-928 
    ISSN: 0271-2091
    Keywords: Direct stress solution ; Vertical velocity profiles ; Three-dimensional circulation model ; Spectral methods ; Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: A simple technique is presented that allows a numerical solution to be sought for the vertical variation of shear stress as a substitute for the vertical variation of velocity in a three-dimensional hydrodynamic model. In its most general form the direct stress solution (DSS) method depends only upon the validity of an eddy viscosity relation between the shear stress and the vertical gradient of velocity. The rationale for preferring a numerical solution for shear stress to one for velocity is that shear stress tends to vary more slowly over the vertical than velocity, particularly near boundaries. Consequently, a numerical solution can be obtained much more efficiently for shear stress than for velocity. When needed, the velocity profile can be recovered from the stress profile by solving a one-dimensional integral equation over the vertical. For most practical problems this equation can be solved in closed form.Comparisons are presented between the DSS technique, the standard velocity solution technique and analytical solutions for wind-driven circulation in an unstratified, closed, rectangular channel governed by the linear equations of motion. In no case was the computational effort required by the velocity solution competitive with the DSS when a physically realistic boundary layer was included.The DSS technique should be particularly beneficial in numerical models of relatively shallow water bodies in which the bottom and surface boundary layers occupy a significant portion of the water column.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    International Journal for Numerical Methods in Fluids 12 (1991), S. 835-857 
    ISSN: 0271-2091
    Keywords: Boundary element ; Free surface ; Hydrodynamic ; Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Free surface phenomena are described by equations that exhibit two types of non-linearities. The first is inherent to the equations themselves and the second is caused by the application of boundary conditions at a free surface at an unknown location. Numerical calculations usually do not specifically recognize the second non-linearity, nor treat it in a fashion consistent with the more obvious non-linearities in the boundary conditions. A consistent formulation is introduced in the present paper. The field equation is integrated and the free surface boundary conditions are applied on the unknown geometry by means of appropriate series expansions. The consistent formulation introduces improvements in accuracy and computing speed. The method is demonstrated on several hydrodynamic free surface problems and an error analysis is included.
    Additional Material: 16 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    International Journal for Numerical Methods in Fluids 19 (1994), S. 295-319 
    ISSN: 0271-2091
    Keywords: Three-dimensional circulation model ; Direct stress solution ; Internal mode solution ; Velocity profile ; Boundary layers ; Tidal flow ; Wind-driven flow ; Finite element method ; Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Velocity varies rapidly near sheared boundaries. Therefore in many practical fluid problems it can be inefficient to solve discrete equations with velocity as the dependent variable. Conversely, shear stress varies slowly near sheared boundaries, suggesting that it may be well suited for use as the dependent variable in discrete equations.This paper describes a formulation of the internal mode equations for a three-dimensional hydrodynamic model using shear stress as the dependent variable. The resulting direct stress solution (DSS), coupled with a spatial discretization using linear finite elements, yields a system matrix that can be set up and solved with the efficiency of a banded matrix with bandwidth 8. If the eddy viscosity distribution is assumed to be piecewise linear over the depth (with an arbitrary number of time-varying segments), the recovery of velocity from stress can be easily accomplished in closed form, thereby avoiding any difficulty resulting from the logarithmic singularity in the velocity profile that occurs at a boundary.Results from tidal and wind-driven test cases with realistic boundary layers are used to demonstrate the accuracy and computational advantages of a DSS formulation versus a standard velocity-based formulation.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
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