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1

Electronic Resource

Understanding drug resistance for monotherapy treatment of HIV infection (1997)

Kirschner, Denise E. ; Webb, G. F.

Springer

Bulletin of mathematical biology 59 (1997), S. 763-785

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ISSN: 1522-9602

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Mathematics

Notes: Abstract The purpose of this study was to investigate strategies in the monotherapy treatment of HIV infection in the presence of drug-resistant (mutant) strains. A mathematical system is developed to model resistance in HIV chemotherapy. It includes the key players in the immune response to HIV infection: virus and both uninfected CD4+ and infected CD4+ T-cell populations. We model the latent and progressive stages of the disease, and then introduce monotherapy treatment. The model is a system of differential equations describing the interaction of two distinct classes of HIV—drug-sensitive (wild type) and drug-resistant (mutant)—with lymphocytes in the peripheral blood. We then introduce chemotherapy effects. In the absence of treatment, the model produces the three types of qualitative clinical behavior—anuninfected steady state, andinfected steady state (latency), andprogression to AIDS. Simulation of treatment is provided for monotherapy, during theprogression to AIDS state, in the consideration of resistance effects. Treatment benefit is based on an increase or retention in CD4+ T-cell counts together with a low viral titer. We explore the following treatment approaches: an antiviral drug which reduces viral infectivity that is administered early—when the CD4+ T-cell count is ≥300/mm3, and late—when the CD4+ T-cell count is less than 300/mm3. We compare all results with data. When treatment is initiated during the progression to AIDS state, treatment prevents T-cell collapse, but gradually loses effectiveness due to drug resistance. We hypothesize that it is the careful balance of mutant and wild-type HIV strains which provides the greatest prolonged benefit from treatment. This is best achieved when treatment is initiated when the CD4+ T-cell counts are greater than 250/mm3, but less than 400/mm3 in this model (i.e. not too early, not too late). These results are supported by clinical data. The work is novel in that it is the first model to accurately simultate data before, during and after monotherapy treatment. Our model also provides insight into recent clinical results, as well as suggests plausible guidelines for clinical testing in the monotherapy of HIV infection.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF02458429

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2

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A model for treatment strategy in the chemotherapy of AIDS (1996)

Kirschner, Denise ; Webb, G. F.

Springer

Bulletin of mathematical biology 58 (1996), S. 367-390

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ISSN: 1522-9602

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Mathematics

Notes: Abstract Mathematical models are developed for the chemotherapy of AIDS. The models are systems of differential equations describing the interaction of the HIV infected immune system with AZT chemotherapy. The models produce the three types of qualitative clinical behavior: anuninfected steady state, aninfected steady state (latency) and aprogression to AIDS state. The effect of treatment is to perturb the system from progression to AIDS back to latency. Simulation of treatment schedules is provided for the consideration of treatment regimes. The following issues of chemotherapy are addressed: (i) daily frequency of treatment, (ii) early versus late initiation of treatment and (iii) intermittent treatment with intervals of no treatment. The simulations suggest the following properties of AZT chemotherapy: (i) the daily period of treatment does not affect the outcome of the treatment, (ii) treatment should not begin until after the final decline of T cells begins (not until the T cell population falls below approximately 300 mm−3) and then, it should be administered immediately and (iii) a possible strategy for treatment which may cope with side effects and/or resistance, is to treat intermittently with chemotherapy followed by interruptions in the treatment during which either a different drug or no treatment is administered. These properties are revealed in the simulations, as the model equations incorporate AZT chemotherapy as a weakly effective treatment process. We incorporate into the model the fact that AZT treatment does not eliminate HIV, but only restrains its progress. The mathematical model, although greatly simplified as a description of an extremely complex process, offers a means to pose hypotheses concerning treatment protocols, simulate alternative strategies and guide the qualitative understanding of AIDS chemotherapy.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF02458312

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3

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A financial model of cable television with a simulation analysis of the 1993 rate regulations (1995)

Webb, G. Kent

Springer

Telecommunication systems 4 (1995), S. 217-239

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ISSN: 1572-9451

Source: Springer Online Journal Archives 1860-2000

Topics: Electrical Engineering, Measurement and Control Technology

Notes: Abstract As an illustration of how a widely accepted financial analysis format can be developed into a simulation tool to investigate economic issues for telecommunications systems, a pro forma cash flow model of cable television is developed using regression analysis of market demand and operating costs, and engineering analysis of capital costs. The model can be used to simulate financial performance for a cable television system to investigate the impact of different market conditions, system or service configurations, and pricing structures. Results of some model simulations indicate that cable systems significantly benefit from higher consumer density, benefit somewhat from system size, and may have some monopoly power with regard to price. Large urban systems seem to be favored by the FCC's 1993 benchmark prices.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF02110088

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4

Electronic Resource

Preface to UMUAI Special Issue on Machine Learning for User Modeling (1998)

Webb, G.

Springer

User modeling and user adapted interaction 8 (1998), S. 1-3

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ISSN: 1573-1391

Source: Springer Online Journal Archives 1860-2000

Topics: Computer Science

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1008297609075

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5

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Lie Algebraic Control for the Stabilization of Nonlinear Multibody System Dynamics Simulation (1999)

Kurdila, A. ; Fitz-Coy, N. ; McDaniel, D. ; [et al.]

Springer

Nonlinear dynamics 20 (1999), S. 55-84

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ISSN: 1573-269X

Keywords: nonlinear multibody dynamics ; Lie algebra ; constraint stabilization

Source: Springer Online Journal Archives 1860-2000

Topics: Mathematics

Notes: Abstract It is well known that when equations of motion are formulated using Lagrange multipliers for multibody dynamic systems, one obtains a redundant set of differential algebraic equations. Numerical integration of these equations can lead to numerical difficulties associated with constraint violation drift. One approach that has been explored to alleviate this difficulty has been contraint stabilization methods. In this paper, a family of stabilization methods are considered as partial feedback linearizing controllers. Several stabilization methods including the range space method, null space method, Baumgarte's method, and the damping and stiffness penalty methods are examined. Each can be construed as a particular partial feedback linearizing controller. The paper closes by comparing several of these constraint stabilization methods to another method suggested by construction: the variable structure sliding (VSS) control. The VSS method is found to be the most efficient, stable, and robust in the presence of singularities.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1008343308662

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6

Electronic Resource

NMR study of some sydnones, isosydnones, and isothiosydnones (1996)

Bocian, W. ; Jaźwiński, J. ; Staszewska, O. ; [et al.]

Springer

Chemistry of heterocyclic compounds 32 (1996), S. 1358-1366

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ISSN: 1573-8353

Keywords: Ab initio calculations ; charge distribution ; mesoionic structures ; multinuclear NMR ; protonation site

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology

Notes: Abstract Multinuclear1H,13C,14N,15N, and17O NMR data are presented for some sydnones, isosydnones and isothiosydnones. The type of valence tautomerism shown in (Fig. 1) is not observed for the compounds studied. At high pH compounds2 and12 are found to undergo transformations. The more suitable NMR parameters are reported for establishing the structures of mesoionic compounds containing three heteroatoms in the five-membered conjugated ring. Someab initio GIAO calculations on a model structure of sydnones and related compounds have been performed.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF01169966

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7

Electronic Resource

15N and 13C NMR study of two adducts containing NHN+ and NHN- hydrogen bonds (1996)

Klimkiewicz, J. ; Stefaniak, L. ; Grech, E. ; [et al.]

Chichester : Wiley-Blackwell

Journal of Physical Organic Chemistry 9 (1996), S. 781-786

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ISSN: 0894-3230

Keywords: Chemistry ; Theoretical, Physical and Computational Chemistry

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Chemistry and Pharmacology , Physics

Notes: 13C and 15N NMR data are reported for two substituted nitronaphthalenes 1,8-bis(4-toluenesulphonamido)-2,4,7-trinitronaphthalene and 1,8-bis(4-toluenesulphonamido)-2,4,5,7-tetranitronaphthalene and their salts with 1,8-dimethylaminonaphthalene. The salts are shown to contain NHN+ and NHN- intramolecular hydrogen-bonded systems in CD3CN solutions, in agreement with x-ray diffraction data on solid samples and 1H NMR studies on solutions. Examples are given of both a symmetrical and an unsymmetrical bonding system for the NHN atoms. 15N NMR is shown to be particularly helpful in these studies, both 15N shielding and 1J(15N, 1H) couplings are of value. Additional assistance is obtained from 3J(13C9, N1H) data. © 1996 John Wiley & Sons, Ltd.

Additional Material: 1 Ill.

Type of Medium: Electronic Resource

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