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  • 1
    Publication Date: 2020-11-12
    Description: Slope dynamics in volcanic environments comprise a wide spectrum of phenomena, from large lateral collapse to shallow debris remobilization, which may represent a major threat for human communities and infrastructures. Many volcanos built up from the ocean floor and large portions of the volcano edifice are submerged. In these settings, only the edifice’s summit can be investigated by terrestrial remote sensing and in-situ approaches. Growth and destruction, including tectonics and gravitational phenomena, affect entire volcano flanks and are not limited to the physical boundary of the sea level but could comprise their subaqueous parts.
    Description: Published
    Description: 2615–2618
    Description: 6V. Pericolosità vulcanica e contributi alla stima del rischio
    Description: JCR Journal
    Keywords: volcanoes ; flanks ; volcano-tectonics ; structure ; collapse ; stability ; 04.08. Volcanology ; 05.08. Risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 2
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    Mycorrhiza 10 (2000), S. 15-21 
    ISSN: 1432-1890
    Keywords: Anthoceros punctatus ; Arbuscular mycorrhiza ; Bryophytes ; Glomus ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Glomus claroideum (Schenck & Smith emend. Walker & Vestberg) were investigated for ability to form arbuscular mycorrhiza-like symbioses with the hornwort Anthoceros punctatus (L.). Spores were transferred to a cellulose acetate filter on water agar and a small portion of an Anthoceros thallus was placed directly upon the spores. Light-microscope observations 20 days after inoculation revealed branched hyphae growing within the thallus. After 45 days, arbuscules and vesicles were studied by light- and electron-microscopy. After 60 days in water agar culture, the colonised Anthoceros thalli were transferred to a low-nutrient medium agar. Hyphae spread in the agar and newly formed spores were observed 5 weeks after the transfer. After 4 months, about 1000 spores were formed in each Petri dish. This is the first report of an experimentally established arbuscular mycorrhiza-like symbiosis between an identified fungus belonging to the Glomales and a bryophyte.
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    Journal of comparative physiology 186 (2000), S. 347-357 
    ISSN: 1432-1351
    Keywords: Key words Crustacean ; Sensorimotor ; Ultrastructure ; Multilamellar sheath ; Myelinated axons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Speed of nerve impulse conduction is greatly increased by myelin, a multi-layered membranous sheath surrounding axons. Myelinated axons are ubiquitous among the vertebrates, but relatively rare among invertebrates. Electron microscopy of calanoid copepods using rapid cryofixation techniques revealed the widespread presence of myelinated axons. Myelin sheaths of up to 60 layers were found around both sensory and motor axons of the first antenna and interneurons of the ventral nerve cord. Except at nodes, individual lamellae appeared to be continuous and circular, without seams, as opposed to the spiral structure of vertebrate and annelid myelin. The highly organized myelin was characterized by the complete exclusion of cytoplasm from the intracellular spaces of the cell generating it. In regions of compaction, extracytoplasmic space was also eliminated. Focal or fenestration nodes, rather than circumferential ones, were locally common. Myelin lamellae terminated in stepwise fashion at these nodes, appearing to fuse with the axolemma or adjacent myelin lamellae. As with vertebrate myelin, copepod sheaths are designed to minimize both resistive and capacitive current flow through the internodal membrane, greatly speeding nerve impulse conduction. Copepod myelin differs from that of any other group described, while sharing features of every group.
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  • 4
    ISSN: 1432-041X
    Keywords: Key words Brain development ; Axonal scaffold ; Extradenticle ; Homothorax ; Drosophila
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  During early brain development in Drosophila a highly stereotyped pattern of axonal scaffolds evolves by precise pioneering and selective fasciculation of neural fibers in the newly formed brain neuromeres. Using an axonal marker, Fasciclin II, we show that the activities of the extradenticle (exd) and homothorax (hth) genes are essential to this axonal patterning in the embryonic brain. Both genes are expressed in the developing brain neurons, including many of the tract founder cluster cells. Consistent with their expression profiles, mutations of exd and hth strongly perturb the primary axonal scaffolds. Furthermore, we show that mutations of exd and hth result in profound patterning defects of the developing brain at the molecular level including stimulation of the orthodenticle gene and suppression of the empty spiracles and cervical homeotic genes. In addition, expression of a Drosophila Pax6 gene, eyeless, is significantly suppressed in the mutants except for the most anterior region. These results reveal that, in addition to their homeotic regulatory functions in trunk development, exd and hth have important roles in patterning the developing brain through coordinately regulating various nuclear regulatory genes, and imply molecular commonalities between the developmental mechanisms of the brain and trunk segments, which were conventionally considered to be largely independent.
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    Development genes and evolution 210 (2000), S. 157-161 
    ISSN: 1432-041X
    Keywords: Key words Swallow ; bicoid ; Drosophila ; mRNA localization ; Oogenesis ; Embryogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  We analyzed a functional homologue of the swallow gene from Drosophila pseudoobscura. The swallow gene of D. melanogaster plays an essential role in localizing bicoid mRNA in oocytes, and swallow mutant embryos show anterior pattern defects that result from the lack of localization of the bicoid morphogen. The pseudoobscura homologue rescues the function of swallow mutants when introduced into the genome of D. melanogaster, and its expression is similar to that of the melanogaster gene. The predicted pseudoobscura and melanogaster proteins are 49% identical and 69% conserved. The coiled-coil domain previously identified in the melanogaster swallow protein is strongly conserved in the pseudoobscura homologue, but the weak similarity of the melanogaster swallow protein to the RNP class of RNA-binding proteins is not conserved in the pseudoobscura homologue. These and other observations suggest a structural role for swallow in localizing bicoid mRNA, perhaps as part of the egg cytoskeleton.
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    Development genes and evolution 210 (2000), S. 190-199 
    ISSN: 1432-041X
    Keywords: Key words Ventral neuroectoderm ; Cell shape ; Achaete-scute complex ; Drosophila
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  In the embryonic ventral neuroectoderm of Drosophila melanogaster the proneural genes achaete, scute, and lethal of scute are expressed in clusters of cells from which the neuroblasts delaminate in a stereotyped orthogonal array. Analyses of the ventral neuroectoderm before and during delamination of the first two populations of neuroblasts show that cells in all regions of proneural gene activity change their form prior to delamination. Furthermore, the form changes in the neuroectodermal cells of embryos lacking the achaete-scute complex, of embryos mutant for the neurogenic gene Delta, and of embryos overexpressing l’sc suggest that these genes are responsible for most of the morphological alterations observed.
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    Circuits, systems and signal processing 19 (2000), S. 13-25 
    ISSN: 1531-5878
    Keywords: Singular systems ; delay ; consistency condition ; stability ; instability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: Abstract In this paper, the general class of singular systems with delay and linear constant coefficient singular systems with delay are discussed. First, several definitions of stability are presented for singular systems with delay, and general sufficient stability conditions and instability conditions are obtained. Second, stability and instability are analyzed for linear constant coefficient singular systems with delay.
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    Circuits, systems and signal processing 19 (2000), S. 423-435 
    ISSN: 1531-5878
    Keywords: Time-varying autoregressive models ; stability ; smoothness priors ; Tihkonov regularization ; constrained optimization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: Abstract The stability of time-varying autoregressive (AR) models is an important issue in such applications as time-varying spectrum estimation and electroencephalography simulation and estimation. In some cases, such as time-varying spectrum estimation, the models that exhibit roots near unit moduli are difficult to use. Thus a tighter stability condition such as stability with a positive margin is needed. A time-varying AR model is stable with a positive margin if the moduli of the roots of the time-varying characteristic polynomial are somewhat less than unity for every time instant. Recently, a new method for the estimation of the time-varying AR models was introduced. This method is based on the interpretation of the underdetermined time-varying prediction equations as an ill-posed inverse problem that is solved by Tikhonov regularization. The method is referred to as the deterministic regression smoothness priors (DRSP) scheme. In this paper, a stabilization method in which the DRSP scheme is augmented with nonlinear stability constrainst is proposed. The problem is formulated so that stability with a positive margin can also be achieved. The problem is solved iteratively with an exterior point algorithm. The performance of the algorithm is studied with a simulation. It is shown that the proposed approach is well suited to stable modeling of signals containing narrowband transitions.
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    Entomologia experimentalis et applicata 94 (2000), S. 159-171 
    ISSN: 1570-7458
    Keywords: Drosophila ; induction ; habituation ; associative learning ; T-maze olfactometer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Experiments reported in this paper investigate the properties of a change in the responsiveness of adult Drosophila melanogaster induced by exposure to different rearing media. This effect has previously been described as habituation or associative learning. Exposure to food medium containing 0.08% menthol induced a positive response to menthol odour in a T-maze olfactometer. A brief (one hour) exposure to mentholic food just before testing was sufficient to induce a change in responsiveness. The effect did not persist through periods of more than an hour of separation from mentholic medium. Effects induced by exposure to a single compound were not specific to that compound alone. Menthol-reared flies (MRFs) differed from plain reared flies (PRFs) in their responsiveness to the odours of benzaldehyde and ethyl acetate, as well as menthol, and exposure to ethyl acetate induced a change in response to menthol odour. That there was an induced positive response to menthol in MRFs suggests that conventional habituation is insufficient to explain the induced change in responsiveness, but the generalised nature of this behavioural induction in MRFs is hard to explain in terms of associative learning. The mechanism underlying the induction remains elusive.
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  • 10
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    Acta biotheoretica 48 (2000), S. 207-218 
    ISSN: 1572-8358
    Keywords: Dynamical population ; fishing efforts ; metapopulation ; time scales ; aggregation method ; equilibrium ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract This work presents a specific stock-effort dynamical model. The stocks correspond to two populations of fish moving and growing between two fishery zones. They are harvested by two different fleets. The effort represents the number of fishing boats of the two fleets that operate in the two fishing zones. The bioeconomical model is a set of four ODE's governing the fishing efforts and the stocks in the two fishing areas. Furthermore, the migration of the fish between the two patches is assumed to be faster than the growth of the harvested stock. The displacement of the fleets is also faster than the variation in the number of fishing boats resulting from the investment of the fishing income. So, there are two time scales: a fast one corresponding to the migration between the two patches, and a slow time scale corresponding to growth. We use aggregation methods that allow us to reduce the dimension of the model and to obtain an aggregated model for the total fishing effort and fish stock of the two fishing zones. The mathematical analysis of the model is shown. Under some conditions, we obtain a stable equilibrium, which is a desired situation, as it leads to a sustainable harvesting equilibrium, keeping the stock at exploitable densities.
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    Ecological research 15 (2000), S. 93-100 
    ISSN: 1440-1703
    Keywords: aggregation ; coexistence ; Drosophila ; parasitism ; patch size
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: We carried out field experiments to investigate the coexistence of Drosophila species in domestic and forest areas on the basis of the aggregation model. Three cosmopolitan species Drosophila simulans Sturtevant, Drosophila melanogaster Meigen and Drosophila immigrans Sturtevant, and a native species, Drosophila auraria Peng, emerged abundantly from banana placed at the domestic station, while Drosophila immigrans and five native species, Drosophila lutescens Okada, Drosophila rufa Kikkawa and Peng, Drosophila bizonata Kikkawa and Peng, Drosophila sternopleuralis Okada and Kurokawa and Scaptodrosophila coracina (Kikkawa and Peng), were abundant at the forest station. The present analysis suggests that their coexistence was facilitated by the aggregation mechanism. In the cosmopolitan species, the density of individuals that emerged from patches increased with the increase of patch size, but the relationship between fly density and patch size was not clear in the native species. This difference in distribution patterns between the cosmopolitan and native species is likely to be due to the difference in the female visiting behavior. In the present analysis, however, it was not clear whether patch size diversity facilitated their coexistence or not. The effect of patch size diversity may have been masked, because the effect of aggregation was more prominent. The rate of parasitism by wasps was high in October at the domestic station, and in May and June at the forest station. The present result suggests that the rate of parasitism was density-dependent, at least at the domestic station, and therefore parasitism facilitates the coexistence of drosophilid species in domestic areas.
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    ISSN: 1572-8889
    Keywords: courtship song ; wingbeat ; sexual isolation ; Drosophila
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    Topics: Biology
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    Catalysis letters 68 (2000), S. 55-58 
    ISSN: 1572-879X
    Keywords: promoting effect ; B2O3 ; Cu/ZnO/Al2O3 catalyst ; methanol synthesis ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The addition of B2O3 to a Cu/ZnO/Al2O3 catalyst increased the activity of the catalyst for methanol synthesis after an induction period during the reaction. The stability of the B2O3-containing Cu/ZnO/Al2O3 catalyst was greatly improved by the addition of a small amount of colloidal silica to the catalyst.
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  • 14
    ISSN: 1572-879X
    Keywords: potassium desorption ; stability ; excitation ; iron catalyst ; Rydberg atoms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Well‐characterized catalyst model compounds of KAlO2 and KFeO2 are investigated by thermal desorption of potassium from the material. The desorbing fluxes of ions, atoms and highly excited states (field ionizable Rydberg states) were studied with surface and field ionization detectors in a vacuum apparatus. From the Arrhenius plots the activation energies for desorption of K and K+ were determined. The chemical state of potassium at the surfaces is concluded to be: ionic on KAlO2 (with the K desorption barrier of 1.76 eV) and covalent on KFeO2 (barrier of 2.73 eV). These results agree with the data obtained earlier for industrial catalysts for ammonia and styrene production. They are interpreted in terms of the Schottky cycle, which is completed for KAlO2 and fails for KFeO2. This failure indicates a non‐equilibrium desorption process. K Rydberg states are only found to desorb from KFeO2, in agreement with the suggestion that such states in some way are responsible for the catalytic activity.
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    Acta applicandae mathematicae 62 (2000), S. 23-130 
    ISSN: 1572-9036
    Keywords: stability ; functional equations ; Cauchy difference ; semigroup ; inequalities ; approximate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract In this paper, we study the stability of functional equations that has its origins with S. M. Ulam, who posed the fundamental problem 60 years ago and with D. H. Hyers, who gave the first significant partial solution in 1941. In particular, during the last two decades, the notion of stability of functional equations has evolved into an area of continuing research from both pure and applied viewpoints. Both classical results and current research are presented in a unified and self-contained fashion. In addition, related problems are investigated. Some of the applications deal with nonlinear equations in Banach spaces and complementarity theory.
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    Journal of intelligent and robotic systems 27 (2000), S. 195-209 
    ISSN: 1573-0409
    Keywords: wall-climbing robot ; electromagnetic grippers ; stability ; additional support element ; sliding and turning over conditions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Legged-climbing robot is considered. Each foot of the robot has an electromagnet system for robot"s holding on a metal surface. This surface can be both vertical and inclined, including negative slope. Analytical calculation of robot stability under turn over or sliding conditions has been made. Critical slopes have been determined. One of these slopes corresponds to minimal reserve of robot stability towards sliding and another to minimal reserve of robot stability towards turning-over. As total reserve of stability of a robot is always equal to the minimal one of these reserves. Additional support elements of elastic material with high coefficient of friction, along with electromagnet, allows to increase minimal reserve of robot stability towards sliding. The use of such support elements leads to redistributing force of normal support reaction between electromagnet (which surface has low coefficient of friction) and additional support element (which surface has high coefficient of friction). It is just what leads to increasing the total friction force and as a consequence to increasing of minimal reserve of robot stability towards sliding.
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    Letters in mathematical physics 53 (2000), S. 313-320 
    ISSN: 1573-0530
    Keywords: partial differential equations ; nonlinearities ; symmetries ; stability ; minimization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics , Physics
    Notes: Abstract We suggest a simple but general method of establishing symmetry properties of stable solutions of nonlinear elliptic equations. The method relies on characterization of symmetry breaking with a help of zero modes and on a generalization of the Perron–Frobenius theory.
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  • 18
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    Celestial mechanics and dynamical astronomy 78 (2000), S. 227-241 
    ISSN: 1572-9478
    Keywords: stability ; normal form ; spin-orbit resonance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We consider a model of spin-orbit interaction, describing the motion of an oblate satellite rotating about an internal spin-axis and orbiting about a central planet. The resulting second order differential equation depends upon the parameters provided by the equatorial oblateness of the satellite and its orbital eccentricity. Normal form transformations around the main spin-orbit resonances are carried out explicitly. As an outcome, one can compute some invariants; the fact that these quantities are not identically zero is a necessary condition to prove the existence of nearby periodic orbits (Birkhoff fixed point theorem). Moreover, the nonvanishing of the invariants provides also the stability of the spin-orbit resonances, since it guarantees the existence of invariant curves surrounding the periodic orbit.
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    Journal of dynamics and differential equations 12 (2000), S. 117-167 
    ISSN: 1572-9222
    Keywords: singular perturbation ; standing pulses ; stability ; Hopf bifurcation ; reaction-diffusion system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract Bifurcation phenomena from standing pulse solutions of the problem $$\varepsilon \tau u_t = \varepsilon ^2 u_{xx} + f(u,v),{\text{ }}v_t = v_{xx} + g(u,v)$$ is considered. ε(〉0) is a sufficiently small parameter and τ is a positive one. It is shown that there exist two types of destabilization of standing pulse solutions when τ decreases. One is the appearance of travelling pulse solutions via the static bifurcation and the other is that of in-phase breathers via the Hopf bifurcation. Furthermore which type of destabilization occurs first with decreasing τ is discussed for the piecewise linear nonlinearities f and g.
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    Queueing systems 34 (2000), S. 1-35 
    ISSN: 1572-9443
    Keywords: multiple access ; CDMA ; rates of convergence ; stability ; functional limit theorems ; transient analysis ; Markov-modulated capture channel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract We consider the slotted ALOHA protocol on a channel with a capture effect. There are M 〈 ∞ users each with an infinite buffer. If in a slot, i packets are transmitted, then the probability of a successful reception of a packet is q i. This model contains the CDMA protocols as special cases. We obtain sufficient rate conditions, which are close to necessary for stability of the system, when the arrival streams are stationary ergodic. Under the same rate conditions, for general regenerative arrival streams, we obtain the rates of convergence to stationarity, finiteness of stationary moments and various functional limit theorems. Our arrival streams contain all the traffic models suggested in the recent literature, including the ones which display long range dependence. We also obtain bounds on the stationary moments of waiting times which can be tight under realistic conditions. Finally, we obtain several results on the transient performance of the system, e.g., first time to overflow and the limits of the overflow process. We also extend the above results to the case of a capture channel exhibiting Markov modulated fading. Most of our results and proofs will be shown to hold also for the slotted ALOHA protocol without capture.
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    Journal of computational analysis and applications 2 (2000), S. 293-308 
    ISSN: 1572-9206
    Keywords: parabolic equations ; ADI scheme ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract An ADI scheme for solving three-dimensional parabolic equations withfirst-order derivatives and variable coefficients has been developed basedon our previous papers and the idea of the modified upwind differencescheme. This ADI scheme is second-order accurate and unconditionallystable. Further, a small parameter can be chosen which makes it suitablefor simulating fast-transient phenomena or for computations on fine spatialmeshes. The method is illustrated with numerical examples.
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    Set-valued analysis 8 (2000), S. 253-266 
    ISSN: 1572-932X
    Keywords: Hausdorff metric ; linear inequality systems ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract In this paper, we propose a Hausdorff metric to measure the “distance” between two linear inequality systems on a real normed space X. For this topology, which comes through a pseudo-metric in the set Σ of linear inequality systems, the closedness of the feasible set mapping is studied, and at the same time a characterization of the stability of the subset Σ c of consistent sytems is given.
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    Annals of operations research 99 (2000), S. 251-265 
    ISSN: 1572-9338
    Keywords: stochastic programming ; bond portfolio management ; interest ratescenarios ; stability ; sensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics , Economics
    Notes: Abstract The bond portfolio management problem is formulated as a multiperiod two-stage or multistage stochastic program based on interest rate scenarios. These scenarios depend on the available market data, on the applied estimation and sampling techniques, etc., and are used to evaluate coefficients of the resulting large scale mathematical program. The aim of the contribution is to analyze stability and sensitivity of this program on small changes of the coefficients – the (scenario dependent) values of future interest rates and prices. We shall prove that under sensible assumptions, the scenario subproblems are stable linear programs and that also the optimal first-stage decisions and the optimal value of the considered stochastic program possess acceptable continuity properties.
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    Queueing systems 36 (2000), S. 327-349 
    ISSN: 1572-9443
    Keywords: multiclass networks ; networks with feedback ; Skorokhod Problem ; Skorokhod Mapping ; Lipschitz continuity ; stability ; load conditions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract We consider a four-class two-station network with feedback, with fluid inputs and a head-of-the-line generalized processor sharing discipline at each station. We derive the Skorokhod Problem associated with the network and obtain algebraic sufficient conditions for Lipschitz continuity of the associated Skorokhod Map. This provides the first example of a multiclass network with feedback for which the associated Skorokhod Problem has been proved to be regular. As an elementary application, we show that under the conditions which guarantee Lipschitz continuity the network is stable if and only if the usual load conditions apply.
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    BIT 40 (2000), S. 226-240 
    ISSN: 1572-9125
    Keywords: Stochastic differential equations ; regularisation ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract This paper is devoted to the numerical analysis of ill-posed problems of evolution equations in Banach spaces using certain classes of stochastic one-step methods. The linear stability properties of these methods are studied. Regularisation is given by the choice of the regularisation parameter as α = $$\sqrt {\tau _n }$$ , where τ n is the stepsize and provides the convergence on smooth initial data. The case of the approximation of well-posed problems is also considered.
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    Applications of mathematics 45 (2000), S. 161-176 
    ISSN: 1572-9109
    Keywords: reaction-diffusion system ; unilateral conditions ; quasivariational inequality ; Leray-Schauder degree ; eigenvalue ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract We consider a reaction-diffusion system of the activator-inhibitor type with unilateral boundary conditions leading to a quasivariational inequality. We show that there exists a positive eigenvalue of the problem and we obtain an instability of the trivial solution also in some area of parameters where the trivial solution of the same system with Dirichlet and Neumann boundary conditions is stable. Theorems are proved using the method of a jump in the Leray-Schauder degree.
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    BIT 40 (2000), S. 62-73 
    ISSN: 1572-9125
    Keywords: Gaussian elimination ; stability ; pivoting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract It has been recently shown that large growth factors might occur in Gaussian Elimination with Partial Pivoting (GEPP) also when solving some plausibly natural systems. In this note we argue that this potential problem could be easily solved, with much smaller risk of failure, by very small (and low cost) modifications of the basic algorithm, thus confirming its inherent robustness. To this end, we first propose an informal model with the goal of providing further support to the comprehension of the stability properties of GEPP. We then report the results of numerical experiments that confirm the viewpoint embedded in the model. Basing on the previous observations, we finally propose a simple scheme that could be turned into (even more) accurate software for the solution of linear systems.
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    BIT 40 (2000), S. 611-639 
    ISSN: 1572-9125
    Keywords: Runge-Kutta methods ; stability ; convergence ; stiff problems
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract This paper studies the stability and convergence properties of general Runge-Kutta methods when they are applied to stiff semilinear systems y′(t) = J(t)y(t) + g(t, y(t)) with the stiffness contained in the variable coefficient linear part. We consider two assumptions on the relative variation of the matrix J(t) and show that for each of them there is a family of implicit Runge-Kutta methods that is suitable for the numerical integration of the corresponding stiff semilinear systems, i.e. the methods of the family are stable, convergent and the stage equations possess a unique solution. The conditions on the coefficients of a method to belong to these families turn out to be essentially weaker than the usual algebraic stability condition which appears in connection with the B-stability and convergence for stiff nonlinear systems. Thus there are important RK methods which are not algebraically stable but, according to our theory, they are suitable for the numerical integration of semilinear problems. This paper also extends previous results of Burrage, Hundsdorfer and Verwer on the optimal convergence of implicit Runge-Kutta methods for stiff semilinear systems with a constant coefficients linear part.
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    ISSN: 1573-904X
    Keywords: stealth and remote loading proliposome ; doxorubicin ; pharmacokinetics ; acute toxicity ; anticancer effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of the study was to prepare stealth and remoteloading proliposome (SRP-L) to carry doxorubicin (DXR) and evaluatethe pharmacokinetics, acute toxicity, and anticancer effect of DXRcarried with SRP-L. Methods. SRP-L was transparent solution. When SRP-L was injectedinto 0.9% NaCl aqueous solution containing DXR, liposomes formedand automatically loaded DXR (SRP-L-DXR). The long circulation ofSRP-L-DXR was evaluated using the pharmacokinetics ofSRP-L-DXR, cardiolipin liposomal DXR (CL-DXR) and free DXR (F-DXR).The acute toxicity and anticancer effect of SRP-L-DXR were evaluatedin C57BL/6 mice and murine hystocytoma M5076 tumor model. Results. The average diameter of SRP-L-DXR in pure water was112.9 ± 8.6 (nm) and the encapsulation efficiency of SRP-L-DXRwas 96.5 ± 0.2% in pure water, 95.5 ± 0.1% in 5% glucose and 98.01± 0.6% in 0.9% NaCl. The plasma concentration of SRP-L-DXR wasmuch higher than those of F-DXR and CL-DXR. Compared with thatof F-DXR, the SRP-L-DXR had lower acute toxicity and its anticancereffects depended upon the therapeutic treatment. Conclusions. A novel proliposome (SRP-L) was developed, whichcould automatically load DXR and form SRP-L-DXR with excellentcharacteristics. SRP-L-DXR had lower acute toxicity but was notalways more effective for the treatment of the ascitic M5076 thanF-DXR.
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  • 30
    ISSN: 1573-904X
    Keywords: SK&F 107647 ; peptide ; pharmacokinetics ; hematore gulatory ; adenocarcinoma ; cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To describe the pharmacokinetics of SK&F 107647, a synthetichematoregulatory peptide, in healthy volunteers and in patientswith adenocarcinoma.Methods. SK&F 107647 pharmacokinetics were evaluated in 2dose-escalation studies. Volunteers received SK&F 107647 as single15-minute iv infusion doses of 1, 10, 100, 500, and 1000 μg/kg. Cancerpatients received 2-hour iv infusions of 0.001, 0.01, 0.1 and 1μg/kg once daily for 10 days. Drug concentrations were quantified in plasmaand urine of healthy volunteers and on days 1 and 10 in plasma ofcancer patients receiving the two top dose levels.Results. In volunteers, mean clearance (CL) ranged from 76.7 to 101ml/hour/kg; mean volume of distribution at steady-state (Vss)rangedfrom 175 to 268 ml/kg. Most of the administered dose was renallyexcreted as intact peptide within 24 hours postinfusion. In patients,mean CL was 57.6 ml/hour/kg, mean Vss ranged from 128 to 150ml/kg and terminal half-life from 2.1 to 3.4 hours. There was littleaccumulation of drug. In both studies, linear pharmacokinetics wasobserved. Clearance approached normal glomerular filtration rate(GFR) in volunteers and correlated with creatinine clearance incancer patients.Conclusions. SK&F 107647 exhibits linear pharmacokinetics, a smallVss, and clearance, primarily renal, approaching normal GFR.
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  • 31
    ISSN: 1573-904X
    Keywords: 1,4-dihydropyridine calcium channel antagonist ; (+)-[3H]PN 200-110 ; senescence-accelerated prone mouse ; brain concentration ; pharmacokinetics ; in vivo receptor binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To characterize the in vivo specific binding andpharmacokinetics of a 1,4-dihydropyridine (DHP) calcium channel antagonist, PN200-110, in the senescent brain, using senescence-accelerated pronemice (SAMP8) and senescence-resistant mice (SAMR1). Methods. Blood, brain, and heart samples were taken periodically fromSAMR1 and SAMP8 following intravenous injection of (+)-[3H]PN200-110, and the concentration of (+)-[3H]PN 200-110 in the plasmaand tissues was determined. In addition, the in vivo specific bindingof (+)-[3H]PN 200-110 in the brains of SAMR1 and SAMP8 wasmeasured periodically after intravenous injection of the radioligand. Results. There was very little significant difference between SAMR1and SAMP8 in terms of the half-life (t1/2), total body clearance (CLtot),steady-state volume of distribution (Vdss), and AUC for the plasmaconcentration of (+)-[3H]PN 200-110 after intravenous injection ofthe radioligand. The brain concentration (AUCbrain) for (+)-[3H]PN200-110 and the brain/plasma AUC ratio (AUCbrain/AUCplasma) weresignificantly lower in SAMP8 than in SAMR1, and the heartconcentration (AUCheart) and the heart/plasma AUC ratio (AUCheart/AUCplasma)were similar in both strains. Also, the brain/plasma unbound AUCratio (AUCbrain/AUCplasma-free) for (+)-[3H]PN 200-110 wassignificantly lower in SAMP8 than in SAMR1. The in vivo specific binding(AUCspecific binding, maximal number of binding sites: Bmax) of(+)-[3H]PN 200-110 was significantly lower in brain particulate fractionsof SAMP8 than SAMR1. Conclusions. The concentration and in vivo specific binding of(+)-[3H]PN 200-110 was significantly reduced in the senescent brain. Thesimultaneous analysis of the concentrations of centrally acting drugsand the in vivo specific binding in the brain in relation to theirpharmacokinetics may be valuable in evaluating their CNS effects.
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  • 32
    ISSN: 1573-904X
    Keywords: amphotericin B ; liposomes ; pharmacokinetics ; toxicokinetics ; tissue distribution ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Amphotericin B in small, unilamellar liposomes (AmBisome) is safer and produces higher plasma concentrations than other formulations. Because liposomes may increase and prolong tissue exposures, the potential for drug accumulation or delayed toxicity after chronic AmBisome was investigated. Methods. Rats (174/sex) received intravenous AmBisome (1, 4, or 12 mg/kg), dextrose, or empty liposomes for 91 days with a 30-day recovery. Safety (including clinical and microscopic pathology) and toxicokinetics in plasma and tissues were evaluated. Results. Chemical and histopathologic changes demonstrated that the kidneys and liver were the target organs for chronic AmBisome toxicity. Nephrotoxicity was moderate (urean nitrogen [BUN] ≤51 mg/dl; creatinine unchanged). Liposome-related changes (vacuolated macrophages and hypercholesterolemia) were also observed. Although plasma and tissue accumulation was nonlinear and progressive (clearance and volume decreased, half-life increased with dose and time), most toxic changes occurred early, stabilized by the end of dosing, and reversed during recovery. There were no delayed toxicities. Concentrations in liver and spleen greatly exceeded those in plasma; kidney and lung concentrations were similar to those in plasma. Elimination half-lives were 1-4 weeks in all tissues. Conclusions. Despite nonlinear accumulation, AmBisome revealed predictable hepatic and renal toxicities after 91 days, with no new or delayed effects after prolonged treatment at high doses that resulted in plasma levels 〉200 μg/ml and tissue levels 〉3000 μg/g.
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  • 33
    ISSN: 1573-904X
    Keywords: paclitaxel ; emulsions ; filter-sterization ; particle size ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Paclitaxel is currently administered i.v. as a slow infusion of asolution of the drug in an ethanol:surfactant:saline admixture. However,poor solubilization and toxicity are associated with this drug therapy.Alternative drug delivery systems, including parenteral emulsions, areunder development in recent years to reduce drug toxicity, improveefficacy and eliminate premedication. Methods. Paclitaxel emulsions were prepared by high-shearhomogenization. The particle size of the emulsions was measured by dynamiclight scattering. Drug concentration was quantified by HPLC and invitro drug release was monitored by membrane dialysis. The physicalstability of emulsions was monitored by particle size changes in boththe mean droplet diameter and 99% cumulative distribution. Paclitaxelpotency and changes in the concentration of known degradants wereused as chemical stability indicators. Single dose acute toxicity studieswere conducted in healthy mice and efficacy studies in B16 melanomatumor-bearing mice. Results. QW8184, a physically and chemically stable sub-micronoil-in-water (o/w) emulsion of paclitaxel, can be prepared at high drugloading (8-10 mg/mL) having a mean droplet diameter of 〈100 nmand 99% cumulative particle size distribution of 〈200 nm. In vitro release studies demonstrated low and sustained drug release both inthe presence and absence of human serum albumin. Based on singledose acute toxicity studies, QW8184 is well tolerated both in miceand rats with about a 3-fold increase in the maximum-tolerated-dose(MTD) over the current marketed drug formulation. Using the B16mouse melanoma model, a significant improvement in drug efficacywas observed with QW8184 over Taxol®. Conclusions. QW8184, a stable sub-micron o/w emulsion of paclitaxelhas been developed that can be filter-sterilized and administered i.v.as a bolus dose. When compared to Taxol®, this emulsion exhibitedreduced toxicity and improved efficacy most likely due to thecomposition and dependent physicochemical characteristics of the emulsion.
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  • 34
    ISSN: 1573-904X
    Keywords: particle size ; PLG microspheres ; protein delivery ; spray-freeze drying ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To investigate the effect of atomization conditions on particle size and stability of spray-freeze dried protein. Methods. Atomization variables were explored for excipient-free (no zinc added) and zinc-complexed bovine serum albumin (BSA). Particle size was measured by laser diffraction light scattering following sonication in organic solvent containing poly(lactide-co-glycolide) (PLG). Powder surface area was determined from the N2 vapor sorption isotherm. Size-exclusion chromatography (SEC) was used to assess decrease in percent protein monomer. Fourier-transform infrared (FTIR) spectroscopy was employed to estimate protein secondary structure. PLG microspheres were made using a non-aqueous, cryogenic process and release of spray-freeze dried BSA was assessed in vitro. Results. The most significant atomization parameter affecting particle size was the mass flow ratio (mass of atomization N2 relative to that for liquid feed). Particle size was inversely related to specific surface area and the amount of protein aggregates formed. Zinc-complexation reduced the specific surface area and stabilized the protein against aggregation. FTIR data indicated perturbations in secondary structure upon spray-freeze drying for both excipient-free and zinc-complexed protein. Conclusions. Upon sonication, spray-freeze dried protein powders exhibited friability, or susceptibility towards disintegration. For excipient-free protein, conditions where the mass flow ratio was 〉 ∼0.3 yielded sub-micron powders with relatively large specific surface areas. Reduced particle size was also linked to a decrease in the percentage of protein monomer upon drying. This effect was ameliorated by zinc-complexation, via a mechanism involving reduction in specific surface area of the powder rather than stabilization of secondary structure. Reduction of protein particle size was beneficial in reducing the initial release (burst) of the protein encapsulated in PLG microspheres.
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  • 35
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    Pharmaceutical research 17 (2000), S. 903-905 
    ISSN: 1573-904X
    Keywords: P-glycoprotein ; hepatic metabolism ; pharmacokinetics ; first-pass metabolism ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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  • 36
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    Mechanics of composite materials 36 (2000), S. 475-480 
    ISSN: 1573-8922
    Keywords: stability ; three-dimensional theory ; tribotechnics ; elastoplastic deformations ; viscoelasticity ; surface ; tracking and dead loads ; laminated coating ; piecewise-homogeneous model ; active loading
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The problem of surface instability of laminated coatings with inelastic properties is considered within the framework of a model of piecewise-homogeneous media on the basis of the three-dimensional linearized theory of stability. A general statement of the problem is formulated and the basic characteristic equations are derived. The solutions of particular problems are obtained for elastoplastic and viscoelastic models of solids.
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  • 37
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    Fish physiology and biochemistry 23 (2000), S. 225-232 
    ISSN: 1573-5168
    Keywords: methylisoborneol ; catfish ; cytochrome P450 ; biotransformation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 2-Methylisoborneol (MIB) and structurally related terpenoid compounds are responsible for millions of dollars of lost revenue to catfish farmers. In an attempt to determine enzymatic pathways of biotransformation and elimination of MIB, the in vitro metabolism of MIB was examined in the Ulvade strain of channel catfish (Ictalurus punctatus). Although cytochrome P450 (CYP) activities were observed and correlated with expression of specific isoforms (i.e. steroid hydroxylation and CYP3A expression), no metabolites of MIB were observed. To determine whether extrahepatic biotransformation may be occurring the in vivo metabolism and disposition of 14C-MIB was examined in Uvalde, USDA-103 channel catfish, and a channel catfish X blue catfish (Ictalurus furcatus) hybrid species. Confirming in vitro hepatic studies, no metabolites were observed in plasma from animals treated with an intra-arterial dose of 14C-MIB. 14C-MIB elimination was predicted using a two compartment model in each strain of fish. There was no significant difference in terminal half-lives between strains but possible differences in total body clearance and apparent volumes of distribution which may be related to higher lipid content in the hybrids. Results of these studies indicate biotransformation has no involvement in MIB elimination and that other physiological processes may play a more significant role in MIB disposition within Ictalurid fish species.
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  • 38
    ISSN: 1573-5168
    Keywords: amberjack ; myosin heavy chain ; cDNA ; α-helix ; coiled coils ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The structural stability of fish myosin depends upon species and temperatures of water in which fish live. Primary, secondary, and quaternary structures of myosin heavy chain (MyHC) from three species of fish living at different temperature ranges have been compared with those of rabbit MyHC in order to investigate the differences in stability. Primary structure of MyHC, although being accessible for warm-water and cold-water fish (carp and walleye pollack), was not available in previous for tropical-water fish literature; so in this study primary structure of MyHC of the tropical-water fish amberjack has been determined by cloning and sequencing its cDNA. The MyHC has 1938 amino acid residues (AA), which are almost as much as as those of carp and walleye pollack. The amberjack MyHC is 91–95% homologous with other fish and rabbit MyHCs. There is a discernible difference between animal species with stable myosin rod (amberjack, carp, and rabbit) and walleye pollack with unstable rod. Stable rod species have a high probability of forming coiled-coil around the COOH-terminal end of the rod, while the pollack has a low coiled-coil formation probability. In addition, the average scores of the coiled-coil for myosin rod were rabbit (1.738) 〉 amberjack (1.691) 〉 carp (1.680) 〉 walleye pollack (1.674) which correlated exactly with the observed stability. The results suggest that coiled-coil forming ability, particularly around the COOH-terminal end, directs structural stability of fish myosin rod.
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  • 39
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    Archive of applied mechanics 70 (2000), S. 17-29 
    ISSN: 1432-0681
    Keywords: Key words free-surface flow ; solidification ; strip casting ; steady state ; nonuniqueness ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Summary The paper is concerned with a one-dimensional analysis of plane open-channel flow with continuous solidification. The process is of relevance for recent developments in the casting of steel and other metals. The bottom of the channel consists of a rotating casting roll and a horizontal cooling table, where the solidified material is withdrawn with given velocity. The study is restricted to the region downstream of the top of the casting roll. Surface tension is neglected. In the main part of the analysis inviscid fluid flow is considered since the Reynolds number is very large in the applications. It is found that the steady-state solutions are nonunique in a certain parameter range. In addition to a continuous solution, there are two solutions including hydraulic jumps, with one hydraulic jump being located on the casting roll, the other one on the cooling table. Regarding the stability of the non unique solutions, the evolution of disturbances is investigated numerically as an initial-value problem. It is concluded that the hydraulic jump on the cooling table is unstable, while the other discontinuous solution as well as the continuous solution are stable for sufficiently small disturbances. Which stable solution is attained in the steady state, depends on the history of the process. Friction at the liquid/solid interface is taken into account in the last part of the analysis. A constant friction coefficient is assumed. It is found that the history of the process determines the steady-state solution if, and only if, the friction coefficient is sufficiently small. For larger values of the friction coefficient, the steady-state solution is unique and independent of the history of the transient process. Furthermore, for sufficiently large friction coefficients, stable hydraulic jumps are found, in contrast to the inviscid case, also on the cooling table.
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  • 40
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    Neural processing letters 12 (2000), S. 129-144 
    ISSN: 1573-773X
    Keywords: associative memory ; dynamical systems ; Glauber dynamics ; Hopfield model ; infinite dimensional state space ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract A generalization of the Little–Hopfield neural network model for associative memories is presented that considers the case of a continuum of processing units. The state space corresponds to an infinite dimensional euclidean space. A dynamics is proposed that minimizes an energy functional that is a natural extension of the discrete case. The case in which the synaptic weight operator is defined through the autocorrelation rule (Hebb rule) with orthogonal memories is analyzed. We also consider the case of memories that are not orthogonal. Finally, we discuss the generalization of the non deterministic, finite temperature dynamics.
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  • 41
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    Journal of bioenergetics and biomembranes 32 (2000), S. 293-300 
    ISSN: 1573-6881
    Keywords: abnormal wing discs ; lethal mutant ; Drosophila ; Killer-of-prune ; prune
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract The abnormal wing discs gene of Drosophila encodes a soluble protein with nucleosidediphosphate kinase activity. This enzymic activity is necessary for the biological function ofthe abnormal wing discs gene product. Complete loss of function, i.e., null, mutations causelethality after the larval stage. Most larval organs in such null mutant larvae appear to benormal, but the imaginal discs are small and incapable of normal differentiation.Killer-of-prune is a neomorphic mutation in the abnormal wing discs gene. It causes dominant lethalityin larvae that lack prune gene activity. The Killer-of-prune mutant protein may have alteredsubstrate specificity. Null mutant larvae have a low level of nucleoside diphosphate kinaseactivity. This suggests that there may be additional Drosophila genes that encode proteinswith nucleoside dipthosphate kinase activity. Candidate genes have been found in theDrosophila genome.
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  • 42
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    Genetica 109 (2000), S. 35-44 
    ISSN: 1573-6857
    Keywords: Drosophila ; heterochromatin ; imprinting ; parental effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Genetic imprinting is a form of epigenetic silencing. But with a twist. The twist is that while imprinting results in the silencing of genes, chromosome regions or entire chromosome sets, this silencing occurs only after transmission of the imprinted region by one sex of parent. Thus genetic imprinting reflects intertwined levels of epigenetic and developmental modulation of gene expression. Imprinting has been well documented and studied in Drosophila, however, these studies have remained largely unknown due to nothing more significant than differences in terminology. Imprinting in Drosophilais invariably associated with heterochromatin or regions with unusual chromatin structure. The imprint appears to spread from imprinted centers that reside within heterochromatin and these are, seemingly, the only regions that are normally imprinted in Drosophila. This is significant as it implies that while imprinting occurs in Drosophila, it is generally without phenotypic consequence. Hence the evolution of imprinting, at least in Drosophila, is unlikely to be driven by the function of specific imprinted genes. Thus, the study of imprinting in Drosophilahas the potential to illuminate the mechanism and biological function of imprinting, and challenge models based solely on imprinting of mammalian genes.
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  • 43
    ISSN: 1573-6857
    Keywords: Drosophila ; brown eye ; eye pigments ; fitness ; gene localization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract By analyzing the progeny of crosses involving brown eye mutants and the wild types in two members of Drosophila nasuta subgroup namely D. n. nasuta and D. n. albomicans we could show that the mutant gene is recessive, located in the chromosome 2 and the alleles of this gene are present at different loci. A study of fitness in the eye color mutants in comparison with the wild types revealed that D. n. nasuta mutant has higher viability at both 25 ± 1°C and ambient temperatures; while D. n. albomicans mutant has faster rate of development only at 25 ± 1°C. Quantitative analysis of eye pigments in the mutants revealed that there is biosynthesis of both pteridines and xanthommatins unlike in bw/bw of D. melanogaster, where only xanthommatins are synthesized. In both the species, the pteridine quantities in mutants are similar; whereas xanthommatin quantity in $$\user1{bw}_n \user1{/bw}_n$$ is 10 times higher than that of $$\user1{bw}_a \user1{/bw}_a$$ . Further, the F1 progeny of intraspecific crosses (wild type X mutant) are found to have high amounts of pteridine, even when compared with parental wild type.
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  • 44
    ISSN: 1573-6857
    Keywords: DmNop56 ; DsNop56 ; Drosophila ; molecular evolution ; snoRNPs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Small nucleolar RNAs (snoRNAs) are trans‐acting factors involved in maturation of rRNA and have been classified into Box C/D and Box H/ACA families. Most of the snoRNAs occur as ribonucleoprotein complexes with snoRNA‐associated proteins (snoRNPs). All Box C/D snoRNAs in yeast form complexes with Nop1p, Nop56p and Nop58p. Similarly, it has been reported that Box H/ACA‐containing snoRNAs form complexes with yeast Gar1p. Nop56p and Nop58p homologs have been described in several species. Here we report the isolation and molecular characterization of the Dnop56 genes from D. melanogaster and D. subobscura which show a very similar structure. Drosophila Nop56p proteins contain lysine‐rich regions at their carboxy‐terminus, and show a high degree of similarity to other Nop56p proteins from different organisms. Phylogenetic relationships among these proteins and other snoRNPs have been established.
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  • 45
    ISSN: 1573-6857
    Keywords: adaptation ; Drosophila ; hydrocarbons ; latitude ; longitude ; natural populations ; polymorphism ; temperaturey ; vapour pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 7-tricosene (7T) and 7-pentacosene (7P) are the major components of cuticular hydrocarbons in Drosophila simulans and D. melanogaster males. A chemical study of 16 isofemale lines of D. melanogaster sampled at the first and eighth generations in laboratory conditions showed the stability of chromatographical profiles. Then a large scale study of male 7T/7P polymorphism was performed with 85 populations of D. melanogaster and 29 of D. simulans collected all over the world. There were significant correlations of the values of the balanced ratio (7T − 7P)/(7T + 7P) with geo-climatic parameters, such as latitude, longitude, mean temperature, temperature range and vapour pressure. Parallel variations were also reported for the homologous linear alkanes (23 and 25 Carbon atoms) but not for the longer branched alkanes (27 and 29 Carbon atoms). No correlation was significant for the D. simulans populations studied. In this species a similar polymorphism of 7T/7P was found but restricted to a few populations from West Equatorial Africa.
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  • 46
    ISSN: 1573-6857
    Keywords: biophysics ; body size ; Drosophila ; ectotherm ; genetic variance ; stress ; temperature extreme
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract An increase in genetic variation in body size has often been observed under stress; an increase in dominance variance and interaction variance as well as in additive genetic variance has been reported. The increase in genetic variation must be caused by physiological mechanisms that are specific to adverse environments. A model is proposed to explain the occurrence of an increase in genetic variation in body size in Drosophila at extreme temperatures. The model has parameters specific to the low- and high-temperature regions of the viable range. Additive genetic variation in the boundary temperatures leads to a marked increase in additive genetic variation in development rate and body size at extreme temperatures. Additive genetic variation in the temperature sensitivity in the low- and high-temperature regions adds non-additive genetic variation. Development rate shows patterns in additive genetic variation that differ from the patterns of genetic variation in body size; therefore, the genetic correlation between development rate and body size changes sign repeatedly as a function of temperature. The existence of dominance in the genetic variation in the boundary temperatures or in the low- and high-temperature sensitivities leads to a higher total genetic variance due to higher dominance and interaction variance, for both development rate and body size.
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  • 47
    ISSN: 1573-6857
    Keywords: chromatin structure ; Drosophila ; mutagenic effect ; retroelements ; white
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Transposable elements represent a large fraction of eukaryotic genomes and they are thought to play an important role in chromatin structure. ZAMand Idefixare two LTR-retrotransposons from Drosophila melanogastervery similar in structure to vertebrate retroviruses. In all the strains where their distribution has been studied, ZAMappears to be present exclusively in the intercalary heterochromatin while Idefixcopies are mainly found in the centromeric heterochromatin with very few copies in euchromatin. Their distribution varies in a specific strain called RevI in which the mobilization of ZAMand Idefixis highly induced. In this strain, 15 copies of ZAMand 30 copies of Idefixare found on the chromosomal arms in addition to their usual distribution. Amongst the loci where new copies are detected, a hotspot for their insertion has been detected at the whitelocus where up to four elements occurred within a 3-kb fragment at the 5′ end of this gene. This property of ZAMand Idefixto accumulate at a defined site provides an interesting paradigm to bring insight into the effect exerted by multiple insertions of transposable elements at an euchromatic locus.
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  • 48
    ISSN: 1573-6857
    Keywords: centromere ; heterochromatin ; non B-DNA structures ; Drosophila
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The molecular basis of centromere formation in a particular chromosomal region is not yet understood. In higher eukaryotes, no specific DNA sequence is required for the assembly of the kinetochore, but similar centromeric chromatins are formed on different centromere DNA sequences. Although epigenesis has been proposed as the main mechanism for centromere specification, DNA recognition must also play a role. Through the analysis of Drosophilacentromeric DNA sequences, we found that dodeca satellite and 18HT satellite are able to form unusual DNA structures similar to those formed by telomeric sequences. These findings suggest the existence of a common centromeric structural DNA motif which we feel merits further investigation.
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  • 49
    ISSN: 1573-6857
    Keywords: Drosophila ; , esterase-6 ; function ; sequence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In most lineages of the subgenus Sophophora esterase-6 is a homodimeric haemolymph protein. In the melanogaster subgroup of species it has become a monomer which is mainly expressed in the male sperm ejaculatory duct. Our analyses of esterase-6 sequences from three melanogaster subgroup species and two close relatives reveal a brief period of accelerated amino acid sequence change during the transition between the ancestral and derived states. In this period of 2–6Myr the ratio of replacement to silent site substitutions (0.51) is about three times higher than the values in other lineages of the phylogeny. There are about 50 more replacements in this period than would be predicted from the ratios of replacement to silent site substitutions found elsewhere in the phylogeny. Modelling on the known structure of a related acetylcholinesterase suggests that an unusually high proportion of the replacements in the transitional branch are non-conservative changes on the protein surface. Up to half the accelerated replacement rate can be accounted for by clusters of changes to the face of the molecule containing the opening of the active site gorge. This includes changes in and around regions homologous to peripheral substrate binding sites in acetylcholinesterase. There are also three changes in glycosylation status. One region predicted to lie on the protein surface which becomes markedly more hydrophilic is proposed to be the ancestral dimerisation site that is lost in the transitional branch.
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  • 50
    ISSN: 1573-6849
    Keywords: Adh ; Drosophila ; FISH ; genome evolution ; repleta group
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The molecular organization of a 1.944-Mb chromosomal region of Drosophila melanogaster around the Adh locus has been analyzed in two repleta group species: D. repleta and D. buzzatii. The extensive genetic and molecular information about this region in D. melanogaster makes it a prime choice for comparative studies of genomic organization among distantly related species. A set of 26 P1 phages from D. melanogaster were successfully hybridized using fluorescence in-situ hybridization (FISH) to the salivary gland chromosomes of both repleta group species. The results show that the Adh region is distributed in D. repleta and D. buzzatii over six distant sites of chromosome 3, homologous to chromosomal arm 2L of D. melanogaster (Muller's element B). This observation implies a density of 2.57 fixed breakpoints per Mb in the Adh region and suggests a considerable reorganization of this chromosomal element via the fixation of paracentric inversions. Nevertheless, breakpoint density in the Adh region is three times lower than that estimated for D. repleta chromosome 2, homologous to D. melanogaster 3R (Muller's element E). Differences in the rate of evolution among chromosomal elements are seemingly persistent in the Drosophila genus over long phylogenetic distances.
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  • 51
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    Genetica 109 (2000), S. 105-111 
    ISSN: 1573-6857
    Keywords: Drosophila ; evolution ; heterochromatin ; Y chromosome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Y chromosome evolution is characterized by the expansion of genetic inertness along the Y chromosome and changes in the chromosome structure, especially the tendency of becoming heterochromatic. It is generally assumed that the sex chromosome pair has developed from a pair of homologues. In an evolutionary process the proto-Y-chromosome, with a very short differential segment, develops in its final stage into a completely heterochromatic and to a great extends genetically eroded Y chromosome. The constraints evolving the Y chromosome have been the objects of speculation since the discovery of sex chromosomes. Several models have been suggested. We use the exceptional situation of the in Drosophila mirandato analyze the molecular process in progress involved in Y chromosome evolution. We suggest that the first steps in the switch from a euchromatic proto-Y-chromosome into a completely heterochromatic Y chromosome are driven by the accumulation of transposable elements, especially retrotransposons inserted along the evolving nonrecombining part of the Y chromosome. In this evolutionary process trapping and accumulation of retrotransposons on the proto-Y-chromosome should lead to conformational changes that are responsible for successive silencing of euchromatic genes, both intact or already mutated ones and eventually transform functionally euchromatic domains into genetically inert heterochromatin. Accumulation of further mutations, deletions, and duplications followed by the evolution and expansion of tandem repetitive sequence motifs of high copy number (satellite sequences) together with a few vital genes for male fertility will then represent the final state of the degenerated Y chromosome.
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  • 52
    ISSN: 1573-6857
    Keywords: chromosomal proteins ; Drosophila ; heterochromatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
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  • 53
    ISSN: 1573-6857
    Keywords: artificial selection ; atavistic structures ; Drosophila ; pattern formation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Artificial selection was carried out for over 45 generations to enhance and suppress expression of the mutation hairy on the Drosophila melanogaster wing. Whole chromosome mapping of X‐linked and autosomal modifiers of sense organ number displayed regional differences in magnitude and direction of their effects. Regional specificity of modifier effects was also seen in some interchromosomal interactions. Scanning electron microscopy allowed precise measurement of sense organ size and position along the L3 longitudinal wing vein. Sense organ size varied in a predictable fashion along the proximal–distal axis, and the dorsal pattern differed from the ventral pattern. The high and low selection lines differed most in the proximal portion of the L3 vein. Extra sense organs in the High line were often associated with vein fragments at locations predicted from ancestral vein patterns. Thus, regional specificity of polygenic or quantitative trait locus modifier effects was identified in several different parts of the wing.
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  • 54
    ISSN: 1573-6857
    Keywords: artificial selection ; Drosophila ; lifespan ; mortality ; paraquat ; DDT ; recovery hypothesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Adult lifespans, age‐specific survival, age‐specific mortality, survival times on paraquat, and survival times on DDT were assayed in seven lines of Drosophila melanogaster, including two genetically heterogeneous wild lines recently collected from nature, and three inbred and recombinant inbred lines derived from an artificial selection experiment for increased lifespan. Survival on paraquat is positively correlated with adult lifespan. DDT resistance is uncorrelated with either paraquat resistance or lifespan. The wild lines are unexceptional with respect to average lifespan, paraquat resistance, age‐specific survivorship, and leveling off of mortality rates at advanced ages, but have high levels of DDT resistance. Cluster analysis groups the wild lines with three unselected laboratory stocks in one cluster, while two long‐lived elite recombinant inbred lines form a second cluster. Long‐lived laboratory‐adapted lines are quantitatively differentiated from the wild stocks, both with respect to average adult lifespans and resistance to an oxidizing agent. We reject the ‘recovery’ hypothesis, which proposes that Drosophila artificially selected for long life have phenotypes that merely recover the wild state.
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  • 55
    ISSN: 1573-6857
    Keywords: Drosophila ; heterochromatin ; telomere ; transcription ; transposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Chromosome length in Drosophilais maintained by the targeted transposition of two families of non-LTR retrotransposons, HeT-Aand TART. Although the rate of transposition to telomeres is sufficient to counterbalance loss from the chromosome ends due to incomplete DNA replication, transposition as a mechanism for elongating chromosome ends raises the possibility of damaged or deleted telomeres, because of its stochastic nature. Recent evidence suggests that HeT-Atransposition is controlled at the levels of transcription and reverse transcription. HeT-Atranscription is found primarily in mitotically active cells, and transcription of a w +reporter gene inserted into the 2L telomere increases when the homologous telomere is partially or completely deleted. The terminal HeT-Aarray may be important as a positive regulator of this activity in cis, and the subterminal satellite appears to be an important negative regulator in cis. A third chromosome modifier has been identified that increases the level of reverse transcriptase activity on a HeT-A RNA template and greatly increases the transposition of HeT-A. Thus, the host appears to play a role in transposition of these elements. Taken together, these results suggest that control of HeT-Atransposition is more complex than previously thought.
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  • 56
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    Chemistry of heterocyclic compounds 36 (2000), S. 115-133 
    ISSN: 1573-8353
    Keywords: thiophthalylium salts ; methods of preparation ; structure ; stability ; reactivity ; electrophilic properties
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Methods of preparation, chemical reactions, the structures and reactivity of thiophthalylium ions are reviewed.
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  • 57
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    Cybernetics and systems analysis 36 (2000), S. 699-721 
    ISSN: 1573-8337
    Keywords: stability ; stochastic functional differential equations ; previous history ; Poisson switchings ; "dangling spider" model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract To study the stability of the stochastic "dangling spider" model, the second Lyapunov method is substantiated for stochastic differential functional equations with the whole previous history.
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  • 58
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    Cybernetics and systems analysis 36 (2000), S. 916-924 
    ISSN: 1573-8337
    Keywords: stochastic model ; "dangling spider problem" ; stability ; Lyapunov-Krasovskii functional
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract To study the stability of the stochastic "dangling spider" model, the second Lyapunov method is substantiated for stochastic differential functional equations with the entire previous history.
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  • 59
    ISSN: 1573-899X
    Keywords: Memory ; suppression of courting ; Drosophila ; mutants ; P insertion mutagenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Four lines were selected from a collection of 33 lines prepared by P insertion mutagenesis using a single-copy P-element system; the males of these four lines showed memory defects after acquisition of conditioned reflex suppression of courting. In two lines (P171 and P95), the dynamics of retention of the conditioned reflex in the repeated impregnated-female courting test were similar to those of known short-term memory mutantsdnc andrut. In line P153, the dynamics were more reminiscent of the memory dynamics in a known medium-term memory mutant,amn. In line P124, the learning index was insignificant immediately after training was completed, which may indicate that this line was unable to acquire conditioned reflex suppression of courting. Determination of the positions of the P elements (P171: 48A-B; P153: 49B-C; P124; 67B–68A; P95: 77C-D) showed no correspondence with previously known mutations producing memory lesions.
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  • 60
    ISSN: 1573-904X
    Keywords: glycyrrhizic acid ; modeling ; enterohepatic cycling ; PBPK ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To analyze the role of the kinetics of glycyrrhizic acid (GD) in its toxicity. A physiologically-based pharmacokinetic (PBPK) model that has been developed for humans. Methods. The kinetics of GD, which is absorbed as glycyrrhetic acid (GA), were described by a human PBPK model, which is based on a rat model. After rat to human extrapolation, the model was validated on plasma concentration data after ingestion of GA and GD solutions or licorice confectionery, and an additional data derived from the literature. Observed interindividual variability in kinetics was quantified by deriving an optimal set of parameters for each individual. Results. The a-priori defined model successfully forecasted GA kinetics in humans, which is characterized by a second absorption peak in the terminal elimination phase. This peak is subscribed to enterohepatic cycling of GA metabolites. The optimized model explained most of the interindividual variance, observed in the clinical study, and adequately described data from the literature. Conclusions. Preclinical information on GD kinetics could be incorporated in the human PBPK model. Model simulations demonstrate that especially in subjects with prolonged gastrointestinal residence times, GA may accumulate after repeated licorice consumption, thus increasing the health risk of this specific subgroup of individuals.
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  • 61
    ISSN: 1573-904X
    Keywords: luteinising hormone-releasing hormone (LH-RH) antagonist ; cetrorelix ; pharmacokinetics ; population PK/PD-modeling ; testosterone ; rat ; dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Population models for thepharmacokinetic-pharmacodynamic relationship for cetrorelix (CET), a luteinising hormone-releasinghormone (LH-RH) antagonist, and the pharmacodynamic response ontestosterone production were investigated in rats and dogs. Methods. The plasma concentrations of CET and testosterone weredetermined after intravenous and subcutaneous injections. Thepopulation PK/PD-models were developed using P-PHARM software. Results. Absolute bioavailability of cetrorelix was 100% in rats and97% in dogs. In rats, the pharmacokinetics was explained by atwo-compartment model with saturable absorption, while athree-compartment model was used in dogs. Testosterone suppression in both specieswas described by a sigmoid Emax model with maximum effect (Emax)considered as total hormonal suppression. The duration of testosteronesuppression in rats was longer at higher doses. The populationelimination half-lifes after iv-dose were 3.0 h in rats and 9.3 h in dogs.Population mean estimates of IC50 were 1.39 and 1.24 ng/ml in ratsand dogs, respectively. Conclusions. A population pharmacokinetic model was developed toexplain the dissolution rate limited absorption from the injection site.The suppression of testosterone could be described by an indirectinhibitory sigmoid Emax model. In both species 1-2 ng/ml CET inplasma was necessary to suppress testosterone production.
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  • 62
    ISSN: 1573-904X
    Keywords: methylphenidate ; average bioequivalence ; individual bioequivalence ; human ; pharmacokinetics ; replicated design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To determine the relative bioavailability of two marketed,immediate-release methylphenidate tablets. The study used a replicatedstudy design to characterize intrasubject variability, and determinebioequivalence using both average and individual bioequivalencecriteria. Methods. A replicated crossover design was employed using 20subjects. Each subject received a single 20 mg dose of the reference tableton two occasions and two doses of the test tablet on two occasions.Blood samples were obtained for 10 hr after dosing, and plasma wasassayed for methylphenidate by GC/MS. Results. The test product was more rapidly dissolved in vitro and morerapidly absorbed in vivo than the reference product. The mean Cmaxand AUC(0 − ∞) differed by 11% and 9%, respectively. Using anaverage bioequivalence criterion, the 90% confidence limits for theLn-transformed Cmax and AUC(0 − ∞), comparing the two replicatesof the test to the reference product, fell within the acceptable range of80–125%. Using an individual bioequivalence criterion the test productfailed to demonstrate equivalence in Cmax to the reference product. Conclusions. The test and reference tablets were bioequivalent usingan average bioequivalence criterion. The intrasubject variability of thegeneric product was greater and the subject-by-formulation interactionvariance was borderline high. For these reasons, the test tablets werenot individually bioequivalent to the reference tablets.
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  • 63
    ISSN: 1573-904X
    Keywords: allometric scaling ; interspecies scaling ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate (1) allometric scaling of systemic clearance (CL)using unbound drug concentration, (2) the potential usage of brainweight (BRW) correction in allometric scaling of both CL and oralclearance (CL/F). Methods. Human clearance was predicted allometrically (CLu = a ·Wbiv) using unbound plasma concentration for eight Parke-Daviscompounds and 29 drugs from literature sources. When the exponent bivwas higher than 0.85, BRW was incorporated into the allometricrelationship (CLu*BRW = a · Wbiv). This approach was also applied tothe prediction of CLu/F for 10 Parke-Davis compounds. Human oralt1/2, Cmax, AUC, and bioavailability were estimated based onallometrically predicted pharmacokinetic (PK) parameters. Results. Human CL and CL/F were more accurately estimated usingunbound drug concentration and the prediction was further improvedwhen BRW was incorporated into the allometric relationship. ForParke-Davis compounds, the predicted human CL and CL/F werewithin 50-200% and 50-220% of the actual values, respectively. Theestimated human oral t1/2, Cmax, and AUC were within 82-220%,56-240%, and 73-190% of the actual values for all 7 compounds,suggesting that human oral PK parameters of those drugs could bereasonably predicted from animal data. Conclusions. Results from the retrospective analysis indicate thatallometric scaling of free concentration could be applied to orallyadministered drugs to gain knowledge of drug disposition in man, and to helpdecision-making at early stages of drug development.
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  • 64
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; recombinant human interleukin-11 ; absorption ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
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  • 65
    ISSN: 1573-904X
    Keywords: (R,S)-Ifosfamide ; R2-, R3-, S2-, S3-DCE-IFF ; iterative-two stage analysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To describe the pharmacokinetics of R- andS-Ifosfamide (IFF), and their respective 2 and 3 N-dechloroethylated (DCE)metabolites (R2-, R3-, S2, S3-DCE-IFF) in cancer patients. Methods. (R,S)-IFF was administered (1.5 g/m2)daily for 5 days in 13 cancer patients. Plasma and urine samples were collectedand analyzed using an enantioselective GC-MS method. An average of 97observations per patient were simultaneously fitted using apharmacokinetic-metabolism (PK-MB) model. A population PK analysis was performedusing an iterative 2-stage method (IT2S). Results. Auto-induction of IFF metabolism was observed over the 5day period. Increases were seen in IFF clearance (R: 4 vs 7 L/h; S: 5vs 10 L/h), and in the formation of DCE (R: 7 vs 9%; S: 14 vs 19%)and active metabolites (4-OHM-IFF; R: 71 vs 77%; S: 67 vs 71%). Anovel finding of this analysis was that the renal excretion of the DCEmetabolites was also induced. Conclusions. This population PK-MB model for (R,S)-IFF may beuseful in the optimization of patient care, and gives new insight intothe metabolism of (R,S)-IFF.
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  • 66
    ISSN: 1573-904X
    Keywords: morphine ; nociceptive effect ; electrical stimulation vocalisation method ; microdialysis ; retrodialysis by drug ; pharmacokinetics ; pharmacodynamics ; modelling ; blood-brain barrier transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To quantify the contribution of distributional processes across the blood-brain barrier (BBB) to the delay in antinociceptive effect of morphine in rats. Methods. Unbound morphine concentrations were monitored in venous blood and in brain extracellular fluid (ECF) using microdialysis (MD) and in arterial blood by regular sampling. Retrodialysis by drug was used for in vivo calibration of the MD probes. Morphine was infused (10 or 40 mg/kg) over 10 min intravenously. Nociception, measured by the electrical stimulation vocalisation method, and blood gas status were determined. Results. The half-life of unbound morphine in striatum was 44 min compared to 30 min in venous and arterial blood (p 〈 0.05). The BBB equilibration of morphine, expressed as the ratio of areas under the curve between striatum and venous blood, was less than unity (0.28 ± 0.09 and 0.22 ± 0.17 for 10 and 40 mg/kg), respectively, indicating active efflux of morphine across the BBB. The concentration-effect relationship exhibited a clear hysterisis with an effect delay half-life of 32 and 5 min based on arterial blood and brain ECF concentrations, respectively. Conclusions. Eighty five percent of the effect delay was caused by morphine transport across the BBB, indicating possible involvement of rate limiting mechanisms at the receptor level or distributional phenomena for the remaining effect delay of 5 min.
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  • 67
    ISSN: 1573-904X
    Keywords: bioequivalence ; dose proportionality ; mixed effects model ; pharmacokinetics ; power model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of this work was a pragmatic, statistically sound and clinically relevant approach to dose-proportionality analyses that is compatible with common study designs. Methods. Statistical estimation is used to derive a (1-α)% confidence interval (CI) for the ratio of dose-normalized, geometric mean values (Rdnm) of a pharmacokinetic variable (PK). An acceptance interval for Rdnm defining the clinically relevant, dose-proportional region is established a priori. Proportionality is declared if the CI for Rdnm is completely contained within the critical region. The approach is illustrated with mixed-effects models based on a power function of the form PK = β0 • Doseβ1; however, the logic holds for other functional forms. Results. It was observed that the dose-proportional region delineated by a power model depends only on the dose ratio. Furthermore, a dose ratio (ρ1) can be calculated such that the CI lies entirely within the pre-specified critical region. A larger ratio (ρ2) may exist such that the CI lies completely outside that region. The approach supports inferences about the PK response that are not constrained to the exact dose levels studied. Conclusion. The proposed method enhances the information from a clinical dose-proportionality study and helps to standardize decision rules.
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  • 68
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    Pharmaceutical research 17 (2000), S. 127-134 
    ISSN: 1573-904X
    Keywords: in-situ head perfusion ; pharmacokinetics ; red blood cells ; water
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To develop a viable, single pass rat head perfusion modeluseful for pharmacokinetic studies. Methods. A viable rat head preparation, perfused with MOPS-bufferedRinger's solution, was developed. Radiolabelled markers (red bloodcells, water and sucrose) were injected in a bolus into the internalcarotid artery and collected from the posterior facial vein over 28minutes. The double inverse Gaussian function was used to estimatethe statistical moments of the markers. Results. The viability of the perfusion was up to one hour, with optimalperfusate being 2% bovine serum albumin at 37°C, pH 7.4. Thedistribution volumes for red blood cells, sucrose and water (from all studies,n = 18) were 1.0 ± 0.3ml, 6.4 ± 4.2ml and 18.3 ± 11.9ml, respectively.A high normalised variance for red blood cells (3.1 ± 2.0) suggestsa marked vascular heterogeneity. A higher normalised variance forwater (6.4 ± 3.3) is consistent with additional diffusive/permeabilitylimitations. Conclusions. Analysis of the physiological parameters derived fromthe moments suggested that the kinetics of the markers were consistentwith distribution throughout the head (weight 25g) rather than justthe brain (weight 2g). This model should assist in studying solutepharmacokinetics in the head.
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  • 69
    ISSN: 1573-904X
    Keywords: α1-acid glycoprotein ; protein binding ; dissociation rate ; species difference ; physiological model ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The extremely low clearance and small distribution volumeof UCN-01 in humans could be partly due to the high degree of bindingto hAGP (1,2). The quantitative effects of hAGP on the pharmacokineticsof UCN-01 at several levels of hAGP and UCN-01 were estimatedin rats given an infusion of hAGP to mimic the clinical situation anda physiological model for analysis was developed. Methods. The plasma concentrations of UCN-01 (72.5–7250 nmol/kgiv) in rats given an infusion of hAGP, 15 or 150 nmol/h/kg, weremeasured by HPLC. Pharmacokinetic analysis under conditionsassuming rapid equilibrium of protein binding and incorporating thedissociation rate was conducted. Results. The Vdss and CLtot of UCN-01 (725 nmol/kg iv) in ratsgiven an infusion of hAGP, 150 nmol/h/kg, fell to about 1/250 and 1/700that in control rats. The Vdss and CLtot following 72.5–7250nmol/kg UCN-01 to rats given 150 nmol/h/kg hAGP were 63.9–688ml/kg and 3.18–32.9 ml/h/kg, respectively, indicating non-linearitydue to saturation of UCN-01 binding. The CLtot estimated by thephysiological model assuming rapid equilibrium of UCN-01 bindingto hAGP, was six times higher than the observed value while the CLtotestimated by the model incorporating koff, measured using DCC, wascomparable with the observed value. Conclusions. These results suggest that the slow dissociation ofUCN-01 from hAGP limits its disposition and elimination.
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  • 70
    ISSN: 1573-904X
    Keywords: IVIVC ; racemate ; enantiomers ; metoprolol ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To investigate the ability of an IVIVC developedwith a racemate drug as well as each enantiomer in predicting the invivo enantiomer drug performance. Methods. Dissolution of metoprolol extended releasetablets with different release characteristics (e.g., fast (F),moderate (M), and slow (S)) was performed using USP ApparatusI, pH 1.2, 50 rpm. Metoprolol racemate tablets (S, M, and F, 100 mg) and 50mg oral solution were administered to healthy volunteers, blood samples werecollected over 24 (solution) and 48 (tablet) hours and assayed. IVIVC modelsdeveloped were: (1) Racemate-fraction of drug dissolved (FRD) vsRacemate-fraction of drug absorbed (FRA), (2) R-FRD vs R-FRA, and (3) S-FRDvs S-FRA for combinations of formulations (S/M/F, S/M, S/F, and M/F).Enantiomer Cmax and AUC prediction errors (PEs) were estimated for modelevaluation after convolution of in vivo release rates. Results. The R-IVIVC and S-IVIVC accurately predicted theR- and S-metoprolol pharmacokinetic profiles, respectively. The averagedprediciton errors (PE) for the enantiomer Cmax and AUC were less than10% for S/M/F, M/F, and S/F IVIVC models. Racemate-IVIVC (M/F) wasable to predict S-enantiomer with an average %PE of 2.52 for S-Cmaxand 4.3 for S-AUC. However, the racemate-IVIVC was unable to predict theR-enantiomer pharmacokinetic profile. Conclusions. Metoprolol racemate data cannot be used toaccurately predict R-enantiomer drug concentrations. However, the racematedata was predictive of the active stereoisomer.
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  • 71
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    Pharmaceutical research 17 (2000), S. 1426-1431 
    ISSN: 1573-904X
    Keywords: eplerenone ; selective aldosterone receptor antagonist ; dog ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The present study was conducted to characterize the pharmacokinetics of eplerenone (EP), a selective aldosterone receptor antagonist, and its open lactone ring form in the dog. Methods. Pharmacokinetic studies of EP were conducted in dogs following i.v., oral, and rectal dosing (15 mg/kg) and following intragastric, intraduodenal, intrajejunal, and intracolonic dosing (7.5 mg/kg). Results. After oral administration, the systemic availability of EP was 79.2%. Systemic availabilities following administration via other routes were similar to that following oral administration. The half-life and plasma clearance of EP were 2.21 hr and 0.329 l/kg/hr, respectively. Plasma concentrations of the open lactone ring form were lower than EP concentrations regardless of the route of administration. The C-14 AUC in red blood cells was approximately 64% and 68% of the plasma AUC for i.v. and oral doses. Percentages of the dose excreted as total radioactivity in urine and feces were 54.2% and 40.6%, respectively, after i.v. administration, and 40.7% and 52.3%, respectively, after oral administration. The percentages of the dose excreted in urine and feces as EP were 13.7% and 2.5%, respectively, after i.v. administration, and 2.1% and 4.6% after oral administration, respectively. Approximately 11% and 15% of the doses were excreted as the open form following i.v. and oral doses. Conclusions. EP was rapidly and efficiently absorbed throughout the gastrointestinal tract, resulting in a good systemic availability. The drug did not preferentially accumulate in red blood cells. EP was extensively metabolized; however, first-pass metabolism after oral and rectal administration was minimal. EP and its metabolites appear to be highly excreted in the bile.
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  • 72
    ISSN: 1573-904X
    Keywords: aspergillosis ; pharmacokinetics ; amphotericin B ; biodistribution ; liposomes ; cholesterol hemisuccinate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This study compared the biodistribution of two amphotericin B formulations in normal and Aspergillus infected mice. Amphotericin B cholesterol hemisuccinate vesicles (ABCV) which reduces the toxicity of amphotericin B and thereby enhances its therapeutic efficacy in a murine model of aspergillosis was compared with conventional amphotericin B deoxycholate suspension (AmBDOC). Methods. ABCV (12 mg/kg wt) and AmBDOC (2 mg/kg wt) were intravenously administered to normal and A.fumigatus infected mice. The concentration of amphotericin B in plasma and other organs was determined at different time points. Results. It was observed that ABCV had a significantly different pharmacokinetic profile compared to conventional amphotericin B. In comparison to AmBDOC significantly lower levels of amphotericin B were observed in kidneys and plasma, the major target organs of toxicity. Animals receiving ABCV demonstrated high levels of amphotericin B in liver (38% retention till 48 h) and spleen (2.6% retention till 48 h) in comparison to AmBDOC (7.3% and 0.21% retention in liver and spleen respectively till 48 h). Biodistribution studies of ABCV in infected mice demonstrated that there was a moderate enhancement in levels of amphotericin B in liver, spleen, lungs and kidneys as compared to normal mice and the plasma levels were reduced. However, such observations were not made after AmBDOC administration to infected mice except for kidneys in which there was a marked increase in uptake as compared to normal mice. Conclusions. Our results suggest that prolonged retention of high concentrations of ABCV in reticuloendothelial system organs is the reason for its reduced toxicity. Enhanced localization of the drug at the infected site may lead to improvement in therapeutic efficacy.
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  • 73
    ISSN: 1573-904X
    Keywords: oral absorption ; humans ; dogs ; rats ; interspecies scale-up ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To conduct a retrospective evaluation of using dog as ananimal model to study the fraction of oral dose absorbed (F) of 43drugs in humans and to briefly discuss potential factors that mighthave contributed to the observed differences in absorption. Methods. Mean human and dog absorption data obtained under fastedstate of 43 drugs with markedly different physicochemical andpharmacological properties and with mean F values ranging from 0.015 to1.0 were obtained from the literature. Correlation of F values betweenhumans and dogs was studied. Based on the same references, additionalF data for humans and rats were also obtained for 18 drugs. Results. Among the 43 drugs studied, 22 drugs were virtuallycompletely absorbed in both dogs and humans. However, the overallcorrelation was relatively poor (r2 = 0.5123) as compared to the earlier ratvs. human study on 64 drugs (r2 = 0.975). Several drugs showed muchbetter absorption in dogs than in humans. Marked differences in thenonliner absorption profiles between the two species were found forsome drugs. Also, some drugs had much longer Tmax values andprolonged absorption in humans than in dogs that might be theoreticallypredicted. Data on 18 drugs further support great similarity in F betweenhumans and rats reported earlier from our laboratory. Conclusions. Although dog has been commonly employed as ananimal model for studying oral absorption in drug discovery anddevelopment, the present study suggests that one may need to exercise cautionin the interpretation of data obtained. Exact reasons for the observedinterspecies differences in oral absorption remain to be explored.
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  • 74
    ISSN: 1573-904X
    Keywords: benzodiazepines ; pharmacokinetics ; EEG ; operational model of agonism ; receptor binding ; muscimol-induced Cl−uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. A mechanism-based model is applied to analyse adaptivechanges in the pharmacodynamics of benzodiazepines upon chronictreatment in rats. Methods. The pharmacodynamics of midazolam was studied in ratswhich received a constant rate infusion of the drug for 14 days, resultingin a steady-state concentration of 102 ± 8 ng·ml−1. Vehicle treated ratswere used as controls. Concentration-EEG effect data were analysed onbasis of the operational model of agonism. The results were comparedto data obtained in vitro in a brain synaptoneurosomal preparation. Results. The relationship between midazolam concentration and EEGeffect was non-linear. In midazolam pre-treated rats the maximum EEGeffect was reduced by 51 ± 23 μV from the original value of 109 ±15 μV in vehicle treated group. Analysis of this change on basis ofthe operational model of agonism showed that it can be explained bya change in the parameter tissue maximum (Em) rather than efficacy(τ). In the in vitro studies no changes in density, affinity or functionalityof the benzodiazepine receptor were observed. Conclusions. It is concluded that the observed changes in theconcentration-EEG effect relationship of midazolam upon chronic treatmentare unrelated to changes in benzodiazepine receptor function.
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  • 75
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    Molecules and cells 10 (2000), S. 61-64 
    ISSN: 0219-1032
    Keywords: Drosophila ; Imprecise Excision ; Null Allele ; P Element ; Rbp9
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The P element has been widely used as a mutagen because of its convenience in locating the site of mutagenesis. However, P element-induced mutations often result in varied mutant phenotypes, making it difficult to identify the null phenotype. Previously, three Rbp9 alleles were isolated using P element mutagenesis. Although the coding regions of Rbp9 were disrupted by P elements in all three cases, they showed different degrees of defects. In order to characterize the null phenotype of Rbp9, Rbp9 alleles with chromosomal deletions were created by inducing imprecise excisions of the P elements. All Rbp9 alleles generated from imprecise excisions showed the same mutant phenotype: female flies were sterile and cystocyte differentiation was blocked. This result reveals that the primary function of Rbp9 resides in the regulation of cystocyte differentiation. In addition, this result shows that a P element does not always completely inactivate gene activity, even when it is incorporated into the coding region.
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  • 76
    ISSN: 0219-1032
    Keywords: Drosophila ; Polycomb Group Genes ; Ultrabithorax ; Visceral Mesoderm
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    Topics: Biology
    Notes: Abstract The Polycomb group (PcG) genes encode repressors of many developmental regulatory genes including homeotic genes and are known to act by modifying chromatin structure through complex formation. We describe how Ultrabithorax (Ubx) expression is affected by the PcG mutants in the visceral mesoderm. Mutant embryos of the genes extra sex combs (esc), Polycomb (Pc), additional sex combs (Asx) and pleiohomeotic (pho) were examined. In each mutation, Ubx was ectopically expressed outside of their normal domains along the anterior-posterior axis in the visceral mesoderm, which is consistent with the effect of PcG proteins repressing the homeotic genes in other tissues. All of these four PcG mutations exhibit complete or partial lack of midgut constriction. However, two thirds of esc mutant embryos did not show Ubx expression in parasegment 7 (PS7). Even in the embryos showing ectopic Ubx expression, the level of Ubx expression in the PcG mutations was weaker than that in normal embryos. We suggest that in PcG mutations the ectopic Ubx expression is caused by lack of PcG repressor proteins, while the weaker or lack of Ubx expression is due to the repression of Ubx by Abd-B protein which is ectopically expressed in PcG mutations as well.
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  • 77
    ISSN: 0219-1032
    Keywords: Drosophila ; Gene Expression ; JHRE ; Juvenile Hormone ; Male Accessory Gland ; Mst57Dc
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Mst57Dc has been isolated as a male accessory gland transcript of Drosophila melanogaster. Its product is a secretory protein, which is phosphorylated by protein kinase A. In the present study, the expression pattern of Mst57Dc was analyzed. It is preferentially expressed in but not restricted to the male accessory glands. Other than in the accessory glands, it is slightly expressed in other body parts, including the head and female body. In the accessory glands, a high level of expression was detected right after eclosion when the titer of juvenile hormone III (JHIII) reaches a peak. Its accumulation was increased by mating, which has been known to act via JH. In ap56f, a JH-deficient mutant, the level of Mst57Dc transcripts was about 60% of the wild type. Moreover a JH-responsive element like palindromic sequence and several sequence motifs were found in the 5′ and 3′ flanking regions of Mst57Dc. Taken together, JH is proposed as a regulator of Mst57Dc gene expression.
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  • 78
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    Dynamics and control 10 (2000), S. 47-61 
    ISSN: 1573-8450
    Keywords: stability ; robust control ; Lyapunov approach ; discrete system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: Abstract Control design of nonlinear discrete-time uncertain systems with (possibly fast) uncertain parameters is considered. We study the effect of only partially compensating the uncertainty. The optimal choice of a design parameter, which indicates the amount of compensation, is recommended.
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  • 79
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    Dynamics and control 10 (2000), S. 255-276 
    ISSN: 1573-8450
    Keywords: continuous-time systems ; frequency weighted model reduction ; gradient flow ; optimization ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: Abstract Inthis paper, a model reduction technique based on optimizationis presented. The objective function minimized is the impulseenergy of the overall system. An extension of the technique tothe frequency weighted case is also presented, where single-sidedor double-sided weightings can be incorporated in the reductionprocedure. The paper proposes an alternative to find an optimizationsolution by solving ordinary differential equations which aregradient flow associated with the objective function to be minimized.Two examples are presented to illustrate the effectiveness ofthe method.
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  • 80
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    Reaction kinetics and catalysis letters 71 (2000), S. 33-40 
    ISSN: 1588-2837
    Keywords: Pt-USY ; de-NOx ; HC-SCR ; propene ; stability
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    Topics: Chemistry and Pharmacology
    Notes: Abstract Selective catalytic reduction of NOx by propene has been investigated on Pt-USY and compared to other Pt-catalysts. The catalyst was characterized by XRD, Ar adsorption at 87 K, TEM, and CO chemisorption, and tested in a gas mixture system in excess oxygen. Pt-USY shows an excellent activity in the reaction, with a molar NOx conversion of 90% at 475 K. Stability during time-on-stream and resistance to SO2 and H2O in the feed stream has also been investigated. Pt-USY performs better under lean-burn conditions than other Pt-catalysts on ZSM-5, Al2O3, or SiO2. The selectivity to N2 was similar for all the catalysts (∼30%), the other major product being N2O.
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  • 81
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    Advances in computational mathematics 12 (2000), S. 229-250 
    ISSN: 1572-9044
    Keywords: numerical analysis ; shallow water problems ; DIRK methods ; stability ; 65L06 ; 65L20 ; 65M12 ; 65M20
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract We construct A‐stable and L‐stable diagonally implicit Runge–Kutta methods of which the diagonal vector in the Butcher matrix has a minimal maximum norm. If the implicit Runge–Kutta relations are iteratively solved by means of the approximately factorized Newton process, then such iterated Runge–Kutta methods are suitable methods for integrating shallow water problems in the sense that the stability boundary is relatively large and that the usually quite fine vertical resolution of the discretized spatial domain is not involved in the stability condition.
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    Journal of statistical physics 101 (2000), S. 731-746 
    ISSN: 1572-9613
    Keywords: attractive Bose–Einstein condensates ; nonlinear Schrödinger equation ; stability ; ground state ; variational arguments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We propose the critical nonlinear Schrödinger equation with a harmonic potential as a model of attractive Bose–Einstein condensates. By an elaborate mathematical analysis we show that a sharp stability threshold exists with respect to the number of condensate particles. The value of the threshold agrees with the existing experimental data. Moreover with this threshold we prove that a ground state of the condensate exists and is orbital stable. We also evaluate the minimum of the condensate energy.
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  • 83
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    Aquatic geochemistry 6 (2000), S. 1-17 
    ISSN: 1573-1421
    Keywords: lakes ; density ; compressibility ; expansibility ; conductivity ; stability ; pvt properties
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract In recent years, a number of workers have studied the stability of deep lakes such as Lake Tanganyika, Lake Baikal and Lake Malawi. In this paper, the methods that can be used to determine the effect that the components of lakes have on the equation of state are examined. The PVT properties of Lakes have been determined by using apparent molal volume data for the major ionic components of the lake. The estimated PVT properties (densities, expansibility and compressibilities) of the lakes are found to be in good agreement with the PVT properties (P) of seawater diluted to the same salinity. This is similar to earlier work that showed that the PVT properties of rivers and estuarine waters could also be estimated from the properties of seawater. The measured densities of Lake Tanganyika were found to be in good agreement (± 2 × 10-6 g cm-3) with the values estimated from partial molal properties and the values of seawater at the same total salinity (ST = 0.568‰). The increase in the densities of Lake Tanganyika waters increased due to changes in the composition of the waters. The measured increase in the measured density (45 × 10-6 g cm-3) is in good agreement (46 × 10-6 g cm-3) with the values calculated for the increase in Na+, HCO3 -, Mg2+, Ca2+ and Si(OH)4. Methods are described that can be used to determine the conductivity salinity of lakes using the equations developed for seawater. By combining these relationships with apparent molal volume data, one can relate the PVT properties of the lake to those of seawater.
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  • 84
    ISSN: 1572-8889
    Keywords: Drosophila ; copulatory courtship ; mate choice ; cryptic female choice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Two endemic Australian Drosophila species, D. birchii and D. serrata, have a copulatory courtship, i.e., the males court the female mainly during copulation. In the present study we found the males of both species to mount their prospective mating partners selectively, exhibiting both sex and species recognition. The males began to sing after mounting the female, and they often exhibited also postcopulatory displays typical to copulatory courtship. D. birchii and D. serrata females discriminated against males which did not sing during mounting/copulation, which suggests that the females utilize cryptic female choice. Our findings raise the question of how widespread a phenomenon cryptic female choice is in Drosophila species.
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  • 85
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    Multidimensional systems and signal processing 11 (2000), S. 109-124 
    ISSN: 1573-0824
    Keywords: 2-D linear systems ; optimal control ; stability ; unit memory linear repetitive processes ; numerical methods
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: Abstract Because many optimal control problems require solution using iterative procedures they fall naturally in the realm of 2-D systems where the two dimensions are response time horizon and iteration index, respectively. The paper uses this observation to employ 2-D systems theory, in the form of unit memory repetitive process techniques, to analyse local stability and convergence behaviour of a continuous optimal control algorithm based on dynamic system optimisation and parameter estimation. Existing work is extended to incorporate unmatched terminal constraints. Necessary and sufficient conditions for stability are obtained whose evaluation require the solution of a difficult eigenvalue problem. The paper shows how solutions can be achieved using numerical and graphical facilities of MATLAB.
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    Multidimensional systems and signal processing 11 (2000), S. 339-358 
    ISSN: 1573-0824
    Keywords: 2-D systems ; descriptor systems ; singular systems ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology
    Notes: Abstract In this paper, we discussthe jump behavior and stability problems for 2-D linear shift-invariantsingular systems under the standard boundary conditions. It isshown that once a boundary condition or the input is inadmissiblein the classical sense, a group of non-causal or backward jumpsof the system states will be incited. This interpretation releasesthe conventional admissibility constraints on the boundary conditionsand inputs. Based on this observation, a systematic stabilitytheory is developed for 2-D singular systems. The well-knownbasic stability theorem for the 1-D singular systems or 2-D regularsystems is thus extended to the 2-D singular case.
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  • 87
    ISSN: 1573-5060
    Keywords: chile ; double haploid ; pepper ; pungency ; stability ; within-genotype variance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The response, in terms of capsaicinoid content, of chile (Capsicum annuum L.) genotypes to different environments was studied. Double haploidlines, an F1 hybrid, and an open-pollinated cultivar estimated the genotype, environment, and genotype-by-environment interaction effect on the total capsaicinoids and on individual capsaicinoids. Significant differences were observed among the genotypes and among genotype-by-environment interactions over the environments. Among the genotypes in an environment, the within-genotype variances were also significantly different. The double haploid line, HDA 207, had low within-genotype variance for individual and total capsaicinoids, with the exception of the isomer of dihydrocapsaicin. Also for HDA 270, the genotype-by-environment interaction was negligible for individual and total capsaicinoids, Indicating stability across environments.
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  • 88
    ISSN: 1573-4943
    Keywords: Methanol dehydrogenase ; Ca2+ ; binding ; activity ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The effects of exogenously added Ca2+ on the enzymatic activity and structural stability of methanol dehydrogenase were studied for various Ca2+ concentrations. Methanol dehydrogenase activity increased significantly with increasing concentration of Ca2+, approaching saturation at 200 mM Ca2+. The effect of Ca2+ on the activation of MDH was time dependent and Ca2+ specific and was due to binding of the metal ions to the enzyme. Addition of increasing concentration of Ca2+ caused a decrease of the intrinsic tryptophan fluorescence intensity in a concentration-dependent manner to a minimum at 200 mM, but with no change in the fluorescence emission maximum wavelength or the CD spectra. The results revealed that the activation of methanol dehydrogenase by Ca2+ occurred concurrently with the conformational change. In addition, exogenously bound Ca2+ destabilized MDH. The potential biological significance of these results is discussed.
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  • 89
    ISSN: 1573-5060
    Keywords: Avena ; genetic correlation ; genotype-environmentinteraction ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract In order to test if selection can improve a population's adaptation to diverse environments simultaneously, three cycles of recurrent selection based on grain yield in Iowa, Idaho, and Norway were practiced in an oat (Avena sativaL.) population developed from North American, Scandinavian, and wild species (A. sterilis L.) germplasm sources. Specific objectives were to determine if selection: increased mean yields across environments and within all environments; changed the genetic correlation of yields in different environments; and changed genetic variation for yield within the population. We evaluated 100 to 210 randomly-chosen families from each cycle of selection at three Iowa locations, in Idaho, and in Norway for two years. Grain yield within each location and mean yields across locations increased significantly over cycles of selection. Mean yields across locations expressed as a percent of the original population mean increased at a rate of 2.6% per year. Several families from the third cycle population exhibited both high mean yields across locations and consistently high yields within all locations. Average genetic correlations of yield in different environments were higher in the second cycle than in the original population. A trend of reduced genetic variation and heritability was observed in Iowa only. These results suggest that we successfully improved mean population yield both within and across locations, and yield stability across environments, and in developing families with outstanding adaptation to diverse environments.
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  • 90
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    Journal of optimization theory and applications 104 (2000), S. 165-174 
    ISSN: 1573-2878
    Keywords: Systems theory ; stability ; robust stability ; linear systems ; discrete-time systems ; robustness ; polynomial theory ; Kharitonov theorem ; inverse Kharitonov problem ; Rouche theorem
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract The paper investigates the problem of the robust stability of Schur polynomials. Recently, a new approach based on the Rouche theorem of classical complex analysis has been adopted for the solution of this problem. In this paper, an improvement of the previous solution is presented. This is the optimum solution of the robust stability problem for Schur polynomials, which is obtained by solving a minimization problem and is better than other methods in robust stability literature. Three numerical examples are given to illustrate the proposed method.
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  • 91
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    Journal of optimization theory and applications 106 (2000), S. 165-182 
    ISSN: 1573-2878
    Keywords: Vector optimization ; asymptotically minimizing sequences ; extended well-posedness ; stability ; vector variational principle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract In this paper, the concept of extended well-posedness of scalar optimization problems introduced by Zolezzi is generalized to vector optimization problems in three ways: weakly extended well-posedness, extended well-posedness, and strongly extended well-posedness. Criteria and characterizations of the three types of extended well-posedness are established, generalizing most of the results obtained by Zolezzi for scalar optimization problems. Finally, a stronger vector variational principle and Palais-Smale type conditions are used to derive sufficient conditions for the three types of extended well-posedness.
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  • 92
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    International journal of fracture 105 (2000), S. 57-79 
    ISSN: 1573-2673
    Keywords: Interface toughness ; interface debonding ; stability ; adhesive interface ; bimaterial.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract In this paper, we studied the interface debonding when a crack perpendicularly approaches an interface between two dissimilar elastic materials. An interface toughness law was first defined according to an adhesive model governing the interface fracture. By analysing the interaction between the normally approaching crack and the interface crack and by tacking account of the adhesive forces at ends of the interfacial crack, a model for studying the interface debonding and the debonding stability was established. It is observed that the interface debonding toughness depends strongly on the mixed mode locally produced over the plastic adhesive zone of the interface. Moreover, the interface debonding may be unstable, i.e. the interface debonding length may jump from an initial value to a certain final value under critical remote loading. This jump may be surprisedly important in certain cases. These results agree with the experimental works gathered so far and can be used to explain the mechanism of 'crack arrestor' formed by an interface.
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  • 93
    ISSN: 1573-3297
    Keywords: Insect ; larval photobehavior ; locomotion ; Drosophila ; behavioral mutants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Psychology
    Notes: Abstract A new assay was designed, named checker, that measures the individual response to light in the fruitfly Drosophila melanogaster larva. In this assay the Drosophila larva apparently modulates its pattern of locomotion when faced with a choice between a dark and lit environment by orienting its movement towards the dark environment. We show that, in this assay, a response to light can be measured as an increase in residence time in the dark versus the lit quadrant. Mutations that disrupt phototransduction in the adult Drosophila abolish the larval response to light, demonstrating that this larval visual function is similar to that of the adult fly. Similarly, no response to light was detected in strains where the larval visual system (photoreceptors and target area) was disrupted by a mutation in the homeobox containing gene sine oculis (so) gene. Ablation of photoreceptors by the targeted expression of the cell death gene hid under the control of the photoreceptor-specific transcription factor glass (gl) abolishes this response entirely. Finally, we demonstrate that this response to light can be mediated by rhodopsins other than the blue absorbing Rh1.
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  • 94
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    Nonlinear dynamics 22 (2000), S. 361-374 
    ISSN: 1573-269X
    Keywords: 4WS vehicle ; time delay ; stability ; Hopf bifurcation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract A mathematical model is presented for four-wheel-steeringvehicles, with the time delay in driver's response and the nonlinearityin lateral tyre forces taken into account. It is proved that thevehicle-driver system has a trivial steady state motion, as well aseight non-trivial steady state motions due to the nonlinearity of tyreforces. The asymptotic stability and Hopf bifurcation of the trivialsteady state are analyzed for two control strategies ofrear-wheel-steering. It is shown through the numerical simulations thatthe four-wheel-steering technique based on the bilinear control strategyworks better when the driver's response involves time delay.
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    Journal of elasticity 61 (2000), S. 49-81 
    ISSN: 1573-2681
    Keywords: collagen structure ; stability ; rupture criterion ; growth mechanics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Intracranial saccular aneurysms remain an enigma; it is not known why they form, why they enlarge, or why only some of them rupture. Nonetheless, there is general agreement that mechanics plays an essential role in each aspect of the natural history of these potentially deadly lesions. In this paper, we review recent findings that discount limit point instabilities under quasi-static increases in pressure and resonance under dynamic loading as possible mechanisms of enlargement of saccular aneurysms. Indeed, recent histopathological data suggest that aneurysms enlarge due to a stress-mediated process of growth and remodeling of collagen, the primary load-bearing constituent within the wall. We submit that advanced theoretical, experimental, and numerical studies of this process are essential to further progress in treating this class of pathologies. The purpose of this review is to provide background and direction that encourages elasticians to contribute to this important area of research.
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    Journal of optimization theory and applications 106 (2000), S. 527-550 
    ISSN: 1573-2878
    Keywords: vector optimization ; set-valued mappings ; constraint sets ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract In vector optimization, several authors have studied the upper and lower semicontinuity for mappings involving constraints in topological vector spaces partially ordered through a cone with nonempty interior. In this paper, we give conditions about the upper and lower semicontinuity in the case that the ordering cone in the parameter space has possibly empty interior, as it happens in many function spaces and seqence spaces.
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    Journal of optimization theory and applications 105 (2000), S. 417-440 
    ISSN: 1573-2878
    Keywords: mixed solutions ; weak Stackelberg problems ; existence ; stability ; weak convergence of probability measures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract We are concerned with ∈-mixed solutions for weak Stackelberg problems corresponding to two-player nonzero-sum noncooperative games. Two cases are considered: (i) mixed strategies for only the second player; (ii) mixed strategies for both players. After giving basic results relating convergence of functions and weak convergence of probability measures, we establish existence and stability results for ∈-mixed solutions under general assumptions of minimal character without any convexity assumption. Our results improve previous work of Mallozzi and Morgan (Refs. 1–2).
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    Journal of optimization theory and applications 106 (2000), S. 431-439 
    ISSN: 1573-2878
    Keywords: multidimensional polynomial theory ; robustness ; Kharitonov theorem ; stability ; Schur polynomials ; inverse Kharitonov problem ; Rouché theorem
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Abstract In this note, the problem of the robust stability for a two-dimensional (two-variable) Schur polynomial which is the characteristic polynomial of a discrete-time linear time-invariant system is investigated. A new approach based on the Rouché theorem is adopted. The extension to the robust stability for multidimensional (multivariable) polynomials is also provided. Interesting sufficient conditions for such robust stability are derived. A two-dimensional example is included to support the theoretical result.
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    Journal of scientific computing 15 (2000), S. 441-456 
    ISSN: 1573-7691
    Keywords: modified conjugate gradient method ; conjugate gradient method ; Krylov space ; convergence rate ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract We consider the modified conjugate gradient procedure for solving A $$\underline x $$ = $$\underline b $$ in which the approximation space is based upon the Krylov space associated with A 1/p and $$\underline b $$ , for any integer p. For the square-root MCG (p=2) we establish a sharpened bound for the error at each iteration via Chebyshev polynomials in $$\sqrt A$$ . We discuss the implications of the quickly accumulating effect of an error in $$\sqrt A$$ $$\underline b $$ in the initial stage, and find an error bound even in the presence of such accumulating errors. Although this accumulation of errors may limit the usefulness of this method when $$\sqrt A$$ $$\underline b $$ is unknown, it may still be successfully applied to a variety of small, “almost-SPD” problems, and can be used to jump-start the conjugate gradient method. Finally, we verify these theoretical results with numerical tests.
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  • 100
    ISSN: 1615-6102
    Keywords: Arabidopsis thaliana ; Cryopreservation ; Dehydration ; Thermal analysis ; Sucrose ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Arabidopsis thaliana suspension cells were preserved in liquid nitrogen for over three years, using embedding of cells in calcium-alginate prior to subculture in sucrose-enriched medium, air-drying, and direct quenching in liquid nitrogen. Survival of cells reached 34%, yielding regrowth at the surface of all cryopreserved beads in less than 7 days. Following pretreatment and dehydration, the water content dropped from 2300% to 34% with respect to dry weight. Differential scanning calorimetry showed that glass transition occurred on cooling, followed by a slight crystallization event on rewarming. The survival of cells was independent of the cooling rate. The tolerance of the acute dehydration step increased progressively with sucrose pretreatment duration, indicating the requirement for adaptative cellular alterations. Ultrastructural studies revealed several changes in cells after sucrose pretreatment prolonged from 1 to 7 days: reversal of the initially plasmolyzed state, microvacuolation, numerous autophagic structures, scarcity of ribosomes, increase in number and size of starch grains. No cell division seemed to occur during this period. After air-drying and after a freeze-thaw cycle, followed by 24 h rehydration, regenerating cells had recovered a high level of ultrastructural organization and contained numerous polysomes suggesting an intense metabolic activity. Trehalose, a cryoprotective disaccharide not considered to be a metabolic substrate, yielded only 70% regrowth after freezing. Biochemical analysis showed that soluble sugars accumulated during the pretreatment, essentially sucrose or trehalose; the monosaccharide content also increased. In the light of these results, the action of sucrose in inducing freezing tolerance is discussed.
    Type of Medium: Electronic Resource
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