Showing papers by "University of Stuttgart published in 2002"

Computational modeling of the dynamics of the MAP kinase cascade activated by surface and internalized EGF receptors.

Abstract: We present a computational model that offers an integrated quantitative, dynamic, and topological representation of intracellular signal networks, based on known components of epidermal growth factor (EGF) receptor signal pathways. The model provides insight into signal‐response relationships between the binding of EGF to its receptor at the cell surface and the activation of downstream proteins in the signaling cascade. It shows that EGF-induced responses are remarkably stable over a 100-fold range of ligand concentration and that the critical parameter in determining signal efficacy is the initial velocity of receptor activation. The predictions of the model agree well with experimental analysis of the effect of EGF on two downstream responses, phosphorylation of ERK-1/2 and expression of the target gene, c-fos.

The Fas Signaling Pathway: More Than a Paradigm

Abstract: Apoptosis and related forms of cell death have central importance in development, homeostasis, tumor surveillance, and the function of the immune system. Apoptosis is initiated by two principal pathways. The intrinsic pathway emerges from mitochondria, whereas the extrinsic pathway is activated by the ligation of death receptors. This Viewpoint introduces the basic mechanisms of the extrinsic pathway, using the example of the prototypical death receptor Fas and its role in apoptosis, but it also points out the increasingly understood importance of this receptor as a non-apoptotic signal transducer.

Fundamental measure theory for hard-sphere mixtures revisited: the White Bear version

Abstract: We develop a density functional for hard-sphere mixtures which keeps the structure of Rosenfeld's fundamental measure theory (FMT) whilst inputting the Mansoori–Carnahan–Starling–Leland bulk equation of state. Density profiles for the pure hard-sphere fluid and for some binary mixtures adsorbed at a planar hard wall obtained from the present functional exhibit some improvement over those from the original FMT. The pair direct correlation function c(2) (r) of the pure hard-sphere fluid, obtained from functional differentiation, is also improved. When a tensor weight function is incorporated for the pure system our functional yields a good description of fluid–solid coexistence and of the properties of the solid phase.

Dynamic modeling of the central carbon metabolism of Escherichia coli.

Abstract: Application of metabolic engineering principles to the rational design of microbial production processes crucially depends on the ability to describe quantitatively the systemic behavior of the central carbon metabolism to redirect carbon fluxes to the product-forming pathways. Despite the importance for several production processes, development of an essential dynamic model for central carbon metabolism of Escherichia coli has been severely hampered by the current lack of kinetic information on the dynamics of the metabolic reactions. Here we present the design and experimental validation of such a dynamic model, which, for the first time, links the sugar transport system (i.e., phosphotransferase system [PTS]) with the reactions of glycolysis and the pentose-phosphate pathway. Experimental observations of intracellular concentrations of metabolites and cometabolites at transient conditions are used to validate the structure of the model and to estimate the kinetic parameters. Further analysis of the detailed characteristics of the system offers the possibility of studying important questions regarding the stability and control of metabolic fluxes. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 79: 53–73; 2002.

Electrodynamics of Solids: Optical Properties of Electrons in Matter

Abstract: 1. Introduction Part I. Concepts and Properties: 2. The interaction of radiation with matter 3. General properties of the optical constants 4. The medium: correlation and response functions 5. Metals 6. Semiconductors 7. Broken-symmetry states of metals Part II. Methods: 8. Techniques: general considerations 9. Propagation and scattering of electromagnetic waves 10. Spectroscopic principles 11. Measurement configurations Part III. Experiments: 12. Metals 13. Semiconductors 14. Broken-symmetry states of metals Appendix A. Fourier and Laplace transformation Appendix B. Medium of finite thickness Appendix C. k.p perturbation theory Appendix D. Sum rules Appendix E. Non-local response Appendix F. Dielectric response in reduced dimensions Appendix G. Important constants and units.

Neurodegenerative and neuroprotective effects of tumor Necrosis factor (TNF) in retinal ischemia: opposite roles of TNF receptor 1 and TNF receptor 2.

Abstract: Tumor necrosis factor (TNF) is an important factor in various acute and chronic neurodegenerative disorders. In retinal ischemia, we show early, transient upregulation of TNF, TNF receptor 1 (TNF-R1), and TNF-R2 6 hr after reperfusion preceding neuronal cell loss. To assess the specific role of TNF and its receptors, we compared ischemia-reperfusion-induced retinal damage in mice deficient for TNF-R1, TNF-R2, or TNF by quantifying neuronal cell loss 8 d after the insult. Surprisingly, TNF deficiency did not affect overall cell loss, yet absence of TNF-R1 led to a strong reduction of neurodegeneration and lack of TNF-R2 led to an enhancement of neurodegeneration, indicative of TNF-independent and TNF-dependent processes in the retina, with TNF-R1 augmenting neuronal death and TNF-R2 promoting neuroprotection. Western blot analyses of retinas revealed that reduction of neuronal cell loss in TNF-R1/ animals correlated with the presence of activated Akt/protein kinase B (PKB). Inhibition of the phosphatidylinositol 3-kinase signaling pathway reverted neuroprotection in TNF-R1-deficient mice, indicating an instrumental role of Akt/PKB in neuroprotection and TNF-R2 dependence of this pathway. Selective inhibition of TNF-R1 function may represent a new approach to reduce ischemia-induced neuronal damage, being potentially superior to strategies aimed at suppression of TNF activity in general.

Protein dislocation from the ER requires polyubiquitination and the AAA-ATPase Cdc48.

Abstract: Endoplasmic reticulum (ER)-associated protein degradation by the ubiquitin-proteasome system requires the dislocation of substrates from the ER into the cytosol. It has been speculated that a functional ubiquitin proteasome pathway is not only essential for proteolysis, but also for the preceding export step. Here, we show that short ubiquitin chains synthesized on proteolytic substrates are not sufficient to complete dislocation; the size of the chain seems to be a critical determinant. Moreover, our results suggest that the AAA proteins of the 26S proteasome are not directly involved in substrate export. Instead, a related AAA complex Cdc48, is required for ER-associated protein degradation upstream of the proteasome.

Computational micro-to-macro transitions of discretized microstructures undergoing small strains

Abstract: The paper investigates algorithms for the computation of homogenized stresses and overall tangent moduli of microstructures undergoing small strains. Typically, these microstructures define representative volumes of nonlinear heterogeneous materials such as inelastic composites, polycrystalline aggregates or particle assemblies. We consider a priori given discretized microstructures, without focusing on details of specific discretization techniques in space and time. The key contribution of the paper is the construction of a family of algorithms and matrix representations of the overall properties of discretized microstructures. It is shown that the overall stresses and tangent moduli of a typical microstructure may exclusively be defined in terms of discrete forces and stiffness properties on the boundary. We focus on deformation-driven microstructures, where the overall macroscopic deformation is controlled. In this context, three classical types of boundary conditions are investigated: (i) linear displacements, (ii) constant tractions and (iii) periodic displacements and antiperiodic tractions. Incorporated by the Lagrangian multiplier method, these constraints generate three classes of algorithms for the computation of equilibrium states and the overall properties of microstructures. The proposed algorithms and matrix representations of the overall properties are formally independent of the interior spatial structure and the local constitutive response of the microstructure and are therefore applicable to a broad class of model problems. We demonstrate their performance for some representative model problems including elastic–plastic deformations of composite materials.

Yeast formins regulate cell polarity by controlling the assembly of actin cables

Abstract: Formins are conserved Rho-GTPase effectors that communicate Rho-GTPase signals to the cytoskeleton. We found that formins were required for the assembly of one of the three budding yeast actin structures: polarized arrays of actin cables. A dominant-active formin induced the assembly of actin cables. The activation and localization of the formin Bni1p required components of the polarisome complex. These findings potentially define the cellular function of formins in budding yeast and explain their involvement in the generation of cell polarity. A requirement for formins in constructing specific actin structures might be the basis for the diverse activities of formins in development.

An Introduction to Nonlinear Model Predictive Control

Abstract: While linear model predictive control is popular since the 70s of the past century, the 90s have witnessed a steadily increasing attention from control theoretists as well as control practitioners in the area of nonlinear model predictive control (NMPC). The practical interest is driven by the fact that today’s processes need to be operated under tighter performance specifications. At the same time more and more constraints, stemming for example from environmental and safety considerations, need to be satisfied. Often these demands can only be met when process nonlinearities and constraints are explicitly considered in the controller. Nonlinear predictive control, the extension of well established linear predictive control to the nonlinear world, appears to be a well suited approach for this kind of problems. In this note the basic principle of NMPC is reviewed, the key advantages/disadvantages of NMPC are outlined and some of the theoretical, computational, and implementational aspects of NMPC are discussed. Furthermore, some of the currently open questions in the area of NMPC are outlined. 1 Principles, Mathematical Formulation and Properties of Nonlinear Model Predictive Control Model predictive control (MPC), also referred to as moving horizon control or receding horizon control, has become an attractive feedback strategy, especially for linear processes. Linear MPC refers to a family of MPC schemes in which linear models are used to predict the system dynamics, even though the dynamics of the closed-loop system is nonlinear due to the presence of constraints. Linear MPC approaches have found successful applications, especially in the process industries. A good overview of industrial linear MPC techniques can be found in [64, 65], where more than 2200 applications in a very wide range from chemicals to aerospace industries are summarized. By now, linear MPC theory is quite mature. Important issues such as online computation, the interplay between modeling/identification and control and system theoretic issues like stability are well addressed [41, 52, 58]. Many systems are, however, in general inherently nonlinear. This, together with higher product quality specifications and increasing productivity demands, tighter environmental regulations and demanding economical considerations in the process industry require to operate systems closer to the boundary of the admissible operating region. In these cases, linear models are often inadequate to describe the process dynamics and nonlinear models have to be used. This motivates the use of nonlinear model predictive control. This paper focuses on the application of model predictive control techniques to nonlinear systems. It provides a review of the main principles underlying NMPC and outlines the key advantages/disadvantages of NMPC and some of the theoretical, computational, and implementational aspects. Note, however, that it is not intended as a complete review of existing NMPC techniques. Instead we refer to the following list for some excellent reviews [4, 16, 22, 52, 58, 68]. In Section 1.1 and Section 1.2 the basic underlying concept of NMPC is introduced. In Section 2 some of the system theoretical aspects of NMPC are presented. After an outline of NMPC schemes that achieve stability one particular NMPC formulation, namely quasi-infinite horizon NMPC (QIH-NMPC) is outlined to exemplify the basic ideas to achieve stability. This approach allows a (computationally) efficient formulation of NMPC while guaranteeing stability and performance of the closed-loop. Besides the basic question of the stability of the closed-loop, questions such as robust formulations of NMPC and some remarks on the performance of the closed-loop are given in Section 2.3 and Section 2.2. Section 2.4 gives some remarks on the output-feedback problem in connection with NMPC. After a short review of existing approaches one

General characteristics of temperature variation in China during the last two millennia

Abstract: Three alternate China-wide temperature composites covering the last 2000 years were established by combining multiple paleoclimate proxy records obtained from ice cores, tree rings, lake sediments and historical documents. Five periods of temperature variation can be identified: a warm stage in AD 0–240, a cold interval between AD 240 and 800, a return to warm conditions from AD 800–1400, including the Medieval Warm Period between AD 800–1100, the cool Little Ice Age period between 1400–1920, and the present warm stage since 1920. Regional temperature variation is found during AD 800–1100, when warm conditions occurred in Eastern China and in the northeastern Tibetan Plateau and in AD 1150–1380, when the southern Tibetan Plateau experienced a warm interval. In contrast, evidence for cool conditions during the LIA is more consistent among the proxy records. The temperature reconstructions for China and the Northern Hemisphere show good agreement over the past millennium.

Non-convex potentials and microstructures in finite-strain plasticity

Abstract: A mathematical model for a finite–strain elastoplastic evolution problem is proposed in which one time–step of an implicit time–discretization leads to generally non–convex minimization problems. The elimination of all internal variables enables a mathematical and numerical analysis of a reduced problem within the general framework of calculus of variations and nonlinear partial differential equations. The results for a single slip–system and von Mises plasticity illustrate that finite–strain elastoplasticity generates reduced problems with non–quasiconvex energy densities and so allows for non–attainment of energy minimizers and microstructures.

Transfer function method to diagnose axial displacement and radial deformation of transformer windings

Abstract: Short circuit currents or forces during transport can cause mechanical displacements of transformer windings. The transfer function method is presented as a tool to detect these displacements. In order to be able to evaluate the measurements, the correlation between the characteristics of transfer functions and possible damages must be known. Axial displacement and radial deformation of transformer windings have been studied in this research work using two test transformers. The primary winding of the first transformer for axial displacement has 31 double disk coils (1.3 MVA, 10 kV) and the secondary winding is a four layer winding. The second transformer for the study of radial deformation has 30 double disk coils (1.2 MVA, 10 kV) as primary winding and a one layer winding as secondary winding. The detailed mathematical models were developed for the test objects and a comparison was carried out between measured and calculated results. It is shown that this model can present the behavior of the transformer windings in the frequency domain in the case of sound and displaced conditions.

Growth kinetics and mechanisms of aluminum-oxide films formed by thermal oxidation of aluminum

Abstract: The growth kinetics and mechanisms of thin aluminum-oxide films formed by the dry, thermal oxidation of a bare Al(431) substrate at a partial oxygen pressure of 1.33×10−4 Pa in the temperature range of 373–773 K were studied using x-ray photoelectron spectroscopy. The initial oxidation of the bare Al substrate proceeds by an island-by-layer growth mechanism, involving the lateral diffusion over the bare Al substrate surface of mobile oxygen species. At low temperatures (T⩽573 K), an amorphous oxide film develops that attains a limiting (uniform) thickness. At high temperatures (T>573 K), growth is not impeded at a limiting thickness. Kinetic analysis established the occurrences of two different oxide-film growth regimes: an initial regime of very fast oxide-film growth and a second, much slower oxidation stage that is observed only at T>573 K. These results could be discussed in terms of electric-field controlled, interstitial, outward transport of Al cations through a close packing of O anions in the amo...

Strain‐driven homogenization of inelastic microstructures and composites based on an incremental variational formulation

Abstract: The paper investigates computational procedures for the treatment of a homogenized macro-continuum with locally attached micro-structures of inelastic constituents undergoing small strains. The point of departure is a general internal variable formulation that determines the inelastic response of the constituents of a typical micro-structure as a generalized standard medium in terms of an energy storage and a dissipation function. Consistent with this type of inelasticity we develop a new incremental variational formulation of the local constitutive response where a quasi-hyperelastic micro-stress potential is obtained from a local minimization problem with respect to the internal variables. It is shown that this local minimization problem determines the internal state of the material for finite increments of time. We specify the local variational formulation for a setting of smooth single-surface inelasticity and discuss its numerical solution based on a time discretization of the internal variables. The existence of the quasi-hyperelastic stress potential allows the extension of homogenization approaches of elasticity to the incremental setting of inelasticity. Focusing on macro-strain-driven micro-structures, we develop a new incremental variational formulation of the global homogenization problem where a quasi-hyperelastic macro-stress potential is obtained from a global minimization problem with respect to the fine-scale displacement fluctuation field. It is shown that this global minimization problem determines the state of the micro-structure for finite increments of time. We consider three different settings of the global variational problem for prescribed linear displacements, periodic fluctuations and constant stresses on the boundary of the micro-structure and discuss their numerical solutions based on a spatial discretization of the fine-scale displacement fluctuation field. The performance of the proposed methods is demonstrated for the model problem of von Mises-type elasto-visco-plasticity of the constituents and applied to a comparative study of micro-to-macro transitions of inelastic composites. Copyright © 2002 John Wiley & Sons, Ltd.

A Variational Formulation of Rate-Independent Phase Transformations Using an Extremum Principle

Abstract: We propose a rate-independent, mesoscopic model for the hysteretic evolution of phase transformations in shape-memory alloys. The model uses the deformation and phase-indicator function as basic unknowns and the potentials for the elastic energy and for the dissipation as constitutive laws. Using the associated functionals, admissible processes are defined to be the ones which are stable at all times and which satisfy the energy inequality.

Foundations of multiphasic and porous materials

Abstract: Miscible multiphasic materials like classical mixtures as well as immiscible materials like saturated and partially saturated porous media can be successfully described on the common basis of the well-founded Theory of Mixtures (TM) or the Theory of Porous Media (TPM). In particular, both the TM and the TPM provide an excellent frame for a macroscopic description of a broad variety of engineering applications and further problems in applied natural sciences. The present article portrays both the standard and the micropolar approaches to multiphasic materials reflecting their mechanical and their thermodynamical frameworks. Including some constitutive models and various illustrative numerical examples, the article can be understood as a reference paper to all the following articles of this volume on theoretical, experimental and numerical investigations in the Theory of Porous Media.

Passive high-power microwave components

Abstract: This review discusses the present state-of-the-art of passive high-power microwave components for applications in microwave systems for RF plasma generation and heating, plasma diagnostics, plasma and microwave materials processing, spectroscopy, communication, radar ranging and imaging, and for drivers of next generation high-field-gradient electron-positron linear colliders. The paper reports on high-power components for overmoded high-power transmission systems such as smooth-wall waveguides, HE/sub 11/ hybrid mode waveguides and quasi-optical TEM/sub 00/ beam waveguides. These include various types of mode converters, polarizers, cross-section tapers, bends, mode selective filters, pulse compressors, DC-breaks, directional couplers, beam combiners and dividers, vacuum windows, and instruments for mode analysis. Problems of ohmic attenuation and unwanted conversion to parasitic modes are discussed in detail and rules for alignment requirements are given. In the case of waveguide transmission, this review mainly concentrates on circular waveguide components but also deals with rectangular waveguide.

Apoptotic crosstalk of TNF receptors: TNF-R2-induces depletion of TRAF2 and IAP proteins and accelerates TNF-R1-dependent activation of caspase-8

Abstract: We have recently shown that stimulation of TNF-R2 selectively enhances apoptosis induction by the death receptor TNF-R1. Here, we demonstrate that stimulation of CD30 or CD40 also leads to selective enhancement of TNF-R1-induced cell death. Enhancement of apoptosis was correlated with the depletion of endogenous TRAF2 within 1 to 6 hours. Selective prestimulation of TNF-R2 for several hours inhibited TNF-R2-induced activation of the anti-apoptotic NF-kappaB pathway up to 90% and dramatically enhanced apoptosis induction by this receptor. When both TNF-receptors were stimulated simultaneously, TNF-R1-induced NF-kappaB activation remained unaffected but TNF-R1-induced apoptosis was still significantly enhanced. Compared with FasL-induced cell death TNF-R1-induced activation of caspase-8 was significantly weaker and delayed. Costimulation or prestimulation of TNF-R2 enhanced caspase-8 processing. Life cell imaging and confocal microscopy revealed that both TNF-R1 and TNF-R2 recruited the anti-apoptotic factor cIAP1 in a TRAF2-dependent manner. Thus, TNF-R2 may compete with TNF-R1 for the recruitment of newly synthesized TRAF2-bound anti-apoptotic factors, thereby promoting the formation of a caspase-8-activating TNF-R1 complex. Hence, TNF-R2 triggering can interfere with TNF-R1-induced apoptosis by inhibition of NF-kappaB-dependent production of anti-apoptotic factors and by blocking the action of anti-apoptotic factors at the post-transcriptional level.

Astrophysical Reaction Rate of 12C(α, γ)16O

Abstract: A new astrophysical reaction rate of 12C(α, γ)16O has been calculated based on our recent determination of the E1- and E2-capture cross sections. The R-matrix method has been applied to describe the SE1- and SE2-factor functions as well as the data of elastic α scattering and the β-delayed α decay of 16N from other experiments. The resulting reaction rate for stellar temperatures of T9 = 0.04-10 is presented in both tabular form and an analytic expression. A new temperature dependence of the reaction rate was obtained when compared with reported evaluations. The associated uncertainties were reduced considerably in comparison to previous determinations.

Tuning the dipolar interaction in quantum gases.

Abstract: We have studied the tunability of the interaction between permanent dipoles in Bose-Einstein condensates. Based on time-dependent control of the anisotropy of the dipolar interaction, we show that even the very weak magnetic dipole coupling in alkali gases can be used to excite collective modes. Furthermore, we discuss how the effective dipolar coupling in a Bose-Einstein condensate can be tuned from positive to negative values and even switched off completely by fast rotation of the orientation of the dipoles.

Expression of Macrophage Migration Inhibitory Factor in Different Stages of Human Atherosclerosis

Abstract: Background - Atherosclerosis is a chronic inflammatory response of the arterial wall to injury. Macrophage migration inhibitory factor (MIF), a cytokine with potent inflammatory functions, was thus considered to be important in atherosclerotic lesion evolution. Methods and Results - We studied the presence and distribution of MIF immunoreactivity (MIF-IR) and MIF mRNA in internal mammary arteries with a normal histology and arteries with plaques in different stages of human atherosclerosis. To address a potential role for the coactivator Jab1 as a cellular mediator of MIF effects in vascular tissue, we correlated the expression of MIF to that of Jab1 by using immunohistochemistry and coimmunoprecipitation. We further sought to determine a potential functional role for endothelium-derived MIF in early atherogenesis by studying the effects of oxidized LDL on MIF expression in cultured human umbilical vascular endothelial cells. The results showed that MIF-IR and Jab1-IR are found in all cell types present in atherosclerotic lesions, that MIF-IR is upregulated during progression of atherosclerosis, that MIF is produced locally in the arterial wall, and that all MIF+ cells are simultaneously Jab1 +. Coimmunoprecipitation experiments demonstrated in vivo complex formation between MIF and Jab1 in plaques. MIF expression in human umbilical vascular endothelial cells and a macrophage line was upregulated after stimulation with oxidized LDL. Conclusions - MIF is produced abundantly by various cells in all types of human atherosclerotic lesions and thus may play an important role in early plaque development and advanced complicated lesions. MIF-Jab1 complexes could serve critical regulatory functions in atherosclerotic lesion evolution. Chemicals/CAS: COPS5 protein, human, EC 3.4.-.-; DNA-Binding Proteins; Intracellular Signaling Peptides and Proteins; Lipoproteins, LDL; Macrophage Migration-Inhibitory Factors; oxidized low density lipoprotein; Peptide Hydrolases, EC 3.4.-; Transcription Factors