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  • 2000-2004  (634)
  • 1985-1989
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  • 1900-1904
  • 2000  (634)
  • Chemistry  (481)
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  • 2000-2004  (634)
  • 1985-1989
  • 1980-1984
  • 1900-1904
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  • 1
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    Two-Dimensional Adaptive Simulation of Dopant Diffusion in Silicon (2000)
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    Publication Date: 2014-02-26
    Description: One important step in the fabrication of silicon-based integrated circuits is the creation of semiconducting areas by diffusion of dopant impurities into silicon. Complex models have been developed to investigate the redistribution of dopants and point defects. In general, numerical analysis of the resulting PDEs is the central tool to assess the modelling process. We present an adaptive approach which is able to judge the quality of the numerical approximation and which provides an automatic mesh improvement. Using linearly implicit methods in time and multilevel finite elements in space, we are able to integrate efficiently the arising reaction-drift-diffusion equations with high accuracy. Two different diffusion processes of practical interest are simulated.
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    Language: English
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  • 2
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    An Uncoupling-Coupling Technique for Markov Chain Monte Carlo Methods (2000)
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    Publication Date: 2014-02-26
    Description: Uncoupling-coupling Monte Carlo (UCMC) combines uncoupling techniques for finite Markov chains with Markov chain Monte Carlo methodology. By determining almost invariant sets of the associated Markov operator, the Monte Carlo sampling splits by a hierarchical annealing process into the essential regions of the state space; therefore UCMC aims at avoiding the typical metastable behavior of Monte Carlo techniques. From the viewpoint of Monte Carlo, a slowly converging long-time Markov chain is replaced by a limited number of rapidly mixing short-time ones. The correct weighting factors for the various Markov chains are obtained via a coupling matrix, that connects the samplings from the different almost invariant sets. The underlying mathematical structure of this approach is given by a general examination of the uncoupling-coupling procedure. Furthermore, the overall algorithmic scheme of UCMC is applied to the $n$-pentane molecule, a well-known example from molecular dynamics.
    Keywords: ddc:000
    Language: English
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  • 3
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    News from the Online Traveling Repairman (2000)
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    Publication Date: 2020-11-13
    Description: The traveling repairman problem (TRP) is a variant of the famous traveling salesman problem (TSP). The objective for the TRP is to minimize the latency, that is the the weighted sum of completion times of the cities, where the completion time of a city is defined to be the time in the tour before the city is reached. In the online traveling repairman problem (OLTRP) requests for visits to cities (points in a metric space) arrive online while the repairman is traveling. We analyze the performance of algorithms using competitive analysis, where the cost of an online algorithm is compared to that of an optimal offline algorithm. An optimal offline algorithm knows the entire request sequence in advance and can serve it with minimum cost. Recently, Feuerstein and Stougie presented a $9$-competitive algorithm for the OLTRP on the real line. In this paper we show how to use techniques from online-scheduling to obtain an $8$-competitive deterministic algorithm which works for any metric space. We also present a randomized algorithm which has a competitive ratio of $\frac{4}{\ln 2}\approx 5.7708$ against an oblivious adversary. All of our results also hold for the ``dial-a-ride'' generalization of the OLTRP, where objects have to be picked up and delivered by a server.
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  • 4
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    The Online-TSP Against Fair Adversaries (2000)
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    Publication Date: 2020-11-13
    Description: In the online traveling salesman problem requests for visits to cities (points in a metric space) arrive online while the salesman is traveling. The salesman moves at no more than unit speed and starts and ends his work at a designated origin. The objective is to find a routing for the salesman which finishes as early as possible. Performance of algorithms is measured through their competitive ratio, comparing the outcome of the algorithms with that of an adversary who provides the problem instance and therefore is able to achieve the optimal offline solution. Objections against such omnipotent adversaries have lead us to devise an adversary that is in a natural way, in the context of routing problems, more restricted in power. For the exposition we consider the online traveling salesman problem on the metric space given by the non-negative part of the real line. We show that a very natural strategy is~$3/2$-competitive against the conventional adversary, which matches the lower bound on competitive ratios achievable for algorithms for this problem. Against the more ``\emph{fair adversary}'', that we propose, we show that there exists an algorithm with competitive ratio $\frac{1+\sqrt{17}}{4}\approx 1.28$ and provide a matching lower bound. We also show competitiveness results for a special class of algorithms (called zealous algorithms) that do not allow waiting time for the server as long as there are requests unserved.
    Keywords: ddc:000
    Language: English
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  • 5
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    Progress Towards a Combined MRI/Hyperthermia System (2000)
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    Publication Date: 2020-03-09
    Description: Regional hyperthermia, a clinical cancer therapy, is the main topic of the Sonderforschungsbereich Hyperthermia: Scientific Methods and Clinical Applications'' at Berlin. In recent years, technological improvements towards a better concentration of heat to the desired target region have been achieved. These include a rather sophisticated integrated software environment for therapy planning and a new hyperthermia applicator. In a next step, a detailed closed loop monitoring of the actual treatment is to be developed. For this purpose the hyperthermia applicator is combined with an MRI system, which will allow to check the positioning of the patients and to measure individual blood perfusion as well as the 3D temperature distribution. The measurements will then be employed for an on-line control of the whole treatment. In this intended setting, new fast feedback control algorithms will come into play.
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  • 6
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    Kooperativer Bibliotheksverbund Berlin-Brandenburg: Erste Erfahrungen im Produkionsbetrieb (2000)
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    Publication Date: 2020-03-11
    Description: In diesem Artikel wird der Status des Projekts Kooperativer Bibliotheksverbund Berlin-Brandenburg beschrieben, der im November 1999 mit der KOBV-Suchmaschine seinen produktiven Betrieb aufgenommen hat. Die Recherchemöglichkeiten im WWW werden erläutert, Zugriffszahlen genannt und Entwicklungsperspektiven skizziert. Dieser Bericht entspricht der schriftlichen Fassung eines gleichnamigen Vortrages, der auf dem 1. Gemeinsamen Kongreß der Bundesvereinigung Deutscher Bibliotheksverbände e.V. und der Deutschen Gesellschaft für Informationswissenschaft und Informationspraxis e.V. Information und Öffentlichkeit gehalten wurde, der vom 20. bis 23. März 2000 in Leipzig stattfand.
    Keywords: ddc:000
    Language: German
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  • 7
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    Asymptotic Results and a Markovian Approximation for the M(n)/M(n)/s+GI System (2000)
    Details
    Publication Date: 2014-02-26
    Description: In this paper for the $M(n)/M(n)/s+GI$ system, i.e.\ for a $s$-server queueing system where the calls in the queue may leave the system due to impatience, we present new asymptotic results for the intensities of calls leaving the system due to impatience and a Markovian system approximation where these results are applied. Furthermore, we present a new proof for the formulae of the conditional density of the virtual waiting time distributions, recently given by Movaghar for the less general $M(n)/M/s+GI$ system. Also we obtain new explicit expressions for refined virtual waiting time characteristics as a byproduct.
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    Language: English
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  • 8
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    Budget Constrained Minimum Cost Connected Medians (2000)
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    Publication Date: 2020-11-13
    Description: Several practical instances of network design problems require the network to satisfy multiple constraints. In this paper, we address the \emph{Budget Constrained Connected Median Problem}: We are given an undirected graph $G = (V,E)$ with two different edge-weight functions $c$ (modeling the construction or communication cost) and $d$ (modeling the service distance), and a bound~$B$ on the total service distance. The goal is to find a subtree~$T$ of $G$ with minimum $c$-cost $c(T)$ subject to the constraint that the sum of the service distances of all the remaining nodes $v \in V\setminus T$ to their closest neighbor in~$T$ does not exceed the specified budget~$B$. This problem has applications in optical network design and the efficient maintenance of distributed databases. We formulate this problem as bicriteria network design problem, and present bicriteria approximation algorithms. We also prove lower bounds on the approximability of the problem that demonstrate that our performance ratios are close to best possible
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  • 9
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    Polyhedral Results for the Edge Capacity Polytope (2000)
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    Publication Date: 2014-02-26
    Description: Network loading problems occur in the design of telecommunication networks, in many different settings. The polyhedral structure of this problem is important in developing solution methods for the problem. In this paper we investigate the polytope of the problem restricted to one edge of the network (the edge capacity problem). We describe classes of strong valid inequalities for the edge capacity polytope, and we derive conditions under which these constraints define facets. As the edge capacity problem is a relaxation of the network loading problem, their polytopes are intimately related. We, therefore, also give conditions under which the inequalities of the edge capacity polytope define facets of the network loading polytope. Furthermore, some structural properties are derived, such as the relation of the edge capacity polytope to the knapsack polytope. We conclude the theoretical part of this paper with some lifting theorems, where we show that this problem is polynomially solvable for most of our classes of valid inequalities. In a computational study the quality of the constraints is investigated. Here, we show that the valid inequalities of the edge capacity polytope are not only important for solving the edge capacity problem, but also for the network loading problem, showing that the edge capacity problem is an important subproblem.
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  • 10
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    Über Suchmaschinen, Verbünde und die Integration von Informationsangeboten (2000)
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    Publication Date: 2014-02-26
    Description: Die Entwicklung einer bibliothekarischen Suchmaschine ist das technisch-organisatorische Herztück des Kooperativen Bibliotheksverbundes Berlin-Brandenburg (KOBV). Auf dem Wege über diese Innovation verfolgen die Länder Berlin und Brandenburg und ihre Bibliotheken das Ziel, ihr Bibliothekswesen zu erneuern und zu reorganisieren. Die Entwicklung der Suchmaschine ist für die Partner im KOBV-Projekt kein Selbstzweck, sondern nur Mittel zum Zweck - insbesondere, um die heterogene Welt der in Berlin und in Brandenburg eingesetzten integrierten Bibliotheksinformationssysteme harmonisch miteinender zu verbinden. Mit der KOBV-Suchmaschine sind informationstechnische Sichtweisen und Methoden entstanden, die sich potentiell auch auf die überregionale Arbeit des KOBV auswirken können und in Kooperation mit den Bibliotheksverbänden auf die Zusammenarbeit der Verbünde insgesamt. Der Artikel konzentriert sich am Beispiel der KOBV-Such¡ma¡schine auch auf diesen Aspekt. Auf die Bibliotheken kommen mit dem Internet und dem World Wide Web für sie neuartige Medien, Mittel und Aufgaben zu, in erster Linie aus dem Bereich der Wissenschaften und der wissenschaftlichen Fachgesellschaften. Die Herausforderung besteht darin, die neuen elektronischen Informationen und Angebote zu integrieren. Das Stichwort hierzu lautet digitale Bibliothek bzw. virtuelle Fachbibliothek. Auch zu der Diskussion um diese aktuelle Entwicklung will der Artikel einen Beitrag leisten.
    Keywords: ddc:000
    Language: German
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  • 11
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    Parallel tempering and decorrelation of topological charge in full QCD (2000)
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    Publication Date: 2014-02-26
    Description: The improvement of simulations of QCD with dynamical Wilson fermions by combining the Hybrid Monte Carlo algorithm with parallel tempering is studied on $10^4$ and $12^4$ lattices. As an indicator for decorrelation the topological charge is used.
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  • 12
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    Re-Optimization of Signaling Transfer Points (2000)
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    Publication Date: 2014-02-26
    Description: In this paper we describe the results of a computational study towards the (re)optimization of signaling transfer points (STPs) in telecommunication networks. The best performance of an STP is achieved whenever the traffic load is evenly distributed among the internal components. Due to the continuously changing traffic pattern, the load of the components has to be re-optimized on a regular basis. Besides the balancing objective also the number of rearrangements have to be taken into account. In this paper we present two alternative formulations to deal with both requirements. Computational results show that for both formulations (near) optimal solutions can be obtained within reasonable time limits.
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  • 13
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    Density functional study of guanine and uracil quartets and of guanine quartet metal/ion complexes (2000)
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    Publication Date: 2014-02-26
    Description: The structures and interaction energies of guanine and uracil quartets have been determined by B3LYP hybrid density functional calculations. The total interaction energy $\Delta$E$^{T}$ of the $\it{C}$$_{4h}$-symmetric guanine quartet consisting of Hoogsteen type base pairs with two hydrogen bonds between two neighbour bases is -66.07 kcal/mol at the highest level. The uracil quartet with C6-H6...O4 interactions between the individual bases has only a small interaction energy of -20.92 kcal/mol and the interaction energy of -24.63 kcal/mol for the alternative structure with N3-H3...O4 hydrogen bonds is only slightly more negative. Cooperative effects contribute between 10 and 25 \% to all interaction energies. Complexes of metal ions with G-quartets can be classified into different structure types. The one with Ca$^{2+}$ in the central cavity adopts a $\it{C}$$_{4h}$-symmetric structure with coplanar bases, whereas the energies of the planar and non-planar Na$^{+}$ complexes are almost identical. The small ions Li$^{+}$, Be$^{2+}$, Cu$^{+}$ and Zn$^{2+}$ prefer a non-planar $\it{S}$$_{4}$-symmetric structure. The lack of co-planarity prevents probably a stacking of these base quartets. The central cavity is too small for K$^{+}$ ions and therefore this ion favours in contrast to all other investigated ions a $\it{C}$$_{4}$-symmetric complex, which is 4.73 kcal/mol more stable than the $\it{C}$$_{4h}$-symmetric one. The distance 1.665 {\AA} between K$^{+}$ and the root mean squares plane of the guanine bases is approximately half of the distance between two stacked G-quartets. The total interaction energy of alkaline earth ion complexes exceeds the ones with alkali ions. Within both groups of ions the interaction energy decreases with an increasing row position in the periodic table. The B3LYP and BLYP methods lead to similar structures and energies. Both methods are suitable for hydrogen-bonded biological systems. Compared with the before mentioned methods the HCTH functional leads to longer hydrogen bonds and different relative energies for two U-quartets. Finally we calculated also structures and relative energies with the MMFF94 forcefield. Contrary to all DFT methods, MMFF94 predicts bifurcated C-H...O contacts in the uracil quartet. In the G-quartet the MMFF94 hydrogen bond distances N2-H22...N7 are shorter than the DFT distances, whereas the N1-H1...O6 distances are longer.
    Keywords: ddc:000
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  • 14
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    Graphentheoretische Konzepte und Algorithmen (2000)
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    Publication Date: 2020-11-13
    Description: Das vorliegende Skript bietet eine Einf{ü}hrung in die Graphentheorie und graphentheoretische Algorithmen. Im zweiten Kapitel werden Grundbegriffe der Graphentheorie vorgestellt. Das dritte Kapitel besch{ä}ftigt sich mit der Existenz von Wegen in Graphen. Hier wird auch die L{ö}suung des ber{ü}hmten K{ö}nigsberger Br{ü}ckenproblems aufgezeigt und der Satz von Euler bewiesen. Im vierten Kapitel wird gezeigt, wie man auf einfache Weise die Zusammenhangskomponenten eines Graphen bestimmen kann. Im Kapitel sechs wird dann sp{ä}ter mit der Tiefensuche ein Verfahren vorgestellt, das schneller arbeitet und mit dessen Hilfe man noch mehr Informationen {ü}ber die Struktur eines Graphen gewinnen kann. In den folgenden Kapiteln werden Algorithmen vorgestellt, um minimale aufspannenden B{ä}ume, k{ü}rzeste Wege und maximale Fl{ü}sse in Graphen zu bestimmen. Am Ende des Skripts wird ein kurzer Einblick in die planaren Graphen und Graphhomomorphismen geboten.
    Keywords: ddc:000
    Language: German
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  • 15
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    Computer-aided design of novel siderophores: Pyridinochelin (2000)
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    Publication Date: 2014-02-26
    Description: Pyridinochelin, a novel catecholate type siderophore, has been designed on the basis of the active analog enterobactin. Growth promotion tests indicate that this synthetic siderophore feeds various pathogenic bacteria effectively with iron even though it lacks one catecholate group compared to enterobactin. The superposition of the siderophore structures suggests that the structure of the skeleton connecting the catecholate groups might be an important factor for the iron transport.
    Keywords: ddc:000
    Language: English
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  • 16
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    Adaptive Linearly Implicit Methods for Heat and Mass Transfer Problems (2000)
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    Publication Date: 2019-05-10
    Description: Dynamical process simulation of complex real-life problems often requires the use of modern algorithms, which automatically adapt both the time and space discretization in order to get error-controlled approximations of the solution. In this paper, a combination of linearly implicit time integrators of Rosenbrock type and adaptive multilevel finite elements based on a posteriori error estimates is presented. This approach has proven to work quite satisfactorily for a wide range of challenging practical problems. We show the performance of our adaptive method for two applications that arise in the study of flame balls and brine transport in porous media.
    Keywords: ddc:000
    Language: English
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  • 17
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    The Essential Spectral Radius and Asymptotic Properties of Transfer Operators (2000)
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    Publication Date: 2014-02-26
    Description: The statistical behavior of deterministic and stochastic dynamical systems may be described using transfer operators, which generalize the notion of Frobenius Perron and Koopman operators. Since numerical techniques to analyze dynamical systems based on eigenvalues problems for the corresponding transfer operator have emerged, bounds on its essential spectral radius became of interest. This article shows that they are also of great theoretical interest. We give an analytical representation of the essential spectral radius in $L^{1}\!(\mu)$, which then is exploited to analyze the asymptotical properties of transfer operators by combining results from functional analysis, Markov operators and Markov chain theory. In particular, it is shown, that an essential spectral radius less than $1$, constrictiveness and some weak form'' of the so--called Doeblin condition are equivalent. Finally, we apply the results to study three main problem classes: deterministic systems, stochastically perturbed deterministic systems and stochastic systems.
    Keywords: ddc:000
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  • 18
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    The Classes of Critically and Anticritically Perfect Graphs (2000)
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    Publication Date: 2014-02-26
    Description: We focus on two new types of extremal graphs with respect to perfectness: critically and anticritically perfect graphs that lose their perfectness by simply deleting and adding an arbitrary edge, respectively. We present examples and study properties in order to compare critically and anticritically perfect graphs with minimally imperfect graphs, another type of extremal graphs with respect to perfectness. We discuss two attempts to characterize the classes of all critically and anticritically perfect graphs and give a brief overview on classes of perfect graphs which contain critically or anticritically perfect graphs.
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    Language: English
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  • 19
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    A path-following method for linear complementarity problems based on the affine invariant Kantorovich Theorem (2000)
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    Publication Date: 2014-02-26
    Description: A path following algorithm for linear complementarity problems is presented. Given a point $z$ that approximates a point $z(\tau)$ on the central path with complementarity gap $\tau$, one determines a parameter $\theta\in (0,1)$ so that this point satisfies the hypothesis of the affine invariant Kantorovich Theorem for the equation defining $z((1-\theta)\tau)$. It is shown that $\theta$ is bounded below by a multiple of $n^{-1/2}$, where $n$ is the dimension of the problem. Since the hypothesis of of the Kantorovich Theorem is satisfied the sequence generated by Newton's method, or by the simplified Newton method, will converge to $z((1-\theta)\tau)$. We show that the number of steps required to obtain an acceptable approximation of $z((1-\theta)\tau)$ is bounded above by a number independent of $n$. Therefore the algorithm has $O(\sqrt{n}L)$-iteration complexity. The parameters of the algorithm can be determined in such a way that only one Newton step is needed each time the complementarity gap is decreased.
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  • 20
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    Counting stable solutions of sparse polynomial systems in chemistry (2000)
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    Publication Date: 2014-02-26
    Description: The polynomial differential system modelling the behavior of a chemical reaction is given by graphtheoretic structures. The concepts from toric geometry are applied to study the steady states and stable steady states. Deformed toric varieties give some insight and enable graph theoretic interpretations. The importance of the circuits in the directed graph are emphazised. The counting of positive solutions of a sparse polynomial system by B.\ Sturmfels is generalized to the counting of stable positive solutions in case of a polynomial differential equation. The generalization is based on a method by sparse resultants to detect whether a system may have a Hopf bifurcation. Special examples from chemistry are used to illustrate the theoretical results.
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  • 21
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    Distributed Visualization with OpenGL Vizserver: Practical Experiences (2000)
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    Publication Date: 2020-03-09
    Description: The increasing demand for distributed solutions in computing technology does not stop when it comes to visualization techniques. However, the capabilities of todays applications to perform remote rendering are limited by historical design legacys. Especially the popular X11 protokoll, which has been proven to be extremely flexible and usefull for remote 2D graphics applications, breaks down for the case of remote 3D rendering. In this white paper, we give a short overview of generic remote rendering technologies available today, and compare their performance to the recently released vizserver by SGI: a network extension to the SGI OpenGL rendering engines.
    Keywords: ddc:000
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  • 22
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    Semidefinite Programming for Combinatorial Optimization (2000)
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    Publication Date: 2020-08-05
    Description: This book offers a self-contained introduction to the field of semidefinite programming, its applications in combinatorial optimization, and its computational methods. We equip the reader with the basic results from linear algebra on positive semidefinite matrices and the cone spanned by them. Starting from linear programming, we introduce semidefinite programs and discuss the associated duality theory. We then turn to semidefinite relaxations of combinatorial optimization and illustrate their interrelation. In the second half we deal with computational methods for solving semidefinite programs. First, the interior point approach, its iteration complexity, and implementational issues are discussed. Next, we explain in great detail the spectral bundle method, which is particularly suited for large scale semidefinite programming. One of the most successful techniques in integer linear programming is the cutting plane approach which improves an initial relaxation by adding violated inequalities. We explore possibilities to combine the two solution methods with the cutting plane approach in order to strengthen semidefinite relaxations of combinatorial optimization problems.
    Keywords: ddc:000
    Language: English
    Type: doctoralthesis , doc-type:doctoralThesis
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  • 23
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    Ermittlung von Programmlaufzeiten anhand von Speicherzugriffen, Microbenchmarks und Simulation vonSpeicherhierarchien (2000)
    Details
    Publication Date: 2021-01-21
    Description: \\{\bf Zusammenfassung:} Kostenmodelle dienen der Ermittlung von Programmlaufzeiten, zum Vergleich der Effizienz von Algorithmen und zur Analyse des Verhaltens von Speicherhierarchien. Ein neuartiges Kostenmodell ist das Latency-of-Data-Access (LDA) Modell, das mehrere hierarchische Speicherebenen mit unterschiedlichen Latenzzeiten berü{}cksichtigt. In dieser Diplomarbeit wird ein Simulator fü{}r Speicherhierarchien prä{}sentiert, der die Berechnung von Programmausfü{}hrungszeiten nach dem LDA-Modell erlaubt. Mit Hilfe des Simulators wird die These geprü{}ft, da\ss{} mit diesem Modell die Ausfü{}hrungszeit eines Programms adä{}quat abgeschä{}tzt werden kann. Mit dem Simulator ist es erstmals praktikabel mö{}glich, Programmausfü{}hrungszeiten nach dem LDA-Modell zu bestimmen. Der Simulator kann fü{}r Systeme mit unterschiedlichen Speicherarchitekturen konfiguriert werden und unterstü{}tzt Mehrprozessorsysteme mit gemeinsamem Speicher (SMP-Systeme) mit verschiedenen Kohä{}renzprotokollen. Der Simulator kann mit den Ergebnissen von Microbenchmarks konfiguriert werden, die die Architekturparameter einer Speicherhierarchie messen. Die Ergebnisse bestä{}tigen die These nicht nur fü{}r Einzelprozessorsysteme, sondern auch fü{}r SMP-Systeme, wo gleichzeitig interagierende Prozessoren gegenseitig ihre Zugriffssequenz auf Zwischenspeicher beeinflussen. Zusä{}tzlich wurde eine neue Einsatzmö{}glichkeit des LDA-Modells entwickelt, um die Ausfü{}hrungszeit von Programmteilen zu bestimmen. Einzelne Zugriffskosten kö{}nnen einem mehrerer parallel laufender Modelle zugeordnet werden. Dadurch kö{}nnen Kosten, die Zugriffe auf einzelne Speicherbereiche verursachen, separat bestimmt werden. Diese Profiling-Technik erlaubt Optimierungen an Datenstrukturen und Speicherzugriffsmustern durch prä{}zise und gezielte Informationsproduktion.Cost models are used to determine the execution time of programs, to compare the efficiency of algorithms, and to analyse the behaviour of memory hierarchies. The Latency-of-Data-Access (LDA) model that takes into account multiple hierarchical memory levels with different latencies, is a newly proposed, innovative cost model. In this diploma-thesis, a simulator for memory hierarchies is presented that allows the calculation of execution times using the LDA-model. The simulator is used to prove the claim that the execution time of a program can be accurately estimated with the LDA-model. With the simulator, it is for the first time possible to determine the execution time of programs with this model in a practical way. The simulator can be configured for systems with various cache architectures and supports shared memory (SMP) multiprocessor systems with different cache coherence protocols. The simulator can be configured with the results from microbenchmarks which measure the architectural properties of a memory hierarchy. The results confirm the claim not only for single processor systems, but also for SMP systems, where concurrently interacting processors influence each others cache access sequence. Additionally, a new field of usage of the LDA-model was developed to determine execution times of program parts. Single access costs can be assigned to one of several parallel running models. As an example the costs of accesses to different memory areas can be split and determined separately. This profiling technique allows to optimise data structures and memory access patterns of sequential and parallel SMP programs by precise production of information.
    Keywords: ddc:000
    Language: German
    Type: reportzib , doc-type:preprint
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    SBmethod --- A C++ Implementation of the Spectral Bundle Method. Manual to Version 1.1 (2000)
    Details
    Publication Date: 2014-02-26
    Description: \texttt{SBmethod}, Version 1.1, is an implementation of the spectral bundle method for eigenvalue optimization problems of the form \begin{displaymath} \min_{y\in \mathbf{R}^m}\;\; a\;\lambda_{\max}(C-\sum_{i=1}^{m} A_i y_i)+b^Ty. \end{displaymath} The design variables $y_i$ may be sign constrained, $C$ and and $A_i$ are given real symmetric matrices, $b\in\mathbf{R}^m$ allows to specify a linear cost term, and $a〉0$ is a constant multiplier for the maximum eigenvalue function $\lambda_{\max}(\cdot)$. The code is intended for large scale problems and allows to exploit structural properties of the matrices such as sparsity and low rank structure. The manual contains instructions for installation and use of the program. It describes in detail input format, options, and output. The meaning of the variables and parameters is made precise by relating them to a mathematical description of the algorithm in pseudocode.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
    Format: application/postscript
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  • 25
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    Stable Multi-Sets (2000)
    Details
    Publication Date: 2014-11-10
    Description: In this paper we introduce a generalization of stable sets: stable multi-sets. A stable multi-set is an assignment of integers to the vertices of a graph, such that specified bounds on vertices and edges are not exceeded. In case all vertex and edge bounds equal one, stable multi-sets are equivalent to stable sets. For the stable multi-set problem, we derive reduction rules and study the associated polytope. We state necessary and sufficient conditions for the extreme points of the linear relaxation to be integer. These conditions generalize the conditions for the stable set polytope. Moreover, the classes of odd cycle and clique inequalities for stable sets are generalized to stable multi-sets and conditions for them to be facet defining are determined. The study of stable multi-sets is initiated by optimization problems in the field of telecommunication networks. Stable multi-sets emerge as an important substructure in the design of optical networks.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
    Format: application/pdf
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  • 26
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    SteinLib: An Updated Library on Steiner Tree Problems in Graphs (2000)
    Details
    Publication Date: 2020-02-11
    Description: In this paper we present the {\em SteinLib}, a library of data sets for the Steiner tree problem in graphs. This library extends former libraries on Steiner tree problems by many new interesting and difficult instances, most of them arising from real-world applications. We give a survey on the difficulty of these problem instances by giving references to state-of-the-art software packages that were the first or are currently among the best to solve these instances.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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  • 27
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    Anatomy of a Resource Management System for HPC-Clusters (2000)
    Details
    Publication Date: 2014-02-26
    Description: Workstation clusters are often not only used for high-throughput computing in time-sharing mode but also for running complex parallel jobs in space-sharing mode. This poses several difficulties to the resource management system, which must be able to reserve computing resources for exclusive use and also to determine an optimal process mapping for a given system topology. On the basis of our CCS software, we describe the anatomy of a modern resource management system. Like Codine, Condor, and LSF, CCS provides mechanisms for the user-friendly system access and management of clusters. But unlike them, CCS is targeted at the effective support of space-sharing parallel and even metacomputers. Among other features, CCS provides a versatile resource description facility, topology-based process mapping, pluggable schedulers, and hooks to metacomputer management.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
    Format: application/postscript
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  • 28
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    Autos, Ziegen und Streithähne (2000)
    Details
    Publication Date: 2021-02-01
    Description: Das aus den Medien bekannte umstrittene Ziegenproblem (auch Drei-Türen-Problem genannt) wird vollständig analysiert und gelöst. In der Streitfrage spielen sprachliche Mehrdeutigkeiten der Problemformulierung eine wesentliche Rolle; zudem werden Zufallsereignisse mit willkürlicher Information über deren Ergebnisse verwechselt. Tatsächlich erweisen sich beide strittigen Lösungen als teilweise richtige Bestandteile der Gesamtlösung. Die Argumentation wird in allgemeinverständlicher Sprache geführt und anschliessend durch eine formale mathematische Betrachtung ergänzt.
    Keywords: ddc:000
    Language: German
    Type: reportzib , doc-type:preprint
    Format: application/postscript
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  • 29
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    Kooperativer Bibliotheksverbund Berlin-Brandenburg (KOBV) - Konzept, Erfahrungen, Ausblick - (2000)
    Details
    Publication Date: 2020-11-13
    Description: Der Aufsatz ist die ausgearbeitete Fassung eines Vortrages, gehalten auf dem 2. BSZ-Kolloquium des Bibliotheksservice-Zentrums Baden-Württemberg (BSZ) am 10. Oktober 2000 in Konstanz. Der Kooperative Bibliotheksverbund Berlin-Brandenburg, kurz KOBV, ist ein sehr junger Verbund - genauer gesagt, befindet er sich im Oktober 2000 immer noch in der Aufbauphase. Das KOBV-Projekt hat am 1. April 1997 begonnen und wird am 31. Dezember 2000 enden. Ab 2001 wird der KOBV in eine institutionalisierte Form überführt, die - wie bereits das Projekt - am Konrad-Zuse-Zentrum für Informationstechnik Berlin (ZIB) - angesiedelt wird. Mit dem KOBV wurde ein in technischer wie auch in organisatorischer Hinsicht neuartiger Bibliotheksverbund aufgebaut, der auf der \glqq Internetphilosophie\grqq basiert: Den technischen Kern bildet eine eigens entwickelte Suchmaschine; die Organisation ist dezentral ausgerichtet und gründet sich auf der Kooperation der KOBV-Partner. In dem Vortrag werden das technische und das organisatorische Verbundkonzept vorgestellt, über die Erfahrungen nach einjähriger Betriebsdauer berichtet und ein kurzer Ausblick darüber gegeben, wie es mit dem KOBV weitergeht.
    Keywords: ddc:000
    Language: German
    Type: reportzib , doc-type:preprint
    Format: application/postscript
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  • 30
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    Spezifikation der Schnittstelle zwischen KOBV-Suchmaschine und Lokalsystemen (2000)
    Details
    Publication Date: 2020-11-13
    Description: Die Kommunikation zwischen der KOBV-Suchmaschine und entfernten Bibliotheksinformationssystemen unterschiedlicher Hersteller wird über das Standardprotokoll Z39.50 abgewickelt. Die Suchmaschine ermöglicht Online-Recherchen in lokalen Bibliotheksinformationssystemen, die dazu ein Z39.50 Target (Server) zur Verfügung stellen müssen. Die Suchmaschine liefert ihre Daten ebenfalls über Z39.50 aus. Ein Lokalsystem benötigt hierfür einen Z39.50 Origin (Client). In dem Papier wird die Schnittstelle zwischen der KOBV-Suchmaschine und lokalen Bibliothekssystemen spezifiziert: Es werden die grundlegenden Anforderungen an Lokalsysteme definiert und die Konfigurationsparameter für die Z39.50-Kommunikation zwischen KOBV-Suchmaschine und Lokalsystemen beschrieben.
    Keywords: ddc:000
    Language: German
    Type: reportzib , doc-type:preprint
    Format: application/postscript
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  • 31
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    Implementation von WAP-Diensten für die SGI/CRAY T3E des ZIB (2000)
    Details
    Publication Date: 2014-02-26
    Description: Die zunehmende Verfügbarkeit von mobilen Geräten, die mit einem Internetanschluß ausgerüstet sind, bringt auch eine steigende Nachfrage nach Informationsdiensten für diese Art von Clients mit sich. Das ZIB stellt mit seinem Höchstleistungsrechner vom Typ SGI/CRAY T3E Wissenschaftlern große Rechenkapazitäten zur Verfügung. Im Rahmen dieser Studienarbeit wurde ein WAP-Interface zur T3E entwickelt, das es den Nutzern ermöglicht, über ein mobiles, WAP-fähiges Gerät Informationen zur Betriebsbereitschaft und zur Auslastung des Höchstleistungsrechners, sowie Informationen zu den von ihnen in Auftrag gegebenen Rechenjobs abzurufen. Die Untersuchung der aktuellen Möglichkeiten in der mobilen Kommunikation brachte einige Einschränkungen für das geplante Informationsangebot mit sich. So mußte auf Grund von Sicherheitsbedenken auf eine tatsächliche Interaktionsmöglichkeit (z.B. neue Rechenjobs zu starten) verzichtet werden. Demgegenüber konnte gezeigt werden, daß die Bereitstellung der gleichen Informationen für unterschiedliche Arten von Clients (WWW-Browser $\rightarrow$ HTML, WAP-Browser $\rightarrow$ WML) durch die Verwendung von XML als internes Datenformat problemlos möglich ist. Es hat sich gezeigt, daß die Bereitstellung eines WAP-Informationsdienstes auf Grund verschiedener Inkompatibilitätsprobleme (verschiedene Gateways, verschiedene WAP-Browser) mit erheblichem Aufwand verbunden sein kann. An dieser Stelle besteht noch Handlungsbedarf seitens der Hersteller dieser Softwarepakete.
    Keywords: ddc:000
    Language: German
    Type: reportzib , doc-type:preprint
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  • 32
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    Jahresbericht 1999 (2000)
    Details
    Publication Date: 2019-10-24
    Keywords: ddc:000
    Language: German
    Type: annualzib , doc-type:report
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  • 33
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    Verkehrsplanung: Bessere Lösungen mit Mathematik (2000)
    Details
    Publication Date: 2014-02-26
    Description: Anwendungen der Mathematik in der Verkehrs- und Transporttechnologie haben eine große und bedeutende Tradition. Natürlich wurden die ersten Fahrzeuge mit der ingenieurmäßigen Methode von Versuch, Irrtum und Verbesserung entworfen. Aber schon sehr bald kamen mathematische Berechnungen hinzu, mit denen mechanische Eigenschaften von Fahrzeugteilen ermittelt und zum Teil optimiert wurden. Die hierzu erforderliche Mathematik wurde in diesem Jahrhundert zu einem mächtigen Werkzeugkasten ausgebaut. Mit diesem kann man heute z.B. hocheffiziente Motoren mit geringem Schadstoffausstoß entwerfen, aerodynamisch günstige Fahrzeugprofile ermitteln und Flugzeugflügel berechnen, die die gewünschte Last sicher und mit geringem Treibstoffaufwand tragen. Die Mathematik unterstützt die Technologie des Verkehrs beginnend bei globalen Designfragen bis hin zur Spezifizierung von Materialeigenschaften kleinster Bauteile; sie berechnet mit hoher Präzision energieoptimale Bahnen von Raumflugkörpern oder zeitoptimale Trajektorien für Flugzeuge, steuert automatische Roboteranlagen oder innerbetriebliche Transportsysteme.
    Keywords: ddc:000
    Language: German
    Type: reportzib , doc-type:preprint
    Format: application/postscript
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  • 34
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    Hierarchical Sparsity in Multistage Convex Stochastic Programs (2000)
    Details
    Publication Date: 2021-02-01
    Description: Interior point methods for multistage stochastic programs involve KKT systems with a characteristic global block structure induced by dynamic equations on the scenario tree. We generalize the recursive solution algorithm proposed in an earlier paper so that its linear complexity extends to a refined tree-sparse KKT structure. Then we analyze how the block operations can be specialized to take advantage of problem-specific sparse substructures. Savings of memory and operations for a financial engineering application are discussed in detail.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
    Format: application/postscript
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  • 35
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    Adaptive hierarchical cluster analysis by Self-Organizing Box Maps (2000)
    Details
    Publication Date: 2014-02-26
    Description: The present paper aims at an extension of {\sc Kohonen's} Self-Organizing Map (SOM) algorithm to be called Self-Organizing Box Map (SOBM) algorithm; it generates box codebooks in lieu of point codebooks. Box codebooks just like point codebooks indirectly define a Voronoi tessellation of the input space, so that each codebook vector represents a unique set of points. Each box codebook vector comprises a multi-dimensional interval that approximates the related partition of the Voronoi tessellation. Upon using the automated cluster identification method that has recently been developed by the authors, the codebook vectors can be grouped in such a way that each group represents a point cluster in the input space. Since the clustering usually depends on the size of the SOM, one cannot be sure, whether the clustering comes out to be optimal. Refinement of part of the identified clusters would often improve the results. This paper presents the concept of an adaptive multilevel cluster algorithm that performs such refinements automatically. Moreover the paper introduces a concept of essential dimensions and suggests a method for their identification based on our herein suggested box codebooks. Applications of the algorithm to molecular dynamics will be described in a forthcoming paper.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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  • 36
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    Capacitated Network Design with Multicast Commodities (2000)
    Details
    Publication Date: 2014-02-26
    Description: This paper addresses the problem of designing a minimum cost network whose capacities are sufficiently large to allow a feasible routing of a given set of multicast commodities. A multicast commodity consists of a set of two or mo re terminals that need to be connected by a so called broadcast tree, which consumes on all of its edges a capacity as large as the demand value associated with that commodity. We model the network design problem with multicast commodities as the problem of packing capacitated Steiner trees in a graph. In the first part of the paper we present three mixed-integer programming formulations for this problem. The first natural formulation uses only one integer capacity variable for each edge and and one binary tree variable for each commodity-edge pair. Applying well-known techniques from the Steiner tree problem, we then develop a stronger directed and a multicommodity flow based mixed-integer programming formulation. In the second part of the paper we study the associated polyhedra and derive valid and even facet defining inequalities for the natural formulation. Finally, we describe separation algorithms for these inequalities and present computational results that demonstrate the strength of our extended formulations.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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  • 37
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    Ermittlung von Programmlaufzeiten anhand von Speicherzugriffen, Microbenchmarks und Simulation von Speicherhierarchien (2000)
    Details
    Publication Date: 2021-01-21
    Description: Kostenmodelle dienen der Ermittlung von Programmlaufzeiten, zum Vergleich der Effizienz von Algorithmen und zur Analyse des Verhaltens von Speicherhierarchien. Ein neuartiges Kostenmodell ist das Latency-of-Data-Access (LDA) Modell, das mehrere hierarchische Speicherebenen mit unterschiedlichen Latenzzeiten berücksichtigt. In dieser Diplomarbeit wird ein Simulator für Speicherhierarchien präsentiert, der die Berechnung von Programmausführungszeiten nach dem LDA-Modell erlaubt. Mit Hilfe des Simulators wird die These geprüft, daß mit diesem Modell die Ausführungszeit eines Programms adäquat abgeschätzt werden kann. Mit dem Simulator ist es erstmals praktikabel möglich, Programmausführungszeiten nach dem LDA-Modell zu bestimmen. Der Simulator kann für Systeme mit unterschiedlichen Speicherarchitekturen konfiguriert werden und unterstützt Mehrprozessorsysteme mit gemeinsamem Speicher (SMP-Systeme) mit verschiedenen Kohärenzprotokollen. Der Simulator kann mit den Ergebnissen von Microbenchmarks konfiguriert werden, die die Architekturparameter einer Speicherhierarchie messen. Die Ergebnisse bestätigen die These nicht nur für Einzelprozessorsysteme, sondern auch für SMP-Systeme, wo gleichzeitig interagierende Prozessoren gegenseitig ihre Zugriffsse-quenz auf Zwischenspeicher beeinflussen. Zusätzlich wurde eine neue Einsatzmöglichkeit des LDA-Modells entwickelt, um die Ausführungszeit von Programmteilen zu bestimmen. Einzelne Zugriffskosten können einem mehrerer parallel laufender Modelle zugeordnet werden. Dadurch können Kosten, die Zugriffe auf einzelne Speicherbereiche verursachen, separat bestimmt werden. Diese Profiling-Technik erlaubt Optimierungen an Datenstrukturen und Speicherzugriffsmustern durch präzise und gezielte Informationsproduktion.
    Description: Cost models are used to determine the execution time of programs, to compare the efficiency of algorithms, and to analyse the behaviour of memory hierarchies. The Latency-of-Data-Access (LDA) model that takes into account multiple hierarchical memory levels with different latencies, is a newly proposed, innovative cost model. In this diploma-thesis, a simulator for memory hierarchies is presented that allows the calculation of execution times using the LDA model. The simulator is used to prove the claim that the execution time of a program can be accurately estimated with the LDA model. With the simulator, it is for the first time possible to determine the execution time of programs with this model in a practical way. The simulator can be configured for systems with various cache architectures and supports shared memory (SMP) multiprocessor systems with different cache coherence protocols. The simulator can be configured with the results from Microbenchmarks which measure the architectural properties of a memory hierarchy. The results confirm the claim not only for single processor systems, but also for SMP systems, where concurrently interacting processors influence each others cache access sequence. Additionally, a new field of usage of the LDA model was developed to determine execution times of program parts. Single access costs can be assigned to one of several parallel running models. As an example the costs of accesses to different memory areas can be split and determined separately. This profiling technique allows to optimise data structures and memory access patterns of sequential and parallel SMP programs by precise production of information.
    Keywords: ddc:000
    Language: German
    Type: masterthesis , doc-type:masterThesis
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  • 38
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    Visions of Numerical Relativity 1999 (2000)
    Details
    Publication Date: 2020-03-09
    Description: We present visualizations of recent supercomputer simulations from numerical relativity, exploiting the progress in visualization techniques and numerical methods also from an artistic point of view. The sequences have been compiled into a video tape, showing colliding black holes, orbiting and merging neutron stars as well as collapsing gravitational waves. In this paper we give some background information and provide a glance at the presented sequences.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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  • 39
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    The Symbolic Integration of Exact PDEs (2000)
    Details
    Publication Date: 2014-02-26
    Description: An algorithm is described to decide if a given polynomial differential expression $\Delta$ of multivariate functions is exact, i.e. whether there exists a first integral $P$ such that $D_xP = \Delta$ for any one of a set of variables $x$ and to provide the integral $P$. A generalization is given to allow integration in the case that the exactness is prohibited by terms which contain only functions of not all the independent variables.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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  • 40
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    Algorithmen- und Softwareoptimierung für die Satellitenbahn- und Schwerefeldmodellierung (2000)
    Details
    Publication Date: 2014-02-26
    Description: Dieser Report enthält die Ergebnisse der Untersuchungen, die gemäss dem Forschungs-- und Entwicklungsvertrag Gravity zwischen dem GeoForschungsZentrum Potsdam und dem Konrad--Zuse--Zentrum Berlin vorgenommen wurden. Die damit vereinbarte wissenschaftliche Kooperation hat die folgenden Ziele: \item{die am GFZ vorhandenen Algorithmen und Softwaremodule auf ihre Effizienz hisichtlich Nutzung der Rechnerresourcen zu untersuchen und Lösungen für einen schnelleren Datendurchsatz zu entwickeln und zu implementieren,} \item{Methoden zur Regularisierung und Lösung schlecht konditionierter Normalgleichungssysteme (für Schwerefeldkoeffizienten) kritisch zu untersuchen und eine mathematisch objektive Strategie der Regularisierung zu entwickeln, und} \item{insbesondere im Hinblick auf die Anforderungen bei GRACE, verschiedene Bahnintegrationsverfahren hinsichtlich ihrer numerischen Genauigkeit und Einsatzmöglichkeiten zu untersuchen.}
    Keywords: ddc:000
    Language: German
    Type: reportzib , doc-type:preprint
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  • 41
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    A Projection Method for Two-Phase Incompressible Flow with Surface Tension and Sharp Interface Resolution (2000)
    Details
    Publication Date: 2014-02-26
    Description: We present a fully second order projection method for the simulation of two-phase incompressible flow with surface tension. The Navier-Stokes equations are solved with a projection method on a fixed Cartesian grid. The free interface between the two fluids is tracked with a level set approach. The conditions at the interface for the pressure, the pressure gradient, and the velocity are explicitly incorporated into the scheme leading to a sharp representation of the pressure discontinuity and the interfacial force. The scheme in the presented form does not introduce additional points in the standard finite difference stencils. Computational results are compared with analytic solutions for a static round bubble, damped surface waves, and Rayleigh-Taylor instabilities.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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  • 42
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    Hyperthermia Treatment Planning with HyperPlan - User's Manual (2000)
    Details
    Publication Date: 2020-03-09
    Description: HyperPlan is a software system for performing 3D-simulations and treatment planning in regional hyperthermia. It allows the user to understand the complex effects of electromagnetic wave propagation and heat transport inside a patient's body. Optimized power amplitudes and phase settings can be calculated for the BSD radiowave applicators Sigma 60 and Sigma 2000 (eye-applicator). HyperPlan is built on top of the modular, object-oriented visualization system Amira. This system already contains powerful algorithms for image processing, geometric modelling and 3D graphics display. HyperPlan provides a number of hyperthermia-specific modules, allowing the user to create 3D tetrahedral patient models suitable for treatment planning. In addition, all numerical simulation modules required for hyperthermia simulation are part of HyperPlan. This guide provides a step-by-step introduction to hyperthermia planning using HyperPlan. It also describes the usage of the underlying visualization system Amira.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
    Format: application/postscript
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  • 43
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    Electromagnetic phased arrays for regional hyperthermia -- optimal frequency and antenna arrangement (2000)
    Details
    Publication Date: 2014-02-26
    Description: In this paper we investigate the effects of the three-dimensional arrangement of antennas and frequency on temperature distributions that can be achieved in regional hyperthermia using an electromagnetic phased array. We compare the results of power-based and temperature-based optimization. Thus we are able to explain the discrepancies between previous studies favouring more antenna rings on the one hand and more antennas per ring on the other hand. We analyze the sensitivity of the results with respect to changes in amplitudes and phases as well as patient position. This analysis can be used for different purposes. First, it provides additional criteria for selecting the optimal frequency. Second, it can be used for specifying the required phase and amplitude accuracy for a real phased array system. Furthermore, it may serve as a basis for technological developments in order to reduce both types of sensitivities described above.
    Keywords: ddc:000
    Language: English
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    Kooperativer Bibliotheksverbund Berlin-Brandenburg (KOBV) (2000)
    Details
    Publication Date: 2020-11-13
    Description: Der Kooperative Bibliotheksverbund Berlin-Brandenburg (KOBV) wurde in den Jahren 1997-2000 im Rahmen eines wissenschaftlichen Projektes eingerichtet. Er stellt eine neuartige Form von Bibliotheksverbund dar. Sein technisches Konzept und sein organisatorischer Aufbau basieren auf der Internetphilosophie. Den informationstechnischen Kern bildet eine Suchmaschine, die die heterogenen lokalen Bibliothekssysteme miteinander verbindet. Die KOBV-Organisation ist dezentral. Sie wird getragen von der Kooperation der Bibliotheken in Berlin und Brandenburg; diese werden von einer kleinen Verbundzentrale unterstützt. Die KOBV-Suchmaschine ist zu erreichen unter: {\begin{rawhtml}〈a href="http://www.kobv.de/suche/"〉 〈i〉 http://www.kobv.de/suche/ 〈/i〉 〈/a〉\end{rawhtml}}
    Keywords: ddc:000
    Language: German
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  • 45
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    Mathematik in der Industrie: interessante Branchen und zukünftige Einsatzfelder (2000)
    Details
    Publication Date: 2014-02-26
    Description: Dieser kurze Artikel hat keine umfassende Übersicht zum Ziel. Basierend auf eigenen Erfahrungen durch Projekte mit Industriefirmen möchte ich einige Branchen erwähnen, bei denen nach meiner Einschätzung Mathematik in Zukunft zunehmend Anwendung finden wird. Ich werde das anhand konkreter Beispiele erläutern. Mathematik ersetzt in der Regel traditionelle Analyse-, Planungs- und Entwurfstechniken. Den (nicht leichten) Schritt zum Einsatz mathematischer Methoden macht ein Praktiker nur, wenn es sich für ihn ``lohnt''. Wann sich dies lohnt, ist schwer abzuschätzen. Man kann aber einige Indikatoren dafür finden, ob eine Branche für den Einsatz von Mathematik ``reif'' ist. Ob es dann dazu kommt, hängt von vielen Faktoren ab, nicht zuletzt von der Psychologie und dem sozialen Umfeld der beteiligten Personen sowie der Bereitschaft, sich auf ein so schwieriges Terrain zu begeben und Kompromisse einzugehen. Gerade letzteres fällt Mathematikern gelegentlich schwer.
    Keywords: ddc:000
    Language: German
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  • 46
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    Circuit Admissible Triangulations of Oriented Matroids (2000)
    Details
    Publication Date: 2014-11-10
    Description: All triangulations of euclidean oriented matroids are of the same PL-homeomorphism type by a result of Anderson. That means all triangulations of euclidean acyclic oriented matroids are PL-homeomorphic to PL-balls and that all triangulations of totally cyclic oriented matroids are PL-homeomorphic to PL-spheres. For non-euclidean oriented matroids this question is wide open. One key point in the proof of Anderson is the following fact: for every triangulation of a euclidean oriented matroid the adjacency graph of the set of all simplices ``intersecting'' a segment $[p_-p_+]$ is a path. We call this graph the $[p_-p_+]$-adjacency graph of the triangulation. While we cannot solve the problem of the topological type of triangulations of general oriented matroids we show in this note that for every circuit admissible triangulation of an arbitrary oriented matroid the $[p_-p_+]$-adjacency graph is a path.
    Keywords: ddc:000
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  • 47
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    Triangulierungen von Punktmengen und Polyedern (2000)
    Details
    Publication Date: 2014-11-10
    Description: Dieser Report wurde im Sommersemester 2000 an der TU Berlin in einer Spezialvorlesung über Triangulierungen von Punktmengen und Polyedern als Skriptum verwendet. Nach einem motivierenden Kapitel werden grundlegende Begriffe und Konstruktionen in der Theorie der Triangulierungen von Punktmengen und Polyedern vorgestellt. Danach werden als weiterführende Themen reguläre Triangulierungen, Sekundärpolytope, bistellare Operationen, höhere Stasheff-Tamari-Halbordnungen und Triangulierungen mit wenigen bzw. gar keinen Flips behandelt. Ein Kapitel über Enumeration und Optimierung beschließt die Zusammenstellung.
    Keywords: ddc:000
    Language: German
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  • 48
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    Optimierung in der Planung und beim Aufbau des G-WiN (2000)
    Details
    Publication Date: 2020-02-11
    Description: Ende Juni diesen Jahres wurde das Gigabit-Wissenschaftsnetz offiziell gestartet. In der zweijährigen Vorbereitungsphase wurden nicht nur die technischen Möglichkeiten der neuen Übertragungstechniken und Dienste getestet. Es wurden auch verschiedene Fragestellungen zum effizienten Einsatz der verfügbaren Ressourcen für den Betrieb des G-WiN untersucht. In diesem Artikel beschreiben wir, wie das G-WiN zu seiner jetzigen Struktur und Topologie gekommen ist.
    Keywords: ddc:000
    Language: German
    Type: reportzib , doc-type:preprint
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  • 49
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    Critical and Anticritical Edges in Perfect Graphs (2000)
    Details
    Publication Date: 2014-02-26
    Description: We call an edge $e$ of a perfect graph $G$ critical if $G-e$ is imperfect and say further that $e$ is anticritical with respect to the complementary graph $\overline G$. We ask in which perfect graphs critical and anticritical edges occur and how to find critical and anticritical edges in perfect graphs. Finally, we study whether we can order the edges of certain perfect graphs such that deleting all the edges yields a sequence of perfect graphs ending up with a stable set.
    Keywords: ddc:000
    Language: English
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  • 50
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    Fast Surface Reconstruction Using a Probe Sphere (2000)
    Details
    Publication Date: 2014-02-26
    Description: We introduce a new method for reconstructing a triangular surface from an unorganized set of points in space. It is based on placing a probe sphere on the point set and rolling it around, connecting all triples of points with a triangle that the sphere comes to rest on. Therefore, the algorithm interpolates, rather than approximates, the input points. The method needs considerably less running time than previous algorithms and yields good results on point sets that are reasonably well-behaved.
    Keywords: ddc:000
    Language: English
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  • 51
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    Frequency Planning and Ramifications of Coloring (2000)
    Details
    Publication Date: 2014-11-11
    Description: This paper surveys frequency assignment problems coming up in planning wireless communication services. It particularly focuses on cellular mobile phone systems such as GSM, a technology that revolutionizes communication. Traditional vertex coloring provides a conceptual framework for the mathematical modeling of many frequency planning problems. This basic form, however, needs various extensions to cover technical and organizational side constraints. Among these ramifications are $T$-coloring and list coloring. To model all the subtleties, the techniques of integer programming have proven to be very useful. The ability to produce good frequency plans in practice is essential for the quality of mobile phone networks. The present algorithmic solution methods employ variants of some of the traditional coloring heuristics as well as more sophisticated machinery from mathematical programming. This paper will also address this issue. Finally, this paper discusses several practical frequency assignment problems in detail, states the associated mathematical models, and also points to public electronic libraries of frequency assignment problems from practice. The associated graphs have up to several thousand nodes and range from rather sparse to almost complete.
    Keywords: ddc:000
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  • 52
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    Hadron masses from dynamical, non-perturbatively O(a) improved Wilson fermions (2000)
    Details
    Publication Date: 2014-02-26
    Description: We present results on light hadron masses from simulations of full QCD and report on experiences in running such simulations on a Hitachi SR8000-F1 supercomputer.
    Keywords: ddc:000
    Language: English
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  • 53
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    Automatic Identification of Metastable Conformations via Self-Organized Neural Networks (2000)
    Details
    Publication Date: 2014-02-26
    Description: As has been shown recently, the identification of metastable chemical conformations leads to a Perron cluster eigenvalue problem for a reversible Markov operator. Naive discretization of this operator would suffer from combinatorial explosion. As a first remedy, a pre-identification of essential degrees of freedom out of the set of torsion angles had been applied up to now. The present paper suggests a different approach based on neural networks: its idea is to discretize the Markov operator via self-organizing (box) maps. The thus obtained box discretization then serves as a prerequisite for the subsequent Perron cluster analysis. Moreover, this approach also permits exploitation of additional structure within embedded simulations. As it turns out, the new method is fully automatic and efficient also in the treatment of biomolecules. This is exemplified by numerical results.
    Keywords: ddc:000
    Language: English
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  • 54
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    An Approximation Algorithm for the Non-Preemptive Capacitated Dial-a-Ride Problem (2000)
    Details
    Publication Date: 2020-11-13
    Description: In the Capacitated Dial-a-Ride Problem (CDARP) we are given a transportation network and a finite set of transportation jobs. Each job specifies the source and target location which are both part of the network. A server which can carry at most $C$~objects at a time can move on the transportation network in order to process the transportation requests. The problem CDARP consists of finding a shortest transportation for the jobs starting and ending at a designated start location. In this paper we are concerned with the restriction of CDARP to graphs which are simple paths. This setting arises for instance when modelling applications in elevator transportation systems. It is known that even for this restricted class of graphs CDARP is NP-hard to solve. We provide a polynomial time approximation algorithm that finds a transportion of length at most thrice the length of the optimal transportation.
    Keywords: ddc:000
    Language: English
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  • 55
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    Affine Invariant Convergence Analysis for Inexact Augmented Lagrangian-SQP Methods (2000)
    Details
    Publication Date: 2019-01-29
    Description: An affine invariant convergence analysis for inexact augmented Lagrangian-SQP methods is presented. The theory is used for the construction of an accuracy matching between iteration errors and truncation errors, which arise from the inexact linear system solves. The theoretical investigations are illustrated numerically by an optimal control problem for the Burgers equation.
    Keywords: ddc:000
    Language: English
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  • 56
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    Online Optimierung (2000)
    Details
    Publication Date: 2020-11-13
    Description: Wie soll man einen Aufzug steuern, wenn man keine Informationen über zukünftige Fahraufträge besitzt? Soll man eine Bahncard kaufen, wenn die nächsten Bahnreisen noch unbekannt sind? In der klassischen kombinatorischen Optimierung geht man davon aus, daß die Daten jeder Probleminstanz vollständig gegeben sind. In vielen Fällen modelliert diese \emph{Offline-Optimierung} jedoch die Situationen aus Anwendungen nur ungenügend. Zahlreiche Problemstellungen in der Praxis sind in natürlicher Weise \emph{online}: Sie erfordern Entscheidungen, die unmittelbar und ohne Wissen zukünftiger Ereignisse getroffen werden müssen. Als ein Standardmittel zur Beurteilung von Online-Algorithmen hat sich die \emph{kompetitive Analyse} durchgesetzt. Dabei vergleicht man den Zielfunktionswert einer vom Online-Algorithmus generierten Lösung mit dem Wert einer optimalen Offline-Lösung. Mit Hilfe der kompetitiven Analyse werden im Skript Algorithmen zum Caching, Netzwerk-Routing, Scheduling und zu Transportaufgaben untersucht. Auch die Schwächen der kompetitiven Analyse werden aufgezeigt und alternative Analysekonzepte vorgestellt. Neben der theoretischen Seite werden auch die Anwendungen der Online-Optimierung in der Praxis, vor allem bei Problemen der innerbetrieblichen Logistik, beleuchtet. Bei der Steuerung automatischer Transportsysteme tritt eine Fülle von Online-Problemen auf. Hierbei werden an die Algorithmen oftmals weitere Anforderungen gestellt. So müssen Entscheidungen unter strikten Zeitbeschränkungen gefällt werden (Echtzeit-Anforderungen). Dieses Skript ist aus dem Online-Teil der Vorlesung -Ausgewählte Kapitel aus der ganzzahligen Optimierung- (Wintersemester~1999/2000) und der Vorlesung -Online Optimierung- (Sommersemester~2000) an der Technischen Universität Berlin entstanden.
    Keywords: ddc:000
    Language: German
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  • 57
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    Portale, Search Engines und Math-Net (2000)
    Details
    Publication Date: 2022-04-11
    Description: Wie sucht ein Wissenschaftler im Internet die ben"otigten Informationen für seine Arbeit? Welche relevanten Informationen gibt es überhaupt im Web? Sind dafür solche Suchmaschinen wie AltaVista, Google oder HotBot die richtigen Werkzeuge? Die Antwort der Mathematiker heisst Math-Net, ein Informations- und Kommunikationssystem für die Mathematik. Math-Net besteht zunächst aus den Informationen von Personen und Institutionen, die ihre für die Mathematik relevanten Informationen dort bereitstellen wollen. Das soll i.a. auf den Web-Servern der Personen oder Institutionen geschehen. Hierin unterscheidet sich die Situation im Math-Net nicht von der im WWW insgesamt. Im Math-Net sollen aber die Informationen in einheitlicher Weise erschlossen werden. Dazu gibt es sowohl für Server als auch für die Dokumente Empfehlungen für deren Strukturierung. Die lokalen Informationen werden dann im Math-Net durch automatische Verfahren gesammelt, ausgewertet und indexiert. Diese Indexe sind die Basis für die Math-Net Dienste. Das sind Search Engines und Portale, die einen qualifizierten und effizienten Zugang zu den Informationen im Math-Net bieten. Die Math-Net Dienste sind auf die Mathematik spezialisiert. Im Gegensatz zu den oben erwähnten universellen Suchmaschinen decken sie nur einen winzigen Bruchteil des Web ab, aber dafür den für die Mathematik relevanten Teil. Math-Net ist mehr als nur Search Engine oder Portal zu Informationen in der Mathematik. Es ist auch ein Informations- und Kommunikationssystem sowie ein Publikationsmedium für die Mathematik. Die mathematische Community hat sich in der Math-Net Initiative organisiert. Diese Initiative wird von der International Mathematical Union (IMU), der weltweiten Dachorganisation der mathematischen Gesellschaften, koordiniert. Die Entwicklung des Math-Net wird von dem breiten Konsens der Mathematiker getragen, den Zugang zu der für die Mathematik relevanten Information zu erleichtern und zu verbessern.
    Keywords: ddc:000
    Language: German
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  • 58
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    A Comparison of Transparent Boundary Conditions for the Fresnel Equation (2000)
    Details
    Publication Date: 2022-07-07
    Description: We establish the relationship between the transparent boundary condition (BPP) of Baskakov and Popov [Wave Motion 14 (1991) 121-128] and Pakpadakis et. al. [J. Acoust. Soc. Am. 92 (1992) 2030-2038] and a second boundary condition (SDY) introduced by Schmidt and Deuflhard [Comp. Math. Appl. 29 (1995) 53-76] and Schmidt and Yevick [J. Compu. Phys. 134 (1997) 96-107], that is explicitly tailored to the form of the underlying numerical propagation scheme. Our analysis demonstrates that if the domain is first discretized in the propagation direction, the SDY expression can be obtained by applying the exact sequence of steps used to derive the BPP procedure. The BPP method is thus an approximate realization of the computationally far simpler and unconditionally stable SDY boundary condition.
    Keywords: ddc:000
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  • 59
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    Discrete Nonreflecting Boundary Conditions for the Helmholtz Equation (2000)
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    Publication Date: 2022-07-07
    Description: We derive exact discrete nonreflecting boundary conditions for time-harmonic scattering problems modeled by the Helmholtz equation. The main idea is to consider the exterior problem as an initial value problem with initial data given on the boundary of the computational domain. The solution of the exterior problem is obtained via Laplace transformation techniques which supply the boundary conditions in terms of discrete Dirichlet-to-Neumann operators.
    Keywords: ddc:000
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  • 60
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    Adaptive Multigrid Methods for the Vectorial Maxwell Eigenvalue Problem for Optical Waveguide Design (2000)
    Details
    Publication Date: 2022-07-07
    Description: This paper has been motivated by the need for a fast robust adaptive multigrid method to solve the vectorial Maxwell eigenvalue problem arising from the design of optical chips. Our nonlinear multigrid methods are based on a previous method for the scalar Helmholtz equation, which must be modified to cope with the null space of the Maxwell operator due to the divergence condition. We present two different approaches. First, we present a multigrid algorithm based on an edge element discretization of time-harmonic Maxwell's equations, including the divergence condition. Second, an explicit elimination of longitudinal magnetic components leads to a nodal discretization known to avoid discrete \emph{spurious modes} also and a vectorial eigenvalue problem, for which we present a multigrid solver. Numerical examples show that the edge element discretization clearly outperforms the nodal element approach.
    Keywords: ddc:000
    Language: English
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  • 61
    Electronic Resource
    Electronic Resource
    Pathologic significance of tumor progression in locally recurrent rectal cancer (2000)
    Springer
    Diseases of the colon & rectum 43 (2000), S. 775-781 
    Details
    ISSN: 1530-0358
    Keywords: Locally recurrent rectal cancer ; Survival ; Prognostic factor ; Angiogenesis ; Apoptosis ; PCNA labeling index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: It has recently been demonstrated that the tumor growth rate is a stronger determinant of survival than the extent of the growth in local recurrence of rectal cancer. We studied which factors controlled the tumor growth rate using modern immunohistochemical methods. METHODS: In 51 patients who underwent extended resection for this condition, paraffin-embedded specimens were examined for 1) tumor angiogenesis by CD31 staining and microvessel counting, 2) apoptosis by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling staining, and 3) cellular proliferative activity using anti-proliferative cell nuclear antigen antibody. The results were compared with carcinoembryonic antigen doubling time and survival. RESULTS: The five-year survival rate was 20 percent. The postoperative carcinoembryonic antigen doubling time, which was the strongest predictor of survival, correlated highly with proliferative cell nuclear antigen labeling index, but did not correlate with the apoptotic index or microvessel counts. CONCLUSION: Our study shows that cancer cell proliferation rather than apoptosis or angiogenesis is a major determinant of tumor growth rate and survival in patients with locally recurrent rectal cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02238013
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  • 62
    Electronic Resource
    Electronic Resource
    Apoptosis and its regulation in flat-type early colorectal carcinoma (2000)
    Springer
    Diseases of the colon & rectum 43 (2000), S. S23 
    Details
    ISSN: 1530-0358
    Keywords: Apoptosis ; Flat-type carcinoma ; Colorectal neoplasms ; p53 ; p21 (WAF1/CIP1) ; Bax
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The aim of this study was to investigate the relationship among apoptotic cell death, proliferative activity, and the expression of apoptosis-regulating proteins (p53, p21 (WAF1/CIP1), and bax) in flat-type early colorectal carcinoma and to compare these factors with those in polypoid-type early colorectal carcinoma. METHODS: Formalin-fixed, paraffin-embedded tissues of 11 flat-type early colorectal carcinomas and 17 polypoid-type early carcinomas were studied. The histologic diagnosis was either well-differentiated adenocarcinoma or carcinoma in adenoma, and the depth of invasion was limited to mucosa or submucosa. Apoptotic cells were detected by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling method, and proliferative activity was determined by Ki-67 immunohistochemistry using monoclonal antibody MIB-1. Apoptosis-regulating proteins were determined by immunohistochemistry using antibody DO-7 (p53), Cip1 (p21 (WAF1/CIP1)), and Bax (bax). RESULTS: There was no significant difference in terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index between flat-type early colorectal carcinoma and polypoid-type early carcinoma, at 1.9vs. 1.1, respectively. In flat-type carcinoma terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index in the p53 protein overexpression group was significantly smaller than that in the p53 protein-negative group (P〈0.05). The Ki-67 labeling index/terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index ratio in the p53 protein overexpression group was significantly higher than that in the p53 protein-negative group (P〈0.05). In polypoid-type carcinoma, the terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index and Ki67/terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling index ratio showed no significant difference between the p53 protein overexpression group and p53 protein-negative group. CONCLUSION: p53-dependent apoptosis may contribute to the development of flat-type early colorectal carcinoma. Apoptosis and its regulation in flat-type early colorectal carcinoma may differ from those in polypoid-type carcinoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02237222
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  • 63
    Electronic Resource
    Electronic Resource
    Angiogenesis, proliferation, and apoptosis in anal high-grade squamous intraepithelial lesions (2000)
    Springer
    Diseases of the colon & rectum 43 (2000), S. 346-352 
    Details
    ISSN: 1530-0358
    Keywords: Anus ; High-grade squamous intraepithelial lesion ; Carcinoma ; Proliferation ; Apoptosis ; Microvessel density
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Management of anal high-grade squamous intraepithelial lesions is controversial. Anal and cervical high-grade squamous intraepithelial lesions are similar in that they occur in transitional squamous epithelium, are associated with human papilloma virus infection, and have increased incidence in the immunocompromised population. Ablation of cervical high-grade squamous intraepithelial lesions is preferred, but similar ablation or excision of anal high-grade squamous intraepithelial lesions may compromise bowel control; thus, there is a need to define the malignant potential of anal high-grade squamous intraepithelial lesions. METHODS: We analyzed 50 paraffin sections of normal anoderm, anal low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and anal squamous-cell carcinoma. Microvessels were detected immunohistochemically with von Willebrand factor and counted manually along the epithelial-stromal junction. Proliferation and apoptosis were determined in the epithelial cells with MIB-1 antibody immunostaining and the terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling, respectively. RESULTS: Microvascular density was significantly greater in anal high-grade squamous intraepithelial lesions (mean, 0.50 vessels/cm)vs. normal anoderm (mean, 0.21 vessels/cm;P=0.0017, Mann-WhitneyU test). The proliferative percentages were greater in low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and squamous-cell carcinoma (mean, 20.4, 21.8, and 23.6 percent)vs. normal anoderm (mean, 14.4 percent), although not significantly (P=0.06, Kruskal-Wallis statistic). Although the mean proliferative proportions were similar in low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions, the apoptotic proportion was lower for high-grade squamous intraepithelial lesions than low-grade squamous intraepithelial lesions (10.13vs. 19.96 percent, respectively;P=NS, Mann-WhitneyU test). CONCLUSIONS: Angiogenesis, increased proliferation, and decreased apoptosis occur in anal high-grade squamous intraepithelial lesions as they do in the cervix before the development of malignancy. These biologic markers support the importance of anal high-grade squamous intraepithelial lesions as a potential premalignant lesion warranting surgical intervention.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02258300
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  • 64
    Electronic Resource
    Electronic Resource
    Apoptosis in rectal cancer (2000)
    Springer
    Diseases of the colon & rectum 43 (2000), S. 1227-1236 
    Details
    ISSN: 1530-0358
    Keywords: Rectal cancer ; Apoptosis ; p53 ; bcl-2 ; Prognosis ; Recurrence ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The aim of this study was to evaluate the prognostic value of the apoptotic index for recurrence and disease-free survival after curative surgery for rectal cancer, particularly in relation to clinicopathologic variables, p53− and bcl-2 expression. METHODS: Formalin-fixed, paraffin-embedded tissue samples of rectal carcinomas resected curatively within a five-year period were used (N=160). Apoptotic cells with fragmented DNA were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphatase-biotin nick-end-labeling method. The ratio of apoptotic tumor cells (in percent) was classified into low apoptotic index (less than 10 percent) and high apoptotic index (10 percent or more). Immunohistochemical analysis was performed using monoclonal antibodies (DO-1 for p53 and clone 124 for bcl-2). Statistics included univariate and multivariate analysis, and survival was calculated using the Kaplan-Meier method. RESULTS: Seventy-five percent of tumors showed a low apoptotic index, and 25 percent had a high apoptotic index. No correlation was found between apoptotic index and International Union Against Cancer stage (P〉0.05). However, significant correlations were documented with histologic differentiation (mean apoptotic index, 5.74 percent in moderatelyvs. 3.98 percent in poorly differentiated carcinomas; P=0.0173), lymph node involvement (mean apoptotic index, 6.11 percent in pN1vs. 3.72 percent in pN2; P=0.0074), p53 status (mean apoptotic index, 6.26 percent in p53−vs. 4.42 percent in p53+; P=0.0085), and bcl-2 expression (mean apoptotic index, 5.13 percent in bcl-2−vs. 6.51 percent in bcl-2+; P=0.0418). Tumors of the lower rectum had a lower apoptotic index than those of the upper rectum (P=0.0277). Neither univariate nor multivariate analysis assessed apoptotic index as predictor of prognosis: Recurrence rates did not differ between tumors related to apoptotic index (22 percent with low apoptotic indexvs. 15 percent with high apoptotic index; P〉0.05), and no significant differences were found regarding survival (P〉0.05). On multivariate analysis, International Union Against Cancer stage (P=0.0002), p53 (P=0.0002), gender (P=0.0136), and bcl-2 (P=0.0243) were independent predictors of recurrence. These variables, except for bcl-2, were also independently related to disease-free survival. CONCLUSIONS: Reflecting tumor biology, apoptotic index as single variable showed no prognostic significance, whereas p53 was an independent predictor for both recurrence and survival, and bcl-2 was independently related to recurrence, but not to survival. Clinically, International Union Against Cancer stage and gender were independent prognostic factors after curative surgery for rectal cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02237426
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    Electronic Resource
    Prognostic Significance of Fas and Fas Ligand System-Associated Apoptosis in Gastric Cancer (2000)
    Springer
    Annals of surgical oncology 7 (2000), S. 750-757 
    Details
    ISSN: 1534-4681
    Keywords: Gastric cancer ; Apoptosis ; Fas ; Fas ligand ; Cytotoxic T lymphocyte.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Previous studies indicate that gastric carcinomas express Fas ligand and downregulate Fas to escape from the host immune attack; however, the prognostic importance of Fas/FasL expression in this tumor is yet to be evaluated. Methods: Specimens from 87 gastric carcinoma patients of different stages treated in a defined period with curative intent were evaluated for apoptosis, Fas, FasL, and CD8 expression using an immunohistochemical method. Results: The percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic cells expressed as apoptotic index (AI) was higher in 43 patients when the cut-off value was set at the median value. There were no significant correlations between AI and clinicopathologic parameters. Thirty-nine patients showed a high number of CD81 cells within cancer nests. Positive FasL and Fas expression was seen in 53 and 72 patients, respectively. CD8 and FasL expressions were related only to patients’ age. Fas expression had significant correlations with tumor invasion and Lauren classification. There were significant direct correlations between AI and number of nest CD81 cells and between AI and grade of Fas expression. Apoptotic index, pT stage, CD8 expression, and Fas expression were identified as independent prognostic factors. Conclusions: Spontaneous apoptosis in gastric carcinoma may be an independent prognosticator for survival and is significantly influenced by tumor Fas expression and number of nest CD81 cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s10434-000-0750-1
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  • 66
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    Electronic Resource
    A model chemosensitivity test examining apoptosis in small specimens of gastric cancer (2000)
    Springer
    Gastric cancer 3 (2000), S. 39-44 
    Details
    ISSN: 1436-3305
    Keywords: Key words Chemosensitivity ; Apoptosis ; TUNEL ; Gastric cancer ; Small specimen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Because chemosensitivity tests usually require a large amount of tissue, they are not used routinely in patients with unresectable gastric cancer. The aim of this study was to investigate whether apoptosis can be used as a sensitivity assay for chemosensitivity in small gastric cancer specimens. Methods. Apoptosis, detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick labeling (TUNEL), was investigated in small specimens of the MKN-1, MKN-45, and TMK-1 human gastric cancer cell lines as a marker of chemosensitivity following exposure to antineoplastic agents. Results. Doxorubicin (DXR), SN-38 (active metabolite of irinotecan), and paclitaxel (Taxol) induced DNA fragmentation in MKN-45 and TMK-1 cells, but not in MKN-1. In contrast, neither 5-fluorouracil (5-FU) nor cisplatin (CDDP) induced DNA fragmentation in any of the three cell lines. Small pieces cut from tumors implanted in nude mice were exposed to the antineoplastic agents in culture medium for 24 h, and the percentage of TUNEL-positive cancer cells (TUNEL positivity) was examined. TUNEL positivity in all three cancers increased after exposure to DXR, SN-38, and Taxol, but not after exposure to CDDP or 5-FU. MKN-45 showed the highest TUNEL positivity with SN-38 and Taxol, and TMK-1 TUNEL positivity was highest with DXR. MKN-45 and TMK-1 were the most sensitive to these three antineoplastic agents in vitro, while MKN-1, with the lowest TUNEL positivity, was the least sensitive to these three antineoplastic agents. TUNEL positivity after exposure to Taxol correlated with the antitumor effects of this compound in an animal model. Conclusion. These results suggest that, in small gastric cancer specimens where apoptosis is implicated, TUNEL positivity may be applicable to a chemosensitivity test.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00011688
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  • 67
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    Electronic Resource
    Morphogenesis of nonpolypoid colorectal adenomas and early carcinomas assessed by cell proliferation and apoptosis (2000)
    Springer
    Virchows Archiv 437 (2000), S. 17-24 
    Details
    ISSN: 1432-2307
    Keywords: Key words Colon ; Nonpolypoid adenoma ; Apoptosis ; Proliferation ; Morphogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Nonpolypoid neoplasms, as well as ordinary polypoid tumours, are occasionally found in the colorectum. To clarify whether cell kinetic status affects the macroscopic morphology of colorectal neoplasms, we investigated proliferative indices (PI), apoptotic indices (AI), and the expression of apoptosis-related gene products. We examined 110 colorectal neoplasms comprised of 36 polypoid, 38 flat elevated and 36 depressed tumours. According to WHO’s criteria these tumours consisted of 61 adenomas with low grade dysplasia (LGD), 30 adenomas with high grade dysplasia (HGD) and 19 carcinomas with submucosal invasion. Apoptotic cells were detected by TUNEL staining. Proliferating cells and apoptosis-related gene products were assessed by immunohistochemistry for Ki-67, p53, Bcl-2, and Bax antigens. AI were closely associated with macroscopic morphology in adenomas but not in carcinomas. PI were relatively constant among the three macroscopic types in adenomas and carcinomas. Median AI values of polypoid, flat elevated and depressed tumours were 1.8%, 2.1% and 4.6% for adenomas with LGD, 0.8%, 2.4% and 6.2% for adenomas with HGD and 2.9%, 4.0% and 3.6% for carcinomas, respectively. Overall PI were significantly higher in carcinomas than in adenomas with LGD, whereas AI were not different. Although the incidence of expression was significantly higher in carcinomas for p53 and in adenomas for Bcl-2 than the others, the expression of apoptosis-related gene products (p53, Bcl-2 and Bax) was similar among polypoid, flat elevated and depressed tumours. Macroscopic morphology of colorectal adenomas is determined by the apoptosis not by proliferation, and high apoptosis found in depressed adenomas implies their low net growth.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280000198
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    Regulation of proliferation and apoptosis in sporadic and hereditary medullary thyroid carcinomas and their putative precursor lesions (2000)
    Springer
    Virchows Archiv 437 (2000), S. 256-263 
    Details
    ISSN: 1432-2307
    Keywords: Keywords Medullary thyroid carcinoma ; MEN2 ; Proliferation ; Apoptosis ; bcl ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  C-cell hyperplasia (CCH) and medullary thyroid carcinoma (MTC) in patients affected by germline mutations of the RET oncogene represent an exceptional opportunity to study the regulation of proliferation and apoptosis during tumour initiation and progression. In 56 specimens [CCH, n=1; MTC with CCH, n=26; MTC, n=20; lymph-node metastasis (LNM), n=9] from 46 patients [multiple endocrine neoplasia type 2a (MEN2a), n=24; MEN2b, n=2; familiar MTC (FMTC), n=4; sporadic MTC, n=16] and 3 cases of non-neoplastic CCH, proliferation activity (MIB1), the rate of apoptosis [dUTP nick end labelling (TUNEL)] and expression of p53, bcl-2, bcl-x and bax were investigated and compared with clinical data. In MEN-associated CCH and small MTC, bcl-2 was strongly expressed, bcl-x was moderately expressed and bax was only weakly expressed. Advanced tumours and LNM did show a more heterogeneous bcl-2 staining accompanied by an increased bax expression and accelerated proliferation. The rate of apoptosis was extremely low in all investigated tumours. P53 was detectable in three patients with rapidly growing and extensively metastasising MTC. No somatic p53 mutations were found. Hereditary MTC with germline RET mutations at codon 918 (MEN2b) and codon 634 revealed a bias towards a higher proliferation activity at a younger age and are more frequently accompanied by LNM. CCH and MTC are characterised with a preponderance of bcl-2 as a factor blocking the programmed cell death. While MTC, in general, is a slowly growing tumour, a minority of tumours do progress rapidly with high proliferation. The factors leading to an accelerated tumour progression do not seem to take their effect via the regulation of apoptosis. Certain alterations of RET are supposed to have a direct or indirect implication on proliferation and, because of this, an effect on the clinical course.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280000233
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  • 69
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    Electronic Resource
    Effects of genistein and synergistic action in combination with eicosapentaenoic acid on the growth of breast cancer cell lines (2000)
    Springer
    Journal of cancer research and clinical oncology 126 (2000), S. 448-454 
    Details
    ISSN: 1432-1335
    Keywords: Key words Genistein ; Eicosapentaenoic acid ; Apoptosis ; Bax ; Bcl-xL ; Caspase-3
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Genistein, a prominent isoflavone in soy products, produced dose- and time-dependent in vitro growth inhibition at high concentrations (at least 185 μM) with an IC50 of 7.0–274.2 μM after 72 h incubation in four breast cancer cell lines (DD-762, Sm-MT, MCF-7 and MDA-MB-231) and one breast epithelial cell line (HBL-100) of human and animal origin; it stimulated estrogen-receptor-positive MCF-7 cells at low concentrations (3.7 nM–37 μM). Genistein-exposed cells underwent apoptosis, confirmed by G2/M arrest followed by the appearance of a sub-G1 fraction in cell-cycle progression, and by a characteristic cell ultrastructure. The apoptosis cascade was due to up-regulation of Bax protein, down-regulation of Bcl-XL protein, and activation of caspase-3. Genistein acted in synergism with eicosapentaenoic acid (EPA), a fish oil component, on human breast cancer MCF-7 cells (genistein 〉 93.2 μM and EPA 〉 210.9 μM) and on MDA-MB-231 cells (genistein 〉 176.1 μM and EPA 〉 609.3 μM). Dietary intake of genistein in combination with EPA may be beneficial for breast cancer control.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050012
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    Electronic Resource
    Expression of the angiogenic factor thymidine phosphorylase in human astrocytic tumors (2000)
    Springer
    Journal of cancer research and clinical oncology 126 (2000), S. 145-152 
    Details
    ISSN: 1432-1335
    Keywords: Key words Angiogenesis ; Apoptosis ; Glioma ; Thymidine phosphorylase ; Vascular endothelial growth factor ; AbbreviationsTP thymidine phosphorylase ; GBM glioblastoma ; AA anaplastic astrocytoma ; LGA low-grade astrocytoma ; VEGF vascular endothelial growth factor ; RT-PCR reverse transcriptase/polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thymidine phosphorylase (TP) has been implicated as a potent angiogenic factor and a prognostic factor in various human solid tumors. We investigated the expression of TP in a series of human astrocytic tumors using immunohistochemistry, enzyme-linked immunosorbent assay, and reverse transcriptase/polymerase chain reaction (RT-PCR) analysis. A total of 63 astrocytic tumors [27 glioblastomas (GBM), 19 anaplastic astrocytomas (AA), 17 low-grade astrocytomas (LGA)] and 5 normal brain tissues were immunohistochemically stained with antibodies to TP, vascular endothelial growth factor (VEGF), p53, MIB-1, and factor-VIII-related antigen. They were also evaluated for the degree of apoptosis by a ApopTag kit. Ten tumors (5 GBM, 2 AA, 3 LGA) and 3 normal brain tissues were evaluated for their expression of VEGF and TP by RT-PCR analysis. TP was constantly localized in the cytoplasm of astrocytic tumor cells, less intensely in the cytoplasm of vascular endothelial cells, but not in the normal brain. Some of the TP-positive cells were of macrophage origin, but most positive cells were the tumor cells themselves. Vascular density, MIB-1 positivity, p53 positivity, VEGF expression, and the apoptotic index were significantly higher in the TP-positive tumors than in TP-negative tumors. There was a significant correlation between TP and VEGF mRNA expression. In a limited number of glioblastoma cases, the apoptotic index was significantly higher in TP-positive glioblastomas than in TP-negative glioblastomas. In human astrocytic tumors, TP was expressed in the tumor, macrophage, and endothelial cells. TP was a potent angiogenic factor closely associated with cell proliferation and tumor apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050024
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  • 71
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    Electronic Resource
    Cycloprodigiosin hydrochloride, a H+/Cl− symporter, induces apoptosis in human breast cancer cell lines (2000)
    Springer
    Journal of cancer research and clinical oncology 126 (2000), S. 191-197 
    Details
    ISSN: 1432-1335
    Keywords: Key words Cycloprodigiosin hydrochloride ; Breast cancer ; Apoptosis ; Intracellular acidification ; Bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of cycloprodigiosin hydrochloride (cPrG · HCl), a H+/Cl− symporter, on five human breast cancer cell lines (KPL-1, T-47D, MCF-7, MKL-F, and MDA-MB-231), a human breast epithelial cell line (HBL-100), and a human fibroblast cell line (WI-38–40) was examined. cPrG · HCl inhibited the growth of all five breast cancer cell lines (IC50: 0.46–0.62 μM) and slightly inhibited HBL-100 and WI-38–40 cell growth (IC50: 1.75 μM and 2.26 μM respectively). cPrG · HCl treatment in KPL-1 cells increased the pH of acidic organelles, decreased intracellular pH, and caused apoptosis, which was confirmed by the appearance of a sub-G1 population by flow cytometry and DNA fragmentation. In addition, cPrG · HCl-induced apoptosis was strongly suppressed by imidazole, a cell-permeable base, suggesting that intracellular acidification was essential for the apoptosis. Further, cPrG · HCl treatment up-regulated Bax and Bak expression, down-regulated Bcl-2 expression, and activated caspase-3. Therefore, the intracellular acidification by cPrG · HCl treatment suppressed the growth of human breast cancer cell lines by inducing apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050032
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  • 72
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    Cell-cycle arrest and p53-independent induction of apoptosis in vitro by the new anticancer drugs 5-FdUrd-P-FdCydOct and dCydPam-P-FdUrd in DU-145 human prostate cancer cells (2000)
    Springer
    Journal of cancer research and clinical oncology 126 (2000), S. 247-256 
    Details
    ISSN: 1432-1335
    Keywords: Key words 5-Fluorodeoxyuridine ; Heterodinucleoside dimers ; Prodrugs ; Prostate cancer ; Cytotoxicity ; Cell cycle ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Purpose: Current therapies have limited impact on the progression of metastatic hormone-refractory prostate cancer. Therefore, we investigated the utility of new heterodinucleoside phosphate dimers of 5-fluorodeoxyuridine (5-FdUrd) in p53-mutated and androgen-independent DU-145 human prostate tumour cells. Methods: The effects of the dimers were assessed in vitro by a cell proliferation assay for cytotoxicity, flow cytometry for cell cycle distribution, confocal laser scanning microscopy for the detection of apoptotic bodies, poly(ADP-ribose) polymerase cleavage for caspase 3 activity and by a thymidylate synthetase assay. Results: The new dimers N 4-palmitoyl-2′-deoxycytidylyl-(3′→5′)-5-fluoro-2′-deoxyuridine (dCydPam-P-FdUrd) and 2′-deoxy-5-fluorouridylyl-(3′→5′)-2′-deoxy-5-fluoro-N 4-octadecylcytidine (5-FdUrd-P-FdCydOct) caused marked cytotoxicity with IC50 values of 3–4 μM. 5-FdUrd-P-FdCydOct at 200 μM was capable of eradicating 100% of tumour cells whereas 10% of the cells were resistant to 5-FdUrd. Cytotoxicity was caused by a dramatic S-phase arrest, resulting in an increase of this cell population from 34% to 85% with 5-FdUrd-P-FdCydOct and to 81% with dCydPam-P-FdUrd. S-phase arrest was followed by apoptosis, as shown by 85% of the cells staining positive for Apo 2.7 antibody, a six- to eight-fold increased caspase 3 activity and DNA fragmentation. Thymidylate synthase activity was inhibited by 50% at 0.6–0.7 μM dimer concentration. The dimers were hydrolysed in vitro by phosphodiesterase I and human serum to the corresponding nucleosides and nucleoside monophosphates. Conclusions: The new dimers dCydPam-P-FdUrd and 5-FdUrd-P-FdCydOct are effective prodrugs of 5-FdUrd and have potential value for the treatment of p53-mutated and hormone-independent human prostate carcinomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050339
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    Apoptose bei multipler Sklerose Ätiopathogenetische Relevanz und Perspektiven für neue therapeutische Strategien (2000)
    Springer
    Der Nervenarzt 71 (2000), S. 767-773 
    Details
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Multiple Sklerose ; Apoptose ; Immunpathogenese ; CD95 ; TNF ; Keywords Multiple sclerosis ; Apoptosis ; Immunopathogenesis ; CD95 ; TNF
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Apoptosis, or programmed cell death, is a physiological cell suicide program mainly leading to selective elimination of useless cells. This mechanism is important for the homeostasis of the immune system and presumably plays a two-sided role in the pathogenesis of multiple sclerosis (MS). On the one hand, evidence has been provided that impaired apoptosis might result in increased numbers or persistence of activated myelin-specific T cells, thus inducing the pathophysiologic processes in MS. On the other hand, local tissue damage might involve apoptosis of glial and neuronal cells and lead to the clinical symptoms. Here, an overview is presented on the current knowledge of the role of apoptosis in the pathogenesis of MS, and implications for related therapeutic strategies are discussed.
    Notes: Zusammenfassung Apoptose, auch programmierter Zelltod genannt, stellt einen physiologischen Prozess zur selektiven Eliminierung vor allem von unerwünschten körpereigenen Zellen dar. Dieser für die Homöostase des Immunsystems wichtige Mechanismus nimmt wahrscheinlich eine ambivalente Schlüsselrolle in der Ätiopathogenese der multiplen Sklerose (MS) ein. So existieren Hinweise dafür, dass bei der MS eine eingeschränkte Apoptose zur pathologischen Existenz und Persistenz aktivierter myelinspezifischer T-Zellen führt, die wiederum für die charakteristische intrazerebrale Entzündung verantwortlich gemacht werden. Gleichzeitig deuten aktuelle Arbeiten aber darauf hin, dass auf der Endstrecke der entzündlichen Reaktion der apoptotische Untergang von Glia- und evtl. auch Nervenzellen zur Gewebeschädigung und somit entscheidend zur klinischen Symptomatik beitragen. Ziel dieser Übersicht ist die Zusammenstellung der bislang gewonnenen Erkenntnisse zur Bedeutung von Apoptose für die Pathogenese der MS und eines Ausblicks auf mögliche apoptoseorientierte Therapiestrategien.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001150050664
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    Molekulargenetische und zellbiologische Grundlagen der Entstehung von malignen Tumoren (2000)
    Springer
    Der Urologe 39 (2000), S. 214-221 
    Details
    ISSN: 1433-0563
    Keywords: Schlüsselwörter Krebs ; Karzinogenese ; Zellzyklus ; Protoonkogene ; Tumorsupressorgene ; DNA-Reparaturgene ; Apoptose ; Telomere ; Key words Multi-step carcinogenesis ; Cell cycle ; Proto-oncogene ; Tumor suppressor gene ; DNA repair gene ; Apoptosis ; Telomeres
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The development of cancer is one of the most intensively studied areas of medical research resulting in an immense quantity of data. Therefore, the purpose of this article is to give an overview of the basic principles of cancer development. Key words such as multi-step carcinogenesis, cell cycle, proto-oncogene, tumor suppressor gene, DNA repair gene, apoptosis and telomeres are explained and described in examples. This paper aims to connect recent information of molecular and cellular biology in an overview of cancer origin and development.
    Notes: Zusammenfassung Die Entstehung von Tumoren und die Entwicklung von entsprechenden Modellen gehört zu den sehr intensiv untersuchten Fragestellungen medizinischer Forschung mit einer schier unerschöpflichen Datenflut. Ziel dieses Artikels ist daher die möglichst anschauliche und daher sicher vereinfachende Darstellung grundlegender Prinzipien der Krebsentstehung. Es werden Begriffe wie Mehrschrittkarzinogenese, Zellzyklus, Protoonkogene, Tumorsupressorgene, DNA-Reparaturgene, Apoptose und Telomere in Zusammenhang gebracht und anhand von Beispielen erklärt. Dieser Artikel soll damit zum Verständnis der Zusammenhänge der Molekular- und Zellbiologie bei der Krebsentstehung beitragen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001200050344
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  • 75
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    Electronic Resource
    Glycine attenuates apoptotic cell death in uranyl acetate-induced acute renal failure in rats (2000)
    Springer
    Clinical and experimental nephrology 4 (2000), S. 24-28 
    Details
    ISSN: 1437-7799
    Keywords: Key words Uranyl acetate ; ARF ; Glycine ; Apoptosis ; Tubular damage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Although uranyl acetate (UA) is known to induce apoptosis in renal tubular cells, the pathophysiological role of apoptotic cell death in UA-induced acute renal failure (ARF) is not clear. In this study, we examined whether glycine, which is known to provide protection against nephrotoxic acute renal failure, attenuated tubular damage in UA-induced ARF in rats, and, if so, whether the attenuation of tubular damage was associated with reduced apoptotic cell death. Methods. Sprague-Dawley rats were allocated to three groups; normal controls, UA-treated, and UA plus glycine-treated. Acute renal failure was induced by the intravenous injection of UA (5 mg/kg). UA plus glycine-treated rats were given glycine at 1 g/kg, i.v. over 3 min at the same time as the UA injection. Serum creatinine concentration (Scr) and tubular damage score were examined 5 days after UA administration. Apoptosis was evaluated by counting the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells in the outer stripe of the outer medulla. Results. Glycine significantly decreased the UA-induced increases in Scr (3.73 ± 0.31 vs 2.74 ± 0.11 mg/dl; P 〈 0.05) and the tubular damage score (3.83 ± 0.13 vs 2.58 ± 0.01; P 〈 0.01). UA significantly increased the number of TUNEL-positive cells in the outer stripe of the outer medulla (0.16 ± 0.04 vs 7.45 ± 0.46/high power field at ×400 magnification; P 〈 0.01 vs normal control value). Glycine infusion significantly lessened the number of TUNEL-positive cells (5.84 ± 0.31/ high power field at ×400 magnification; P 〈 0.01 vs UA-treated rats). A significant correlation was found between the number of TUNEL-positive cells and the tubular damage score (r = 0.93; P 〈 0.01). Conclusion. Glycine ameliorated the severity of UA-induced ARF and the degree of apoptotic cell death. This finding suggested that the protective effect of glycine in UA-induced ARF may be mediated, at least in part, through a reduction of apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101570050057
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  • 76
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    The contribution of the adriamycin-induced rat model of the VATER association to our understanding of congenital abnormalities and their embryogenesis (2000)
    Springer
    Pediatric surgery international 16 (2000), S. 465-472 
    Details
    ISSN: 1437-9813
    Keywords: Key words Adriamycin ; Apoptosis ; Embryogenesis ; Esophageal atresia ; Notochord ; VATER association
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The adriamycin-induced rat model of the VATER association has provided a means of studying the morphogenesis of a variety of major congenital structural abnormalities similar to those seen in humans with the VATER association. Most interest has been centered on the foregut, where the model has clarified some aspects of the development of esophageal atresia (EA), tracheal agenesis, and other communicating bronchopulmonary foregut malformations. It has demonstrated aberrations in the nerve supply to the esophagus in EA and allowed the study of tracheomalacia. A relationship between an abnormal notochord, foregut abnormalities, and vertebral defects has been shown, and the model has reignited interest in the role of the notochord as a regional organizer of axial development. The normal temporospatial characteristics of apoptosis during fore- and hindgut development is disturbed in this model, resulting in abnormal morphology. The indications are that this model will continue to clarify the processes that lead to many of the structural congenital abnormalities that are seen in infants born with the VATER association.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830000426
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    Electronic Resource
    Apoptosis in murine duodenum during embryonic development (2000)
    Springer
    Pediatric surgery international 16 (2000), S. 485-487 
    Details
    ISSN: 1437-9813
    Keywords: Key words Duodenum ; Apoptosis ; Fetus ; Rat ; Duodenal atresia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Duodenum is thought to go through a solid-core stage followed by recanalization during its development. This study investigates the role of apoptosis in normal duodenal development, especially during widening of the lumen, and hence, the possible role of apoptosis in duodenal atresia (DA). Twenty-four time-mated Sprague-Dawley rats were killed from day 13 to day 20 of gestation. Duodenums of 3 fetuses were chosen randomly from each rat and processed. Apoptosis was determined by the terminal deoxytransferase-mediated biotin dUTP nick-end labeling (TUNEL) technique (ApopTag). Apoptosis count and cross-sectional areas were measured with an image analyzer (MetaMorph). The number of apoptotic cells per unit area duodenum peaked on day 15 for the mucosal/submucosal layer and on day 14 for the muscular/mesenchymal layer. The maximal number of apoptotic cells per cross-section of duodenum was between 7 and 8. The cross-sectional areas of the duodenal wall and lumen increased exponentially between day 17 and day 19 while duodenal-wall thickness remained relatively constant throughout duodenal development. The localization, timing, and intensity of apoptosis do not suggest that apoptosis is responsible for the widening of the duodenal lumen; enlargement of the lumen is related to the increase in duodenal circumference. Apoptosis thus may not be involved in the pathogenesis of DA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830000408
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    Induction of apoptosis and manganese superoxide dismutase gene by photodynamic therapy in cervical carcinoma cell lines (2000)
    Springer
    International journal of clinical oncology 5 (2000), S. 97-103 
    Details
    ISSN: 1437-7772
    Keywords: Key words Photodynamic therapy ; Cervical cancer ; Apoptosis ; MnSOD ; Gene induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Photodynamic therapy (PDT) is a cancer treatment modality in which systemic administration of a tumor-localizing photosensitizer is followed by irradiation of the tumor with visible light. Although PDT is undergoing clinical trials for various cancers, the mechanisms of its action are not fully understood. To investigate the mechanism of cell death by PDT, we performed in-vitro PDT, using Photofrin II as a photosensitizer, in two human cervical carcinoma cell lines, HeLa and CaSki. Methods. Cells were incubated with Photofrin II for 24 h, followed by illumination, using a YAG-OPO laser. Cell survivability after PDT was evaluated by an MTT assay. Cytotoxicity was assayed by measuring the release of lactate dehydrogenase (LDH) into the supernatant. DNA of the PDT-treated cells was electrophoresed in an agarose gel to determine fragmentation. In situ detection of apoptosis in the PDT-treated cells was performed by identification of the 3′-OH ends of DNA. In addition, induction of manganese superoxide dismutase mRNA (MnSOD) was analyzed in the PDT-treated cells. Results. The CaSki cells were more sensitive to this PDT treatment than were the HeLa cells. DNA fragmentation was observed with less than 5 μg/ml of Photofrin II in both cell lines, whereas PDT-induced cell membrane destruction, determined by LDH release, was observed only at 10 μg/ml. The MnSOD mRNA was induced in the HeLa cells in the early hours after PDT with a non-lethal dose of Photofrin II, but was reduced with a high dose, whereas the CaSki cells did not show any induction of the MnSOD gene by PDT. Conclusion. The present results suggest that PDT induces cell death by a mechanism involving membrane destruction and apoptosis. Differences in cell susceptibilities to PDT may depend upon a protective mechanism, such as MnSOD gene induction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101470050098
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    An analysis of the therapeutic efficacy of protracted infusion of low-dose 5-fluorouracil and cisplatin in advanced gastric cancer (2000)
    Springer
    Journal of infection and chemotherapy 6 (2000), S. 222-228 
    Details
    ISSN: 1437-7780
    Keywords: Key words Gastric cancer ; Low-dose FP ; Pharmacokinetics ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To analyze the clinical efficacy of a protracted infusion of low-dose 5-fluorouracil (5-FU) and cisplatin (CDDP), a phase II study was performed in 36 patients with advanced gastric cancer. The treatment schedule of the low-dose administration of 5-FU and CDDP (FP) was a continuous infusion of 5-FU (250 mg/m2) for 28 consecu-tive days and a drip infusion of CDDP (3.5 mg/m2) for 5 consecutive days, followed by a 2-day interval each week in one cycle. The overall response rate was 47.2%. Of importance, the improvement in quality of life assessed by performance status (PS) and oral intake was 13.9% and 33.3%, respectively. The toxicity in low-dose FP treatment was less than grade 2, including gastrointestinal toxicities and bone marrow suppression, and this was tolerable during the treatment. The median survival time (MST) and 1-year survival rate were 8 months and 36.2%, respectively. In a pharmacokinetic analysis following the protracted infusion of low-dose FP, the plasma concentrations of 5-FU and CDDP were increased to about 120–130 ng/ml and 0.3–0.5 μg/ml on day 21 after the treatment, respectively. The plasma concentrations of 5-FU and CDDP were not significantly different between responders and non-responders. The tumor response to low-dose FP treatment was associated with the induction of apoptotic cell death and with the overexpression of apoptosis-related genes, such as Bax and Bcl-Xs, in cancer cells. These results indicate that the protracted infusion of low-dose FP could be a useful regimen for patients with advanced gastric cancer, in terms of the high response rate and low toxi-city, possibly leading to the prolongation of survival and improvement in the quality of life.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s101560070007
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  • 80
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    BCG (bacille Calmette-Guérin)-activated lymphocytes (BAK cells) induce apoptosis in urinary bladder carcinoma cell line T24 in vitro (2000)
    Springer
    International journal of clinical oncology 5 (2000), S. 253-261 
    Details
    ISSN: 1437-7772
    Keywords: Key words BAK cells ; T24 cells ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. We previously reported the basic characteristics of BCG (bacille Calmette-Guérin)-activated killer (BAK) cells, which exhibited antitumor effects against the bladder cancer cell line T24. Our study suggested that both BCG and BAK cells were responsible for the inhibition of tumor cell proliferation; however, the basic mechanism of BCG or BAK cells in this inhibition was not clear. We here report the antitumor effects of BAK cells, which correlated with the induction of apoptosis in T24 cells. Methods. Lymphocytes were cultured with BCG to examine 3H-thymidine uptake, and the subpopulation was evaluated by immunocytometry. T24 cells were then cultured with BAK cells for the analysis of 3H-thymidine uptake and apoptosis induction by DNA electrophoresis; pathology study, and cell-cycle analysis were also done. Culture supernatants of BAK and T24 cells were also investigated to detect interferon-γ (IFN-γ), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Results. The 3H-thymidine uptake study of lymphocytes showed that BCG activated the lymphocytes. Evaluation by immunocytometry revealed that CD4+ and CD8+ T cells were induced by BCG. The 3H-thymidine uptake study of T24 cells revealed that BAK cells inhibited tumor cell proliferation. DNA electrophoresis, the morphological study, and cell-cycle analysis by immunocytometry demonstrated that apoptosis in T24 cells was induced when they were cultured with BAK cells. IFN-γ, IL-6, and TNF-α were detected in the culture supernatants of BAK and T24 cells. Conclusions. Cytokine production and the induction of apoptosis may, together, be the major mechanisms of the antitumor action seen when BAK cells were employed against T24 cells; BAK cells could be employed as clinical effectors against bladder cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00012046
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  • 81
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    Caspase inhibition protects from liver injury following ischemia and reperfusion in rats (2000)
    Springer
    Transplant international 13 (2000), S. S568 
    Details
    ISSN: 1432-2277
    Keywords: Key words Normothermic liver ischemia ; Apoptosis ; Caspases ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Normothermic ischemia and reperfusion of the liver results in microcirculatory failure followed by necrosis and cell death. Recently, another type of cell death, apoptosis or programmed cell death, was found to be activated during the early phase of reperfusion after liver ischemia. Caspases are cysteine proteinases specifically involved in the initiation and execution phases of apoptosis. The aim of this study was to demonstrate that inhibition of apoptosis by a specific inhibitor of caspases might protect the liver against ischemia/reperfusion injury. Rats were divided into three groups: group 1, control, PBS administration; group 2, Z-Asp-cmk (Z-Asp-2,6-dichlorobenzoyl-oxymethylketone) treatment; group 3, sham-operated control animals. Z-Asp-cmk (0.5 mg Z-Asp-cmk dissolved in 300 μl PBS solution containing 1 % DMSO) was injected intravenously, 2 min prior to induction of 120 min ischemia. Survival rates were compared and serum activities of aspartate aminotransferases and alanine aminotransferases were assessed in the blood collected from the suprahepatic vena cava. Histology of the liver was assessed 6 h after the end of ischemia. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP-FITC nick end-labeling method (TUNEL method) and by electrophoresis for analysis of DNA fragmentation. Caspase activity was determined by measuring hydrolysis of the CPP32-like substrate Ac-DEVD-pNA and absorption of paranitroaniline. Z-Asp-cmk treatment significantly increased 7-day survival (95 %) compared with that in nontreated rats (30 %, P 〈 0.001). Serum activities of aminotransferases and the extent of liver congestion and necrosis were significantly (P 〈 0.001) decreased after treatment with Z-Asp-cmk. TUNEL-positive cells were detected 3–6 h after reperfusion in the control group. In Z-Asp-cmk pretreated rats, a dramatic decrease in the number of TUNEL-positive cells was observed. Analysis of DNA fragmentation of freshly isolated hepatocytes confirmed these results. Caspase activity was increased 3–6 h after reperfusion in the control group, but significantly (P 〈 0.001) decreased after treatment with Z-Asp-cmk. These findings demonstrate that liver injury following ischemia and reperfusion can be prevented by inhibition of caspases. Caspase inhibitors may have important implications for therapy in liver disease and after liver transplantation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050405
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    Apoptotic cell death and fertility in three unilateral cryptorchid rat models (2000)
    Springer
    Urological research 28 (2000), S. 332-337 
    Details
    ISSN: 1434-0879
    Keywords: Key words Cryptorchidism ; Contralateral descended testis ; Apoptosis ; Fertility ; Rat model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three rat strains have been studied, using a sensitive apoptotic detection method for germ-cell degeneration, to resolve the controversy regarding the effect of cryptorchidism on the contralateral descended testis (CDT). Sprague Dawley and Buffalo rats were made cryptorchid by operation at 20–22 days of age, while trans-scrotal (T-S) rats were a congenitally unilateral cryptorchid strain. Sham operated rats or normal T-S littermates were used as controls. Experiments were performed over a period ranging from 2 weeks to 18 months. Testis weight was assayed, as was the detection of apoptosis by agarose gel laddering and immunohistochemistry by using the TUNEL method. Labeled cells in 150 cross-sectioned testis tubules were counted on the TUNEL stained slides and the mean number of labeled cells per tubule was calculated. Paternity studies on Sprague Dawley and T-S rats were carried out at 12 and 24 weeks of age to assess fertility by the resultant number of pregnancies and litter sizes. Both Sprague Dawley and T-S rat models showed a biphasic distribution of apoptosis levels. This biphasic distribution was not observed in Buffalo rats as they were only studied at later time points (12–20 weeks). A significant effect on either testis weight or apoptosis in the CDT compared with the control descended testis (P ≥ 0.1) has not been found in these three cryptorchid models, and the present results are discussed with reference to observations of other researchers in rodents and humans. While the cryptorchid testis showed a high level of labeled apoptotic cells per tubule in all rat strains, fertility was not affected and remained the same as controls at 12 and 24 weeks. There was, however, a marked strain difference in fertility in T-S as compared with Sprague Dawley rats. After 24 weeks of cryptorchidism, both control and cryptorchid T-S rats had a 44% pregnancy incidence compared with a 90% pregnancy incidence in Sprague Dawley rats. In addition, litter size in T-S control and cryptorchid rats were small compared with those of Sprague Dawley rats at 12 and 24 weeks.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002400000121
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    Renal tubular apoptosis after complete ureteral obstruction in the presence of hyperoxaluria (2000)
    Springer
    Urological research 28 (2000), S. 220-222 
    Details
    ISSN: 1434-0879
    Keywords: Key words Kidney ; Ureter ; Urinary obstruction ; Hydronephrosis ; Hyperoxaluria ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hyperoxaluria is a well-known cause of renal stone disease and in vitro studies have shown that oxalate crystals have a stimulatory effect on apoptosis of renal tubular epithelial cells. Total and partial ureteral obstruction also have an accelerating effect on apoptosis of renal tubular epithelial cells. The aim of the present study was to investigate the apoptotic effect of unilateral ureteral obstruction in the presence of hyperoxaluria on the rat kidney. Twenty-eight male Wistar rats were divided into four groups, with seven rats in each. The groups were named G1 (control), G2 (hyperoxaluric), G3 (obstructive) and G4 (hyperoxaluric + obstructive). G2 and G4 rats were given 1% ethylene glycol (a precursor for oxalates) in their drinking water. G1 and G2 rats underwent sham operation, while left proximal ureteral ligation with a 5-zero silk suture was performed on G3 and G4 animals. The rats were sacrificed 2 weeks after the operation; left nephrectomy was then performed. We searched for the apoptotic cells by direct immuno-peroxidase detection of digoxigenin-labeled genomic DNA. The mean ± SD values of the apoptotic cell count was 0.86 ± 0.90 in G1 and 4.33 ± 3.81 in G2. The values for G3 and G4 were 30.17 ± 16.85 and 302.67 ± 184.45, respectively. We found a statistically significant difference between all groups (P 〈 0.001). When compared with the control group (G1), the mean apoptotic cell count was fivefold that of G2 and 35- and 351-fold those of G3 and G4, respectively. Our study demonstrated that hyperoxaluria with complete ureteral obstruction induces an excessive level of apoptosis, which is responsible for renal damage, and that ureteral obstruction is a more important factor for apoptosis than hyperoxaluria. Considering these data, we also believe that research studies for medical preventive measures must be considered for patients with ureteral obstruction and/or hyperoxaluria.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002400000128
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    Neuronal nuclear DNA fragmentation in the aged canine brain: apoptosis or nuclear DNA fragility? (2000)
    Springer
    Acta neuropathologica 99 (2000), S. 402-408 
    Details
    ISSN: 1432-0533
    Keywords: Key words Ageing ; Dog brain ; Apoptosis ; DNA ¶fragmentation ; TUNEL method
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neuronal DNA fragmentation, as revealed with the method of in situ end-labeling of nuclear DNA fragmentation (TUNEL), has been reported in both the canine and human brains in normal ageing, and in some human age-related neurodegenerative diseases. These results have suggested that apoptosis plays an important role in age-related neuronal loss. It is not clear, however, whether the TUNEL method is highly specific for apoptosis, as DNA fragmentation also occurs in the late stages o necrosis. In this study we have examined 27 dogs aged from ¶8 to 18 years, to investigate the occurrence of nuclear DNA fragmentation. An autolysis index based on current histological criteria was assigned to each animal to evaluate the effects of autolysis on nuclear DNA integrity. Our results have shown that neuronal nuclear DNA fragmentation is frequent in aged dogs, although it is not accompanied by apoptotic morphology. Yet, a positive relation between TUNEL labelling and the degree of tissue autolysis was observed. In contrast, no TUNEL labelling was detected in young control dogs despite autolysis indices being similar to those in aged dogs. Taken together, these results suggest that neuronal nuclear DNA fragmentation is an age-related phenomenon, not due to apoptosis, whenever other factors render neuronal DNA more susceptible to autolytic fragmentation. We confirm the effect of autolysis in a subpopulation of neurons in the aged canine brain, inducing nuclear DNA fragmentation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051142
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    N-[4-(3-Ethoxy-2-hydropropoxy)phenyl] acrylamide selectively induces apoptosis of cerebellar granule cells in vivo and in vitro in rats (2000)
    Springer
    Acta neuropathologica 99 (2000), S. 337-344 
    Details
    ISSN: 1432-0533
    Keywords: Key words Cerebellar selective injury ; Acrylamide ; Granule cell degeneration ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Oral administration of N-[4-(3-ethoxy-2-hydropropoxy)phenyl] acrylamide (EHA) induced selective granule cell destruction in the granular layer of the cerebellar cortex together with neurological signs, such as delayed righting reflex, gait or truncal ataxia, and convulsion. Neuropathologically, it caused multifocal granule cell destruction with nuclear pyknosis and spongiosis of the neuropile in the granular layer. Other neurons, including Purkinje cells, were spared. Ultrastructurally, damaged granule cells showed aggregation of nuclear chromatin and cytoplasmic edema, but cytoplasmic organelles were preserved. The brain uptake index of 14C-labeled EHA was similar to that of H2O. When EHA was added to rat cerebellar tissue cultures, only the granule cells showed nuclear pyknosis, aggregation of nuclear chromatin, and karyorrhexis with cytoplasmic swelling. These granule cells were positive for DNA fragmentation by the TUNEL method. These results suggest that EHA permeates the blood vessel wall and directly affects the cerebellar granule cells, resulting in selective granule cell apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010051133
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    Apoptosis of perineurial cells in sensory perineuritis (2000)
    Springer
    Acta neuropathologica 99 (2000), S. 317-320 
    Details
    ISSN: 1432-0533
    Keywords: Key words Perineuritis ; Neuropathy ; Nerve biopsy ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 71-year-old man presented a 6-month history of progressive paresthesia of all four limbs. Sural nerve biopsy specimens showed dense mononuclear infiltrates in the perineurium and subperineurium, indicating sensory perineuritis. One section revealed disruption of the perineurial barrier. Perforin and granzyme B were present in the infiltrates, and apoptosis of perineurial cells was indicated by a terminal deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method. These findings suggest T cell-mediated apoptosis of the perineurium and nerve injury caused by perineurial damage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00007444
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    Soluble Fas levels in patients with systemic sclerosis (2000)
    Springer
    Archives of dermatological research 292 (2000), S. 522-523 
    Details
    ISSN: 1432-069X
    Keywords: Key words Serum soluble Fas ; Systemic sclerosis ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030000170
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    15-Hydroxyeicosatrienoic acid (15-HETrE) suppresses epidermal hyperproliferation via the modulation of nuclear transcription factor (AP-1) and apoptosis (2000)
    Springer
    Archives of dermatological research 292 (2000), S. 397-403 
    Details
    ISSN: 1432-069X
    Keywords: Key words Docosahexaenoic acid (DHA) ; 15-hydroxyeicosatrienoic acid (15-HETrE) ; AP-1 ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to ascertain whether the antiproliferative effect of 15-hydroxyeicosatrienoic acid (15-HETrE), a monohydroxy fatty acid generated from dihomo-Á-linolenic acid, in an experimentally induced guinea pig hyperproliferative model involves alterations in nuclear transcription factor (AP-1) and apoptosis. The topical application of docosahexaenoic acid (DHA) to normal guinea pig skin elicited a severe hyperplasia which was accompanied by the suppression of AP-1 expression in a time-dependent manner. Since apoptosis is pivotal in tissue turnover, the expression of two apoptotic proteins (Bcl-2 and caspase-3) after DHA and 15-HETrE treatment was explored. DHA-induced hyperproliferation enhanced the expression of Bcl-2 (an antiapoptotic protein) but inhibited the expression of caspase-3 (an apoptotic protein). 15-HETrE, on the other hand, reversed the DHA-induced epidermal hyperplasia, and upregulated epidermal AP-1 expression. These events paralleled the suppression of Bcl-2 and the elevation of caspase-3. Taken together, these results suggest that the antiproliferative effect of 15-HETrE may, at least in part, be via the modulation of AP-1 and apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030000139
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    Critical role of nitric oxide for proliferation and apoptosis of bone-marrow cells under septic conditions (2000)
    Springer
    Annals of hematology 79 (2000), S. 249-254 
    Details
    ISSN: 1432-0584
    Keywords: Nitric oxide ; Bone marrow ; Proliferation ; Apoptosis ; Sepsis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: α , interferon γ and interleukin-1β for 48 h. The basal proliferation rate of the cells remained unchanged, but granulocyte–macrophage colony stimulating factor-induced proliferation was suppressed and the percentage of apoptotic cells significantly raised. Levels of nitrite in the culture supernatants were inversely correlated with the suppression of proliferation, but directly correlated with apoptosis. The NO synthesis inhibitor N-methyl-arginine inhibited the suppression of proliferation as well as the induction of apoptosis and NO synthesis. Our results indicate that NO is a negative feedback regulator of cell turnover in sepsis, which limits growth-factor-induced proliferation and induces apoptosis of bone marrow cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770050588
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    Altered expression of insulin-like growth factor -1 and insulin like growth factor binding proteins-2 and 5 in the mouse mutant Hypodactyly (Hd) correlates with sites of apoptotic activity (2000)
    Springer
    Anatomy and embryology 202 (2000), S. 1-11 
    Details
    ISSN: 1432-0568
    Keywords: Key words Mouse ; Gene expression ; Insulin-like growth factor (IGF) ; IGF binding protein (IGFBP) ; Hypodactyly (Hd) ; Limb bud ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Insulin-like growth factor-I (IGF-I) mediated signalling has been implicated to be of significant importance during vertebrate embryonic development. IGF-I signalling has also been shown to be modulated by a number of IGF binding proteins that are thought to act as either agonists or antagonists of IGF activity. IGF-I has been implicated in a number of cellular processes, including cell division and programmed cell death (apoptosis). We have used the mouse mutant Hypodactyly (Hd) as a tool to determine the role of IGF-I and two key IGF binding proteins (IGFBP-2 and IGFBP-5) during embryonic development. The Hd mutant is a good model with which to study developmental cascades, since it has a distinct phenotype in the limb where cellular and molecular circuits have been thoroughly investigated. The distinctive pointed limb buds observed in Hd mutant embryos have been shown to be the result of a massive increase in apoptosis. We show that all three genes, IGF-1, IGFBP-2 and IGFBP-5, display restricted expression patterns during limb development. Indeed, IGFBP-5 shows a remarkable similarity to the expression of Engrailed-1, which is the vertebrate homologue of the Drosophila selector gene Engrailed. We show that there is downregulation in the expression of IGFBP-2 in the entire apical ectodermal ridge (AER) in homozygous Hd/Hd limb buds, whereas IGFBP-5 is downregulated in specific regions in the mutant AER. IGF-I expression is downregulated in Hd limb buds in regions undergoing high levels of cell death, consistent with its proposed role as an anti-apoptotic factor, while IGFBP-5 is found at higher levels in regions of cell death, consistent with reports of its association with apoptosis in adult tissues. We propose that these three components of the IGF axis could be involved in the manifestation of the mutant phenotype in Hypodactyly, and that this is probably a result of their ability to regulate cell survival and cell death.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00008239
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    Overexpression of HSP70 prevents ultraviolet B-induced apoptosis of a human melanoma cell line (2000)
    Springer
    Archives of dermatological research 292 (2000), S. 482-487 
    Details
    ISSN: 1432-069X
    Keywords: Keywords HSP70 ; Human melanoma cells ; Ultraviolet B ; Apoptosis ; Caspase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The heat shock response is a highly conserved reaction common to all cells and organisms. It has been reported that hyperthermic treatment can induce the expression of the heat shock protein (HSP) and can protect cells from ultraviolet (UV) B radiation. In this study, we evaluated the effects of induced HSP70 on resistance to UV radiation. G361 amelanotic human melanoma cells were irradiated with increasing doses of UVB. UVB irradiation caused apoptotic cell death in these cells. Following transfection with MFG.hsp70.puro plasmid, the expression of HSP70 was determined. Compared to control vector-transfected cells, hsp70-transfected cells showed significantly elevated levels of HSP70 and were highly resistant to UVB irradiation. In order to investigate the effects of HSP70 on the apoptotic pathway, the changes in caspase-3 and PARP were analyzed. Following UVB irradiation, activation of caspase-3 and cleavage of PARP were observed in control vector-transfected cells, and the changes in these molecules were inhibited in the hsp70-transfected cells. These results suggest that UVB-induced apoptosis of melanoma cells is accompanied by caspase-3 activation and PARP cleavage, which can be prevented by an overexpression of HSP70.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030000173
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    Expression of IFNγ, coexpression of TNFα and matrix metalloproteinases and apoptosis of T lymphocytes and macrophages in granuloma annulare (2000)
    Springer
    Archives of dermatological research 292 (2000), S. 384-390 
    Details
    ISSN: 1432-069X
    Keywords: Key words Granuloma annulare ; Cytokine ; Apoptosis ; Lymphocytes ; Macrophages
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Granuloma annulare, a prototype noninfectious granulomatous dermatitis, is morphologically characterized by a necrobiotic core surrounded by a cellular infiltrate. Because of many morphological similarities to tuberculosis, granuloma annulare has been suggested to represent a delayed-type hypersensitivity (Th1) reaction in the course of which inflammatory cells elicit matrix degradation. In the present study we (1) investigated the expression of interferon-Á as the most important Th1-associated cytokine, (2) sought in situ evidence for the coexpression of the proinflammatory cytokine tumor necrosis factor-· and cytokine-regulated matrix metalloproteinases 2 (gelatinase A) and 9 (gelatinase B), and (3) sought to determine whether shrunken cells seen within necrobiotic areas of granuloma annulare are apoptotic cells. In situ hybridization combined with immunofluorescence showed that large numbers of infiltrating CD3+ lymphocytes express interferon-Á. Application of catalyzed signal amplification in immunodetection revealed that the vast majority of CD3+ lymphocytes and CD68+ macrophages contained tumor necrosis factor-·. Immunohistochemistry demonstrated that macrophages producing tumor necrosis factor-· coexpress matrix metalloproteinases 2 and 9. In situ end-labeling combined with immunofluorescence detected few apoptotic T cells in perivascular regions and numerous apoptotic macrophages within necrobiotic areas. These results suggest that in granuloma annulare interferon-Á+ Th-1 lymphocytes may cause a delayed-type hypersensitivity reaction whereby macrophages are differentiated to aggressive effector cells expressing tumor necrosis factor-α and matrix metalloproteinases. In parallel, activation-induced apoptosis in lymphocytes and macrophages may serve to restrict the destructive potential of the inflammatory cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030000150
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    Bcl-2 transfected HaCaT keratinocytes resist apoptotic signals of ceramides, tumor necrosis factor α and 1α,25-dihydroxyvitamin D3 (2000)
    Springer
    Archives of dermatological research 292 (2000), S. 455-462 
    Details
    ISSN: 1432-069X
    Keywords: Key words Ceramide ; 1α,25-Dihydroxyvitamin D3 ; TNFα ; Apoptosis ; Bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract During the last few years increasing evidence has shown that sphingolipid metabolites are highly bioactive compounds that play important roles in cellular regulation. The induction of ceramide signalling in primary human keratinocytes and HaCaT keratinocytes has recently been demonstrated using 1·,25-dihydroxyvitamin D3. The data obtained indicate that approximately one-third of the proapoptotic effect of 1·,25-dihydroxyvitamin D3 is mediated by an intracellular ceramide increase induced via tumor necrosis factor · expression and autocrine stimulation of sphingomyelin hydrolysis. In the present study the role of bcl-2 in this process was investigated. HaCaT keratinocytes were transfected with bcl-2 and the effects of C2-ceramide, tumor necrosis factor · and 1·,25-dihydroxyvitamin D3 on HaCaT keratinocytes stably overexpressing bcl-2 were determined. Apoptosis was measured by detection of soluble DNA-histone complexes using the ELISA technique. In situ analysis of apoptotic cells was also carried out by detecting phosphatidylserine flip using the annexin V method and by detecting DNA fragmentation using the TUNEL assay. The results obtained showed that apoptosis induced by C2-ceramide, tumor necrosis factor · or 1·,25-dihydroxyvitamin D3 occurred in a vector-transfected clone but not in a bcl-2-transfected HaCaT clone. This indicates the important role of bcl-2 in the regulation of ceramide-mediated signalling pathways in human keratinocytes and supports the involvement of ceramide as a signalling molecule in 1α,25-dihydroxyvitamin D3-induced biological responses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030000158
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  • 94
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    Electronic Resource
    Overexpression of bcl-2 in transient abnormal myelopoiesis associated with Down syndrome (2000)
    Springer
    Annals of hematology 79 (2000), S. 319-321 
    Details
    ISSN: 1432-0584
    Keywords: Key words Down syndrome ; Transient abnormal myelopoiesis ; Apoptosis ; bcl-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Transient abnormal myelopoiesis (TAM) is a haematological complication found in Down syndrome. To determine the mechanisms of sustained proliferation of TAM cells, we studied the expression of apoptosis-related proteins, such as bcl-2, Fas (APO-1/CD95) and p-53, in peripheral blood cells from a new-born infant with Down syndrome and TAM. Using flow cytometry, peripheral blood mononuclear cells (PBMCs), consisting mostly of blast cells, showed marked expression of bcl-2 protein but not of Fas or p-53 products. DNA gel electrophoresis of PBMCs, cultured in the absence of serum factors, revealed no marked fragmentation. Our findings suggest that bcl-2 overexpression may be associated with prolonged cell survival of TAM cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002779900138
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  • 95
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    Electronic Resource
    Induction of apoptosis using 2′,2′difluorodeoxycytidine (gemcitabine) in combination with antimetabolites or anthracyclines on malignant lymphatic and myeloid cells. Antagonism or synergism depends on incubation schedule and origin of neoplastic cells (2000)
    Springer
    Annals of hematology 79 (2000), S. 485-492 
    Details
    ISSN: 1432-0584
    Keywords: Key words Gemcitabine ; Apoptosis ; Chronic lymphocytic leukemia ; Acute myeloid leukemia ; Cell lines ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Induction of apoptosis in vitro using gemcitabine (dFdC) in combination with cladribine (2-CdA) and other cytotoxic drugs on malignant mononuclear cells (MNCs) of patients with acute myeloid leukemia (AML, n=20) and chronic lymphocytic leukemia (CLL, n=20) in myeloid (HL60, HEL) and lymphatic cell lines (HUT78, JURKAT) was investigated using different incubation conditions (simultaneous and consecutive). Furthermore, the influence of dFdC on the level of intracellular metabolites of 2-CdA was studied using high-performance liquid chromatography (HPLC). Apoptosis was evaluated using flow cytometry with 7-aminoactinomycin D. In MNCs of patients with CLL, dFdC+2-CdA showed an antagonistic effect when applied simultaneously. This antagonism was reduced by consecutive application. The combination of dFdC with doxorubicin was synergistic, independent of incubation schedule. In blasts from newly diagnosed patients with de novo AML, all drug combinations (dFdC+2-CdA, doxorubicin, or cytosine arabinoside) were antagonistic by simultaneous incubation. Reduced antagonism or even synergism was shown (P〈0.001) by consecutive incubation. The simultaneous combination of dFdC with 2-CdA in all tested cell lines resulted in a competitive inhibition on the rate of apoptosis. By changing the incubation period to a consecutive schedule, the antagonism was diminished or synergism of apoptosis was measured (P〈0.001). Using similar incubation conditions, these experiments were supported by HPLC measurement of intracellular metabolites of 2-CdA influenced by dFdC application. In conclusion, we demonstrated that the efficacy of dFdC in vitro in combination with other cytotoxic drugs depends on the incubation condition and on the origin of neoplastic cells (lymphatic vs myeloid). The data suggest that simultaneous combination therapy with purine and pyrimidine analogues may not improve the clinical efficacy of one or the other drug administered alone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770000181
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  • 96
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    Electronic Resource
    Identification of okadaic-acid-induced genes by mRNA differential display in glioma cells (2000)
    Springer
    Journal of biomedical science 7 (2000), S. 152-159 
    Details
    ISSN: 1423-0127
    Keywords: Apoptosis ; Differential display ; Glioma ; Okadaic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract To identify novel genes associated with apoptosis in glioma cells, we treated T98G glioma cells with okadaic acid (OA). Differential display using 15 random primers was performed on RNA extracted from these cells. Upregulated bands were excised from polyacrylamide gels and cloned. Northern blots were used to confirm RNA expression in T98G cells. 18 RNA fragments corresponding to the untranslated region of genes were identified and sequenced. Three unknown gene fragments were used to screen a fetal brain cDNA library resulting in three complete cDNA sequences. The three sequences corresponded to a human gene homologous to the yeast translation initiation factor Sui-1, a cAMP-regulated phosphoprotein, ARPP-16/19, and a novel gene designated O48. Transcription of Sui-1 increased in response to all stress factors tested, whereas ARPP only responded to OA. 2-kb and 4-kb O48 RNA species were identified. OA and stress factors increased 2-kb expression while K252a (protein kinase inhibitor) increased 4-kb expression. Differential display is effective for identifying genes associated with apoptosis. Novel genes may be identified by further analysis of the gene fragments identified in this study. The function of O48 is unknown.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02256622
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  • 97
    Electronic Resource
    Electronic Resource
    Delta opioid peptide [D-Ala2,D-Leu5]enkephalin promotes cell survival (2000)
    Springer
    Journal of biomedical science 7 (2000), S. 195-199 
    Details
    ISSN: 1423-0127
    Keywords: Opioid ; Enkephalin ; DADLE ; Transplantation ; Hibernation ; Apoptosis ; Methamphetamine ; Dopamine ; Ischemia ; Reperfusion ; PC12 cells ; Neuroprotection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract By studying the hibernation in ground squirrels, a protein factor termed hibernation induction trigger (HIT) was found to induce hibernation in summer-active ground squirrels. Further purification of HIT yielded an 88-kD peptide that is enriched in winter hibernator. Partial sequence of the 88-kD protein indicates that it may be related to the inhibitor of metalloproteinase. Delta opioid [D-Ala2,D-Leu5]enkephalin (DADLE) also induced hibernation. HIT and DADLE were found to prolong survival of peripheral organs preserved en bloc or as a single preparation. These organs include the lung, the heart, liver and kidney. DADLE also promotes survival of neurons in the central nervous system. Methamphetamine (METH) is known to cause destruction of dopaminergic (DA) terminals in the brain. DADLE blocked and reversed the DA terminal damage induced by METH. DADLE acted against this effect of METH at least in part by attenuating the mRNA expressions of a tumor necrosis factor p53 and an immediate early gene c-fos. DADLE also blocked the neuronal damage induced by ischemia-reperfusion following a transient middle cerebral artery occlusion. In PC12 cells, DADLE blocked the cell death caused by serum deprivation in a naltrexone-sensitive manner. Thus, DADLE, and by extension the endogenous delta opioid peptides and delta opioid receptors, may play an important role in organ and neuronal survival. Here, critical developments concerning these fascinating cell protective properties of DADLE are reviewed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02255466
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  • 98
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    Electronic Resource
    Differential apoptosis effects of primate lentiviral Vpr and Vpx in mammalian cells (2000)
    Springer
    Journal of biomedical science 7 (2000), S. 322-333 
    Details
    ISSN: 1423-0127
    Keywords: Apoptosis ; HIV ; SIV ; Vpr ; Vpx ; Bcl-2 ; Bax
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The growth inhibitory effects of Vpr and Vpx are species-and cell type-dependent. HIV-1, HIV-2 and SIV Vpr are primarily cytostatic in mammalian cells and HIV-1 Vpr has been reported to induce apoptosis in human cells. Our previous studies have shown that HIV-1, HIV-2 and SIV Vpr and Vpx have differential cytostatic and cytotoxic effects in the yeast cells [Zhang et al.: Virology, 230:103–112; 1997]. Here, we further examined the apoptosis function of HIV-1 Vpr in different species of mammalian cells and investigated if other primate lentiviral Vpr and Vpx exert similar functions. Our results show that none of the primate lentiviral Vpr or Vpx we tested induces apoptosis in nonhuman species of mammalian cells. However, HIV-1 Vpr, but not HIV-2 or SIV Vpr and/or Vpx, induced apoptosis in different types of human cell lines. Further, the apoptotic effect of HIV-1 Vpr can be distinguished from that of the human interferon-γ, a known proapoptotic protein, that HIV-1 Vpr shows little to no paracrine and/or bystander effect. When coexpressed with Bcl-2 or Bcl-XL, the apoptotic effect of HIV-1 Vpr became markedly attenuated. These results indicate that the apoptotic effect of HIV-1 Vpr is species-dependent and is intracellularly modulated by the Bcl-2 family of proteins. Our study also suggests that the proapoptotic function of HIV-1 Vpr is developmentally associated with human but not nonhuman primate species.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02253252
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  • 99
    Electronic Resource
    Electronic Resource
    The consequences of the mutual recognition of measurement standards for international metrology (2000)
    Springer
    Accreditation and quality assurance 5 (2000), S. 409-413 
    Details
    ISSN: 1432-0517
    Keywords: Key words Metrology ; Comparisons ; Chemistry ; Standards
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract  After stressing the importance in the modern world of accurate and reproducible measurements, the actions taken by the Bureau International des Poids et Mesures to set up, together with the regional metrology organizations, a series of key comparisons are described. They are the technical foundation of a mutual recognition of national measurement standards arrangement prepared in conjunction with the National Metrology Institutes (NMIs). This arrangement also includes the recognition of calibration and measurement certificates issued by these institutes. Then, the consequences of this arrangement for trade are described. The case of chemical analysis is illustrated by the application of the Kyoto protocol on the reduction of greenhouse gases. But the global workload to be taken up by the International Committee of Weights and Measures, its Consultative Committee for Amount of Substance and the NMIs is huge.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007690000228
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  • 100
    Electronic Resource
    Electronic Resource
    Corneal infection of herpes simplex virus type 2 – induced neuronal apoptosis in the brain stem of mice with expression of tumor suppressor gene (p53) and transcription factors (2000)
    Springer
    Acta neuropathologica 100 (2000), S. 647-653 
    Details
    ISSN: 1432-0533
    Keywords: Key words HSV ; Immunohistochemistry ; Apoptosis ; p53 ; Transcription factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To understand the mechanism of neuronal apoptosis induced by herpes simplex virus (HSV) infection in vivo, the distribution of viral antigen, the appearance of apoptotic bodies, and the expressions of the tumor suppressor gene p53 and several transcription factors such as c-fos, c-jun and NF-κB were examined immunohistochemically and histopathologically after corneal infection of mice with HSV type 2 strain 186. Five days after HSV infection, viral antigen was diffusely detected in the corneal epithelium, the trigeminal ganglion and the pars caudalis of the spinal trigeminal nucleus. Neuronal apoptosis was observed in the brain stem ipsilateral to the HSV-infected side with the immunoreactivities of c-fos, c-jun, NF-κB and p53. Dual-labeling immunohistochemical studies revealed that almost all of the viral antigen-positive neurons and glia in the brain stem also showed p53 immunoreactivity. On the other hand, no neuronal apoptosis but only with the expression of c-jun was found in the trigeminal ganglion. Our results suggest that the different expression of transcription factors between the brain stem and the trigeminal ganglion may influence the neuronal apoptosis induced by HSV infection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004010000240
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