TY - JOUR
AB - Wingless (ergatoid) males of the tramp ant Cardiocondyla minutior attack and kill their young ergatoid rivals and thus attempt to monopolize mating with female sexuals reared in the colony. Because of the different strength of local mate competition in colonies with one or several reproductive queens, we expected the production of new ergatoid males to vary with queen number. Sex ratios were mostly female-biased, but in contrast to the sympatric species C. obscurior (Cremer and Heinze, 2002) neither the percentage of ergatoid males nor of female sexuals among the first 20 sexuals produced varied considerably with queen number. As in C. obscurior, experimental colony fragmentation led to the production of winged males, whereas in unfragmented control colonies only ergatoid males eclosed.
AU - Heinze, Jürgen
AU - Böttcher, A.
AU - Cremer, Sylvia
ID - 3918
IS - 3
JF - Insectes Sociaux
TI - Production of winged and wingless males in the ant, Cardiocondyla minutior
VL - 51
ER -
TY - JOUR
AB - The Nef protein of human and simian immunodeficiency virus (HIV/SIV) is believed to interfere with T cell activation signals by forming a signaling complex at the plasma membrane. Composition and function of the complex are not fully understood. Here we report that Nef recruits the Polycomb Group (PcG) protein Eed, so far known as a nuclear factor and repressor of transcription, to the membrane of cells. The Nef-induced translocation of Eed led to a potent stimulation of Tat-dependent HIV transcription, implying that Eed removal from the nucleus is required for optimal Tat function. Similar to Nef action, activation of integrin receptors recruited Eed to the plasma membrane, also leading to enhanced Tat/Nef-mediated transcription. Our results suggest a link between membrane-associated activation processes and transcriptional derepression and demonstrate how HIV exploits this mechanism.
AU - Witte, Vanessa
AU - Laffert, Bernd
AU - Rosorius, Olaf
AU - Lischka, Peter
AU - Blume, Katja
AU - Galler, Gunther
AU - Stilper, Andrea
AU - Willbold, Dieter
AU - D'Aloja, Paola
AU - Michael Sixt
AU - Kolanus, Johanna
AU - Ott, Melanie
AU - Kolanus, Waldemar
AU - Schuler, Gerold
AU - Baur, Andreas S
ID - 3929
IS - 2
JF - Molecular Cell
TI - HIV-1 Nef mimics an integrin receptor signal that recruits the polycomb group protein Eed to the plasma membrane
VL - 13
ER -
TY - JOUR
AB - Hyaluronan is an unsulfated glycosaminoglycan (GAG) that is ubiquitously expressed in the extracellular matrix (ECM) of all vertebrates, where hyaluronan rich matrices constitute a particular permissive environment for the development of complex biological structures and also for tumor progression. Because of its conserved structure and ubiquitous expression, antibodies for its histochemical detection cannot be produced. We have engineered a fusion protein, neurocan-GFP, and expressed it as a secreted molecule in mammalian cells. Neurocan-GFP fusion protein specifically binds to hyaluronan and directly visualizes hyaluronan on tissue sections, revealing a very detailed picture of hyaluronan distribution. The fluorescent fusion protein can be used in combination with antibodies and nuclear markers for double or triple staining. In addition, it is suitable to visualize hyaluronan on living cells by time-lapse video microscopy. The successful production and application of the neurocan-GFP fusion protein opens up new perspectives for using GFP fusion proteins as detection tools in histological and cytological studies complementing conventional antibody and biotin/avidin techniques.
AU - Zhang, Hui
AU - Baader, Stephan L
AU - Michael Sixt
AU - Kappler, Joachim
AU - Rauch, Uwe
ID - 3931
IS - 7
JF - Journal of Histochemistry and Cytochemistry
TI - Neurocan-GFP fusion protein: a new approach to detect hyaluronan on tissue sections and living cells
VL - 52
ER -
TY - JOUR
AB - We combine topological and geometric methods to construct a multiresolution representation for a function over a two-dimensional domain. In a preprocessing stage, we create the Morse-Smale complex of the function and progressively simplify its topology by cancelling pairs of critical points. Based on a simple notion of dependency among these cancellations, we construct a hierarchical data structure supporting traversal and reconstruction operations similarly to traditional geometry-based representations. We use this data structure to extract topologically valid approximations that satisfy error bounds provided at runtime.
AU - Bremer, Peer-Timo
AU - Herbert Edelsbrunner
AU - Hamann, Bernd
AU - Pascucci, Valerio
ID - 3984
IS - 4
JF - IEEE Transactions on Visualization and Computer Graphics
TI - A topological hierarchy for functions on triangulated surfaces
VL - 10
ER -
TY - JOUR
AB - Given a Morse function f over a 2-manifold with or without boundary, the Reeb graph is obtained by contracting the connected components of the level sets to points. We prove tight upper and lower bounds on the number of loops in the Reeb graph that depend on the genus, the number of boundary components, and whether or not the 2-manifold is orientable. We also give an algorithm that constructs the Reeb graph in time O(n log n), where n is the number of edges in the triangulation used to represent the 2-manifold and the Morse function.
AU - Cole-McLaughlin, Kree
AU - Herbert Edelsbrunner
AU - Harer, John
AU - Natarajan, Vijay
AU - Pascucci, Valerio
ID - 3985
IS - 2
JF - Discrete & Computational Geometry
TI - Loops in Reeb graphs of 2-manifolds
VL - 32
ER -
TY - JOUR
AB - The motion of a biomolecule greatly depends on the engulfing solution, which is mostly water. Instead of representing individual water molecules, it is desirable to develop implicit solvent models that nevertheless accurately represent the contribution of the solvent interaction to the motion. In such models, hydrophobicity is expressed as a weighted sum of atomic surface areas. The derivatives of these weighted areas contribute to the force that drives the motion. In this paper we give formulas for the weighted and unweighted area derivatives of a molecule modeled as a space-filling diagram made up of balls in motion. Other than the radii and the centers of the balls, the formulas are given in terms of the sizes of circular arcs of the boundary and edges of the power diagram. We also give inclusion-exclusion formulas for these sizes.
AU - Bryant, Robert
AU - Herbert Edelsbrunner
AU - Koehl, Patrice
AU - Levitt, Michael
ID - 3986
IS - 3
JF - Discrete & Computational Geometry
TI - The area derivative of a space-filling diagram
VL - 32
ER -
TY - JOUR
AB - We consider scientific data sets that describe density functions over three-dimensional geometric domains. Such data sets are often large and coarsened representations are needed for visualization and analysis. Assuming a tetrahedral mesh representation, we construct such representations with a simplification algorithm that combines three goals: the approximation of the function, the preservation of the mesh topology, and the improvement of the mesh quality. The third goal is achieved with a novel extension of the well-known quadric error metric. We perform a number of computational experiments to understand the effect of mesh quality improvement on the density map approximation. In addition, we study the effect of geometric simplification on the topological features of the function by monitoring its critical points.
AU - Natarajan, Vijay
AU - Herbert Edelsbrunner
ID - 3987
IS - 5
JF - IEEE Transactions on Visualization and Computer Graphics
TI - Simplification of three-dimensional density maps
VL - 10
ER -
TY - CONF
AB - We give an algorithm that locally improves the fit between two proteins modeled as space-filling diagrams. The algorithm defines the fit in purely geometric terms and improves by applying a rigid motion to one of the two proteins. Our implementation of the algorithm takes between three and ten seconds and converges with high likelihood to the correct docked configuration, provided it starts at a position away from the correct one by at most 18 degrees of rotation and at most 3.0Angstrom of translation. The speed and convergence radius make this an attractive algorithm to use in combination with a coarse sampling of the six-dimensional space of rigid motions.
AU - Choi, Vicky
AU - Agarwal, Pankaj K
AU - Herbert Edelsbrunner
AU - Rudolph, Johannes
ID - 3988
TI - Local search heuristic for rigid protein docking
VL - 3240
ER -
TY - CONF
AB - We introduce local and global comparison measures for a collection of k less than or equal to d real-valued smooth functions on a common d-dimensional Riemannian manifold. For k = d = 2 we relate the measures to the set of critical points of one function restricted to the level sets of the other. The definition of the measures extends to piecewise linear functions for which they ace easy to compute. The computation of the measures forms the centerpiece of a software tool which we use to study scientific datasets.
AU - Herbert Edelsbrunner
AU - Harer, John
AU - Natarajan, Vijay
AU - Pascucci, Valerio
ID - 3989
TI - Local and global comparison of continuous functions
ER -
TY - JOUR
AB - The writhing number measures the global geometry of a closed space curve or knot. We show that this measure is related to the average winding number of its Gauss map. Using this relationship, we give an algorithm for computing the writhing number for a polygonal knot with n edges in time roughly proportional to n(1.6). We also implement a different, simple algorithm and provide experimental evidence for its practical efficiency.
AU - Agarwal, Pankaj K
AU - Herbert Edelsbrunner
AU - Wang, Yusu
ID - 3990
IS - 1
JF - Discrete & Computational Geometry
TI - Computing the writhing number of a polygonal knot
VL - 32
ER -
TY - JOUR
AB - During vertebrate gastrulation, a relatively limited number of blastodermal cells undergoes a stereotypical set of cellular movements that leads to formation of the three germ layers: ectoderm, mesoderm and endoderm. Gastrulation, therefore, provides a unique developmental system in which to study cell movements in vivo in a fairly simple cellular context. Recent advances have been made in elucidating the cellular and molecular mechanisms that underlie cell movements during zebrafish gastrulation. These findings can be compared with observations made in other model systems to identify potential general mechanisms of cell migration during development.
AU - Montero, Juan
AU - Heisenberg, Carl-Philipp J
ID - 4172
IS - 11
JF - Trends in Cell Biology
TI - Gastrulation dynamics: cells move into focus
VL - 14
ER -
TY - JOUR
AB - Developing cells acquire positional information by reading the graded distribution of morphogens. In Drosophila, the Dpp morphogen forms a long-range concentration gradient by spreading from a restricted source in the developing wing. It has been assumed that Dpp spreads by extracellular diffusion. Under this assumption, the main role of endocytosis in gradient formation is to downregulate receptors at the cell surface. These surface receptors bind to the ligand and thereby interfere with its long-range movement. Recent experiments indicate that Dpp spreading is mediated by Dynamin-dependent endocytosis in the target tissue, suggesting that extracellular diffusion alone cannot account for Dpp dispersal. Here, we perform a theoretical study of a model for morphogen spreading based on extracellular diffusion, which takes into account receptor binding and trafficking. We compare profiles of ligand and surface receptors obtained in this model with experimental data. To this end, we monitored directly the pool of surface receptors and extracellular Dpp with specific antibodies. We conclude that current models considering pure extracellular diffusion cannot explain the observed role of endocytosis during Dpp long-range movement.
AU - Kruse, Karsten
AU - Pantazis, Periklis
AU - Bollenbach, Mark Tobias
AU - Julicher, Frank
AU - Gonzalez Gaitan, Marcos
ID - 4224
IS - 19
JF - Development
TI - Dpp gradient formation by dynamin-dependent endocytosis: receptor trafficking and the diffusion model
VL - 131
ER -
TY - CHAP
AU - Harold Vladar
AU - Cipriani, Roberto
AU - Scharifker, Benjamin
AU - Bubis, Jose
ED - Hanslmeier,A.
ED - Kempe,S.
ED - Seckbach,J.
ID - 4230
T2 - Life in the Universe From the Miller Experiment to the Search for Life on Other Worlds
TI - A mechanism for the prebiotic emergence of proteins
ER -
TY - THES
AU - de Vladar, Harold
ID - 4236
TI - Métodos no lineales y sus aplicaciones en dinámicas aleatorias de poblaciones celulares
ER -
TY - JOUR
AB - The dynamical basis of tumoral growth has been controversial. Many models have been proposed to explain cancer development. The descriptions employ exponential, potential, logistic or Gompertzian growth laws. Some of these models are concerned with the interaction between cancer and the immunological, system. Among other properties, these models are concerned with the microscopic behavior of tumors and the emergence of cancer. We propose a modification of a previous model by Stepanova, which describes the specific immunological response against cancer. The modification consists of the substitution of a Gompertian law for the exponential rate used for tumoral growth. This modification is motivated by the numerous works confirming that Gompertz's equation correctly describes solid tumor growth. The modified model predicts that near zero, tumors always tend to grow. Immunological contraposition never suffices to induce a complete regression of the tumor. Instead, a stable microscopic equilibrium between cancer and immunological activity can be attained. In other words, our model predicts that the theory of immune surveillance is plausible. A macroscopic equilibrium in which the system develops cancer is also possible. In this case, immunological activity is depleted. This is consistent with the phenomena of cancer tolerance. Both equilibrium points can coexist or can exist without the other. In all cases the fixed point at zero tumor size is unstable. Since immunity cannot induce a complete tumor regression, a therapy is required. We include constant-dose therapies and show that they are insufficient. Final levels of immunocompetent cells and tumoral cells are finite, thus post-treatment regrowth of the tumor is certain. We also evaluate late-intensification therapies which are successful. They induce an asymptotic regression to zero tumor size. Immune response is also suppressed by the therapy, and thus plays a negligible role in the remission. We conclude that treatment evaluation should be successful without taking into account immunological effects. (C) 2003 Elsevier Ltd. All rights reserved.
AU - de Vladar, Harold
AU - González, J.
ID - 4238
IS - 3
JF - Journal of Theoretical Biology
TI - Dynamic response of cancer under the influence of immunological activity and therapy
VL - 227
ER -
TY - CHAP
AU - Harold Vladar
AU - Cipriani, Roberto
AU - Scharifker, Benjamin
AU - Bubis, Jose
ED - Seckbach,J.
ED - Chela-Flores,J.
ED - Owen,T.
ED - Raulin,F.
ID - 4239
T2 - Life in the Universe From the Miller Experiment to the Search for Life on Other Worlds
TI - A Mechanism for the Prebiotic Emergence of Proteins
VL - 7
ER -
TY - JOUR
AB - We consider a single genetic locus which carries two alleles, labelled P and Q. This locus experiences selection and mutation. It is linked to a second neutral locus with recombination rate r. If r = 0, this reduces to the study of a single selected locus. Assuming a Moran model for the population dynamics, we pass to a diffusion approximation and, assuming that the allele frequencies at the selected locus have reached stationarity, establish the joint generating function for the genealogy of a sample from the population and the frequency of the P allele. In essence this is the joint generating function for a coalescent and the random background in which it evolves. We use this to characterize, for the diffusion approximation, the probability of identity in state at the neutral locus of a sample of two individuals (whose type at the selected locus is known) as solutions to a system of ordinary differential equations. The only subtlety is to find the boundary conditions for this system. Finally, numerical examples are presented that illustrate the accuracy and predictions of the diffusion approximation. In particular, a comparison is made between this approach and one in which the frequencies at the selected locus are estimated by their value in the absence of fluctuations and a classical structured coalescent model is used.
AU - Nicholas Barton
AU - Etheridge, Alison M
AU - Sturm, Anja K
ID - 4253
IS - 2
JF - Annals of Applied Probability
TI - Coalescence in a Random Background
VL - 14
ER -
TY - CONF
AU - Maler, Oded
AU - Dejan Nickovic
ID - 4372
TI - Monitoring Temporal Properties of Continuous Signals
ER -
TY - THES
AB - The enormous cost and ubiquity of software errors necessitates the need for techniques and tools that can precisely analyze large systems and prove that they meet given specifications, or if they don't, return counterexample behaviors showing how the system fails. Recent advances in model checking, decision procedures, program analysis and type systems, and a shift of focus to partial specifications common to several systems (e.g., memory safety and race freedom) have resulted in several practical verification methods. However, these methods are either precise or they are scalable, depending on whether they track the values of variables or only a fixed small set of dataflow facts (e.g., types), and are usually insufficient for precisely verifying large programs.
We describe a new technique called Lazy Abstraction (LA) which achieves both precision and scalability by localizing the use of precise information. LA automatically builds, explores and refines a single abstract model of the program in a way that different parts of the model exhibit different degrees of precision, namely just enough to verify the desired property. The algorithm automatically mines the information required by partitioning mechanical proofs of unsatisfiability of spurious counterexamples into Craig Interpolants. For multithreaded systems, we give a new technique based on analyzing the behavior of a single thread executing in a context which is an abstraction of the other (arbitrarily many) threads. We define novel context models and show how to automatically infer them and analyze the full system (thread + context) using LA.
LA is implemented in BLAST. We have run BLAST on Windows and Linux Device Drivers to verify API conformance properties, and have used it to find (or guarantee the absence of) data races in multithreaded Networked Embedded Systems (NESC) applications. BLAST is able to prove the absence of races in several cases where earlier methods, which depend on lock-based synchronization, fail.
AU - Jhala, Ranjit
ID - 4424
TI - Program verification by lazy abstraction
ER -
TY - CONF
AB - We present a type system for E code, which is an assembly language that manages the release, interaction, and termination of real-time tasks. E code specifies a deadline for each task, and the type system ensures that the deadlines are path-insensitive. We show that typed E programs allow, for given worst-case execution times of tasks, a simple schedulability analysis. Moreover, the real-time programming language Giotto can be compiled into typed E~code. This shows that typed E~code identifies an easily schedulable yet expressive class of real-time programs. We have extended the Giotto compiler to generate typed E code, and enabled the run-time system for E code to perform a type and schedulability check before executing the code.
AU - Thomas Henzinger
AU - Kirsch, Christoph M
ID - 4445
TI - A typed assembly language for real-time programs
ER -