TY - JOUR
AB - Tripartite G-protein-coupled receptors (GPCRs) represent one of the largest groups of signal transducers, transmitting signals from hormones, neuropeptides, odorants, food and light. Ligand-bound receptors catalyse GDP/GTP exchange on the G-protein α-subunit (Gα), leading to α-GTP separation from the βγ subunits and pathway activation. Activating mutations in the receptors or G proteins underlie many human diseases, including some cancers, dwarfism and premature puberty. Regulators of G-protein signalling (RGS proteins) are known to modulate the level and duration of ligand-induced signalling by accelerating the intrinsic GTPase activity of the Gα subunit, and thus reformation of the inactive GDP-bound Gα. Here we find that even in the absence of receptor, mutation of the RGS family member Sst2 (refs 6-9) permits spontaneous activation of the G-protein-coupled mating pathway in Saccharomyces cerevisiae at levels normally seen only in the presence of ligand. Our work demonstrates the occurence of spontaneous tripartite G-protein signalling in vivo and identifies a requirement for RGS proteins in preventing such receptor-independent activation.
AU - Daria Siekhaus
AU - Drubin, David G
ID - 3150
IS - 3
JF - Nature Cell Biology
TI - Spontaneous receptor-independent heterotrimeric G-protein signalling in an RGS mutant
VL - 5
ER -
TY - JOUR
AB - Biosynthesis of most peptide hormones and neuropeptides requires proteolytic excision of the active peptide from inactive proprotein precursors, an activity carried out by subtilisin-like proprotein convertases (SPCs) in constitutive or regulated secretory pathways. The Drosophila amontillado (amon) gene encodes a homolog of the mammalian PC2 protein, an SPC that functions in the regulated secretory pathway in neuroendocrine tissues. We have identified amon mutants by isolating ethylmethanesulfonate (EMS)-induced lethal and visible mutations that define two complementation groups in the amon interval at 97D1 of the third chromosome. DNA sequencing identified the amon complementation group and the DNA sequence change for each of the nine amon alleles isolated. amon mutants display partial embryonic lethality, are defective in larval growth, and arrest during the first to second instar larval molt. Mutant larvae can be rescued by heat-shock-induced expression of the amon protein. Rescued larvae arrest at the subsequent larval molt, suggesting that amon is also required for the second to third instar larval molt. Our data indicate that the amon proprotein convertase is required during embryogenesis and larval development in Drosophila and support the hypothesis that AMON acts to proteolytically process peptide hormones that regulate hatching, larval growth, and larval ecdysis.
AU - Rayburn, Lowell Y
AU - Gooding, Holly C
AU - Choksi, Semil P
AU - Maloney, Dhea
AU - Kidd, Ambrose R
AU - Daria Siekhaus
AU - Bender, Michael
ID - 3151
IS - 1
JF - Genetics
TI - Amontillado, the Drosophila homolog of the prohormone processing protease PC2, is required during embryogenesis and early larval development
VL - 163
ER -
TY - JOUR
AB - For any number field k, upper bounds are established for the number of k-rational points of bounded height on non-singular del Pezzo surfaces defined over k, which are equipped with suitable conic bundle structures over k.
AU - Browning, Timothy D
AU - Swarbick Jones, M
ID - 166
JF - Proceedings of the Bonn session in analytic number theory and diophantine equations
TI - Counting rational points on del Pezzo surfaces of degree 5
VL - 360
ER -
TY - JOUR
AB - The molecular organization of bacterial NADH: ubiquinone oxidoreductase (complex I or NDH-1) is not established, apart from a rough separation into dehydrogenase, connecting and membrane domains. In this work, complex I was purified from Escherichia coli and fragmented by replacing dodecylmaltoside with other detergents. Exchange into decyl maltoside led to the removal of the hydrophobic subunit NuoL from the otherwise intact complex. Diheptanoyl phosphocholine led to the loss of NuoL and NuoM subunits, whereas other subunits remained in the complex. The presence of N,N-dimethyldodecylamine N-oxide or Triton X-100 led to further disruption of the membrane domain into fragments containing NuoL/M/N, NuoA/K/N, and NuoH/J subunits. Among the hydrophilic subunits, NuoCD was most readily dissociated from the complex, whereas NuoB was partially dissociated from the peripheral arm assembly in N,N-dimethyldodecylamine N-oxide. A model of subunit arrangement in bacterial complex I based on these data is proposed. Subunits NuoL and NuoM, which are homologous to antiporters and are implicated in proton pumping, are located at the distal end of the membrane arm, spatially separated from the redox centers of the peripheral arm. This is consistent with proposals that the mechanism of proton pumping by complex I is likely to involve long range conformational changes.
AU - Holt, Peter J
AU - Morgan, David J
AU - Leonid Sazanov
ID - 1959
IS - 44
JF - Journal of Biological Chemistry
TI - The location of NuoL and NuoM subunits in the membrane domain of the Escherichia coli Complex I: implications for the mechanism of proton pumping
VL - 278
ER -
TY - JOUR
AB - NADH-ubiquinone oxidoreductase (complex I or NDH-1) was purified from the BL21 strain of Escherichia coli using an improved procedure. The complex was effectively stabilized by addition of divalent cations and lipids, making the preparation suitable for structural studies. The ubiquinone reductase activity of the enzyme was fully restored by addition of native E. coli lipids. Two different two-dimensional crystal forms, with p2 and p3 symmetry, were obtained using lipids containing native E. coli extracts. Analysis of the crystals showed that they are formed by fully intact complex I in an L-shaped conformation. Activity assays and single particle analysis indicated that complex I maintains this structure in detergent solution and does not adopt a different conformation in the active state. Thus, we provide the first experimental evidence that complex I from E. coli has an L-shape in a lipid bilayer and confirm that this is also the case for the active enzyme in solution. This suggests strongly that bacterial complex I exists in an L-shaped conformation in vivo. Our results also indicate that native lipids play an important role in the activation, stabilization and, as a consequence, crystallization of purified complex I from E. coli.
AU - Leonid Sazanov
AU - Carroll, Joe D
AU - Holt, Peter J
AU - Toime, Laurence J
AU - Fearnley, Ian M
ID - 1960
IS - 21
JF - Journal of Biological Chemistry
TI - A role for native lipids in the stabilization and two dimensional crystallization of the Escherichia coli NADH ubiquinone oxidoreductase (complex I)
VL - 278
ER -
TY - JOUR
AB - The accumulation of genome-wide information on single nucleotide polymorphisms in humans provides an unprecedented opportunity to detect the evolutionary forces responsible for heterogeneity of the level of genetic variability across loci. Previous studies have shown that history of recombination events has produced long haplotype blocks in the human genome, which contribute to this heterogeneity. Other factors, however, such as natural selection or the heterogeneity of mutation rates across loci, may also lead to heterogeneity of genetic variability. We compared synonymous and non-synonymous variability within human genes with their divergence from murine orthologs. We separately analyzed the non-synonymous variants predicted to damage protein structure or function and the variants predicted to be functionally benign. The predictions were based on comparative sequence analysis and, in some cases, on the analysis of protein structure. A strong correlation between non-synonymous, benign variability and non-synonymous human-mouse divergence suggests that selection played an important role in shaping the pattern of variability in coding regions of human genes. However, the lack of correlation between deleterious variability and evolutionary divergence shows that a substantial proportion of the observed non-synonymous single-nucleotide polymorphisms reduces fitness and never reaches fixation. Evolutionary and medical implications of the impact of selection on human polymorphisms are discussed.
AU - Sunyaev, Shamil R
AU - Fyodor Kondrashov
AU - Bork, Peer
AU - Ramensky, Vasily
ID - 847
IS - 24
JF - Human Molecular Genetics
TI - Impact of selection, mutation rate and genetic drift on human genetic variation
VL - 12
ER -
TY - JOUR
AB - Alternative splicing is thought to be a major source of functional diversity in animal proteins. We analyzed the evolutionary conservation of proteins encoded by alternatively spliced genes and predicted the ancestral state for 73 cases of alternative splicing (25 insertions and 48 deletions). The amino acid sequences of most of the inserts in proteins produced by alternative splicing are as conserved as the surrounding sequences. Thus, alternative splicing often creates novel isoforms by the insertion of new, functional protein sequences that probably originated from noncoding sequences of introns.
AU - Fyodor Kondrashov
AU - Koonin, Eugene V
ID - 876
IS - 3
JF - Trends in Genetics
TI - Evolution of alternative splicing: Deletions, insertions and origin of functional parts of proteins from intron sequences
VL - 19
ER -
TY - JOUR
AB - Among the major mathematical approaches to mirror symmetry are those of Batyrev-Borisov and Stromdnger-Yau-Zaslow (SYZ). The first is explicit and amenable to computation but is not clearly related to the physical motivation; the second is the opposite. Furthermore, it is far from obvious that mirror partners in one sense will also be mirror partners in the other. This paper concerns a class of examples that can be shown to satisfy the requirements of SYZ, but whose Hodge numbers are also equal. This provides significant evidence in support of SYZ. Moreover, the examples are of great interest in their own right: they are spaces of flat SLr-connections on a smooth curve. The mirror is the corresponding space for the Langlands dual group PGLr. These examples therefore throw a bridge from mirror symmetry to the duality theory of Lie groups and, more broadly, to the geometric Langlands program.
AU - Tamas Hausel
AU - Thaddeus, Michael
ID - 1457
IS - 1
JF - Inventiones Mathematicae
TI - Mirror symmetry, langlands duality, and the Hitchin system
VL - 153
ER -
TY - JOUR
AB - The moduli space of stable bundles of rank $2$ and degree $1$ on a Riemann surface has rational cohomology generated by the so-called universal classes. The work of Baranovsky, King-Newstead, Siebert-Tian and Zagier provided a complete set of relations between these classes, expressed in terms of a recursion in the genus. This paper accomplishes the same thing for the noncompact moduli spaces of Higgs bundles, in the sense of Hitchin and Simpson. There are many more independent relations than for stable bundles, but in a sense the answer is simpler, since the formulas are completely explicit, not recursive. The results of Kirwan on equivariant cohomology for holomorphic circle actions are of key importance.
AU - Tamas Hausel
AU - Thaddeus, Michael
ID - 1458
IS - 2
JF - Journal of the American Mathematical Society
TI - Relations in the cohomology ring of the moduli space of rank 2 Higgs bundles
VL - 16
ER -
TY - JOUR
AB - In this paper we explicitly calculate the analogue of the 't Hooft SU (2) Yang-Mills instantons on Gibbons-Hawking multi-centered gravitational instantons, which come in two parallel families: the multi-Eguchi-Hanson, or Ak ALE gravitational instantons and the multi-Taub-NUT spaces, or Ak ALF gravitational instantons. We calculate their energy and find the reducible ones. Following Kronheimer we also exploit the U(1) invariance of our solutions and study the corresponding explicit singular SU (2) magnetic monopole solutions of the Bogomolny equations on flat ℝ3.
AU - Etesi, Gábor
AU - Tamas Hausel
ID - 1459
IS - 2
JF - Communications in Mathematical Physics
TI - On Yang-Mills instantons over multi-centered gravitational instantons
VL - 235
ER -
TY - CONF
AB - Geodesic active contours and graph cuts are two standard image segmentation techniques. We introduce a new segmentation method combining some of their benefits. Our main intuition is that any cut on a graph embedded in some continuous space can be interpreted as a contour (in 2D) or a surface (in 3D). We show how to build a grid graph and set its edge weights so that the cost of cuts is arbitrarily close to the length (area) of the corresponding contours (surfaces) for any anisotropic Riemannian metric. There are two interesting consequences of this technical result. First, graph cut algorithms can be used to find globally minimum geodesic contours (minimal surfaces in 3D) under arbitrary Riemannian metric for a given set of boundary conditions. Second, we show how to minimize metrication artifacts in existing graph-cut based methods in vision. Theoretically speaking, our work provides an interesting link between several branches of mathematics -differential geometry, integral geometry, and combinatorial optimization. The main technical problem is solved using Cauchy-Crofton formula from integral geometry.
AU - Boykov, Yuri
AU - Vladimir Kolmogorov
ID - 3170
TI - Computing geodesics and minimal surfaces via graph cuts
VL - 1
ER -
TY - CONF
AB - Reconstructing a 3-D scene from more than one camera is a classical problem in computer vision. One of the major sources of difficulty is the fact that not all scene elements are visible from all cameras. In the last few years, two promising approaches have been developed 11,12 that formulate the scene reconstruction problem in terms of energy minimization, and minimize the energy using graph cuts. These energy minimization approaches treat the input images symmetrically, handle visibility constraints correctly, and allow spatial smoothness to be enforced. However, these algorithm propose different problem formulations, and handle a limited class of smoothness terms. One algorithm 11 uses a problem formulation that is restricted to two-camera stereo, and imposes smoothness between a pair of cameras. The other algorithm 12 can handle an arbitrary number of cameras, but imposes smoothness only with respect to a single camera. In this paper we give a more general energy minimization formulation for the problem, which allows a larger class of spatial smoothness constraints. We show that our formulation includes both of the previous approaches as special cases, as well as permitting new energy functions. Experimental results on real data with ground truth are also included.
AU - Vladimir Kolmogorov
AU - Zabih, Ramin
AU - Gortler, Steven
ID - 3171
TI - Generalized multi camera scene reconstruction using graph cuts
VL - 2683
ER -
TY - CONF
AB - We address visual correspondence problems without assuming that scene points have similar intensities in different views. This situation is common, usually due to non-lambertian scenes or to differences between cameras. We use maximization of mutual information, a powerful technique for registering images that requires no a priori model of the relationship between scene intensities in different views. However, it has proven difficult to use mutual information to compute dense visual correspondence. Comparing fixed-size windows via mutual information suffers from the well-known problems of fixed windows, namely poor performance at discontinuities and in low-texture regions. In this paper, we show how to compute visual correspondence using mutual information without suffering from these problems. Using 'a simple approximation, mutual information can be incorporated into the standard energy minimization framework used in early vision. The energy can then be efficiently minimized using graph cuts, which preserve discontinuities and handle low-texture regions. The resulting algorithm combines the accurate disparity maps that come from graph cuts with the tolerance for intensity changes that comes from mutual information.
AU - Kim, Junhwan
AU - Vladimir Kolmogorov
AU - Zabih, Ramin
ID - 3174
TI - Visual correspondence using energy minimization and mutual information
VL - 2
ER -
TY - JOUR
AB - We show that the fixed alphabet shortest common supersequence (SCS) and the fixed alphabet longest common subsequence (LCS) problems parameterized in the number of strings are W[1]-hard. Unless W[1]=FPT, this rules out the existence of algorithms with time complexity of O(f(k)nα) for those problems. Here n is the size of the problem instance, α is constant, k is the number of strings and f is any function of k. The fixed alphabet version of the LCS problem is of particular interest considering the importance of sequence comparison (e.g. multiple sequence alignment) in the fixed length alphabet world of DNA and protein sequences.
AU - Krzysztof Pietrzak
ID - 3209
IS - 4
JF - Journal of Computer and System Sciences
TI - On the parameterized complexity of the fixed alphabet shortest common supersequence and longest common subsequence problems
VL - 67
ER -
TY - CONF
AB - Luby and Rackoff showed how to construct a (super-)pseudo-random permutation {0,1}2n→ {0,1}2n from some number r of pseudo-random functions {0,1}n → {0,1}n. Their construction, motivated by DES, consists of a cascade of r Feistel permutations. A Feistel permutation 1for a pseudo-random function f is defined as (L, R) → (R,L ⊕ f (R)), where L and R are the left and right part of the input and ⊕ denotes bitwise XOR or, in this paper, any other group operation on {0,1}n. The only non-trivial step of the security proof consists of proving that the cascade of r Feistel permutations with independent uniform random functions {0,1}n → {0,1}n, denoted Ψ2nr is indistinguishable from a uniform random permutation {0,1}2n → {0,1}2n by any computationally unbounded adaptive distinguisher making at most O(2cn) combined chosen plaintext/ciphertext queries for any c < α, where a is a security parameter. Luby and Rackoff proved α = 1/2 for r = 4. A natural problem, proposed by Pieprzyk is to improve on α for larger r. The best known result, α = 3/4 for r = 6, is due to Patarin. In this paper we prove a = 1 -O(1/r), i.e., the trivial upper bound α = 1 can be approached. The proof uses some new techniques that can be of independent interest.
AU - Maurer, Ueli M
AU - Krzysztof Pietrzak
ID - 3210
TI - The security of many round Luby Rackoff pseudo random permutations
VL - 2656
ER -
TY - CHAP
AU - Peter Jonas
AU - Unsicker, Klaus
ED - Schmidt, R. F.
ID - 3458
T2 - Lehrbuch Vorklinik
TI - Molekulare und zelluläre Grundlagen des Nervensystems.
VL - B
ER -
TY - JOUR
AB - Neurons can produce action potentials with high temporal precision(1). A fundamental issue is whether, and how, this capability is used in information processing. According to the `cell assembly' hypothesis, transient synchrony of anatomically distributed groups of neurons underlies processing of both external sensory input and internal cognitive mechanisms(2-4). Accordingly, neuron populations should be arranged into groups whose synchrony exceeds that predicted by common modulation by sensory input. Here we find that the spike times of hippocampal pyramidal cells can be predicted more accurately by using the spike times of simultaneously recorded neurons in addition to the animals location in space. This improvement remained when the spatial prediction was refined with a spatially dependent theta phase modulation(5-8). The time window in which spike times are best predicted from simultaneous peer activity is 10-30 ms, suggesting that cell assemblies are synchronized at this timescale. Because this temporal window matches the membrane time constant of pyramidal neurons(9), the period of the hippocampal gamma oscillation(10) and the time window for synaptic plasticity(11), we propose that cooperative activity at this timescale is optimal for information transmission and storage in cortical circuits.
AU - Harris, Kenneth D
AU - Jozsef Csicsvari
AU - Hirase, Hajima
AU - Dragoi, George
AU - Buzsáki, György
ID - 3526
IS - 6948
JF - Nature
TI - Organization of cell assemblies in the hippocampus
VL - 424
ER -
TY - JOUR
AB - Gamma frequency oscillations (30-100 Hz) have been suggested to underlie various cognitive and motor functions. Here, we examine the generation of gamma oscillation currents in the hippocampus, using two-dimensional, 96-site silicon probes. Two gamma generators were identified, one in the dentate gyrus and another in the CA3-CA1 regions. The coupling strength between the two oscillators varied during both theta and nontheta states. Both pyramidal cells and interneurons were phase-locked to gamma waves. Anatomical connectivity, rather than physical distance, determined the coupling strength of the oscillating neurons. CA3 pyramidal neurons discharged CA3 and CA1 interneurons at latencies indicative of monosynaptic connections. Intrahippocampal gamma oscillation emerges in the CA3 recurrent system, which entrains the CA1 region via its interneurons.
AU - Jozsef Csicsvari
AU - Jamieson, Brian G
AU - Wise, Kensall D
AU - Buzsáki, György
ID - 3528
IS - 2
JF - Neuron
TI - Mechanisms of gamma oscillations in the hippocampus of the behaving rat
VL - 37
ER -
TY - JOUR
AB - Parallel recording of neuronal activity in the behaving animal is a prerequisite for our understanding of neuronal representation and storage of information. Here we describe the development of micro-machined silicon microelectrode arrays for unit and local field recordings. The two-dimensional probes with 96 or 64 recording sites provided high-density recording of unit and field activity with minimal tissue displacement or damage. The on-chip active circuit eliminated movement and other artifacts and greatly reduced the weight of the headgear. The precise geometry of the recording tips allowed for the estimation of the spatial location of the recorded neurons and for high-resolution estimation of extracellular current source density. Action potentials could be simultaneously recorded from the soma and dendrites of the same neurons. Silicon technology is a promising approach for high-density, high-resolution sampling of neuronal activity in both basic research and prosthetic devices.
AU - Jozsef Csicsvari
AU - Henze, Darrell A
AU - Jamieson, Brian G
AU - Harris, Kenneth D
AU - Sirota, Anton M
AU - Bartho, Peter
AU - Wise, Kensall D
AU - Buzsáki, György
ID - 3529
IS - 2
JF - Journal of Neurophysiology
TI - Massively parallel recording of unit and local field potentials with silicon-based electrodes
VL - 90
ER -
TY - JOUR
AB - Genetic engineering of the mouse brain allows investigators to address novel hypotheses in vivo. Because of the paucity of information on the network patterns of the mouse hippocampus, we investigated the electrical patterns in the behaving animal using multisite silicon probes and wire tetrodes. Theta (6-9 Hz) and gamma (40-100 Hz) oscillations were present during exploration and rapid eye movement sleep. Gamma power and theta power were comodulated and gamma power varied as a function of the theta cycle. Pyramidal cells and putative interneurons were phase-locked to theta oscillations. During immobility, consummatory behaviors and slow-wave sleep, sharp waves were present in cornu ammonis region CA1 of the hippocampus stratum radiatum associated with 140-200-Hz “ripples” in the pyramidal cell layer and population burst of CA1 neurons. In the hilus, large-amplitude “dentate spikes” occurred in association with increased discharge of hilar neurons. The amplitude of field patterns was larger in the mouse than in the rat, likely reflecting the higher neuron density in a smaller brain. We suggest that the main hippocampal network patterns are mediated by similar pathways and mechanisms in mouse and rat.
AU - Buzsáki, György
AU - Buhl, Derek L
AU - Harris, Kenneth D
AU - Jozsef Csicsvari
AU - Czéh, Boldizsár
AU - Morozov, Alexei
ID - 3536
IS - 1
JF - Neuroscience
TI - Hippocampal network patterns of activity in the mouse
VL - 116
ER -
TY - JOUR
AB - Both neocortical and hippocampal networks organize the firing patterns of their neurons by prominent oscillations during sleep, but the functional role of these rhythms is not well understood. Here, we show a robust correlation of neuronal discharges between the somatosensory cortex and hippocampus on both slow and fine time scales in the mouse and rat. Neuronal bursts in deep cortical layers, associated with sleep spindles and delta waves/slow rhythm, effectively triggered hippocampal discharges related to fast (ripple) oscillations. We hypothesize that oscillation-mediated temporal links coordinate specific information transfer between neocortical and hippocampal cell assemblies. Such a neocortical-hippocampal interplay may be important for memory consolidation.
AU - Sirota, Anton M
AU - Jozsef Csicsvari
AU - Buhl, Derek L
AU - Buzsáki, György
ID - 3543
IS - 4
JF - PNAS
TI - Communication between neocortex and hippocampus during sleep in rodents
VL - 100
ER -
TY - CONF
AB - We define the Morse-Smale complex of a Morse function over a 3-manifold as the overlay of the descending and as- cending manifolds of all critical points. In the generic case, its 3-dimensional cells are shaped like crystals and are sepa- rated by quadrangular faces. In this paper, we give a combi- natorial algorithm for constructing such complexes for piece- wise linear data.
AU - Herbert Edelsbrunner
AU - Harer, John
AU - Natarajan, Vijay
AU - Pascucci, Valerio
ID - 3556
TI - Morse-Smale complexes for piecewise linear 3-manifolds
ER -
TY - CHAP
AB - Given a finite point set in R, the surface reconstruction problem asks for a surface that passes through many but not necessarily all points. We describe an unambigu- ous definition of such a surface in geometric and topological terms, and sketch a fast algorithm for constructing it. Our solution overcomes past limitations to special point distributions and heuristic design decisions.
AU - Herbert Edelsbrunner
ID - 3573
T2 - Discrete & Computational Geometry
TI - Surface reconstruction by wrapping finite sets in space
ER -
TY - JOUR
AB - We develop fast algorithms for computing the linking number of a simplicial complex within a filtration.We give experimental results in applying our work toward the detection of non-trivial tangling in biomolecules, modeled as alpha complexes.
AU - Edelsbrunner, Herbert
AU - Zomorodian, Afra
ID - 3584
IS - 2
JF - Homology, Homotopy and Applications
TI - Computing linking numbers of a filtration
VL - 5
ER -
TY - JOUR
AB - Temporal logics such as Computation Tree Logic (CTL) and Linear Temporal Logic (LTL) have become popular for specifying temporal properties over a wide variety of planning and verification problems. In this paper we work towards building a generalized framework for automated reasoning based on temporal logics. We present a powerful extension of CTL with first-order quantification over the set of reachable states for reasoning about extremal properties of weighted labeled transition systems in general. The proposed logic, which we call Weighted Quantified Computation Tree Logic (WQCTL), captures the essential elements common to the domain of planning and verification problems and can thereby be used as an effective specification language in both domains. We show that in spite of the rich, expressive power of the logic, we are able to evaluate WQCTL formulas in time polynomial in the size of the state space times the length of the formula. Wepresent experimental results on the WQCTL verifier.
AU - Krishnendu Chatterjee
AU - Dasgupta, Pallab
AU - Chakrabarti, Partha P
ID - 3593
IS - 2
JF - Journal of Automated Reasoning
TI - A branching time temporal framework for quantitative reasoning
VL - 30
ER -
TY - JOUR
AB - There are several analyses in evolutionary ecology which assume that a family of offspring has come from only two parents. Here, we present a simple test for detecting when a batch involves two or more subfamilies. It is based on the fact that the mixing of families generates associations amongst unlinked marker loci. We also present simulations illustrating the power of our method for varying numbers of loci, alleles per locus and genotyped individuals.
AU - Vines, Timothy H
AU - Nicholas Barton
ID - 3618
IS - 7
JF - Molecular Ecology
TI - A new approach to detecting mixed families
VL - 12
ER -
TY - JOUR
AB - What is the chance that some part of a stretch of genome will survive? In a population of constant size, and with no selection, the probability of survival of some part of a stretch of map length y<1 approaches View the MathML source for View the MathML source. Thus, the whole genome is certain to be lost, but the rate of loss is extremely slow. This solution extends to give the whole distribution of surviving block sizes as a function of time. We show that the expected number of blocks at time t is 1+yt and give expressions for the moments of the number of blocks and the total amount of genome that survives for a given time. The solution is based on a branching process and assumes complete interference between crossovers, so that each descendant carries only a single block of ancestral material. We consider cases where most individuals carry multiple blocks, either because there are multiple crossovers in a long genetic map, or because enough time has passed that most individuals in the population are related to each other. For species such as ours, which have a long genetic map, the genome of any individual which leaves descendants (∼80% of the population for a Poisson offspring number with mean two) is likely to persist for an extremely long time, in the form of a few short blocks of genome.
AU - Baird, Stuart J
AU - Nicholas Barton
AU - Etheridge, Alison M
ID - 3619
IS - 4
JF - Theoretical Population Biology
TI - The distribution of surviving blocks of an ancestral genome
VL - 64
ER -
TY - JOUR
AB - Stable hybrid zones in which ecologically divergent taxa give rise to a range of recombinants are natural laboratories in which the genetic basis of adaptation and reproductive isolation can be unraveled. One such hybrid zone is formed by the fire-bellied toads Bombina bombina and B. variegata (Anura: Discoglossidae). Adaptations to permanent and ephemeral breeding habitats, respectively, have shaped numerous phenotypic differences between the taxa. All of these are, in principle, candidates for a genetic dissection via QTL mapping. We present here a linkage map of 28 codominant and 10 dominant markers in the Bombina genome. In an F2 cross, markers that were mainly microsatellites, SSCPs or allozymes were mapped to 20 linkage groups. Among the 40 isolated CA microsatellites, we noted a preponderance of compound and frequently interleaved CA-TA repeats as well as a striking polarity at the 5′ end of the repeats.
AU - Nürnberger, Beate
AU - Hofman, Sebastian
AU - Förg-Brey, Bqruni
AU - Praetzel, Gabriele
AU - Maclean, Alan W
AU - Szymura, Jacek M
AU - Abbott, Catherine M
AU - Nicholas Barton
ID - 3620
IS - 2
JF - Heredity
TI - A linkage map for the hybridising toads Bombina bombina and B. variegata (Anura: Discoglossidae)
VL - 91
ER -
TY - THES
AU - Christoph Lampert
ID - 3678
T2 - Bonner Mathematische Schriften
TI - The Neumann operator in strictly pseudoconvex domains with weighted Bergman metric
VL - 356
ER -
TY - JOUR
AB - The combination of high-resolution atomic force microscopy (AFM) imaging and single-molecule force-spectroscopy was employed to unfold single bacteriorhodopsins (BR) from native purple membrane patches at various physiologically relevant temperatures. The unfolding spectra reveal detailed insight into the stability of individual structural elements of BR against mechanical unfolding. Intermittent states in the unfolding process are associated with the stepwise unfolding of alpha-helices, whereas other states are associated with the unfolding of polypeptide loops connecting the alpha-helices. It was found that the unfolding forces of the secondary structures considerably decreased upon increasing the temperature from 8 to 52°C. Associated with this effect, the probability of individual unfolding pathways of BR was significantly influenced by the temperature. At lower temperatures, transmembrane alpha-helices and extracellular polypeptide loops exhibited sufficient stability to individually establish potential barriers against unfolding, whereas they predominantly unfolded collectively at elevated temperatures. This suggests that increasing the temperature decreases the mechanical stability of secondary structural elements and changes molecular interactions between secondary structures, thereby forcing them to act as grouped structures.
AU - Harald Janovjak
AU - Kessler, Max
AU - Oesterhelt, Dieter
AU - Gaub, Hermann
AU - Mueller, Daniel J
ID - 3725
IS - 19
JF - EMBO Journal
TI - Unfolding pathways of native bacteriorhodopsin depend on temperature
VL - 22
ER -
TY - JOUR
AB - We use the lac operon in Escherichia coli as a prototype system to illustrate the current state, applicability, and limitations of modeling the dynamics of cellular networks. We integrate three different levels of description (molecular, cellular, and that of cell population) into a single model, which seems to capture many experimental aspects of the system.
AU - Vilar,Jose M
AU - Calin Guet
AU - Leibler, Stanislas
ID - 3752
IS - 3
JF - Journal of Cell Biology
TI - Modeling network dynamics: the lac operon, a case study
VL - 161
ER -
TY - JOUR
AB - Kv3 channels are thought to be essential for the fast-spiking (FS) phenotype in GABAergic interneurons, but how these channels confer the ability to generate action potentials (APs) at high frequency is unknown. To address this question, we developed a fast dynamic-clamp system (approximately 50 kHz) that allowed us to add a Kv3 model conductance to CA1 oriens alveus (OA) interneurons in hippocampal slices. Selective pharmacological block of Kv3 channels by 0.3 mm 4-aminopyridine or 1 mm tetraethylammonium ions led to a marked broadening of APs during trains of short stimuli and a reduction in AP frequency during 1 sec stimuli. The addition of artificial Kv3 conductance restored the original AP pattern. Subtraction of Kv3 conductance by dynamic clamp mimicked the effects of the blockers. Application of artificial Kv3 conductance also led to FS in OA interneurons after complete K+ channel block and even induced FS in hippocampal pyramidal neurons in the absence of blockers. Adding artificial Kv3 conductance with altered deactivation kinetics revealed a nonmonotonic relationship between mean AP frequency and deactivation rate, with a maximum slightly above the original value. Insertion of artificial Kv3 conductance with either lowered activation threshold or inactivation also led to a reduction in the mean AP frequency. However, the mechanisms were distinct. Shifting the activation threshold induced adaptation, whereas adding inactivation caused frequency-dependent AP broadening. In conclusion, Kv3 channels are necessary for the FS phenotype of OA interneurons, and several of their gating properties appear to be optimized for high-frequency repetitive activity.
AU - Lien, Cheng-Chang
AU - Peter Jonas
ID - 3804
IS - 6
JF - Journal of Neuroscience
TI - Kv3 potassium conductance is necessary and kinetically optimized for high-frequency action potential generation in hippocampal interneurons
VL - 23
ER -
TY - JOUR
AB - To probe exocytosis at a cortical glutamatergic synapse, we made capacitance measurements in whole-cell recorded hippocampal mossy fiber terminals. Evaluation of different methods by using a morphology-based equivalent electrical model revealed that quantitative capacitance measurements are possible in this presynaptic structure. Voltage pulses leading to presynaptic Ca2+ inflow evoked large capacitance signals that showed saturation with increasing pulse duration. The mean peak capacitance increase was 100 fF, corresponding to a pool of approximately 1,400 releasable vesicles. Thus hippocampal mossy fiber synapses have a vesicular "maxipool." Large pool size and rapid vesicle recycling may underlie the uniquely large extent of activity-dependent plasticity in this synapse.
AU - Hallermann, Stefan
AU - Pawlu, Christian
AU - Peter Jonas
AU - Heckmann, Manfred
ID - 3806
IS - 15
JF - PNAS
TI - A large pool of releasable vesicles in a cortical glutamatergic synapse
VL - 100
ER -
TY - CONF
AB - Many verification, planning, and control problems can be modeled as games played on state-transition graphs by one or two players whose conflicting goals are to form a path in the graph. The focus here is on simple stochastic parity games, that is, two-player games with turn-based probabilistic transitions and omega-regular objectives formalized as parity (Rabin chain) winning conditions. An efficient translation from simple stochastic parity games to nonstochastic parity games is given. As many algorithms are known for solving the latter, the translation yields efficient algorithms for computing the states of a simple stochastic parity game from which a player can win with probability 1. An important special case of simple stochastic parity games are the Markov decision processes with Buchi objectives. For this special case a first provably subquadratic algorithm is given for computing the states from which the single player has a strategy to achieve a Buchi objective with probability 1. For game graphs with m edges the algorithm works in time O(mrootm). Interestingly, a similar technique sheds light on the question of the computational complexity of solving simple Buchi games and yields the first provably subquadratic algorithm, with a running time of O(n(2)/log n) for game graphs with n vertices and O(n) edges.
AU - Krishnendu Chatterjee
AU - Jurdziński, Marcin
AU - Thomas Henzinger
ID - 3897
TI - Simple stochastic parity games
VL - 2803
ER -
TY - CONF
AB - We study the problem of determining stack boundedness and the exact maximum stack size for three classes of interrupt-driven programs. Interrupt-driven programs axe used in many real-time applications that require responsive interrupt handling. In order to ensure responsiveness, programmers often enable interrupt processing in the body of lower-priority interrupt handlers. In such programs a programming error can allow interrupt handlers to be interrupted in cyclic fashion to lead to an unbounded stack, causing the system to crash. For a restricted class of interrupt-driven programs, we show that there is a polynomial-time procedure to check stack boundedness, while determining the exact maximum stack size is PSPACE-complete. For a larger class of programs, the two problems are both PSPACE-complete, and for the largest class of programs we consider, the two problems are PSPACE-hard and can be solved in exponential time.
AU - Krishnendu Chatterjee
AU - Ma, Di
AU - Majumdar, Ritankar S
AU - Zhao, Tian
AU - Thomas Henzinger
AU - Palsberg, Jens
ID - 3898
TI - Stack size analysis for interrupt-driven programs
VL - 2694
ER -
TY - CONF
AU - Bollenbach, Mark Tobias
AU - Strother, T.
AU - Bauer, Wolfgang
ID - 3425
TI - 3D supernova collapse calculations
VL - 166
ER -
TY - JOUR
AU - Bauer, Wolfgang
AU - Kleine Berkenbusch, Marco
AU - Bollenbach, Mark Tobias
ID - 3797
IS - 4
JF - Revista Mexicana De Fisica
TI - Breaking atomic nuclei into little pieces: evidence for a phase transition
VL - 49
ER -
TY - JOUR
AB - During vertebrate gastrulation, highly coordinated cellular rearrangements lead to the formation of the three germ layers, ectoderm, mesoderm and endoderm. In zebrafish, silberblick (slb)/wnt11 regulates normal gastrulation movements by activating a signalling pathway similar to the Frizzled-signalling pathway, which establishes epithelial planar cell polarity (PCP) in Drosophila. However, the cellular mechanisms by which slb/wnt11 functions during zebrafish gastrulation are still unclear. Using high-resolution two-photon confocal imaging followed by computer-assisted reconstruction and motion analysis, we have analysed the movement and morphology of individual cells in three dimensions during the course of gastrulation. We show that in slb-mutant embryos, hypoblast cells within the forming germ ring have slower, less directed migratory movements at the onset of gastrulation. These aberrant cell movements are accompanied by defects in the orientation of cellular processes along the individual movement directions of these cells. We conclude that slb/wnt11-mediated orientation of cellular processes plays a role in facilitating and stabilising movements of hypoblast cells in the germ ring, thereby pointing at a novel function of the slb/wnt11 signalling pathway for the regulation of migratory cell movements at early stages of gastrulation.
AU - Ulrich, Florian
AU - Concha, Miguel
AU - Heid, Paul
AU - Voss, Ed
AU - Witzel, Sabine
AU - Roehl, Henry
AU - Tada, Masazumi
AU - Wilson, Stephen
AU - Adams, Richard
AU - Soll, David
AU - Heisenberg, Carl-Philipp J
ID - 4146
IS - 22
JF - Development
TI - Slb/Wnt11 controls hypoblast cell migration and morphogenesis at the onset of zebrafish gastrulation
VL - 130
ER -
TY - JOUR
AB - Background: During vertebrate gastrulation, cell polarization and migration are core components in the cellular rearrangements that lead to the formation of the three germ layers, ectoderm, mesoderm, and endoderm. Previous studies have implicated the Wnt/planar cell polarity (PCP) signaling pathway in controlling cell morphology and movement during gastrulation. However, cell polarization and directed cell migration are reduced but not completely abolished in the absence of Wnt/PCP signals; this observation indicates that other signaling pathways must be involved. Results: We show that Phosphoinositide 3-Kinases (PI3Ks) are required at the onset of zebrafish gastrulation in mesendodermal cells for process formation and cell polarization. Platelet Derived Growth Factor (PDGF) functions upstream of PI3K, while Protein Kinase B (PKB), a downstream effector of PI3K activity, localizes to the leading edge of migrating mesendodermal cells. In the absence of PI3K activity, PKB localization and cell polarization are strongly reduced in mesendodermal cells and are followed by slower but still highly coordinated and directed movements of these cells. Conclusions: We have identified a novel role of a signaling pathway comprised of PDGF, PI3K, and PKB in the control of morphogenetic cell movements during gastrulation. Furthermore, our findings provide insight into the relationship between cell polarization and directed cell migration at the onset of zebrafish gastrulation.
AU - Montero, Juan
AU - Kilian, Beate
AU - Chan, Joanne
AU - Bayliss, Peter
AU - Heisenberg, Carl-Philipp J
ID - 4169
IS - 15
JF - Current Biology
TI - Phosphoinositide 3-kinase is required for process outgrowth and cell polarization of gastrulating mesendodermal cells
VL - 13
ER -
TY - JOUR
AB - Recent studies show that signaling through integrin receptors is required for normal cell movements during Xenopus gastrulation. Integrins function in this process by modulating the activity of cadherin adhesion molecules within tissues undergoing convergence and extension movements.
AU - Montero, Juan
AU - Heisenberg, Carl-Philipp J
ID - 4168
IS - 2
JF - Developmental Cell
TI - Adhesive crosstalk in gastrulation
VL - 5
ER -
TY - JOUR
AB - Wnt genes play important roles in regulating patterning and morphogenesis during vertebrate gastrulation. In zebrafish, slb/wnt11 is required for convergence and extension movements, but not cell fate specification during gastrulation. To determine if other Wnt genes functionally interact with slb/wnt11, we analysed the role of ppt/wnt5 during zebrafish gastrulation. ppt/wnt5 is maternally provided and zygotically expressed at all stages during gastrulation. The analysis of ppt mutant embryos reveals that Ppt/Wnt5 regulates cell elongation and convergent extension movements in posterior regions of the gastrula, while its function in more anterior regions is largely redundant to that of Slb/Wnt11. Frizzled-2 functions downstream of ppt/wnt5, indicating that it might act as a receptor for Ppt/Wnt5 in this process. The characterisation of the role of Ppt/Wnt5 provides insight into the functional diversity of Wnt genes in regulating vertebrate gastrulation movements. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
AU - Kilian, Beate
AU - Mansukoski, Hannu
AU - Barbosa, Filipa
AU - Ulrich, Florian
AU - Tada, Masazumi
AU - Heisenberg, Carl-Philipp J
ID - 4185
IS - 4
JF - Mechanisms of Development
TI - The role of Ppt/Wnt5 in regulating cell shape and movement during zebrafish gastrulation
VL - 120
ER -
TY - JOUR
AU - González, J.
AU - de Vladar, Harold
AU - Rebolledo, Morella
ID - 4240
JF - Acta Científica Venezolana
TI - New Late–Intensification Schedules for Cancer Treatments
VL - 54
ER -
TY - THES
AB - Methods for the formal specification and verification of systems are indispensible for the development of complex yet correct systems. In formal verification, the designer describes the system in a modeling language with a well-defined semantics, and this system description is analyzed against a set of correctness requirements. Model checking is an algorithmic technique to check that a system description indeed satisfies correctness requirements given as logical specifications. While successful in hardware verification, the potential for model checking for software and embedded systems has not yet been realized. This is because traditional model checking focuses on systems modeled as finite state-transition graphs. While a natural model for hardware (especially synchronous hardware), state-transition graphs often do not capture software and embedded systems at an appropriate level of granularity. This dissertation considers two orthogonal extensions to finite state-transition graphs making model checking techniques applicable to both a wider class of systems and a wider class of properties.
The first direction is an extension to infinite-state structures finitely represented using constraints and operations on constraints. Infinite state arises when we wish to model variables with unbounded range (e.g., integers), or data structures, or real time. We provide a uniform framework of symbolic region algebras to study model checking of infinite-state systems. We also provide sufficient language-independent termination conditions for symbolic model checking algorithms on infinite state systems.
The second direction supplements verification with game theoretic reasoning. Games are natural models for interactions between components. We study game theoretic behavior with winning conditions given by temporal logic objectives both in the deterministic and in the probabilistic context. For deterministic games, we provide an extremal model characterization of fixpoint algorithms that link solutions of verification problems to solutions for games. For probabilistic games we study fixpoint characterization of winning probabilities for games with omega-regular winning objectives, and construct (epsilon-)optimal winning strategies.
AU - Majumdar, Ritankar
ID - 4416
TI - Symbolic algorithms for verification and control
ER -
TY - THES
AB - Giotto provides a time-triggered programmer’s model for the implementation of embedded control systems with hard real-time constraints. Giotto’s precise semantics and predictabil- ity make it suitable for safety-critical applications.
Giotto is based around the idea that time-triggered task invocation together with time-triggered mode switching can form a useful programming model for real-time systems. To substantiate this claim, we describe the use of Giotto to refactor the software of a small, autonomous helicopter. The ease with which Giotto expresses the existing software provides evidence that Giotto is an appropriate programming language for control systems.
Since Giotto is a real-time programming language, ensuring that Giotto programs meet their deadlines is crucial. To study precedence-constrained Giotto scheduling, we first examine single-mode, single-processor scheduling. We extend to an infinite, periodic setting the classical problem of meeting deadlines for a set of tasks with release times, deadlines, precedence constraints, and preemption. We then develop an algorithm for scheduling Giotto programs on a single processor by representing Giotto programs as instances of the extended scheduling problem.
Next, we study multi-mode, single-processor Giotto scheduling. This problem is different from classical scheduling problems, since in our precedence-constrained approach, the deadlines of tasks may vary depending on the mode switching behavior of the program. We present conditional scheduling models which capture this varying-deadline behavior. We develop polynomial-time algorithms for some conditional scheduling models, and prove oth- ers to be computationally hard. We show how to represent multi-mode Giotto programs as instances of the model, resulting in an algorithm for scheduling multi-mode Giotto programs on a single processor.
Finally, we show that the problem of scheduling Giotto programs for multiple net- worked processors is strongly NP-hard.
AU - Horowitz, Benjamin
ID - 4425
TI - Giotto: A time-triggered language for embedded programming
ER -
TY - JOUR
AU - Kaloshin, Vadim
ID - 8519
IS - 3
JF - Inventiones mathematicae
KW - General Mathematics
SN - 0020-9910
TI - The existential Hilbert 16-th problem and an estimate for cyclicity of elementary polycycles
VL - 151
ER -
TY - JOUR
AB - Let k⩾5 be an integer, and let x⩾1 be an arbitrary real number. We derive a bound[Formula presented] for the number of positive integers less than or equal to x which can be represented as a sum of two non-negative coprime kth powers, in essentially more than one way.
AU - Timothy Browning
ID - 204
IS - 2
JF - Journal of Number Theory
TI - Equal Sums of Two kth Powers
VL - 96
ER -
TY - CHAP
AU - Lieb, Élliott H
AU - Solovej, Jan P
AU - Robert Seiringer
AU - Yngvason, Jakob
ID - 2338
T2 - Current Developments in Mathematics, 2001
TI - The ground state of the Bose gas
ER -
TY - CONF
AU - Robert Seiringer
ED - Weder, Richardo
ED - Exner, Pavel
ED - Grébert, Benoit
ID - 2339
TI - Symmetry breaking in a model of a rotating Bose gas
VL - 307
ER -
TY - JOUR
AB - The Bose-Einstein condensation (BEC) of the ground state of bosonic atoms in a trap was discussed. The BEC was proved for bosons with two-body repulsive interaction potentials in the dilute limit, starting from the basic Schrodinger equation. The BEC was 100% into the state which minimized the Gross-Pitaevskii energy functional. The analysis also included rigorous proof of BEC in a physically realistic, continuum model.
AU - Lieb, Élliott H
AU - Robert Seiringer
ID - 2349
IS - 17
JF - Physical Review Letters
TI - Proof of Bose-Einstein condensation for dilute trapped gases
VL - 88
ER -
TY - JOUR
AB - Using the Pauli-Fierz model of non-relativistic quantum electrodynamics, we calculate the binding energy of an electron in the field of a nucleus of charge Z and in presence of the quantized radiation field. We consider the case of small coupling constant α, but fixed Zα and ultraviolet cut-off Λ. We prove that after renormalizing the mass the binding energy has, to leading order in α, a finite limit as Λ goes to infinity; i.e., the cut-off can be removed. The expression for the ground state energy shift thus obtained agrees with Bethe's formula for small values of Zα, but shows a different behavior for bigger values.
AU - Hainzl, Christian
AU - Robert Seiringer
ID - 2350
IS - 5
JF - Advances in Theoretical and Mathematical Physics
TI - Mass renormalization and energy level shift in non-relativistic QED
VL - 6
ER -