@article{3529, abstract = {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.}, author = {Jozsef Csicsvari and Henze, Darrell A and Jamieson, Brian G and Harris, Kenneth D and Sirota, Anton M and Bartho, Peter and Wise, Kensall D and Buzsáki, György}, journal = {Journal of Neurophysiology}, number = {2}, pages = {1314 -- 1323}, publisher = {American Physiological Society}, title = {{Massively parallel recording of unit and local field potentials with silicon-based electrodes}}, doi = {10.1152/jn.00116.2003}, volume = {90}, year = {2003}, } @article{3528, abstract = {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.}, author = {Jozsef Csicsvari and Jamieson, Brian G and Wise, Kensall D and Buzsáki, György}, journal = {Neuron}, number = {2}, pages = {311 -- 322}, publisher = {Elsevier}, title = {{Mechanisms of gamma oscillations in the hippocampus of the behaving rat}}, doi = {10.1016/S0896-6273(02)01169-8}, volume = {37}, year = {2003}, } @article{3543, abstract = {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.}, author = {Sirota, Anton M and Jozsef Csicsvari and Buhl, Derek L and Buzsáki, György}, journal = {PNAS}, number = {4}, pages = {2065 -- 2069}, publisher = {National Academy of Sciences}, title = {{Communication between neocortex and hippocampus during sleep in rodents}}, doi = {10.1073/pnas.0437938100}, volume = {100}, year = {2003}, } @article{3593, abstract = {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.}, author = {Krishnendu Chatterjee and Dasgupta, Pallab and Chakrabarti, Partha P}, journal = {Journal of Automated Reasoning}, number = {2}, pages = {205 -- 232}, publisher = {Springer}, title = {{A branching time temporal framework for quantitative reasoning}}, doi = {10.1023/A:1023217515688}, volume = {30}, year = {2003}, } @phdthesis{3678, author = {Christoph Lampert}, booktitle = {Bonner Mathematische Schriften}, pages = {1 -- 165}, publisher = {Universität Bonn, Fachbibliothek Mathematik}, title = {{The Neumann operator in strictly pseudoconvex domains with weighted Bergman metric }}, volume = {356}, year = {2003}, } @article{3725, abstract = {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.}, author = {Harald Janovjak and Kessler, Max and Oesterhelt, Dieter and Gaub, Hermann and Mueller, Daniel J}, journal = {EMBO Journal}, number = {19}, pages = {5220 -- 5229}, publisher = {Wiley-Blackwell}, title = {{Unfolding pathways of native bacteriorhodopsin depend on temperature}}, doi = {10.1093/emboj/cdg509}, volume = {22}, year = {2003}, } @article{3804, abstract = {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.}, author = {Lien, Cheng-Chang and Peter Jonas}, journal = {Journal of Neuroscience}, number = {6}, pages = {2058 -- 68}, publisher = {Society for Neuroscience}, title = {{Kv3 potassium conductance is necessary and kinetically optimized for high-frequency action potential generation in hippocampal interneurons}}, volume = {23}, year = {2003}, } @article{3806, abstract = {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.}, author = {Hallermann, Stefan and Pawlu, Christian and Peter Jonas and Heckmann, Manfred}, journal = {PNAS}, number = {15}, pages = {8975 -- 80}, publisher = {National Academy of Sciences}, title = {{A large pool of releasable vesicles in a cortical glutamatergic synapse}}, doi = {10.1073/pnas.1432836100}, volume = {100}, year = {2003}, } @article{3921, abstract = {Unlike most social insects, many Cardiocondyla ant species have two male morphs: wingless (ergatoid) males, who remain in the natal nest, and winged males who disperse but, strangely, before leaving may also mate within the nest. Whereas ergatoid males are highly intolerant of each other and fight among themselves, they tend to tolerate their winged counterparts. This is despite the fact that these winged males, like ergatoid males, represent mating competition. Why should ergatoid males tolerate their winged rivals? We developed a mathematical model to address this question. Our model focuses on a number of factors likely toinfluence whether ergatoid males are tolerant of winged males: ergatoid male–winged male relatedness, number of virgin queens, number of winged males, and the number of ejaculates a winged male has (winged males are sperm limited, whereas ergatoid males have lifelong spermatogenesis). Surprisingly, we found that increasing the number of virgin queens favors a kill strategy, whereas an increase in the other factors favors a let-live strategy; these predictions appear true for C. obscurior and for a number of other Cardiocondyla species. Two further aspects, unequal insemination success and multiple mating in queens, were also incorporated into the model and predictions made about their effects on toleration of winged males. The model is applicable more generally in species that have dimorphic males, such as some other ants, bees, and fig wasps.}, author = {Anderson, Carl and Cremer, Sylvia and Heinze, Jürgen}, journal = {Behavioral Ecology}, number = {1}, pages = {54 -- 62}, publisher = {Oxford University Press}, title = {{Live and let die: Why fighter males of the ant Cardiocondyla kill each other but tolerate their winged rivals}}, doi = {10.1093/beheco/14.1.54}, volume = {14}, year = {2003}, } @article{3922, abstract = {Dispersal is advantageous, but, at the same time, it implies high costs and risks. Due to these counteracting selection pressures, many species evolved dispersal polymorphisms, which, in ants, are typically restricted to the female sex (queens). Male polymorphism is presently only known from a few genera, such as Cardiocondyla, in which winged dispersing males coexist with wingless fighter males that mate exclusively inside their maternal nests. We studied the developmental mechanisms underlying these alternative male morphs and found that, first, male dimorphism is not genetically determined, but is induced by environmental conditions (decreasing temperature and density). Second, male morph is not yet fixed at the egg stage, but it differentiates during larval development. This flexible developmental pattern of male morphs allows Cardiocondyla ant colonies to react quickly to changes in their environment. Under good conditions, they invest exclusively in philopatric wingless males. But, when environmental conditions turn bad, colonies start to produce winged dispersal males, even though these males require a many times higher investment by the colony than their much smaller wingless counterparts. Cardiocondyla ants share this potential of optimal resource allocation with other colonial animals and some seed dimorphic plants.}, author = {Cremer, Sylvia and Heinze, Jürgen}, journal = {Current Biology}, number = {3}, pages = {219 -- 223}, publisher = {Cell Press}, title = {{Stress grows wings: Environmental induction of winged dispersal males in Cardiocondyla ants}}, doi = {10.1016/S0960-9822(03)00012-5}, volume = {13}, year = {2003}, } @article{3917, abstract = {Male dimorphism is not genetically determined, but is induced by environmental conditions particularly decreasing temperature and density.}, author = {Cremer, Sylvia and Heinze, Jürgen}, journal = {Blick in die Wissenschaft}, number = {15}, pages = {32 -- 36}, publisher = {Schnell und Steiner}, title = {{Zwischen Hochzeitsflug und Brudermord: reproduktive Taktiken bei Ameisenmännchen}}, volume = {12}, year = {2003}, } @phdthesis{4416, abstract = {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.}, author = {Majumdar, Ritankar}, pages = {1 -- 201}, publisher = {University of California, Berkeley}, title = {{Symbolic algorithms for verification and control}}, year = {2003}, } @phdthesis{4425, abstract = {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.}, author = {Horowitz, Benjamin}, pages = {1 -- 237}, publisher = {University of California, Berkeley}, title = {{Giotto: A time-triggered language for embedded programming}}, year = {2003}, } @article{576, abstract = {We study the free expansion of a pancake-shaped Bose-condensed gas, which is initially trapped under harmonic confinement and containing a vortex at its centre. In the case of a radial expansion holding the axial confinement fixed we consider various models for the interactions, depending on the thickness of the condensate relative to the value of the scattering length. We are thus able to evaluate different scattering regimes ranging from quasi-three-dimensional (Q3D) to strictly two-dimensional (2D). We find that as the system goes from Q3D to 2D the expansion rate of the condensate increases whereas that of the vortex core decreases. In the Q3D scattering regime we also examine a fully free expansion in 3D and find oscillatory behaviour for the vortex core radius: an initial fast expansion of the vortex core is followed by a slowing down. Such a nonuniform expansion rate of the vortex core implies that the timing of its observation should be chosen appropriately.}, author = {Onur Hosten and Vignolo, Patrizia and Minguzzi, Anna and Tanatar, Bilal and Tosi, Mario P}, journal = {Journal of Physics B: Atomic, Molecular and Optical Physics}, number = {12}, pages = {2455 -- 2463}, publisher = {IOP Publishing Ltd.}, title = {{Free expansion of two-dimensional condensates with a vortex}}, doi = {10.1088/0953-4075/36/12/306}, volume = {36}, year = {2003}, } @article{6156, abstract = {Social and solitary feeding in natural Caenorhabditis elegans isolates are associated with two alleles of the orphan G-protein-coupled receptor (GPCR) NPR-1: social feeders contain NPR-1 215F, whereas solitary feeders contain NPR-1 215V. Here we identify FMRFamide-related neuropeptides (FaRPs) encoded by the flp-18 and flp-21 genes as NPR-1 ligands and show that these peptides can differentially activate the NPR-1 215F and NPR-1 215V receptors. Multicopy overexpression of flp-21 transformed wild social animals into solitary feeders. Conversely, a flp-21 deletion partially phenocopied the npr-1(null) phenotype, which is consistent with NPR-1 activation by FLP-21 in vivo but also implicates other ligands for NPR-1. Phylogenetic studies indicate that the dominant npr-1 215V allele likely arose from an ancestral npr-1 215F gene in C. elegans. Our data suggest a model in which solitary feeding evolved in an ancestral social strain of C. elegans by a gain-of-function mutation that modified the response of NPR-1 to FLP-18 and FLP-21 ligands.}, author = {Rogers, Candida and Reale, Vincenzina and Kim, Kyuhyung and Chatwin, Heather and Li, Chris and Evans, Peter and de Bono, Mario}, issn = {1097-6256}, journal = {Nature Neuroscience}, number = {11}, pages = {1178--1185}, publisher = {Springer Nature}, title = {{Inhibition of Caenorhabditis elegans social feeding by FMRFamide-related peptide activation of NPR-1}}, doi = {10.1038/nn1140}, volume = {6}, year = {2003}, } @article{6157, abstract = {In many animal species individuals aggregate to live in groups. A range of experimental approaches in different animals, including studies of social feeding in nematodes, maternal behavior in rats and sheep, and pair-bonding in voles, are providing insights into the neural bases for these behaviors. These studies are delineating multiple neural circuits and gene networks in the brain that interact in ways that are as yet poorly understood to coordinate social behavior.}, author = {de Bono, Mario}, issn = {0022-3034}, journal = {Journal of Neurobiology}, number = {1}, pages = {78--92}, publisher = {Wiley}, title = {{Molecular approaches to aggregation behavior and social attachment}}, doi = {10.1002/neu.10162}, volume = {54}, year = {2003}, } @article{847, abstract = {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.}, author = {Sunyaev, Shamil R and Fyodor Kondrashov and Bork, Peer and Ramensky, Vasily}, journal = {Human Molecular Genetics}, number = {24}, pages = {3325 -- 3330}, publisher = {Oxford University Press}, title = {{Impact of selection, mutation rate and genetic drift on human genetic variation}}, doi = {10.1093/hmg/ddg359}, volume = {12}, year = {2003}, } @article{876, abstract = {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.}, author = {Fyodor Kondrashov and Koonin, Eugene V}, journal = {Trends in Genetics}, number = {3}, pages = {115 -- 119}, publisher = {Elsevier}, title = {{Evolution of alternative splicing: Deletions, insertions and origin of functional parts of proteins from intron sequences}}, doi = {10.1016/S0168-9525(02)00029-X}, volume = {19}, year = {2003}, } @article{9495, abstract = {RNA interference is a conserved process in which double-stranded RNA is processed into 21–25 nucleotide siRNAs that trigger posttranscriptional gene silencing. In addition, plants display a phenomenon termed RNA-directed DNA methylation (RdDM) in which DNA with sequence identity to silenced RNA is de novo methylated at its cytosine residues. This methylation is not only at canonical CpG sites but also at cytosines in CpNpG and asymmetric sequence contexts. In this report, we study the role of the DRM and CMT3 DNA methyltransferase genes in the initiation and maintenance of RdDM. Neither drm nor cmt3 mutants affected the maintenance of preestablished RNA-directed CpG methylation. However, drm mutants showed a nearly complete loss of asymmetric methylation and a partial loss of CpNpG methylation. The remaining asymmetric and CpNpG methylation was dependent on the activity of CMT3, showing that DRM and CMT3 act redundantly to maintain non-CpG methylation. These DNA methyltransferases appear to act downstream of siRNAs, since drm1 drm2 cmt3 triple mutants show a lack of non-CpG methylation but elevated levels of siRNAs. Finally, we demonstrate that DRM activity is required for the initial establishment of RdDM in all sequence contexts including CpG, CpNpG, and asymmetric sites.}, author = {Cao, Xiaofeng and Aufsatz, Werner and Zilberman, Daniel and Mette, M.Florian and Huang, Michael S. and Matzke, Marjori and Jacobsen, Steven E.}, issn = {1879-0445}, journal = {Current Biology}, number = {24}, pages = {2212--2217}, publisher = {Elsevier}, title = {{Role of the DRM and CMT3 methyltransferases in RNA-directed DNA methylation}}, doi = {10.1016/j.cub.2003.11.052}, volume = {13}, year = {2003}, } @article{8519, author = {Kaloshin, Vadim}, issn = {0020-9910}, journal = {Inventiones mathematicae}, keywords = {General Mathematics}, number = {3}, pages = {451--512}, publisher = {Springer Nature}, title = {{The existential Hilbert 16-th problem and an estimate for cyclicity of elementary polycycles}}, doi = {10.1007/s00222-002-0244-9}, volume = {151}, year = {2003}, }