TY - JOUR
AB - Spontaneous release of glutamate is important for maintaining synaptic strength and controlling spike timing in the brain. Mechanisms regulating spontaneous exocytosis remain poorly understood. Extracellular calcium concentration ([Ca2+]o) regulates Ca2+ entry through voltage-activated calcium channels (VACCs) and consequently is a pivotal determinant of action potential-evoked vesicle fusion. Extracellular Ca 2+ also enhances spontaneous release, but via unknown mechanisms. Here we report that external Ca2+ triggers spontaneous glutamate release more weakly than evoked release in mouse neocortical neurons. Blockade of VACCs has no effect on the spontaneous release rate or its dependence on [Ca2+]o. Intracellular [Ca2+] slowly increases in a minority of neurons following increases in [Ca2+]o. Furthermore, the enhancement of spontaneous release by extracellular calcium is insensitive to chelation of intracellular calcium by BAPTA. Activation of the calcium-sensing receptor (CaSR), a G-protein-coupled receptor present in nerve terminals, by several specific agonists increased spontaneous glutamate release. The frequency of spontaneous synaptic transmission was decreased in CaSR mutant neurons. The concentration-effect relationship for extracellular calcium regulation of spontaneous release was well described by a combination of CaSR-dependent and CaSR-independent mechanisms. Overall these results indicate that extracellular Ca2+ does not trigger spontaneous glutamate release by simply increasing calcium influx but stimulates CaSR and thereby promotes resting spontaneous glutamate release.
AU - Vyleta, Nicholas
AU - Smith, Stephen
ID - 469
IS - 12
JF - European Journal of Neuroscience
TI - Spontaneous glutamate release is independent of calcium influx and tonically activated by the calcium-sensing receptor
VL - 31
ER -
TY - JOUR
AB - BioSig is an open source software library for biomedical signal processing. The aim of the BioSig project is to foster research in biomedical signal processing by providing free and open source software tools for many different application areas. Some of the areas where BioSig can be employed are neuroinformatics, brain-computer interfaces, neurophysiology, psychology, cardiovascular systems, and sleep research. Moreover, the analysis of biosignals such as the electroencephalogram (EEG), electrocorticogram (ECoG), electrocardiogram (ECG), electrooculogram (EOG), electromyogram (EMG), or respiration signals is a very relevant element of the BioSig project. Specifically, BioSig provides solutions for data acquisition, artifact processing, quality control, feature extraction, classification, modeling, and data visualization, to name a few. In this paper, we highlight several methods to help students and researchers to work more efficiently with biomedical signals.
AU - Schlögl, Alois
AU - Vidaurre, Carmen
AU - Sander, Tilmann
ID - 490
JF - Computational Intelligence and Neuroscience
TI - BioSig: The free and open source software library for biomedical signal processing
VL - 2011
ER -
TY - JOUR
AB - Cancer stem cells or cancer initiating cells are believed to contribute to cancer recurrence after therapy. MicroRNAs (miRNAs) are short RNA molecules with fundamental roles in gene regulation. The role of miRNAs in cancer stem cells is only poorly understood. Here, we report miRNA expression profiles of glioblastoma stem cell-containing CD133 + cell populations. We find that miR-9, miR-9 * (referred to as miR-9/9 *), miR-17 and miR-106b are highly abundant in CD133 + cells. Furthermore, inhibition of miR-9/9 * or miR-17 leads to reduced neurosphere formation and stimulates cell differentiation. Calmodulin-binding transcription activator 1 (CAMTA1) is a putative transcription factor, which induces the expression of the anti-proliferative cardiac hormone natriuretic peptide A (NPPA). We identify CAMTA1 as an miR-9/9 * and miR-17 target. CAMTA1 expression leads to reduced neurosphere formation and tumour growth in nude mice, suggesting that CAMTA1 can function as tumour suppressor. Consistently, CAMTA1 and NPPA expression correlate with patient survival. Our findings could provide a basis for novel strategies of glioblastoma therapy.
AU - Schraivogel, Daniel
AU - Weinmann, Lasse
AU - Beier, Dagmar
AU - Tabatabai, Ghazaleh
AU - Eichner, Alexander
AU - Zhu, Jia
AU - Anton, Martina
AU - Sixt, Michael K
AU - Weller, Michael
AU - Beier, Christoph
AU - Meister, Gunter
ID - 518
IS - 20
JF - EMBO Journal
TI - CAMTA1 is a novel tumour suppressor regulated by miR-9/9 * in glioblastoma stem cells
VL - 30
ER -
TY - JOUR
AB - Software transactional memories (STM) are described in the literature with assumptions of sequentially consistent program execution and atomicity of high level operations like read, write, and abort. However, in a realistic setting, processors use relaxed memory models to optimize hardware performance. Moreover, the atomicity of operations depends on the underlying hardware. This paper presents the first approach to verify STMs under relaxed memory models with atomicity of 32 bit loads and stores, and read-modify-write operations. We describe RML, a simple language for expressing concurrent programs. We develop a semantics of RML parametrized by a relaxed memory model. We then present our tool, FOIL, which takes as input the RML description of an STM algorithm restricted to two threads and two variables, and the description of a memory model, and automatically determines the locations of fences, which if inserted, ensure the correctness of the restricted STM algorithm under the given memory model. We use FOIL to verify DSTM, TL2, and McRT STM under the memory models of sequential consistency, total store order, partial store order, and relaxed memory order for two threads and two variables. Finally, we extend the verification results for DSTM and TL2 to an arbitrary number of threads and variables by manually proving that the structural properties of STMs are satisfied at the hardware level of atomicity under the considered relaxed memory models.
AU - Guerraoui, Rachid
AU - Henzinger, Thomas A
AU - Singh, Vasu
ID - 531
IS - 3
JF - Formal Methods in System Design
TI - Verification of STM on relaxed memory models
VL - 39
ER -
TY - GEN
AB - Computing the winning set for Büchi objectives in alternating games on graphs is a central problem in computer aided verification with a large number of applications. The long standing best known upper bound for solving the problem is ̃O(n·m), where n is the number of vertices and m is the number of edges in the graph. We are the first to break the ̃O(n·m) boundary by presenting a new technique that reduces the running time to O(n2). This bound also leads to O(n2) time algorithms for computing the set of almost-sure winning vertices for Büchi objectives (1) in alternating games with probabilistic transitions (improving an earlier bound of O(n·m)), (2) in concurrent graph games with constant actions (improving an earlier bound of O(n3)), and (3) in Markov decision processes (improving for m > n4/3 an earlier bound of O(min(m1.5, m·n2/3)). We also show that the same technique can be used to compute the maximal end-component decomposition of a graph in time O(n2), which is an improvement over earlier bounds for m > n4/3. Finally, we show how to maintain the winning set for Büchi objectives in alternating games under a sequence of edge insertions or a sequence of edge deletions in O(n) amortized time per operation. This is the first dynamic algorithm for this problem.
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika
ID - 5379
SN - 2664-1690
TI - An O(n2) time algorithm for alternating Büchi games
ER -
TY - GEN
AB - We consider 2-player games played on a finite state space for an infinite number of rounds. The games are concurrent: in each round, the two players (player 1 and player 2) choose their moves independently and simultaneously; the current state and the two moves determine the successor state. We study concurrent games with ω-regular winning conditions specified as parity objectives. We consider the qualitative analysis problems: the computation of the almost-sure and limit-sure winning set of states, where player 1 can ensure to win with probability 1 and with probability arbitrarily close to 1, respectively. In general the almost-sure and limit-sure winning strategies require both infinite-memory as well as infinite-precision (to describe probabilities). We study the bounded-rationality problem for qualitative analysis of concurrent parity games, where the strategy set for player 1 is restricted to bounded-resource strategies. In terms of precision, strategies can be deterministic, uniform, finite-precision or infinite-precision; and in terms of memory, strategies can be memoryless, finite-memory or infinite-memory. We present a precise and complete characterization of the qualitative winning sets for all combinations of classes of strategies. In particular, we show that uniform memoryless strategies are as powerful as finite-precision infinite-memory strategies, and infinite-precision memoryless strategies are as powerful as infinite-precision finite-memory strategies. We show that the winning sets can be computed in O(n2d+3) time, where n is the size of the game structure and 2d is the number of priorities (or colors), and our algorithms are symbolic. The membership problem of whether a state belongs to a winning set can be decided in NP ∩ coNP. While this complexity is the same as for the simpler class of turn-based parity games, where in each state only one of the two players has a choice of moves, our algorithms,that are obtained by characterization of the winning sets as μ-calculus formulas, are considerably more involved than those for turn-based games.
AU - Chatterjee, Krishnendu
ID - 5380
SN - 2664-1690
TI - Bounded rationality in concurrent parity games
ER -
TY - GEN
AB - In two-player finite-state stochastic games of partial obser- vation on graphs, in every state of the graph, the players simultaneously choose an action, and their joint actions determine a probability distri- bution over the successor states. The game is played for infinitely many rounds and thus the players construct an infinite path in the graph. We consider reachability objectives where the first player tries to ensure a target state to be visited almost-surely (i.e., with probability 1) or pos- itively (i.e., with positive probability), no matter the strategy of the second player.
We classify such games according to the information and to the power of randomization available to the players. On the basis of information, the game can be one-sided with either (a) player 1, or (b) player 2 having partial observation (and the other player has perfect observation), or two- sided with (c) both players having partial observation. On the basis of randomization, (a) the players may not be allowed to use randomization (pure strategies), or (b) they may choose a probability distribution over actions but the actual random choice is external and not visible to the player (actions invisible), or (c) they may use full randomization.
Our main results for pure strategies are as follows: (1) For one-sided games with player 2 perfect observation we show that (in contrast to full randomized strategies) belief-based (subset-construction based) strate- gies are not sufficient, and present an exponential upper bound on mem- ory both for almost-sure and positive winning strategies; we show that the problem of deciding the existence of almost-sure and positive winning strategies for player 1 is EXPTIME-complete and present symbolic algo- rithms that avoid the explicit exponential construction. (2) For one-sided games with player 1 perfect observation we show that non-elementary memory is both necessary and sufficient for both almost-sure and posi- tive winning strategies. (3) We show that for the general (two-sided) case finite-memory strategies are sufficient for both positive and almost-sure winning, and at least non-elementary memory is required. We establish the equivalence of the almost-sure winning problems for pure strategies and for randomized strategies with actions invisible. Our equivalence re- sult exhibit serious flaws in previous results in the literature: we show a non-elementary memory lower bound for almost-sure winning whereas an exponential upper bound was previously claimed.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 5381
SN - 2664-1690
TI - Partial-observation stochastic games: How to win when belief fails
ER -
TY - GEN
AB - We consider two-player stochastic games played on a finite state space for an infinite num- ber of rounds. The games are concurrent: in each round, the two players (player 1 and player 2) choose their moves independently and simultaneously; the current state and the two moves determine a probability distribution over the successor states. We also consider the important special case of turn-based stochastic games where players make moves in turns, rather than concurrently. We study concurrent games with ω-regular winning conditions specified as parity objectives. The value for player 1 for a parity objective is the maximal probability with which the player can guarantee the satisfaction of the objective against all strategies of the opponent. We study the problem of continuity and robustness of the value function in concurrent and turn-based stochastic parity games with respect to imprecision in the transition probabilities. We present quantitative bounds on the difference of the value function (in terms of the imprecision of the transition probabilities) and show the value continuity for structurally equivalent concurrent games (two games are structurally equivalent if the support of the transition func- tion is same and the probabilities differ). We also show robustness of optimal strategies for structurally equivalent turn-based stochastic parity games. Finally we show that the value continuity property breaks without the structurally equivalent assumption (even for Markov chains) and show that our quantitative bound is asymptotically optimal. Hence our results are tight (the assumption is both necessary and sufficient) and optimal (our quantitative bound is asymptotically optimal).
AU - Chatterjee, Krishnendu
ID - 5382
SN - 2664-1690
TI - Robustness of structurally equivalent concurrent parity games
ER -
TY - GEN
AB - We present a new decidable logic called TREX for expressing constraints about imperative tree data structures. In particular, TREX supports a transitive closure operator that can express reachability constraints, which often appear in data structure invariants. We show that our logic is closed under weakest precondition computation, which enables its use for automated software verification. We further show that satisfiability of formulas in TREX is decidable in NP. The low complexity makes it an attractive alternative to more expensive logics such as monadic second-order logic (MSOL) over trees, which have been traditionally used for reasoning about tree data structures.
AU - Wies, Thomas
AU - Muñiz, Marco
AU - Kuncak, Viktor
ID - 5383
SN - 2664-1690
TI - On an efficient decision procedure for imperative tree data structures
ER -
TY - GEN
AB - We consider probabilistic automata on infinite words with acceptance defined by parity conditions. We consider three qualitative decision problems: (i) the positive decision problem asks whether there is a word that is accepted with positive probability; (ii) the almost decision problem asks whether there is a word that is accepted with probability 1; and (iii) the limit decision problem asks whether for every ε > 0 there is a word that is accepted with probability at least 1 − ε. We unify and generalize several decidability results for probabilistic automata over infinite words, and identify a robust (closed under union and intersection) subclass of probabilistic automata for which all the qualitative decision problems are decidable for parity conditions. We also show that if the input words are restricted to lasso shape words, then the positive and almost problems are decidable for all probabilistic automata with parity conditions.
AU - Chatterjee, Krishnendu
AU - Tracol, Mathieu
ID - 5384
SN - 2664-1690
TI - Decidable problems for probabilistic automata on infinite words
ER -