TY - JOUR
AB - Changes in gene expression are an important mode of evolution; however, the proximate mechanism of these changes is poorly understood. In particular, little is known about the effects of mutations within cis binding sites for transcription factors, or the nature of epistatic interactions between these mutations. Here, we tested the effects of single and double mutants in two cis binding sites involved in the transcriptional regulation of the Escherichia coli araBAD operon, a component of arabinose metabolism, using a synthetic system. This system decouples transcriptional control from any posttranslational effects on fitness, allowing a precise estimate of the effect of single and double mutations, and hence epistasis, on gene expression. We found that epistatic interactions between mutations in the araBAD cis-regulatory element are common, and that the predominant form of epistasis is negative. The magnitude of the interactions depended on whether the mutations are located in the same or in different operator sites. Importantly, these epistatic interactions were dependent on the presence of arabinose, a native inducer of the araBAD operon in vivo, with some interactions changing in sign (e.g., from negative to positive) in its presence. This study thus reveals that mutations in even relatively simple cis-regulatory elements interact in complex ways such that selection on the level of gene expression in one environment might perturb regulation in the other environment in an unpredictable and uncorrelated manner.
AU - Lagator, Mato
AU - Igler, Claudia
AU - Moreno, Anaisa
AU - Guet, Calin C
AU - Bollback, Jonathan P
ID - 1427
IS - 3
JF - Molecular Biology and Evolution
TI - Epistatic interactions in the arabinose cis-regulatory element
VL - 33
ER -
TY - CONF
AB - We report on a mathematically rigorous analysis of the superfluid properties of a Bose- Einstein condensate in the many-body ground state of a one-dimensional model of interacting bosons in a random potential.
AU - Könenberg, Martin
AU - Moser, Thomas
AU - Seiringer, Robert
AU - Yngvason, Jakob
ID - 1428
IS - 1
T2 - Journal of Physics: Conference Series
TI - Superfluidity and BEC in a Model of Interacting Bosons in a Random Potential
VL - 691
ER -
TY - JOUR
AB - Solitons are localized waves formed by a balance of focusing and defocusing effects. These nonlinear waves exist in diverse forms of matter yet exhibit similar properties including stability, periodic recurrence and particle-like trajectories. One important property is soliton fission, a process by which an energetic higher-order soliton breaks apart due to dispersive or nonlinear perturbations. Here we demonstrate through both experiment and theory that nonlinear photocarrier generation can induce soliton fission. Using near-field measurements, we directly observe the nonlinear spatial and temporal evolution of optical pulses in situ in a nanophotonic semiconductor waveguide. We develop an analytic formalism describing the free-carrier dispersion (FCD) perturbation and show the experiment exceeds the minimum threshold by an order of magnitude. We confirm these observations with a numerical nonlinear Schrödinger equation model. These results provide a fundamental explanation and physical scaling of optical pulse evolution in free-carrier media and could enable improved supercontinuum sources in gas based and integrated semiconductor waveguides.
AU - Husko, Chad
AU - Wulf, Matthias
AU - Lefrançois, Simon
AU - Combrié, Sylvain
AU - Lehoucq, Gaëlle
AU - De Rossi, Alfredo
AU - Eggleton, Benjamin
AU - Kuipers, Laurens
ID - 1429
JF - Nature Communications
TI - Free-carrier-induced soliton fission unveiled by in situ measurements in nanophotonic waveguides
VL - 7
ER -
TY - JOUR
AB - The rare socially parasitic butterfly Maculinea alcon occurs in two forms, which are characteristic of hygric or xeric habitats and which exploit different host plants and host ants. The status of these two forms has been the subject of considerable controversy. Populations of the two forms are usually spatially distinct, but at Răscruci in Romania both forms occur on the same site (syntopically). We examined the genetic differentiation between the two forms using eight microsatellite markers, and compared with a nearby hygric site, Şardu. Our results showed that while the two forms are strongly differentiated at Răscruci, it is the xeric form there that is most similar to the hygric form at Şardu, and Bayesian clustering algorithms suggest that these two populations have exchanged genes relatively recently. We found strong evidence for population substructuring, caused by high within host ant nest relatedness, indicating very limited dispersal of most ovipositing females, but not association with particular host ant species. Our results are consistent with the results of larger scale phylogeographic studies that suggest that the two forms represent local ecotypes specialising on different host plants, each with a distinct flowering phenology, providing a temporal rather than spatial barrier to gene flow.
AU - Tartally, András
AU - Kelager, Andreas
AU - Fürst, Matthias
AU - Nash, David
ID - 1431
IS - 3
JF - PeerJ
TI - Host plant use drives genetic differentiation in syntopic populations of Maculinea alcon
VL - 2016
ER -
TY - JOUR
AB - CA3–CA3 recurrent excitatory synapses are thought to play a key role in memory storage and pattern completion. Whether the plasticity properties of these synapses are consistent with their proposed network functions remains unclear. Here, we examine the properties of spike timing-dependent plasticity (STDP) at CA3–CA3 synapses. Low-frequency pairing of excitatory postsynaptic potentials (EPSPs) and action potentials (APs) induces long-term potentiation (LTP), independent of temporal order. The STDP curve is symmetric and broad (half-width ~150 ms). Consistent with these STDP induction properties, AP–EPSP sequences lead to supralinear summation of spine [Ca2+] transients. Furthermore, afterdepolarizations (ADPs) following APs efficiently propagate into dendrites of CA3 pyramidal neurons, and EPSPs summate with dendritic ADPs. In autoassociative network models, storage and recall are more robust with symmetric than with asymmetric STDP rules. Thus, a specialized STDP induction rule allows reliable storage and recall of information in the hippocampal CA3 network.
AU - Mishra, Rajiv Kumar
AU - Kim, Sooyun
AU - Guzmán, José
AU - Jonas, Peter M
ID - 1432
JF - Nature Communications
TI - Symmetric spike timing-dependent plasticity at CA3–CA3 synapses optimizes storage and recall in autoassociative networks
VL - 7
ER -
TY - JOUR
AB - We prove that the system of subordination equations, defining the free additive convolution of two probability measures, is stable away from the edges of the support and blow-up singularities by showing that the recent smoothness condition of Kargin is always satisfied. As an application, we consider the local spectral statistics of the random matrix ensemble A+UBU⁎A+UBU⁎, where U is a Haar distributed random unitary or orthogonal matrix, and A and B are deterministic matrices. In the bulk regime, we prove that the empirical spectral distribution of A+UBU⁎A+UBU⁎ concentrates around the free additive convolution of the spectral distributions of A and B on scales down to N−2/3N−2/3.
AU - Bao, Zhigang
AU - Erdös, László
AU - Schnelli, Kevin
ID - 1434
IS - 3
JF - Journal of Functional Analysis
TI - Local stability of the free additive convolution
VL - 271
ER -
TY - JOUR
AB - ATP released from neurons and astrocytes during neuronal activity or under pathophysiological circumstances is able to influence information flow in neuronal circuits by activation of ionotropic P2X and metabotropic P2Y receptors and subsequent modulation of cellular excitability, synaptic strength, and plasticity. In the present paper we review cellular and network effects of P2Y receptors in the brain. We show that P2Y receptors inhibit the release of neurotransmitters, modulate voltage- and ligand-gated ion channels, and differentially influence the induction of synaptic plasticity in the prefrontal cortex, hippocampus, and cerebellum. The findings discussed here may explain how P2Y1 receptor activation during brain injury, hypoxia, inflammation, schizophrenia, or Alzheimer's disease leads to an impairment of cognitive processes. Hence, it is suggested that the blockade of P2Y1 receptors may have therapeutic potential against cognitive disturbances in these states.
AU - Guzmán, José
AU - Gerevich, Zoltan
ID - 1435
JF - Neural Plasticity
TI - P2Y receptors in synaptic transmission and plasticity: Therapeutic potential in cognitive dysfunction
VL - 2016
ER -
TY - JOUR
AB - We study the time evolution of a system of N spinless fermions in R3 which interact through a pair potential, e.g., the Coulomb potential. We compare the dynamics given by the solution to Schrödinger's equation with the time-dependent Hartree-Fock approximation, and we give an estimate for the accuracy of this approximation in terms of the kinetic energy of the system. This leads, in turn, to bounds in terms of the initial total energy of the system.
AU - Bach, Volker
AU - Breteaux, Sébastien
AU - Petrat, Sören P
AU - Pickl, Peter
AU - Tzaneteas, Tim
ID - 1436
IS - 1
JF - Journal de Mathématiques Pures et Appliquées
TI - Kinetic energy estimates for the accuracy of the time-dependent Hartree-Fock approximation with Coulomb interaction
VL - 105
ER -
TY - CONF
AB - In this paper, we consider termination of probabilistic programs with real-valued variables. The questions concerned are: (a) qualitative ones that ask (i) whether the program terminates with probability 1 (almost-sure termination) and (ii) whether the expected termination time is finite (finite termination); (b) quantitative ones that ask (i) to approximate the expected termination time (expectation problem) and (ii) to compute a bound B such that the probability to terminate after B steps decreases exponentially (concentration problem). To solve these questions, we utilize the notion of ranking supermartingales which is a powerful approach for proving termination of probabilistic programs. In detail, we focus on algorithmic synthesis of linear ranking-supermartingales over affine probabilistic programs (APP's) with both angelic and demonic non-determinism. An important subclass of APP's is LRAPP which is defined as the class of all APP's over which a linear ranking-supermartingale exists. Our main contributions are as follows. Firstly, we show that the membership problem of LRAPP (i) can be decided in polynomial time for APP's with at most demonic non-determinism, and (ii) is NP-hard and in PSPACE for APP's with angelic non-determinism; moreover, the NP-hardness result holds already for APP's without probability and demonic non-determinism. Secondly, we show that the concentration problem over LRAPP can be solved in the same complexity as for the membership problem of LRAPP. Finally, we show that the expectation problem over LRAPP can be solved in 2EXPTIME and is PSPACE-hard even for APP's without probability and non-determinism (i.e., deterministic programs). Our experimental results demonstrate the effectiveness of our approach to answer the qualitative and quantitative questions over APP's with at most demonic non-determinism.
AU - Chatterjee, Krishnendu
AU - Fu, Hongfei
AU - Novotny, Petr
AU - Hasheminezhad, Rouzbeh
ID - 1438
TI - Algorithmic analysis of qualitative and quantitative termination problems for affine probabilistic programs
VL - 20-22
ER -
TY - CONF
AB - Fault-tolerant distributed algorithms play an important role in many critical/high-availability applications. These algorithms are notoriously difficult to implement correctly, due to asynchronous communication and the occurrence of faults, such as the network dropping messages or computers crashing. We introduce PSYNC, a domain specific language based on the Heard-Of model, which views asynchronous faulty systems as synchronous ones with an adversarial environment that simulates asynchrony and faults by dropping messages. We define a runtime system for PSYNC that efficiently executes on asynchronous networks. We formalize the relation between the runtime system and PSYNC in terms of observational refinement. The high-level lockstep abstraction introduced by PSYNC simplifies the design and implementation of fault-tolerant distributed algorithms and enables automated formal verification. We have implemented an embedding of PSYNC in the SCALA programming language with a runtime system for asynchronous networks. We show the applicability of PSYNC by implementing several important fault-tolerant distributed algorithms and we compare the implementation of consensus algorithms in PSYNC against implementations in other languages in terms of code size, runtime efficiency, and verification.
AU - Dragoi, Cezara
AU - Henzinger, Thomas A
AU - Zufferey, Damien
ID - 1439
TI - PSYNC: A partially synchronous language for fault-tolerant distributed algorithms
VL - 20-22
ER -