A rule-based kinetic model of RNA polymerase II C-terminal domain phosphorylation

The complexity ofmany RNA processing pathways is such that a conventional systemsmodelling approach is inadequate to represent all themolecular species involved. We demonstrate that rule-based modelling permits a detailed model of a complex RNA signalling pathway to be defined. Phosphorylation of the RNApolymerase II (RNAPII)C-terminal domain (CTD; a flexible tail-like extension of the largest subunit) couples pre-messenger RNA capping, splicing and 30 end maturation to transcriptional elongation and termination, and plays a central role in integrating these processes. The phosphorylation states of the serine residues of many heptapeptide repeats of the CTD alter along the coding region of genes as a function of distance from the promoter. From a mechanistic perspective, both the changes in phosphorylation and the location atwhich they take place on the genes are a function of the time spent byRNAPII in elongation as this interval provides the opportunity for the kinases and phosphatases to interactwith theCTD.On this basis,we synthesize the available data to create a kinetic model of the action of the known kinases and phosphatases to resolve the phosphorylation pathways and their kinetics.</p

Insulation bonding test system

A method and a system for testing the bonding of foam insulation attached to metal is described. The system involves the use of an impacter which has a calibrated load cell mounted on a plunger and a hammer head mounted on the end of the plunger. When the impacter strikes the insulation at a point to be tested, the load cell measures the force of the impact and the precise time interval during which the hammer head is in contact with the insulation. This information is transmitted as an electrical signal to a load cell amplifier where the signal is conditioned and then transmitted to a fast Fourier transform (FFT) analyzer. The FFT analyzer produces energy spectral density curves which are displayed on a video screen. The termination frequency of the energy spectral density curve may be compared with a predetermined empirical scale to determine whether a igh quality bond, good bond, or debond is present at the point of impact

Non-Geometric Fluxes, Quasi-Hopf Twist Deformations and Nonassociative Quantum Mechanics

We analyse the symmetries underlying nonassociative deformations of geometry in non-geometric R-flux compactifications which arise via T-duality from closed strings with constant geometric fluxes. Starting from the non-abelian Lie algebra of translations and Bopp shifts in phase space, together with a suitable cochain twist, we construct the quasi-Hopf algebra of symmetries that deforms the algebra of functions and the exterior differential calculus in the phase space description of nonassociative R-space. In this setting nonassociativity is characterised by the associator 3-cocycle which controls non-coassociativity of the quasi-Hopf algebra. We use abelian 2-cocycle twists to construct maps between the dynamical nonassociative star product and a family of associative star products parametrized by constant momentum surfaces in phase space. We define a suitable integration on these nonassociative spaces and find that the usual cyclicity of associative noncommutative deformations is replaced by weaker notions of 2-cyclicity and 3-cyclicity. Using this star product quantization on phase space together with 3-cyclicity, we formulate a consistent version of nonassociative quantum mechanics, in which we calculate the expectation values of area and volume operators, and find coarse-graining of the string background due to the R-flux.Comment: 38 pages; v2: typos corrected, reference added; v3: typos corrected, comments about cyclicity added in section 4.2, references updated; Final version to be published in Journal of Mathematical Physic

Periodic Neural Activity Induced by Network Complexity

We study a model for neural activity on the small-world topology of Watts and Strogatz and on the scale-free topology of Barab\'asi and Albert. We find that the topology of the network connections may spontaneously induce periodic neural activity, contrasting with chaotic neural activities exhibited by regular topologies. Periodic activity exists only for relatively small networks and occurs with higher probability when the rewiring probability is larger. The average length of the periods increases with the square root of the network size.Comment: 4 pages, 5 figure

Signal integration enhances the dynamic range in neuronal systems

The dynamic range measures the capacity of a system to discriminate the intensity of an external stimulus. Such an ability is fundamental for living beings to survive: to leverage resources and to avoid danger. Consequently, the larger is the dynamic range, the greater is the probability of survival. We investigate how the integration of different input signals affects the dynamic range, and in general the collective behavior of a network of excitable units. By means of numerical simulations and a mean-field approach, we explore the nonequilibrium phase transition in the presence of integration. We show that the firing rate in random and scale-free networks undergoes a discontinuous phase transition depending on both the integration time and the density of integrator units. Moreover, in the presence of external stimuli, we find that a system of excitable integrator units operating in a bistable regime largely enhances its dynamic range.Comment: 5 pages, 4 figure

A complex pathway for 3 ' processing of the yeast U3 snoRNA

Mature U3 snoRNA in yeast is generated from the 3′-extended precursors by endonucleolytic cleavage followed by exonucleolytic trimming. These precursors terminate in poly(U) tracts and are normally stabilised by binding of the yeast La homologue, Lhp1p. We report that normal 3′ processing of U3 requires the nuclear Lsm proteins. On depletion of any of the five essential proteins, Lsm2–5p or Lsm8p, the normal 3′-extended precursors to the U3 snoRNA were lost. Truncated fragments of both mature and pre-U3 accumulated in the Lsm-depleted strains, consistent with substantial RNA degradation. Pre-U3 species were co-precipitated with TAP-tagged Lsm3p, but the association with spliced pre-U3 was lost in strains lacking Lhp1p. The association of Lhp1p with pre-U3 was also reduced on depletion of Lsm3p or Lsm5p, indicating that binding of Lhp1p and the Lsm proteins is interdependent. In contrast, a tagged Sm-protein detectably co-precipitated spliced pre-U3 species only in strains lacking Lhp1p. We propose that the Lsm2–8p complex functions as a chaperone in conjunction with Lhp1p to stabilise pre-U3 RNA species during 3′ processing. The Sm complex may function as a back-up to stabilise 3′ ends that are not protected by Lhp1p

Interaction of yeast eIF4G with spliceosome components Implications in pre-mRNA processing events

International audienceAs evidenced from mammalian cells the eukaryotic translation initiation factor eIF4G has a putative role in nuclear RNA metabolism. Here we investigate whether this role is conserved in the yeast Saccharomyces cerevisiae. Using a combination of in vitro and in vivo methods, we show that, similar to mammalian eIF4G, yeast eIF4G homologues, Tif4631p and Tif4632p, are present both in the nucleus and the cytoplasm. We show that both eIF4G proteins interact efficiently in vitro with UsnRNP components of the splicing machinery. More specifically, Tif4631p and Tif4632p interact efficiently with U1 snRNA in vitro. In addition, Tif4631p and Tif4632p associate with protein components of the splicing machinery, namely Snu71p and Prp11p. To further delineate these interactions, we map the regions of Tif4631p and Tif4632p that are important for the interaction with Prp11p and Snu71p and we show that addition of these regions to splicing reactions in vitro has a dominant inhibitory effect. The observed interactions implicate eIF4G in aspects of pre-mRNA processing. In support of this hypothesis, deletion of one of the eIF4G isoforms results in accumulation of un-spliced precursors for a number of endogenous genes, in vivo. In conclusion these observations are suggestive of the involvement of yeast eIF4G in pre-mRNA metabolism

Bandit Online Optimization Over the Permutahedron

The permutahedron is the convex polytope with vertex set consisting of the vectors $(\pi(1),\dots, \pi(n))$ for all permutations (bijections) $\pi$ over $\{1,\dots, n\}$. We study a bandit game in which, at each step $t$, an adversary chooses a hidden weight weight vector $s_t$, a player chooses a vertex $\pi_t$ of the permutahedron and suffers an observed loss of $\sum_{i=1}^n \pi(i) s_t(i)$. A previous algorithm CombBand of Cesa-Bianchi et al (2009) guarantees a regret of $O(n\sqrt{T \log n})$ for a time horizon of $T$. Unfortunately, CombBand requires at each step an $n$-by-$n$ matrix permanent approximation to within improved accuracy as $T$ grows, resulting in a total running time that is super linear in $T$, making it impractical for large time horizons. We provide an algorithm of regret $O(n^{3/2}\sqrt{T})$ with total time complexity $O(n^3T)$. The ideas are a combination of CombBand and a recent algorithm by Ailon (2013) for online optimization over the permutahedron in the full information setting. The technical core is a bound on the variance of the Plackett-Luce noisy sorting process's "pseudo loss". The bound is obtained by establishing positive semi-definiteness of a family of 3-by-3 matrices generated from rational functions of exponentials of 3 parameters

Scaling law for the transient behavior of type-II neuron models

We study the transient regime of type-II biophysical neuron models and determine the scaling behavior of relaxation times $\tau$ near but below the repetitive firing critical current, $\tau \simeq C (I_c-I)^{-\Delta}$. For both the Hodgkin-Huxley and Morris-Lecar models we find that the critical exponent is independent of the numerical integration time step and that both systems belong to the same universality class, with $\Delta = 1/2$. For appropriately chosen parameters, the FitzHugh-Nagumo model presents the same generic transient behavior, but the critical region is significantly smaller. We propose an experiment that may reveal nontrivial critical exponents in the squid axon.Comment: 6 pages, 9 figures, accepted for publication in Phys. Rev.

The Serre spectral sequence of a noncommutative fibration for de Rham cohomology

For differential calculi on noncommutative algebras, we construct a twisted de Rham cohomology using flat connections on modules. This has properties similar, in some respects, to sheaf cohomology on topological spaces. We also discuss generalised mapping properties of these theories, and relations of these properties to corings. Using this, we give conditions for the Serre spectral sequence to hold for a noncommutative fibration. This might be better read as giving the definition of a fibration in noncommutative differential geometry. We also study the multiplicative structure of such spectral sequences. Finally we show that some noncommutative homogeneous spaces satisfy the conditions to be such a fibration, and in the process clarify the differential structure on these homogeneous spaces. We also give two explicit examples of differential fibrations: these are built on the quantum Hopf fibration with two different differential structures.Comment: LaTeX, 33 page