Multiscale motion and deformation of bumps in stochastic neural fields with dynamic connectivity

The distinct timescales of synaptic plasticity and neural activity dynamics play an important role in the brain's learning and memory systems. Activity-dependent plasticity reshapes neural circuit architecture, determining spontaneous and stimulus-encoding spatiotemporal patterns of neural activity. Neural activity bumps maintain short term memories of continuous parameter values, emerging in spatially-organized models with short term excitation and long-range inhibition. Previously, we demonstrated nonlinear Langevin equations derived using an interface method accurately describe the dynamics of bumps in continuum neural fields with separate excitatory/inhibitory populations. Here we extend this analysis to incorporate effects of slow short term plasticity that modifies connectivity described by an integral kernel. Linear stability analysis adapted to these piecewise smooth models with Heaviside firing rates further indicate how plasticity shapes bumps' local dynamics. Facilitation (depression), which strengthens (weakens) synaptic connectivity originating from active neurons, tends to increase (decrease) stability of bumps when acting on excitatory synapses. The relationship is inverted when plasticity acts on inhibitory synapses. Multiscale approximations of the stochastic dynamics of bumps perturbed by weak noise reveal the plasticity variables evolve to slowly diffusing and blurred versions of that arising in the stationary solution. Nonlinear Langevin equations associated with bump positions or interfaces coupled to slowly evolving projections of plasticity variables accurately describe the wandering of bumps underpinned by these smoothed synaptic efficacy profiles.Comment: 19 pages, 11 figure

E2F4 actively promotes the initiation and maintenance of nerve growth factor-induced cell differentiation

E2F transcription factors play a critical role in cell cycle progression through the regulation of genes required for G(1)/S transition. They are also thought to be important for growth arrest; however, their potential role in the cell differentiation process has not been previously examined. Here, we demonstrate that E2F4 is highly upregulated following the neuronal differentiation of PC12 cells with nerve growth factor (NGF), while E2F1, E2F3, and E2F5 are downregulated. Immunoprecipitation and subcellular fractionation studies demonstrated that both the nuclear localization of E2F4 and its association with the Rb family member p130 increased following neuronal differentiation. The forced expression of E2F4 markedly enhanced the rate of PC12 cell differentiation induced by NGF and also greatly lowered the rate at which cells lost their neuronal phenotype following NGF removal. Importantly, this effect occurred in the absence of any significant change in the growth regulation of PC12 cells by NGF. Further, the downregulation of E2F4 expression with antisense oligodeoxynucleotides inhibited NGF-induced neurite outgrowth, indicating an important role for this factor during PC12 cell differentiation. Finally, E2F4 expression was found to increase dramatically in the developing rat cerebral cortex and cerebellum, as neuroblasts became postmitotic and initiated terminal differentiation. These findings demonstrate that, in addition to its effects on cell proliferation, E2F4 actively promotes the neuronal differentiation of PC12 cells as well as the retention of this state. Further, this effect is independent of alterations in cell growth and may involve interactions between E2F4 and the neuronal differentiation program itself. E2F4 may be an important participant in the terminal differentiation of neuroblasts

Direct observation of yield in films by flat punch indentation

In regular indentation many strain states are simultaneously present in the indented region, so measured parameters such as hardness and modulus are average values over a wide range of strains. Testing of structures such as pillars, levers or film bulges enables determination of yield point and modulus with uniform strains in the sample, but requires specialised sample preparation and can be significantly affected by surface condition. Here we show how in-situ indentation with a flat punch allows direct observation of a discrete yield point in soft films on more rigid substrates. The yield point is clearly observable from the load displacement behaviour and from post indent AFM imaging. The film is in uniform uniaxial strain. Finite element simulations show that effective self-confinement by surrounding film material leads to uniformity throughout the film material down to surprisingly low aspect ratios around 4:1. This occurs for a significant range of stresses above the yield point. Eventually at even higher stresses the film material is extruded laterally. The characteristics of the yield event will be described as a function of temperature and film thickness for thin to ultrathin films. At higher aspect ratio and with sufficient stiffness of punch and substrate, quantitative, in-situ measurement of intrinsic stress vs. strain to well beyond the elastic limit becomes possible for thin films. The extent to which full constitutive relations for polymer films can be determied will be discussed, along with limitations of the technique

Happiness Scale Interval Study. Methodological Considerations

The Happiness Scale Interval Study deals with survey questions on happiness, using verbal response options, such as ‘very happy’ and ‘pretty happy’. The aim is to estimate what degrees of happiness are denoted by such terms in different questions and languages. These degrees are expressed in numerical values on a continuous [0,10] scale, which are then used to compute ‘transformed’ means and standard deviations. Transforming scores on different questions to the same scale allows to broadening the World Database of Happiness considerably. The central purpose of the Happiness Scale Interval Study is to identify the happiness values at which respondents change their judgment from e.g. ‘very happy’ to ‘pretty happy’ or the reverse. This paper deals with the methodological/statistical aspects of this approach. The central question is always how to convert the frequencies at which the different possible responses to the same question given by a sample into information on the happiness distribution in the relevant population. The primary (cl)aim of this approach is to achieve this in a (more) valid way. To this end, a model is introduced that allows for dealing with happiness as a latent continuous random variable, in spite of the fact that it is measured as a discrete one. The [0,10] scale is partitioned in as many contiguous parts as the number of possible ratings in the primary scale sums up to. Any subject with a (self-perceived) happiness in the same subinterval is assumed to select the same response. For the probability density function of this happiness random variable, two options are discussed. The first one postulates a uniform distribution within each of the different subintervals of the [0,10] scale. On the basis of these results, the mean value and variance of the complete distribution can be estimated. The method is described, including the precision of the estimates obtained in this way. The second option assumes the happiness distribution to be described as a beta distribution on the interval [0,10] with two shape parameters (α and β). From their estimates on the basis of the primary information, the mean value and the variance of the happiness distribution in the population can be estimated. An illustration is given in which the method is applied to existing measurement results of 20 surveys in The Netherlands in the period 1990–2008. The results clarify our recommendation to apply the model with a uniform distribution within each of the category intervals, in spite of a better validity of the alternative on the basis of a beta distribution. The reason is that the recommended model allows to construct a confidence interval for the true but unknown population happiness distribution. The paper ends with a listing of actual and potential merits of this approach, which has been described here for verbal happiness questions, but which is also applicable to phenomena which are measured along similar lines

Levinson's theorem and scattering phase shift contributions to the partition function of interacting gases in two dimensions

We consider scattering state contributions to the partition function of a two-dimensional (2D) plasma in addition to the bound-state sum. A partition function continuity requirement is used to provide a statistical mechanical heuristic proof of Levinson's theorem in two dimensions. We show that a proper account of scattering eliminates singularities in thermodynamic properties of the nonideal 2D gas caused by the emergence of additional bound states as the strength of an attractive potential is increased. The bound-state contribution to the partition function of the 2D gas, with a weak short-range attraction between its particles, is found to vanish logarithmically as the binding energy decreases. A consistent treatment of bound and scattering states in a screened Coulomb potential allowed us to calculate the quantum-mechanical second virial coefficient of the dilute 2D electron-hole plasma and to establish the difference between the nearly ideal electron-hole gas in GaAs and the strongly correlated exciton/free-carrier plasma in wide-gap semiconductors such as ZnSe or GaN.Comment: 10 pages, 3 figures; new version corrects some minor typo

Suboptimal human inference can invert the bias-variance trade-off for decisions with asymmetric evidence

Solutions to challenging inference problems are often subject to a fundamental trade-off between: 1) bias (being systematically wrong) that is minimized with complex inference strategies, and 2) variance (being oversensitive to uncertain observations) that is minimized with simple inference strategies. However, this trade-off is based on the assumption that the strategies being considered are optimal for their given complexity and thus has unclear relevance to forms of inference based on suboptimal strategies. We examined inference problems applied to rare, asymmetrically available evidence, which a large population of human subjects solved using a diverse set of strategies that varied in form and complexity. In general, subjects using more complex strategies tended to have lower bias and variance, but with a dependence on the form of strategy that reflected an inversion of the classic bias-variance trade-off: subjects who used more complex, but imperfect, Bayesian-like strategies tended to have lower variance but higher bias because of incorrect tuning to latent task features, whereas subjects who used simpler heuristic strategies tended to have higher variance because they operated more directly on the observed samples but lower, near-normative bias. Our results help define new principles that govern individual differences in behavior that depends on rare-event inference and, more generally, about the information-processing trade-offs that can be sensitive to not just the complexity, but also the optimality, of the inference process. &nbsp;</p

The reductive activation of CO2 across a Ti═Ti double bond: synthetic, structural, and mechanistic studies

[Image: see text] The reactivity of the bis(pentalene)dititanium double-sandwich compound Ti(2)Pn(†)(2) (1) (Pn(†) = 1,4-{Si(i)Pr(3)}(2)C(8)H(4)) with CO(2) is investigated in detail using spectroscopic, X-ray crystallographic, and computational studies. When the CO(2) reaction is performed at −78 °C, the 1:1 adduct 4 is formed, and low-temperature spectroscopic measurements are consistent with a CO(2) molecule bound symmetrically to the two Ti centers in a μ:η(2),η(2) binding mode, a structure also indicated by theory. Upon warming to room temperature the coordinated CO(2) is quantitatively reduced over a period of minutes to give the bis(oxo)-bridged dimer 2 and the dicarbonyl complex 3. In situ NMR studies indicated that this decomposition proceeds in a stepwise process via monooxo (5) and monocarbonyl (7) double-sandwich complexes, which have been independently synthesized and structurally characterized. 5 is thermally unstable with respect to a μ-O dimer in which the Ti–Ti bond has been cleaved and one pentalene ligand binds in an η(8) fashion to each of the formally Ti(III) centers. The molecular structure of 7 shows a “side-on” bound carbonyl ligand. Bonding of the double-sandwich species Ti(2)Pn(2) (Pn = C(8)H(6)) to other fragments has been investigated by density functional theory calculations and fragment analysis, providing insight into the CO(2) reaction pathway consistent with the experimentally observed intermediates. A key step in the proposed mechanism is disproportionation of a mono(oxo) di-Ti(III) species to yield di-Ti(II) and di-Ti(IV) products. 1 forms a structurally characterized, thermally stable CS(2) adduct 8 that shows symmetrical binding to the Ti(2) unit and supports the formulation of 4. The reaction of 1 with COS forms a thermally unstable complex 9 that undergoes scission to give mono(μ-S) mono(CO) species 10. Ph(3)PS is an effective sulfur transfer agent for 1, enabling the synthesis of mono(μ-S) complex 11 with a double-sandwich structure and bis(μ-S) dimer 12 in which the Ti–Ti bond has been cleaved