Hebbian and homeostatic plasticity mechanisms in regular spiking and intrinsic bursting cells of cortical layer 5

Layer 5 contains the major projection neurons of the neocortex and is composed of two major cell types: regular spiking (RS) cells, which have cortico-cortical projections, and intrinsic bursting cells (IB), which have subcortical projections. Little is known about the plasticity processes and specifically the molecular mechanisms by which these two cell classes develop and maintain their unique integrative properties. In this study, we find that RS and IB cells show fundementally different experience-dependent plasticity processes and integrate Hebbian and homeostatic components of plasticity differently. Both RS and IB cells showed TNFα-dependent homeostatic plasticity in response to sensory deprivation, but IB cells were capable of a much faster synaptic depression and homeostatic rebound than RS cells. Only IB cells showed input-specific potentiation that depended on CaMKII autophosphorylation. Our findings demonstrate that plasticity mechanisms are not uniform within the neocortex, even within a cortical layer, but are specialized within subcircuits.

Optimal design for correlated processes with input-dependent noise

Optimal design for parameter estimation in Gaussian process regression models with input-dependent noise is examined. The motivation stems from the area of computer experiments, where computationally demanding simulators are approximated using Gaussian process emulators to act as statistical surrogates. In the case of stochastic simulators, which produce a random output for a given set of model inputs, repeated evaluations are useful, supporting the use of replicate observations in the experimental design. The findings are also applicable to the wider context of experimental design for Gaussian process regression and kriging. Designs are proposed with the aim of minimising the variance of the Gaussian process parameter estimates. A heteroscedastic Gaussian process model is presented which allows for an experimental design technique based on an extension of Fisher information to heteroscedastic models. It is empirically shown that the error of the approximation of the parameter variance by the inverse of the Fisher information is reduced as the number of replicated points is increased. Through a series of simulation experiments on both synthetic data and a systems biology stochastic simulator, optimal designs with replicate observations are shown to outperform space-filling designs both with and without replicate observations. Guidance is provided on best practice for optimal experimental design for stochastic response models. © 2013 Elsevier Inc. All rights reserved.

Regression with input-dependent noise: A Gaussian process treatment

Gaussian processes provide natural non-parametric prior distributions over regression functions. In this paper we consider regression problems where there is noise on the output, and the variance of the noise depends on the inputs. If we assume that the noise is a smooth function of the inputs, then it is natural to model the noise variance using a second Gaussian process, in addition to the Gaussian process governing the noise-free output value. We show that prior uncertainty about the parameters controlling both processes can be handled and that the posterior distribution of the noise rate can be sampled from using Markov chain Monte Carlo methods. Our results on a synthetic data set give a posterior noise variance that well-approximates the true variance.

A basis function approach to Bayesian inference in diffusion processes

In this paper, we present a framework for Bayesian inference in continuous-time diffusion processes. The new method is directly related to the recently proposed variational Gaussian Process approximation (VGPA) approach to Bayesian smoothing of partially observed diffusions. By adopting a basis function expansion (BF-VGPA), both the time-dependent control parameters of the approximate GP process and its moment equations are projected onto a lower-dimensional subspace. This allows us both to reduce the computational complexity and to eliminate the time discretisation used in the previous algorithm. The new algorithm is tested on an Ornstein-Uhlenbeck process. Our preliminary results show that BF-VGPA algorithm provides a reasonably accurate state estimation using a small number of basis functions.

People, technology, processes and risk knowledge sharing

The present global economic crisis creates doubts about the good use of accumulated experience and knowledge in managing risk in financial services. Typically, risk management practice does not use knowledge management (KM) to improve and to develop new answers to the threats. A key reason is that it is not clear how to break down the “organizational silos” view of risk management (RM) that is commonly taken. As a result, there has been relatively little work on finding the relationships between RM and KM. We have been doing research for the last couple of years on the identification of relationships between these two disciplines. At ECKM 2007 we presented a general review of the literature(s) and some hypotheses for starting research on KM and its relationship to the perceived value of enterprise risk management. This article presents findings based on our preliminary analyses, concentrating on those factors affecting the perceived quality of risk knowledge sharing. These come from a questionnaire survey of RM employees in organisations in the financial services sector, which yielded 121 responses. We have included five explanatory variables for the perceived quality of risk knowledge sharing. These comprised two variables relating to people (organizational capacity for work coordination and perceived quality of communication among groups), one relating to process (perceived quality of risk control) and two related to technology (web channel functionality and RM information system functionality). Our findings so far are that four of these five variables have a significant positive association with the perceived quality of risk knowledge sharing: contrary to expectations, web channel functionality did not have a significant association. Indeed, in some of our exploratory regression studies its coefficient (although not significant) was negative. In stepwise regression, the variable organizational capacity for work coordination accounted for by far the largest part of the variation in the dependent variable perceived quality of risk knowledge sharing. The “people” variables thus appear to have the greatest influence on the perceived quality of risk knowledge sharing, even in a sector that relies heavily on technology and on quantitative approaches to decision making. We have also found similar results with the dependent variable perceived value of Enterprise Risk Management (ERM) implementation.

Task classification and decision processes in monitoring behaviour

Task classification is introduced as a method for the evaluation of monitoring behaviour in different task situations. On the basis of an analysis of different monitoring tasks, a task classification system comprising four task 'dimensions' is proposed. The perceptual speed and flexibility of closure categories, which are identified with signal discrimination type, comprise the principal dimension in this taxonomy, the others being sense modality, the time course of events, and source complexity. It is also proposed that decision theory provides the most complete method for the analysis of performance in monitoring tasks. Several different aspects of decision theory in relation to monitoring behaviour are described. A method is also outlined whereby both accuracy and latency measures of performance may be analysed within the same decision theory framework. Eight experiments and an organizational study are reported. The results show that a distinction can be made between the perceptual efficiency (sensitivity) of a monitor and his criterial level of response, and that in most monitoring situations, there is no decrement in efficiency over the work period, but an increase in the strictness of the response criterion. The range of tasks exhibiting either or both of these performance trends can be specified within the task classification system. In particular, it is shown that a sensitivity decrement is only obtained for 'speed' tasks with a high stimulation rate. A distinctive feature of 'speed' tasks is that target detection requires the discrimination of a change in a stimulus relative to preceding stimuli, whereas in 'closure' tasks, the information required for the discrimination of targets is presented at the same point In time. In the final study, the specification of tasks yielding sensitivity decrements is shown to be consistent with a task classification analysis of the monitoring literature. It is also demonstrated that the signal type dimension has a major influence on the consistency of individual differences in performance in different tasks. The results provide an empirical validation for the 'speed' and 'closure' categories, and suggest that individual differences are not completely task specific but are dependent on the demands common to different tasks. Task classification is therefore shovn to enable improved generalizations to be made of the factors affecting 1) performance trends over time, and 2) the consistencv of performance in different tasks. A decision theory analysis of response latencies is shown to support the view that criterion shifts are obtained in some tasks, while sensitivity shifts are obtained in others. The results of a psychophysiological study also suggest that evoked potential latency measures may provide temporal correlates of criterion shifts in monitoring tasks. Among other results, the finding that the latencies of negative responses do not increase over time is taken to invalidate arousal-based theories of performance trends over a work period. An interpretation in terms of expectancy, however, provides a more reliable explanation of criterion shifts. Although the mechanisms underlying the sensitivity decrement are not completely clear, the results rule out 'unitary' theories such as observing response and coupling theory. It is suggested that an interpretation in terms of the memory data limitations on information processing provides the most parsimonious explanation of all the results in the literature relating to sensitivity decrement. Task classification therefore enables the refinement and selection of theories of monitoring behaviour in terms of their reliability in generalizing predictions to a wide range of tasks. It is thus concluded that task classification and decision theory provide a reliable basis for the assessment and analysis of monitoring behaviour in different task situations.

A three dimensional numerical investigation of hillslope flow processes

Physically based distributed models of catchment hydrology are likely to be made available as engineering tools in the near future. Although these models are based on theoretically acceptable equations of continuity, there are still limitations in the present modelling strategy. Of interest to this thesis are the current modelling assumptions made concerning the effects of soil spatial variability, including formations producing distinct zones of preferential flow. The thesis contains a review of current physically based modelling strategies and a field based assessment of soil spatial variability. In order to investigate the effects of soil nonuniformity a fully three dimensional model of variability saturated flow in porous media is developed. The model is based on a Galerkin finite element approximation to Richards equation. Accessibility to a vector processor permits numerical solutions on grids containing several thousand node points. The model is applied to a single hillslope segment under various degrees of soil spatial variability. Such variability is introduced by generating random fields of saturated hydraulic conductivity using the turning bands method. Similar experiments are performed under conditions of preferred soil moisture movement. The results show that the influence of soil variability on subsurface flow may be less significant than suggested in the literature, due to the integrating effects of three dimensional flow. Under conditions of widespread infiltration excess runoff, the results indicate a greater significance of soil nonuniformity. The recognition of zones of preferential flow is also shown to be an important factor in accurate rainfall-runoff modelling. Using the results of various fields of soil variability, experiments are carried out to assess the validity of the commonly used concept of `effective parameters'. The results of these experiments suggest that such a concept may be valid in modelling subsurface flow. However, the effective parameter is observed to be event dependent when the dominating mechanism is infiltration excess runoff.

Flt1 acts as a negative regulator of tip cell formation and branching morphogenesis in the zebrafish embryo

Endothelial tip cells guide angiogenic sprouts by exploring the local environment for guidance cues such as vascular endothelial growth factor (VegfA). Here we present Flt1 (Vegf receptor 1) loss- and gain-of-function data in zebrafish showing that Flt1 regulates tip cell formation and arterial branching morphogenesis. Zebrafish embryos expressed soluble Flt1 (sFlt1) and membrane-bound Flt1 (mFlt1). In Tg(flt1(BAC):yfp) × Tg(kdrl:ras-cherry)(s916) embryos, flt1:yfp was expressed in tip, stalk and base cells of segmental artery sprouts and overlapped with kdrl:cherry expression in these domains. flt1 morphants showed increased tip cell numbers, enhanced angiogenic behavior and hyperbranching of segmental artery sprouts. The additional arterial branches developed into functional vessels carrying blood flow. In support of a functional role for the extracellular VEGF-binding domain of Flt1, overexpression of sflt1 or mflt1 rescued aberrant branching in flt1 morphants, and overexpression of sflt1 or mflt1 in controls resulted in short arterial sprouts with reduced numbers of filopodia. flt1 morphants showed reduced expression of Notch receptors and of the Notch downstream target efnb2a, and ectopic expression of flt4 in arteries, consistent with loss of Notch signaling. Conditional overexpression of the notch1a intracellular cleaved domain in flt1 morphants restored segmental artery patterning. The developing nervous system of the trunk contributed to the distribution of Flt1, and the loss of flt1 affected neurons. Thus, Flt1 acts in a Notch-dependent manner as a negative regulator of tip cell differentiation and branching. Flt1 distribution may be fine-tuned, involving interactions with the developing nervous system.

Super-high temperature sensitivity of long-period gratings in B/Ge co-doped fiber

Long period fiber grating (LPFG) can be used as active gain controlling device in EDFA. However, LPFGs fabricated in the standard telecom fiber only have a typical temperature sensitivity of 3-10nm/100°C, which may not be sufficient for implementing tuneable filters capable of wide tuning range and high tuning efficiency. In this paper, we report a theoretical and experimental investigation of thermal properties of LPFGs fabricated in B/Ge co-doped optical fiber. We have found that the temperature sensitivity of the LPFGs in the B/Ge fiber is considerably increased compared with those produced in the standard fiber. The LPFGs written in the B/Ge fiber have achieved, on average, one order of magnitude higher sensitivity than that of the LPFGs produced in the standard telecom fiber. We have also identified that the thermal response of LPFG is strongly dependent on the order of the coupled resonant cladding mode. The maximum sensitivity of 1.75nm/°C achieved by the 10th cladding mode of the 240μm LPFG is nearly 24 times that of the minimum value (0.075nm/C) exhibited by the 30th mode of the 34μm LPFG. Such devices may lead to high-efficiency and low-cost thermal/electrical tunable loss filters or sensors with extremely high temperature resolution.

Does the MK2-dependent production of TNFα regulate mGluR-dependent synaptic plasticity?

The molecular mechanisms and signalling cascades that trigger the induction of group I metabotropic glutamate receptor (GI-mGluR)-dependent long-term depression (LTD) have been the subject of intensive investigation for nearly two decades. The generation of genetically modified animals has played a crucial role in elucidating the involvement of key molecules regulating the induction and maintenance of mGluR-LTD. In this review we will discuss the requirement of the newly discovered MAPKAPK-2 (MK2) and MAPKAPK-3 (MK3) signalling cascade in regulating GI-mGluR-LTD. Recently, it has been shown that the absence of MK2 impaired the induction of GI-mGluR-dependent LTD, an effect that is caused by reduced internalization of AMPA receptors (AMPAR). As the MK2 cascade directly regulates tumour necrosis factor alpha (TNFα) production, this review will examine the evidence that the release of TNFα acts to regulate glutamate receptor expression and therefore may play a functional role in the impairment of GI-mGluRdependent LTD and the cognitive deficits observed in MK2/3 double knockout animals. The strong links of increased TNFα production in both aging and neurodegenerative disease could implicate the action of MK2 in these processes.