260 research outputs found

    Packing of concave polyhedra with continuous rotations using nonlinear optimisation

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    We study the problem of packing a given collection of arbitrary, in general concave, polyhedra into a cuboid of minimal volume. Continuous rotations and translations of polyhedra are allowed. In addition, minimal allowable distances between polyhedra are taken into account. We derive an exact mathematical model using adjusted radical free quasi phi-functions for concave polyhedra to describe non-overlapping and distance constraints. The model is a nonlinear programming formulation. We develop an efficient solution algorithm, which employs a fast starting point algorithm and a new compaction procedure. The procedure reduces our problem to a sequence of nonlinear programming subproblems of considerably smaller dimension and a smaller number of nonlinear inequalities. The benefit of this approach is borne out by the computational results, which include a comparison with previously published instances and new instances

    Astroglia-Derived BDNF and MSK-1 Mediate Experience- and Diet-Dependent Synaptic Plasticity

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    Experience- and diet-dependent regulation of synaptic plasticity can underlie beneficial effects of active lifestyle on the aging brain. Our previous results demonstrate a key role for brain-derived neurotrophic factor (BDNF) and MSK1 kinase in experience-related homeostatic synaptic scaling. Astroglia has been recently shown to release BDNF via a calcium-dependent mechanism. To elucidate a role for astroglia-derived BDNF in homeostatic synaptic plasticity in the aging brain, we explored the experience- and diet-related alterations of synaptic transmission and plasticity in transgenic mice with impairment of the BDNF/MSK1 pathway (MSK1 kinase dead knock-in mice, MSK1 KD) and impairment of glial exocytosis (dnSNARE mice). We found that prolonged tonic activation of astrocytes caused BDNF-dependent increase in the efficacy of excitatory synapses accompanied by enlargement of synaptic boutons. We also observed that exposure to environmental enrichment (EE) and caloric restriction (CR) enhanced the Ca2+ signalling in cortical astrocytes and strongly up-regulated the excitatory and down-regulated inhibitory synaptic currents in old wild-type mice, thus counterbalancing the impact of ageing on astroglial and synaptic signalling. The EE- and CR-induced up-scaling of excitatory synaptic transmission in neocortex was accompanied by the enhancement of long-term synaptic potentiation. Importantly, effects of EE and CR on synaptic transmission and plasticity was significantly reduced in the MSK1 KD and dnSNARE mice. Combined, our results suggest that astroglial release of BDNF is important for the homeostatic regulation of cortical synapses and beneficial effects of EE and CR on synaptic transmission and plasticity in aging brain

    Optimal clustering of a pair of irregular objects

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    Cutting and packing problems arise in many fields of applications and theory. When dealing with irregular objects, an important subproblem is the identification of the optimal clustering of two objects. Within this paper we consider a container (rectangle, circle, convex polygon) of variable sizes and two irregular objects bounded by circular arcs and/or line segments, that can be continuously translated and rotated. In addition minimal allowable distances between objects and between each object and the frontier of a container, may be imposed. The objects should be arranged within a container such that a given objective will reach its minimal value. We consider a polynomial function as the objective, which depends on the variable parameters associated with the objects and the container. The paper presents a universal mathematical model and a solution strategy which are based on the concept of phi-functions and provide new benchmark instances of finding the containing region that has either minimal area, perimeter or homothetic coefficient of a given container, as well as finding the convex polygonal hull (or its approximation) of a pair of objects

    Resonant enhancement of the jump rate in a double-well potential

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    We study the overdamped dynamics of a Brownian particle in the double-well potential under the influence of an external periodic (AC) force with zero mean. We obtain a dependence of the jump rate on the frequency of the external force. The dependence shows a maximum at a certain driving frequency. We explain the phenomenon as a switching between different time scales of the system: interwell relaxation time (the mean residence time) and the intrawell relaxation time. Dependence of the resonant peak on the system parameters, namely the amplitude of the driving force A and the noise strength (temperature) D has been explored. We observe that the effect is well pronounced when A/D > 1 and if A/D 1 the enhancement of the jump rate can be of the order of magnitude with respect to the Kramers rate.Comment: Published in J. Phys. A: Math. Gen. 37 (2004) 6043-6051; 6 figure

    ATP from synaptic terminals and astrocytes regulates NMDA receptors and synaptic plasticity through PSD-95 multi-protein complex

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    Recent studies highlighted the importance of astrocyte-secreted molecules, such as ATP, for the slow modulation of synaptic transmission in central neurones. Biophysical mechanisms underlying the impact of gliotransmitters on the strength of individual synapse remain, however, unclear. Here we show that purinergic P2X receptors can bring significant contribution to the signalling in the individual synaptic boutons. ATP released from astrocytes facilitates a recruitment of P2X receptors into excitatory synapses by Ca2+-dependent mechanism. P2X receptors, co-localized with NMDA receptors in the excitatory synapses, can be activated by ATP co-released with glutamate from pre-synaptic terminals and by glia-derived ATP. An activation of P2X receptors in turn leads to down-regulation of postsynaptic NMDA receptors via Ca2+-dependent de-phosphorylation and interaction with PSD-95 multi-protein complex. Genetic deletion of the PSD-95 or P2X4 receptors obliterated ATP-mediated down-regulation of NMDA receptors. Impairment of purinergic modulation of NMDA receptors in the PSD-95 mutants dramatically decreased the threshold of LTP induction and increased the net magnitude of LTP. Our findings show that synergistic action of glia- and neurone-derived ATP can pre-modulate efficacy of excitatory synapses and thereby can have an important role in the glia-neuron communications and brain meta-plasticity

    Role for Astroglia-Derived BDNF and MSK1 in Homeostatic Synaptic Plasticity

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    Homeostatic scaling of synaptic strength in response to environmental stimuli may underlie the beneficial effects of an active lifestyle on brain function. Our previous results highlighted a key role for brain-derived neurotrophic factor (BDNF) and mitogen- and stress-activated protein kinase 1 (MSK1) in experience-related homeostatic synaptic plasticity. Astroglia have recently been shown to serve as an important source of BDNF. To elucidate a role for astroglia-derived BDNF, we explored homeostatic synaptic plasticity in transgenic mice with an impairment in the BDNF/MSK1 pathway (MSK1 kinase dead knock-in (KD) mice) and impairment of glial exocytosis (dnSNARE mice). We observed that prolonged tonic activation of astrocytes caused BDNF-dependent upregulation of excitatory synaptic currents accompanied by enlargement of synaptic boutons. We found that exposure to environmental enrichment (EE) and caloric restriction (CR) strongly upregulated excitatory but downregulated inhibitory synaptic currents in old wild-type mice, thus counterbalancing the impact of ageing on synaptic transmission. In parallel, EE and CR enhanced astrocytic Ca2+-signalling. Importantly, we observed a significant deficit in the effects of EE and CR on synaptic transmission in the MSK1 KD and dnSNARE mice. Combined, our results strongly support the importance of astrocytic exocytosis of BDNF for the beneficial effects of EE and CR on synaptic transmission and plasticity in the ageing brain

    miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity

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    miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP) induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity

    Long-term (trophic) purinergic signalling: purinoceptors control cell proliferation, differentiation and death

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    The purinergic signalling system, which uses purines and pyrimidines as chemical transmitters, and purinoceptors as effectors, is deeply rooted in evolution and development and is a pivotal factor in cell communication. The ATP and its derivatives function as a 'danger signal' in the most primitive forms of life. Purinoceptors are extraordinarily widely distributed in all cell types and tissues and they are involved in the regulation of an even more extraordinary number of biological processes. In addition to fast purinergic signalling in neurotransmission, neuromodulation and secretion, there is long-term (trophic) purinergic signalling involving cell proliferation, differentiation, motility and death in the development and regeneration of most systems of the body. In this article, we focus on the latter in the immune/defence system, in stratified epithelia in visceral organs and skin, embryological development, bone formation and resorption, as well as in cancer. Cell Death and Disease (2010) 1, e9; doi:10.1038/cddis.2009.11; published online 14 January 201

    Strongly Correlated Electrons on a Silicon Surface: Theory of a Mott Insulator

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    We demonstrate theoretically that the electronic ground state of the potassium-covered Si(111)-B surface is a Mott insulator, explicitly contradicting band theory but in good agreement with recent experiments. We determine the physical structure by standard density-functional methods, and obtain the electronic ground state by exact diagonalization of a many-body Hamiltonian. The many-body conductivity reveals a Brinkman-Rice metal-insulator transition at a critical interaction strength; the calculated interaction strength is well above this critical value.Comment: 4 pages; 4 figures included in text; Revte
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