About Homological Mirror Symmetry

The B-side of Kontsevich's Homological Mirror Symmetry Conjecture is discussed. We give first a self-contained study of derived categories and their homological algebra, and later restrict to the bounded derived category of schemes and ultimately Calabi--Yau manifolds, with particular emphasis on the basics of the underlying sheaf theory, and the algebraic features therein. Finally, we loosely discuss the lowest dimensional manifestations of homological mirror symmetry, namely for elliptic curves and $K3$ surfaces. The present work is a sequel to the author's survey "Towards Homological Mirror Symmetry" on the A-side of homological mirror symmetry.Comment: 138 pages, 2 figure

Sisyphus Effect in Pulse Coupled Excitatory Neural Networks with Spike-Timing Dependent Plasticity

The collective dynamics of excitatory pulse coupled neural networks with spike timing dependent plasticity (STDP) is studied. Depending on the model parameters stationary states characterized by High or Low Synchronization can be observed. In particular, at the transition between these two regimes, persistent irregular low frequency oscillations between strongly and weakly synchronized states are observable, which can be identified as infraslow oscillations with frequencies 0.02 - 0.03 Hz. Their emergence can be explained in terms of the Sisyphus Effect, a mechanism caused by a continuous feedback between the evolution of the coherent population activity and of the average synaptic weight. Due to this effect, the synaptic weights have oscillating equilibrium values, which prevents the neuronal population from relaxing into a stationary macroscopic state.Comment: 18 pages, 24 figures, submitted to Physical Review

Towards Homological Mirror Symmetry

This is an expository article on the A-side of Kontsevich's Homological Mirror Symmetry conjecture. We give first a self-contained study of $A_\infty$-categories and their homological algebra, and later restrict to Fukaya categories, with particular emphasis on the basics of the underlying Floer theory, and the geometric features therein. Finally, we place the theory in the context of mirror symmetry, building towards its main predictions.Comment: 139 pages, 15 figures. Corrected a few minor typos, fixed an issue with hyperlink

Pathways of mechanical unfolding of FnIII10: Low force intermediates

We study the mechanical unfolding pathways of the $FnIII_{10}$ domain of fibronectin by means of an Ising--like model, using both constant force and constant velocity protocols. At high forces and high velocities our results are consistent with experiments and previous computational studies. Moreover, the simplicity of the model allows us to probe the biologically relevant low force regime, where we predict the existence of two intermediates with very close elongations. The unfolding pathway is characterized by stochastic transitions between these two intermediates

Exact firing time statistics of neurons driven by discrete inhibitory noise

Neurons in the intact brain receive a continuous and irregular synaptic bombardment from excitatory and inhibitory pre-synaptic neurons, which determines the firing activity of the stimulated neuron. In order to investigate the influence of inhibitory stimulation on the firing time statistics, we consider Leaky Integrate-and-Fire neurons subject to inhibitory instantaneous post-synaptic potentials. In particular, we report exact results for the firing rate, the coefficient of variation and the spike train spectrum for various synaptic weight distributions. Our results are not limited to stimulations of infinitesimal amplitude, but they apply as well to finite amplitude post-synaptic potentials, thus being able to capture the effect of rare and large spikes. The developed methods are able to reproduce also the average firing properties of heterogeneous neuronal populations.Comment: 20 pages, 8 Figures, submitted to Scientific Report

Unfolding times for proteins in a force clamp

The escape process from the native valley for proteins subjected to a constant stretching force is examined using a model for a Beta-barrel. For a wide range of forces, the unfolding dynamics can be treated as one-dimensional diffusion, parametrized in terms of the end-to-end distance. In particular, the escape times can be evaluated as first passage times for a Brownian particle moving on the protein free-energy landscape, using the Smoluchowski equation. At strong forces, the unfolding process can be viewed as a diffusive drift away from the native state, while at weak forces thermal activation is the relevant mechanism. An escape-time analysis within this approach reveals a crossover from an exponential to an inverse Gaussian escape-time distribution upon passing from weak to strong forces. Moreover, a single expression valid at weak and strong forces can be devised both for the average unfolding time as well as for the corresponding variance. The analysis offers a possible explanation of recent experimental findings for ddFLN4 and ubiquitin.Comment: 6 pages, 4 figures, submitted for pubblication to Physical Review Letter

Reconstructing the free energy landscape of a mechanically unfolded model protein

The equilibrium free energy landscape of an off-lattice model protein as a function of an internal (reaction) coordinate is reconstructed from out-of-equilibrium mechanical unfolding manipulations. This task is accomplished via two independent methods: by employing an extended version of the Jarzynski equality (EJE) and the protein inherent structures (ISs). In a range of temperatures around the ``folding transition'' we find a good quantitative agreement between the free energies obtained via EJE and IS approaches. This indicates that the two methodologies are consistent and able to reproduce equilibrium properties of the examined system. Moreover, for the studied model the structural transitions induced by pulling can be related to thermodynamical aspects of folding

Free energy landscape of mechanically unfolded model proteins: extended Jarzinsky versus inherent structure reconstruction

The equilibrium free energy landscape of off-lattice model heteropolymers as a function of an internal coordinate, namely the end-to-end distance, is reconstructed from out-of-equilibrium steered molecular dynamics data. This task is accomplished via two independent methods: by employing an extended version of the Jarzynski equality (EJE) and the inherent structure (IS) formalism. A comparison of the free energies estimated with these two schemes with equilibrium results obtained via the umbrella sampling technique reveals a good quantitative agreement among all the approaches in a range of temperatures around the ``folding transition'' for the two examined sequences. In particular, for the sequence with good foldability properties, the mechanically induced structural transitions can be related to thermodynamical aspects of folding. Moreover, for the same sequence the knowledge of the landscape profile allows for a good estimation of the life times of the native configuration for temperatures ranging from the folding to the collapse temperature. For the random sequence, mechanical and thermal unfolding appear to follow different paths along the landscape.Comment: Latex manuscript, 20 pages, 23 figures, submitted to Physical Review

Changing the mechanical unfolding pathway of FnIII10 by tuning the pulling strength

We investigate the mechanical unfolding of the tenth type III domain from fibronectin, FnIII10, both at constant force and at constant pulling velocity, by all-atom Monte Carlo simulations. We observe both apparent two-state unfolding and several unfolding pathways involving one of three major, mutually exclusive intermediate states. All the three major intermediates lack two of seven native beta-strands, and share a quite similar extension. The unfolding behavior is found to depend strongly on the pulling conditions. In particular, we observe large variations in the relative frequencies of occurrence for the intermediates. At low constant force or low constant velocity, all the three major intermediates occur with a significant frequency. At high constant force or high constant velocity, one of them, with the N- and C-terminal beta-strands detached, dominates over the other two. Using the extended Jarzynski equality, we also estimate the equilibrium free-energy landscape, calculated as a function of chain extension. The application of a constant pulling force leads to a free-energy profile with three major local minima. Two of these correspond to the native and fully unfolded states, respectively, whereas the third one can be associated with the major unfolding intermediates.Comment: 15 pages, 9 figure

Exact firing time statistics of neurons driven by discrete inhibitory noise

Neurons in the intact brain receive a continuous and irregular synaptic bombardment from excitatory and inhibitory pre-synaptic neurons, which determines the firing activity of the stimulated neuron. In order to investigate the influence of inhibitory stimulation on the firing time statistics, we consider Leaky Integrate-and-Fire neurons subject to inhibitory instantaneous post-synaptic potentials. In particular, we report exact results for the firing rate, the coefficient of variation and the spike train spectrum for various synaptic weight distributions. Our results are not limited to stimulations of infinitesimal amplitude, but they apply as well to finite amplitude post-synaptic potentials, thus being able to capture the effect of rare and large spikes. The developed methods are able to reproduce also the average firing properties of heterogeneous neuronal populations