Franciszek Rakowski

Implementation of a symplectic multiple-time-step molecular dynamics algorithm, based on the united-residue mesoscopic potential energy function.

A symplectic multiple-time-step (MTS) algorithm has been developed for the united-residue (UNRES) force field. In this algorithm, the slow-varying forces (which contain most of the long-range interactions and are, therefore, expensive to compute) are integrated with a larger time step, termed the basic time step, and the fast-varying forces are integrated with a shorter time step, which is an integral fraction of the basic time step. Based on the split operator formalism, the equations of motion were derived. Separation of the fast- and slow-varying forces leads to stable molecular dynamics with longer time steps. The algorithms were tested with the Ala(10) polypeptide chain and two versions of the UNRES force field: the current one in which the energy components accounting for the energetics of side-chain rotamers (U(rot)) can lead to numerically unstable forces and a modified one in which the the present U(rot) was replaced by a numerically stable expression which, at present, is parametrized only for polyalanine chains. With the modified UNRES potential, stable trajectories were obtained even when extending the basic time step to 15 fs and, with the original UNRES potentials, the basic time step is 1 fs. An adaptive multiple-time-step (A-MTS) algorithm is proposed to handle instabilities in the forces; in this method, the number of substeps in the basic time step varies depending on the change of the magnitude of the acceleration. With this algorithm, the basic time step is 1 fs but the number of substeps and, consequently, the computational cost are reduced with respect to the MTS algorithm. The use of the UNRES mesoscopic energy function and the algorithms derived in this work enables one to increase the simulation time period by several orders of magnitude compared to conventional atomic-resolution molecular dynamics approaches and, consequently, such an approach appears applicable to simulating protein-folding pathways, protein functional dynamics in a real molecular environment, and dynamical molecular recognition processes.

Synaptic polarity of the interneuron circuit controlling C. elegans locomotion

Caenorhabditis elegans is the only animal for which a detailed neural connectivity diagram has been constructed. However, synaptic polarities in this diagram, and thus, circuit functions are largely unknown. Here, we deciphered the likely polarities of seven pre-motor neurons implicated in the control of worms locomotion, using a combination of experimental and computational tools. We performed single and multiple laser ablations in the locomotor interneuron circuit and recorded times the worms spent in forward and backward locomotion. We constructed a theoretical model of the locomotor circuit and searched its all possible synaptic polarity combinations and sensory input patterns in order to find the best match to the timing data. The optimal solution is when either all or most of the interneurons are inhibitory and forward interneurons receive the strongest input, which suggests that inhibition governs the dynamics of the locomotor interneuron circuit. From the five pre-motor interneurons, only AVB and AVD are equally likely to be excitatory, i.e., they have probably similar number of inhibitory and excitatory connections to distant targets. The method used here has a general character and thus can be also applied to other neural systems consisting of small functional networks.

Brief Communication: A model of influenza virus spread as a function of temperature and humidity

The influence that atmospheric conditions might have on the efficiency of the spread of influenza virus is important for epidemiological and evolutionary research. However, it has not been satisfactorily recognized and quantified so far. Here we provide a statistical model of influenza transmission between individuals. It has been derived from the results of recent experiments, which involved infecting guinea pigs with influenza at various temperatures and relative air humidity levels. The wide range of transmission rates in those experiments reflects the ensemble-independent phenomena. The correlation between most of our simulations and the experimental results is satisfactory. For several different conditions, we obtained transmissibility values which seem to be sufficiently accurate to provide partial input for an intended large-scale epidemiological study in the near future.

Functional and effective brain connectivity for discrimination between Alzheimer's patients and healthy individuals: A study on resting state EEG rhythms.

OBJECTIVE This exploratory study provided a proof of concept of a new procedure using multivariate electroencephalographic (EEG) topographic markers of cortical connectivity to discriminate normal elderly (Nold) and Alzheimers disease (AD) individuals. METHOD The new procedure was tested on an existing database formed by resting state eyes-closed EEG data (19 exploring electrodes of 10-20 system referenced to linked-ear reference electrodes) recorded in 42 AD patients with dementia (age: 65.9years±8.5 standard deviation, SD) and 42 Nold non-consanguineous caregivers (age: 70.6years±8.5 SD). In this procedure, spectral EEG coherence estimated reciprocal functional connectivity while non-normalized directed transfer function (NDTF) estimated effective connectivity. Principal component analysis and computation of Mahalanobis distance integrated and combined these EEG topographic markers of cortical connectivity. The area under receiver operating curve (AUC) indexed the classification accuracy. RESULTS A good classification of Nold and AD individuals was obtained by combining the EEG markers derived from NDTF and coherence (AUC=86%, sensitivity=0.85, specificity=0.70). CONCLUSION These encouraging results motivate a cross-validation study of the new procedure in age- and education-matched Nold, stable and progressing mild cognitive impairment individuals, and de novo AD patients with dementia. SIGNIFICANCE If cross-validated, the new procedure will provide cheap, broadly available, repeatable over time, and entirely non-invasive EEG topographic markers reflecting abnormal cortical connectivity in AD patients diagnosed by direct or indirect measurement of cerebral amyloid β and hyperphosphorylated tau peptides.

Brief Communication: Probabilistic model of influenza virus transmissibility at various temperature and humidity conditions

The spread efficiency of influenza virus is significantly affected by several environmental parameters. However, neither the underlying reasons, nor the exact character and magnitude of the phenomena involved are sufficiently well understood. Here we present a probabilistic approach to the virus transmission events. For a sample ensemble, we construct a model of the infectivity as a function of the ambient conditions, and we determine its parameter values on the basis of the available experimental data.

Parallel Differential Evolution in the PGAS Programming Model Implemented with PCJ Java Library

New ways to exploit parallelism of large scientific codes are still researched on. In this paper we present parallelization of the differential evolution algorithm. The simulations are implemented in Java programming language using PGAS programing paradigm enabled by the PCJ library. The developed solution has been used to test differential evolution on a number of mathematical function as well as to fine-tune the parameters of nematode’s C. Elegans connectome model. The results have shown that a good scalability and performance was achieved with relatively simple and easy to develop code.

Generic Framework for Simulation of Cognitive Systems: A Case Study of Color Category Boundaries

We present a generic model of a cognitive system, which is based on a population of communicating agents. Following the earlier models (Steels and Belpaeme, 2005) we give communication an important role in shaping the cognitive categories of individual agents. Yet in this paper we underscore the importance of other constraints on cognition: the structure of the environment, in which a system evolves and learns and the learning capacities of individual agents. Thus our agent-based model of cultural emergence of colour categories shows that boundaries might be seen as a product of agent’s communication in a given environment.We discuss the methodological issues related to real data characterization, as well as to the process of modeling the emergence of perceptual categories in human subjects.

Optimal synaptic signaling connectome for locomotory behavior in Caenorhabditis elegans: Design minimizing energy cost

The detailed knowledge of C. elegans connectome for 3 decades has not contributed dramatically to our understanding of worm’s behavior. One of main reasons for this situation has been the lack of data on the type of synaptic signaling between particular neurons in the worm’s connectome. The aim of this study was to determine synaptic polarities for each connection in a small pre-motor circuit controlling locomotion. Even in this compact network of just 7 neurons the space of all possible patterns of connection types (excitation vs. inhibition) is huge. To deal effectively with this combinatorial problem we devised a novel and relatively fast technique based on genetic algorithms and large-scale parallel computations, which we combined with detailed neurophysiological modeling of interneuron dynamics and compared the theory to the available behavioral data. As a result of these massive computations, we found that the optimal connectivity pattern that matches the best locomotory data is the one in which all interneuron connections are inhibitory, even those terminating on motor neurons. This finding is consistent with recent experimental data on cholinergic signaling in C. elegans, and it suggests that the system controlling locomotion is designed to save metabolic energy. Moreover, this result provides a solid basis for a more realistic modeling of neural control in these worms, and our novel powerful computational technique can in principle be applied (possibly with some modifications) to other small-scale functional circuits in C. elegans.

A case study of software load balancing policies implemented with the PGAS programming model

Differential evolution algorithm was used to calculate the parameters C. Elegans connectome model. The calculations were carried out using the Java programming language coupled with PCJ library that enabled PGAS features within the JVM. The calculations clearly exhibited load imbalance, as some of the programs threads of execution were taking three times longer to complete the calculations compared to the fastest one. The computing resources were thus used sub-optimally. The paper describes the steps undertaken to mitigate the problem. Three software load balancing strategies are described, and performance results are discussed.