Revealing Network Connectivity From Dynamics

We present a method to infer network connectivity from collective dynamics in networks of synchronizing phase oscillators. We study the long-term stationary response to temporally constant driving. For a given driving condition, measuring the phase differences and the collective frequency reveals information about how the oscillators are interconnected. Sufficiently many repetitions for different driving conditions yield the entire network connectivity from measuring the dynamics only. For sparsely connected networks we obtain good predictions of the actual connectivity even for formally under-determined problems.Comment: 10 pages, 4 figure

Evidence for an evolutionary antagonism between Mrr and Type III modification systems

The Mrr protein of Escherichia coli is a laterally acquired Type IV restriction endonuclease with specificity for methylated DNA. While Mrr nuclease activity can be elicited by high-pressure stress in E. coli MG1655, its (over)expression per se does not confer any obvious toxicity. In this study, however, we discovered that Mrr of E. coli MG1655 causes distinct genotoxicity when expressed in Salmonella typhimurium LT2. Genetic screening enabled us to contribute this toxicity entirely to the presence of the endogenous Type III restriction modification system (StyLTI) of S. typhimurium LT2. The StyLTI system consists of the Mod DNA methyltransferase and the Res restriction endonuclease, and we revealed that expression of the LT2 mod gene was sufficient to trigger Mrr activity in E. coli MG1655. Moreover, we could demonstrate that horizontal acquisition of the MG1655 mrr locus can drive the loss of endogenous Mod functionality present in S. typhimurium LT2 and E. coli ED1a, and observed a strong anti-correlation between close homologues of MG1655 mrr and LT2 mod in the genome database. This apparent evolutionary antagonism is further discussed in the light of a possible role for Mrr as defense mechanism against the establishment of epigenetic regulation by foreign DNA methyltransferases

Binaural Interaction in the Nucleus Laminaris of the Barn Owl : A Quantitative Model

A quantitative, neuronal model is proposed for the computation of interaural time difference (ITD) in the auditory system of the barn owl. The model uses a general, probabilistic approach, and is composed of two stages, the characteristics of which are based on anatomical and physiological evidence. Excitatory inputs from both ears, phase-locked to the waveform of tonal stimuli, together with phase-independent inhibitory inputs are summated linearly. The result is transformed into a probability of spike generation by a sigmoid nonlinearity, constituting a stochastic, ’soft’ threshold with saturation. The model incorporates inhibition as a control parameter on the nonlinearity, and includes the usual crosscorrelation-type models as a special case. It has a minimum number of parameters, the values of which can be estimated from physiological data in a straightforward manner. This simple, general model accounts for the binaural response properties of physiologically recorded neurons. In particular, it explains the experimentally observed ITD-tuning and the increase of phase-locking from input to output neurons. The model predicts that a decrease in inhibition causes a non-monotonic change in sensitivity to ITD

Interactive Medical Image Segmentation using Deep Learning with Image-specific Fine-tuning

Convolutional neural networks (CNNs) have achieved state-of-the-art performance for automatic medical image segmentation. However, they have not demonstrated sufficiently accurate and robust results for clinical use. In addition, they are limited by the lack of image-specific adaptation and the lack of generalizability to previously unseen object classes. To address these problems, we propose a novel deep learning-based framework for interactive segmentation by incorporating CNNs into a bounding box and scribble-based segmentation pipeline. We propose image-specific fine-tuning to make a CNN model adaptive to a specific test image, which can be either unsupervised (without additional user interactions) or supervised (with additional scribbles). We also propose a weighted loss function considering network and interaction-based uncertainty for the fine-tuning. We applied this framework to two applications: 2D segmentation of multiple organs from fetal MR slices, where only two types of these organs were annotated for training; and 3D segmentation of brain tumor core (excluding edema) and whole brain tumor (including edema) from different MR sequences, where only tumor cores in one MR sequence were annotated for training. Experimental results show that 1) our model is more robust to segment previously unseen objects than state-of-the-art CNNs; 2) image-specific fine-tuning with the proposed weighted loss function significantly improves segmentation accuracy; and 3) our method leads to accurate results with fewer user interactions and less user time than traditional interactive segmentation methods.Comment: 11 pages, 11 figure

Structure Learning in a Sensorimotor Association Task

Learning is often understood as an organism's gradual acquisition of the association between a given sensory stimulus and the correct motor response. Mathematically, this corresponds to regressing a mapping between the set of observations and the set of actions. Recently, however, it has been shown both in cognitive and motor neuroscience that humans are not only able to learn particular stimulus-response mappings, but are also able to extract abstract structural invariants that facilitate generalization to novel tasks. Here we show how such structure learning can enhance facilitation in a sensorimotor association task performed by human subjects. Using regression and reinforcement learning models we show that the observed facilitation cannot be explained by these basic models of learning stimulus-response associations. We show, however, that the observed data can be explained by a hierarchical Bayesian model that performs structure learning. In line with previous results from cognitive tasks, this suggests that hierarchical Bayesian inference might provide a common framework to explain both the learning of specific stimulus-response associations and the learning of abstract structures that are shared by different task environments

Synthetic reconstruction of extreme high hydrostatic pressure resistance in Escherichia coli

Although high hydrostatic pressure (HHP) is an interesting parameter to be applied in bioprocessing, its potential is currently limited by the lack of bacterial chassis capable of surviving and maintaining homeostasis under pressure. While several efforts have been made to genetically engineer microorganisms able to grow at sublethal pressures, there is little information for designing backgrounds that survive more extreme pressures. In this investigation, we analyzed the genome of an extreme HHP-resistant mutant of E. coli MG1655 (designated as DVL1), from which we identified four mutations (in the cra, cyaA, aceA and rpoD loci) causally linked to increased HHP resistance. Analysing the functional effect of these mutations we found that the coupled effect of downregulation of cAMP/CRP, Cra and the glyoxylate shunt activity, together with the upregulation of RpoH and RpoS activity, could mechanistically explain the increased HHP resistance of the mutant. Using combinations of three mutations, we could synthetically engineer E. coli strains able to comfortably survive pressures of 600-800 MPa, which could serve as genetic backgrounds for HHP-based biotechnological applications

Incremental Mutual Information: A New Method for Characterizing the Strength and Dynamics of Connections in Neuronal Circuits

Understanding the computations performed by neuronal circuits requires characterizing the strength and dynamics of the connections between individual neurons. This characterization is typically achieved by measuring the correlation in the activity of two neurons. We have developed a new measure for studying connectivity in neuronal circuits based on information theory, the incremental mutual information (IMI). By conditioning out the temporal dependencies in the responses of individual neurons before measuring the dependency between them, IMI improves on standard correlation-based measures in several important ways: 1) it has the potential to disambiguate statistical dependencies that reflect the connection between neurons from those caused by other sources (e. g. shared inputs or intrinsic cellular or network mechanisms) provided that the dependencies have appropriate timescales, 2) for the study of early sensory systems, it does not require responses to repeated trials of identical stimulation, and 3) it does not assume that the connection between neurons is linear. We describe the theory and implementation of IMI in detail and demonstrate its utility on experimental recordings from the primate visual system

Electrical Stimulation of the Human Cerebral Cortex by Extracranial Muscle Activity: Effect Quantification With Intracranial EEG and FEM Simulations

Objective: Electric fields (EF) of approx. 0.2 V/m have been shown to be sufficiently strong to both modulate neuronal activity in the cerebral cortex and have measurable effects on cognitive performance. We hypothesized that the EF caused by the electrical activity of extracranial muscles during natural chewing may reach similar strength in the cerebral cortex and hence might act as an endogenous modality of brain stimulation. Here, we present first steps toward validating this hypothesis. Methods: Using a realistic volume conductor head model of an epilepsy patient having undergone intracranial electrode placement and utilizing simultaneous intracranial and extracranial electrical recordings during chewing, we derive predictions about the chewing-related cortical EF strength to be expected in healthy individuals. Results: We find that in the region of the temporal poles, the expected EF strength may reach amplitudes in the order of 0.1-1 V/m. Conclusion: The cortical EF caused by natural chewing could be large enough to modulate ongoing neural activity in the cerebral cortex and influence cognitive performance. Significance: The present study lends first support for the assumption that extracranial muscle activity might represent an endogenous source of electrical brain stimulation. This offers a new potential explanation for the puzzling effects of gum chewing on cognition, which have been repeatedly reported in the literature

Characterization of the Prophage Repertoire of African Salmonella Typhimurium ST313 Reveals High Levels of Spontaneous Induction of Novel Phage BTP1

In the past 30 years,Salmonella bloodstream infections have become a significant health problem in sub-Saharan Africa and are responsible for the deaths of anestimated 390,000 people each year. The disease is predominantly caused by a recently described sequence type of SalmonellaTyphimurium: ST313, which has a distinctive set of prophage sequences. We have thoroughly characterized the ST313-associated prophages both genetically and experimentally. ST313 representative strain D23580 contains five full-length prophages: BTP1, Gifsy-2D23580, ST64BD23580, Gifsy-1D23580,and BTP5. We show that commonS.Typhimurium prophages Gifsy-2, Gifsy-1, andST64B are inactivated in ST313 by mutations. Prophage BTP1 was found to be a functional novel phage, and the first isolate of the proposed new species “Salmonellavirus BTP1”, belonging to the P22virusgenus. Surprisingly,∼109BTP1 virus particlesperml were detected in the supernatant of non-induced, stationary-phase culturesof strain D23580, representing the highest spontaneously induced phage titer so farreported for a bacterial prophage. High spontaneous induction is shown to be anintrinsic property of prophage BTP1, and indicates the phage-mediated lysis of around0.2% of the lysogenic population. The fact that BTP1 is highly conserved in ST313 poses interesting questions about the potential fitness costs and benefits of novel prophagesin epidemicS.Typhimurium ST313