Recognizing recurrent neural networks (rRNN): Bayesian inference for recurrent neural networks

Recurrent neural networks (RNNs) are widely used in computational neuroscience and machine learning applications. In an RNN, each neuron computes its output as a nonlinear function of its integrated input. While the importance of RNNs, especially as models of brain processing, is undisputed, it is also widely acknowledged that the computations in standard RNN models may be an over-simplification of what real neuronal networks compute. Here, we suggest that the RNN approach may be made both neurobiologically more plausible and computationally more powerful by its fusion with Bayesian inference techniques for nonlinear dynamical systems. In this scheme, we use an RNN as a generative model of dynamic input caused by the environment, e.g. of speech or kinematics. Given this generative RNN model, we derive Bayesian update equations that can decode its output. Critically, these updates define a 'recognizing RNN' (rRNN), in which neurons compute and exchange prediction and prediction error messages. The rRNN has several desirable features that a conventional RNN does not have, for example, fast decoding of dynamic stimuli and robustness to initial conditions and noise. Furthermore, it implements a predictive coding scheme for dynamic inputs. We suggest that the Bayesian inversion of recurrent neural networks may be useful both as a model of brain function and as a machine learning tool. We illustrate the use of the rRNN by an application to the online decoding (i.e. recognition) of human kinematics

Cardiac Resynchronization Therapy in Patients with Mild Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

# The Author(s) 2011. This article is published with open access at Springerlink.com Objective This review aims at updating the results of cardiac resynchronization therapy (CRT) in mild heart failure patients, and investigating whether CRT can prevent or reverse heart failure progression in an earlier stage. Methods Randomized controlled trials of CRT in patients with New York Heart Association (NYHA) Class I or II heart failure were identified. The effects of CRT on worsening heart failure hospitalization, all-cause mortality, and overall adverse events were meta-analyzed, and the effects of CRT on left ventricular (LV) were systematically reviewed and meta-analyzed. Results Eight studies were identified with a total of 4,302 patients. CRT was associated with a substantial improvement in LVend-systolic volume (WMD −39, 95%CI −41.56 to −36.45). CRT also had a marked effect in reducing new hospitalizations for worsening heart failure by 31 % (RR 0.69, 95%CI 0.60 to 0.79). In addition, CRTsignificantly decreased all-cause mortality by 21 % (RR 0.79, 95%CI 0.67 to 0.93). However, complications in patients with CRT increased by 74 % (RR 1.74, 95%CI 1.44 to 2.11). Conclusions This meta-analysis suggests that CRT could improve the prognosis in patients with mild heart failure and ventricular dyssynchrony, but these improvements are accompanied by more adverse events. Since most patients in the included trials had received ICD therapy, our analysis suggests that CRT could offer an additional benefit. Key words Heart failure. Cardiac resynchronization therapy. Meta-analysi

The Abdominal Circulatory Pump

Blood in the splanchnic vasculature can be transferred to the extremities. We quantified such blood shifts in normal subjects by measuring trunk volume by optoelectronic plethysmography, simultaneously with changes in body volume by whole body plethysmography during contractions of the diaphragm and abdominal muscles. Trunk volume changes with blood shifts, but body volume does not so that the blood volume shifted between trunk and extremities (Vbs) is the difference between changes in trunk and body volume. This is so because both trunk and body volume change identically with breathing and gas expansion or compression. During tidal breathing Vbs was 50–75 ml with an ejection fraction of 4–6% and an output of 750–1500 ml/min. Step increases in abdominal pressure resulted in rapid emptying presumably from the liver with a time constant of 0.61±0.1SE sec. followed by slower flow from non-hepatic viscera. The filling time constant was 0.57±0.09SE sec. Splanchnic emptying shifted up to 650 ml blood. With emptying, the increased hepatic vein flow increases the blood pressure at its entry into the inferior vena cava (IVC) and abolishes the pressure gradient producing flow between the femoral vein and the IVC inducing blood pooling in the legs. The findings are important for exercise because the larger the Vbs the greater the perfusion of locomotor muscles. During asystolic cardiac arrest we calculate that appropriate timing of abdominal compression could produce an output of 6 L/min. so that the abdominal circulatory pump might act as an auxiliary heart

Population genomics applications for conservation: the case of the tropical dry forest dweller Peromyscus melanophrys

Recent advances in genomic sequencing have opened new horizons in the study of population genetics and evolution in non-model organisms. However, very few population genomic studies have been performed on wild mammals to understand how the landscape affects the genetic structure of populations, useful information for the conservation of biodiversity. Here, we applied a genomic approach to evaluate the relationship between habitat features and genetic patterns at spatial and temporal scales in an endangered ecosystem, the Tropical Dry Forest (TDF). We studied populations of the Plateau deer mouse Peromyscus melanophrys to analyse its genomic diversity and structure in a TDF protected area in the Huautla Mountain Range (HMR), Mexico based on 8,209 SNPs obtained through Genotyping-by-Sequencing. At a spatial scale, we found a significant signature of isolation-by-distance, few significant differences in genetic diversity indices among study sites, and no significant differences between habitats with different levels of human perturbation. At a temporal scale, while genetic diversity levels fluctuated significantly over time, neither seasonality nor disturbance levels had a significant effect. Also, outlier analysis revealed loci potentially under selection. Our results suggest that the population genetics of P. melanophrys may be little impacted by anthropogenic disturbances, or by natural spatial and temporal habitat heterogeneity in our study area. The genome-wide approach adopted here provides data of value for conservation planning, and a baseline to be used as a reference for future studies on the effects of habitat fragmentation and seasonality in the HMR and in TDF

Mutations with pathogenic potential in proteins located in or at the composite junctions of the intercalated disk connecting mammalian cardiomyocytes: a reference thesaurus for arrhythmogenic cardiomyopathies and for Naxos and Carvajal diseases

In the past decade, an avalanche of findings and reports has correlated arrhythmogenic ventricular cardiomyopathies (ARVC) and Naxos and Carvajal diseases with certain mutations in protein constituents of the special junctions connecting the polar regions (intercalated disks) of mature mammalian cardiomyocytes. These molecules, apparently together with some specific cytoskeletal proteins, are components of (or interact with) composite junctions. Composite junctions contain the amalgamated fusion products of the molecules that, in other cell types and tissues, occur in distinct separate junctions, i.e. desmosomes and adherens junctions. As the pertinent literature is still in an expanding phase and is obviously becoming important for various groups of researchers in basic cell and molecular biology, developmental biology, histology, physiology, cardiology, pathology and genetics, the relevant references so far recognized have been collected and are presented here in the following order: desmocollin-2 (Dsc2, DSC2), desmoglein-2 (Dsg2, DSG2), desmoplakin (DP, DSP), plakoglobin (PG, JUP), plakophilin-2 (Pkp2, PKP2) and some non-desmosomal proteins such as transmembrane protein 43 (TMEM43), ryanodine receptor 2 (RYR2), desmin, lamins A and C, striatin, titin and transforming growth factor-β3 (TGFβ3), followed by a collection of animal models and of reviews, commentaries, collections and comparative studies

Bidirectional Coupling between Astrocytes and Neurons Mediates Learning and Dynamic Coordination in the Brain: A Multiple Modeling Approach

In recent years research suggests that astrocyte networks, in addition to nutrient and waste processing functions, regulate both structural and synaptic plasticity. To understand the biological mechanisms that underpin such plasticity requires the development of cell level models that capture the mutual interaction between astrocytes and neurons. This paper presents a detailed model of bidirectional signaling between astrocytes and neurons (the astrocyte-neuron model or AN model) which yields new insights into the computational role of astrocyte-neuronal coupling. From a set of modeling studies we demonstrate two significant findings. Firstly, that spatial signaling via astrocytes can relay a “learning signal” to remote synaptic sites. Results show that slow inward currents cause synchronized postsynaptic activity in remote neurons and subsequently allow Spike-Timing-Dependent Plasticity based learning to occur at the associated synapses. Secondly, that bidirectional communication between neurons and astrocytes underpins dynamic coordination between neuron clusters. Although our composite AN model is presently applied to simplified neural structures and limited to coordination between localized neurons, the principle (which embodies structural, functional and dynamic complexity), and the modeling strategy may be extended to coordination among remote neuron clusters