Making neurophysiological data analysis reproducible. Why and how?

Manuscript submitted to "The Journal of Physiology (Paris)". Second version.Reproducible data analysis is an approach aiming at complementing classical printed scientific articles with everything required to independently reproduce the results they present. ''Everything'' covers here: the data, the computer codes and a precise description of how the code was applied to the data. A brief history of this approach is presented first, starting with what economists have been calling replication since the early eighties to end with what is now called reproducible research in computational data analysis oriented fields like statistics and signal processing. Since efficient tools are instrumental for a routine implementation of these approaches, a description of some of the available ones is presented next. A toy example demonstrates then the use of two open source software for reproducible data analysis: the ''Sweave family'' and the org-mode of emacs. The former is bound to R while the latter can be used with R, Matlab, Python and many more ''generalist'' data processing software. Both solutions can be used with Unix-like, Windows and Mac families of operating systems. It is argued that neuroscientists could communicate much more efficiently their results by adopting the reproducible research paradigm from their lab books all the way to their articles, thesis and books

Real-time biomimetic Central Pattern Generators in an FPGA for hybrid experiments

This investigation of the leech heartbeat neural network system led to the development of a low resources, real-time, biomimetic digital hardware for use in hybrid experiments. The leech heartbeat neural network is one of the simplest central pattern generators (CPG). In biology, CPG provide the rhythmic bursts of spikes that form the basis for all muscle contraction orders (heartbeat) and locomotion (walking, running, etc.). The leech neural network system was previously investigated and this CPG formalized in the Hodgkin–Huxley neural model (HH), the most complex devised to date. However, the resources required for a neural model are proportional to its complexity. In response to this issue, this article describes a biomimetic implementation of a network of 240 CPGs in an FPGA (Field Programmable Gate Array), using a simple model (Izhikevich) and proposes a new synapse model: activity-dependent depression synapse. The network implementation architecture operates on a single computation core. This digital system works in real-time, requires few resources, and has the same bursting activity behavior as the complex model. The implementation of this CPG was initially validated by comparing it with a simulation of the complex model. Its activity was then matched with pharmacological data from the rat spinal cord activity. This digital system opens the way for future hybrid experiments and represents an important step toward hybridization of biological tissue and artificial neural networks. This CPG network is also likely to be useful for mimicking the locomotion activity of various animals and developing hybrid experiments for neuroprosthesis development

Azaphosphatrane Organocatalysts in Confined Space: Cage Effect in CO2 Conversion

International audienceThe endohedral functionalization of a molecular cage by an azaphosphatrane unit has allowed for the creation of highly engineered catalytic cavities for efficient conversion of CO2 into cyclic carbonates. Strong structure/activity/stability correlations have been demonstrated by careful adjustment of the size, shape, and electronic properties of the hemicryptophane host

Une conception universelle mise en oeuvre via des modes d'usages

International audienc

Quantitative definition and monitoring of the host cell protein proteome using iTRAQ: a study of an industrial mAb producing CHO-S cell line

There are few studies defining CHO host cell proteins (HCPs) and the flux of these throughout a downstream purification process. Here we have applied quantitative iTRAQ proteomics to follow the HCP profile of an antibody (mAb) producing CHO-S cell line throughout a standard downstream purification procedure consisting of a Protein A, cation and anion exchange process. We used both 6 sample iTRAQ experiment to analyze technical replicates of three samples, which were culture harvest (HCCF), Protein A flow through and Protein A eluate and an 8 sample format to analyze technical replicates of four sample types; HCCF compared to Protein A eluate and subsequent cation and anion exchange purification. In the 6 sample iTRAQ experiment, 8781 spectra were confidently matched to peptides from 819 proteins (including the mAb chains). Across both the 6 and 8 sample experiments 936 proteins were identified. In the 8 sample comparison, 4187 spectra were confidently matched to peptides from 219 proteins. We then used the iTRAQ data to enable estimation of the relative change of individual proteins across the purification steps. These data provide the basis for application of iTRAQ for process development based upon knowledge of critical HCPs

Main Results of Phase IV BEMUSE Project: Simulation of LBLOCA in an NPP

Phase IV of BEMUSE Program is a necessary step for a subsequent uncertainty analysis. It includes the simulation of the reference scenario and a sensitivity study. The scenario is a LBLOCA and the reference plant is Zion 1 NPP, a 4 loop PWR unit. Thirteen participants coming from ten different countries have taken part in the exercise. The BEMUSE (Best Estimate Methods plus Uncertainty and Sensitivity Evaluation) Programhas been promoted by theWorking Group on AccidentManagement and Analysis (WGAMA) and endorsed by the Committee on the Safety of Nuclear Installations (CSNI). The paper presents the results of the calculations performed by participants and emphasizes its usefulness for future uncertainty evaluation, to be performed in next phase. The objectives of the activity are basically to simulate the LBLOCA reproducing the phenomena associated to the scenario and also to build a common, well-known, basis for the future comparison of uncertainty evaluation results among different methodologies and codes. The sensitivity calculations performed by participants are also presented. They allow studying the influence of different parameters such as material properties or initial and boundary conditions, upon the behaviour of the most relevant parameters related to the scenario

Recent Insights into the Pathogenesis of Acute Porphyria Attacks and Increasing Hepatic PBGD as an Etiological Treatment

Rare diseases, especially monogenic diseases, which usually affect a single target protein, have attracted growing interest in drug research by encouraging pharmaceutical companies to design and develop therapeutic products to be tested in the clinical arena. Acute intermittent porphyria (AIP) is one of these rare diseases. AIP is characterized by haploinsufficiency in the third enzyme of the heme biosynthesis pathway. Identification of the liver as the target organ and a detailed molecular characterization have enabled the development and approval of several therapies to manage this disease, such as glucose infusions, heme replenishment, and, more recently, an siRNA strategy that aims to down-regulate the key limiting enzyme of heme synthesis. Given the involvement of hepatic hemoproteins in essential metabolic functions, important questions regarding energy supply, antioxidant and detoxifying responses, and glucose homeostasis remain to be elucidated. This review reports recent insights into the pathogenesis of acute attacks and provides an update on emerging treatments aimed at increasing the activity of the deficient enzyme in the liver and restoring the physiological regulation of the pathway. While further studies are needed to optimize gene therapy vectors or large-scale production of liver-targeted PBGD proteins, effective protection of PBGD mRNA against the acute attacks has already been successfully confirmed in mice and large animals, and mRNA transfer technology is being tested in several clinical trials for metabolic diseases

Expression of alternansucrase in potato plants

Alternan, which consists of alternating α-(1→3)/α-(1→6)-linked glucosyl residues, was produced in potato tubers by expressing a mature alternansucrase (Asr) gene from Leuconostoc mesenteroides NRRL B-1355 in potato. Detection of alternan was performed by enzyme-linked immunosorbent assay in tuber juices, revealing a concentration between 0.3 and 1.2 mg g-1 fresh wt. The Asr transcript levels correlated well with alternan accumulation in tuber juices. It appeared that the expression of sucrose-regulated starch-synthesizing genes (ADP-glucose pyrophosphorylase subunit S and granule-bound starch synthase I) was down-regulated. Despite this, the physico-chemical properties of the transgenic starches were unaltered. These results are compared to those obtained with other transgenic potato plants producing mutan [α-(1→3)-linked glucosyl residues] and dextran [α-(1→6)-linked glucosyl residues]

Analyse des signaux pour un dispositif de mesure et de stimulation du système nerveux central

- Un des enjeux actuels en Neurosciences est de pouvoir enregistrer simultanément les activités d'un grand nombre de cellules au sein de grands réseaux de neurones, et de pouvoir stimuler de manière dynamique ces réseaux afin d'en contrôler les activités. Le but du projet Neurocom est de réaliser un système multiélectrode haute densité intégré sur silicium, permettant d'enregistrer et de stimuler de grands réseaux de neurones in vitro. Ce dispositif sera constitué d'une microstructure d'électrodes stérilisable hybridée sur un circuit analogique intégré (préamplification, filtrage, multiplexage, stimulation), lui-même interfacé via une carte numérique de commande et acquisition reliée à un PC. Afin de pouvoir mieux appréhender les phénomènes bioélectriques et électrochimiques à l'interface capteur et donc mieux spécifier le cahier des charges et l'architecture du système, la maquette de test NEUROCOM1 a été conçue en électronique discrète et est actuellement utilisée pour conduire différents tests

Differential modulation of excitatory and inhibitory neurons during periodic stimulation

Non-invasive transcranial neuronal stimulation, in addition to deep brain stimulation, is seen as a promising therapeutic and diagnostic approach for an increasing number of neurological diseases such as epilepsy, cluster headaches, depression, specific type of blindness, and other central nervous system disfunctions. Improving its effectiveness and widening its range of use may strongly rely on development of proper stimulation protocols that are tailored to specific brain circuits and that are based on a deep knowledge of different neuron types response to stimulation. To this aim, we have performed a simulation study on the behavior of excitatory and inhibitory neurons subject to sinusoidal stimulation. Due to the intrinsic difference in membrane conductance properties of excitatory and inhibitory neurons, we show that their firing is differentially modulated by the wave parameters. We analyzed the behavior of the two neuronal types for a broad range of stimulus frequency and amplitude and demonstrated that, within a small-world network prototype, parameters tuning allow for a selective enhancement or suppression of the excitation/inhibition ratio