265 research outputs found
Spatial representation of temporal information through spike timing dependent plasticity
We suggest a mechanism based on spike time dependent plasticity (STDP) of
synapses to store, retrieve and predict temporal sequences. The mechanism is
demonstrated in a model system of simplified integrate-and-fire type neurons
densely connected by STDP synapses. All synapses are modified according to the
so-called normal STDP rule observed in various real biological synapses. After
conditioning through repeated input of a limited number of of temporal
sequences the system is able to complete the temporal sequence upon receiving
the input of a fraction of them. This is an example of effective unsupervised
learning in an biologically realistic system. We investigate the dependence of
learning success on entrainment time, system size and presence of noise.
Possible applications include learning of motor sequences, recognition and
prediction of temporal sensory information in the visual as well as the
auditory system and late processing in the olfactory system of insects.Comment: 13 pages, 14 figures, completely revised and augmented versio
Comment on Spracklandus Hoser, 2009 (Reptilia, Serpentes, ELAPIDAE): request for confirmation of the availability of the generic name and for the nomenclatural validation of the journal in which it was published (Case 3601; see BZN 70: 234–237; 71: 30–38, 133–135, 181–182, 252–253)
The effectiveness of interventions to change six health behaviours: a review of reviews
Background: Several World Health Organisation reports over recent years have highlighted the high incidence of chronic diseases such as diabetes, coronary heart disease and cancer. Contributory factors include unhealthy diets, alcohol and tobacco use and sedentary lifestyles. This paper reports the findings of a review of reviews of behavioural change interventions to reduce unhealthy behaviours or promote healthy behaviours. We included six different health-related behaviours in the review: healthy eating, physical exercise, smoking, alcohol misuse, sexual risk taking (in young people) and illicit drug use. We excluded reviews which focussed on pharmacological treatments or those which required intensive treatments (e. g. for drug or alcohol dependency).
Methods: The Cochrane Library, Database of Abstracts of Reviews of Effectiveness (DARE) and several Ovid databases were searched for systematic reviews of interventions for the six behaviours (updated search 2008). Two reviewers applied the inclusion criteria, extracted data and assessed the quality of the reviews. The results were discussed in a narrative synthesis.
Results: We included 103 reviews published between 1995 and 2008. The focus of interventions varied, but those targeting specific individuals were generally designed to change an existing behaviour (e. g. cigarette smoking, alcohol misuse), whilst those aimed at the general population or groups such as school children were designed to promote positive behaviours (e. g. healthy eating). Almost 50% (n = 48) of the reviews focussed on smoking (either prevention or cessation). Interventions that were most effective across a range of health behaviours included physician advice or individual counselling, and workplace- and school-based activities. Mass media campaigns and legislative interventions also showed small to moderate effects in changing health behaviours. Generally, the evidence related to short-term effects rather than sustained/longer-term impact and there was a relative lack of evidence on how best to address inequalities.
Conclusions: Despite limitations of the review of reviews approach, it is encouraging that there are interventions that are effective in achieving behavioural change. Further emphasis in both primary studies and secondary analysis (e.g. systematic reviews) should be placed on assessing the differential effectiveness of interventions across different population subgroups to ensure that health inequalities are addressed.</p
Astroparticle Physics with a Customized Low-Background Broad Energy Germanium Detector
The MAJORANA Collaboration is building the MAJORANA DEMONSTRATOR, a 60 kg
array of high purity germanium detectors housed in an ultra-low background
shield at the Sanford Underground Laboratory in Lead, SD. The MAJORANA
DEMONSTRATOR will search for neutrinoless double-beta decay of 76Ge while
demonstrating the feasibility of a tonne-scale experiment. It may also carry
out a dark matter search in the 1-10 GeV/c^2 mass range. We have found that
customized Broad Energy Germanium (BEGe) detectors produced by Canberra have
several desirable features for a neutrinoless double-beta decay experiment,
including low electronic noise, excellent pulse shape analysis capabilities,
and simple fabrication. We have deployed a customized BEGe, the MAJORANA
Low-Background BEGe at Kimballton (MALBEK), in a low-background cryostat and
shield at the Kimballton Underground Research Facility in Virginia. This paper
will focus on the detector characteristics and measurements that can be
performed with such a radiation detector in a low-background environment.Comment: Submitted to NIMA Proceedings, SORMA XII. 9 pages, 4 figure
The MAJORANA DEMONSTRATOR: A Search for Neutrinoless Double-beta Decay of Germanium-76
The observation of neutrinoless double-beta decay would determine whether the
neutrino is a Majorana particle and provide information on the absolute scale
of neutrino mass. The MAJORANA Collaboration is constructing the DEMONSTRATOR,
an array of germanium detectors, to search for neutrinoless double-beta decay
of 76-Ge. The DEMONSTRATOR will contain 40 kg of germanium; up to 30 kg will be
enriched to 86% in 76-Ge. The DEMONSTRATOR will be deployed deep underground in
an ultra-low-background shielded environment. Operation of the DEMONSTRATOR
aims to determine whether a future tonne-scale germanium experiment can achieve
a background goal of one count per tonne-year in a 4-keV region of interest
around the 76-Ge neutrinoless double-beta decay Q-value of 2039 keV.Comment: Submitted to AIP Conference Proceedings, 19th Particles & Nuclei
International Conference (PANIC 2011), Massachusetts Institute of Technology,
Cambridge, MA, USA, July 24-29, 2011; 3 pages, 1 figur
The Majorana experiment: an ultra-low background search for neutrinoless double-beta decay
The observation of neutrinoless double-beta decay would resolve the Majorana
nature of the neutrino and could provide information on the absolute scale of
the neutrino mass. The initial phase of the Majorana experiment, known as the
Demonstrator, will house 40 kg of Ge in an ultra-low background shielded
environment at the 4850' level of the Sanford Underground Laboratory in Lead,
SD. The objective of the Demonstrator is to determine whether a future 1-tonne
experiment can achieve a background goal of one count per tonne-year in a
narrow region of interest around the 76Ge neutrinoless double-beta decay peak.Comment: Presentation for the Rutherford Centennial Conference on Nuclear
Physic
LSST: from Science Drivers to Reference Design and Anticipated Data Products
(Abridged) We describe here the most ambitious survey currently planned in
the optical, the Large Synoptic Survey Telescope (LSST). A vast array of
science will be enabled by a single wide-deep-fast sky survey, and LSST will
have unique survey capability in the faint time domain. The LSST design is
driven by four main science themes: probing dark energy and dark matter, taking
an inventory of the Solar System, exploring the transient optical sky, and
mapping the Milky Way. LSST will be a wide-field ground-based system sited at
Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m
effective) primary mirror, a 9.6 deg field of view, and a 3.2 Gigapixel
camera. The standard observing sequence will consist of pairs of 15-second
exposures in a given field, with two such visits in each pointing in a given
night. With these repeats, the LSST system is capable of imaging about 10,000
square degrees of sky in a single filter in three nights. The typical 5
point-source depth in a single visit in will be (AB). The
project is in the construction phase and will begin regular survey operations
by 2022. The survey area will be contained within 30,000 deg with
, and will be imaged multiple times in six bands, ,
covering the wavelength range 320--1050 nm. About 90\% of the observing time
will be devoted to a deep-wide-fast survey mode which will uniformly observe a
18,000 deg region about 800 times (summed over all six bands) during the
anticipated 10 years of operations, and yield a coadded map to . The
remaining 10\% of the observing time will be allocated to projects such as a
Very Deep and Fast time domain survey. The goal is to make LSST data products,
including a relational database of about 32 trillion observations of 40 billion
objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures
available from https://www.lsst.org/overvie
Effective Stimuli for Constructing Reliable Neuron Models
The rich dynamical nature of neurons poses major conceptual and technical challenges for unraveling their nonlinear membrane properties. Traditionally, various current waveforms have been injected at the soma to probe neuron dynamics, but the rationale for selecting specific stimuli has never been rigorously justified. The present experimental and theoretical study proposes a novel framework, inspired by learning theory, for objectively selecting the stimuli that best unravel the neuron's dynamics. The efficacy of stimuli is assessed in terms of their ability to constrain the parameter space of biophysically detailed conductance-based models that faithfully replicate the neuron's dynamics as attested by their ability to generalize well to the neuron's response to novel experimental stimuli. We used this framework to evaluate a variety of stimuli in different types of cortical neurons, ages and animals. Despite their simplicity, a set of stimuli consisting of step and ramp current pulses outperforms synaptic-like noisy stimuli in revealing the dynamics of these neurons. The general framework that we propose paves a new way for defining, evaluating and standardizing effective electrical probing of neurons and will thus lay the foundation for a much deeper understanding of the electrical nature of these highly sophisticated and non-linear devices and of the neuronal networks that they compose
Empirical correlation of triggered activity and spatial and temporal re-entrant substrates with arrhythmogenicity in a murine model for Jervell and Lange-Nielsen syndrome
KCNE1 encodes the β-subunit of the slow component of the delayed rectifier K+ current. The Jervell and Lange-Nielsen syndrome is characterized by sensorineural deafness, prolonged QT intervals, and ventricular arrhythmogenicity. Loss-of-function mutations in KCNE1 are implicated in the JLN2 subtype. We recorded left ventricular epicardial and endocardial monophasic action potentials (MAPs) in intact, Langendorff-perfused mouse hearts. KCNE1−/− but not wild-type (WT) hearts showed not only triggered activity and spontaneous ventricular tachycardia (VT), but also VT provoked by programmed electrical stimulation. The presence or absence of VT was related to the following set of criteria for re-entrant excitation for the first time in KCNE1−/− hearts: Quantification of APD90, the MAP duration at 90% repolarization, demonstrated alterations in (1) the difference, ∆APD90, between endocardial and epicardial APD90 and (2) critical intervals for local re-excitation, given by differences between APD90 and ventricular effective refractory period, reflecting spatial re-entrant substrate. Temporal re-entrant substrate was reflected in (3) increased APD90 alternans, through a range of pacing rates, and (4) steeper epicardial and endocardial APD90 restitution curves determined with a dynamic pacing protocol. (5) Nicorandil (20 µM) rescued spontaneous and provoked arrhythmogenic phenomena in KCNE1−/− hearts. WTs remained nonarrhythmogenic. Nicorandil correspondingly restored parameters representing re-entrant criteria in KCNE1−/− hearts toward values found in untreated WTs. It shifted such values in WT hearts in similar directions. Together, these findings directly implicate triggered electrical activity and spatial and temporal re-entrant mechanisms in the arrhythmogenesis observed in KCNE1−/− hearts
Free Energy Simulations of a GTPase: GTP and GDP Binding to Archaeal Initiation Factor 2
International audienceArchaeal initiation factor 2 (aIF2) is a protein involved in the initiation of protein biosynthesis. In its GTP-bound, "ON" conformation, aIF2 binds an initiator tRNA and carries it to the ribosome. In its GDP-bound, "OFF" conformation, it dissociates from tRNA. To understand the specific binding of GTP and GDP and its dependence on the ON or OFF conformational state of aIF2, molecular dynamics free energy simulations (MDFE) are a tool of choice. However, the validity of the computed free energies depends on the simulation model, including the force field and the boundary conditions, and on the extent of conformational sampling in the simulations. aIF2 and other GTPases present specific difficulties; in particular, the nucleotide ligand coordinates a divalent Mg(2+) ion, which can polarize the electronic distribution of its environment. Thus, a force field with an explicit treatment of electronic polarizability could be necessary, rather than a simpler, fixed charge force field. Here, we begin by comparing a fixed charge force field to quantum chemical calculations and experiment for Mg(2+):phosphate binding in solution, with the force field giving large errors. Next, we consider GTP and GDP bound to aIF2 and we compare two fixed charge force fields to the recent, polarizable, AMOEBA force field, extended here in a simple, approximate manner to include GTP. We focus on a quantity that approximates the free energy to change GTP into GDP. Despite the errors seen for Mg(2+):phosphate binding in solution, we observe a substantial cancellation of errors when we compare the free energy change in the protein to that in solution, or when we compare the protein ON and OFF states. Finally, we have used the fixed charge force field to perform MDFE simulations and alchemically transform GTP into GDP in the protein and in solution. With a total of about 200 ns of molecular dynamics, we obtain good convergence and a reasonable statistical uncertainty, comparable to the force field uncertainty, and somewhat lower than the predicted GTP/GDP binding free energy differences. The sign and magnitudes of the differences can thus be interpreted at a semiquantitative level, and are found to be consistent with the experimental binding preferences of ON- and OFF-aIF2
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