955 research outputs found
Simple, Fast and Accurate Implementation of the Diffusion Approximation Algorithm for Stochastic Ion Channels with Multiple States
The phenomena that emerge from the interaction of the stochastic opening and
closing of ion channels (channel noise) with the non-linear neural dynamics are
essential to our understanding of the operation of the nervous system. The
effects that channel noise can have on neural dynamics are generally studied
using numerical simulations of stochastic models. Algorithms based on discrete
Markov Chains (MC) seem to be the most reliable and trustworthy, but even
optimized algorithms come with a non-negligible computational cost. Diffusion
Approximation (DA) methods use Stochastic Differential Equations (SDE) to
approximate the behavior of a number of MCs, considerably speeding up
simulation times. However, model comparisons have suggested that DA methods did
not lead to the same results as in MC modeling in terms of channel noise
statistics and effects on excitability. Recently, it was shown that the
difference arose because MCs were modeled with coupled activation subunits,
while the DA was modeled using uncoupled activation subunits. Implementations
of DA with coupled subunits, in the context of a specific kinetic scheme,
yielded similar results to MC. However, it remained unclear how to generalize
these implementations to different kinetic schemes, or whether they were faster
than MC algorithms. Additionally, a steady state approximation was used for the
stochastic terms, which, as we show here, can introduce significant
inaccuracies. We derived the SDE explicitly for any given ion channel kinetic
scheme. The resulting generic equations were surprisingly simple and
interpretable - allowing an easy and efficient DA implementation. The algorithm
was tested in a voltage clamp simulation and in two different current clamp
simulations, yielding the same results as MC modeling. Also, the simulation
efficiency of this DA method demonstrated considerable superiority over MC
methods.Comment: 32 text pages, 10 figures, 1 supplementary text + figur
Regularity Properties and Pathologies of Position-Space Renormalization-Group Transformations
We reconsider the conceptual foundations of the renormalization-group (RG)
formalism, and prove some rigorous theorems on the regularity properties and
possible pathologies of the RG map. Regarding regularity, we show that the RG
map, defined on a suitable space of interactions (= formal Hamiltonians), is
always single-valued and Lipschitz continuous on its domain of definition. This
rules out a recently proposed scenario for the RG description of first-order
phase transitions. On the pathological side, we make rigorous some arguments of
Griffiths, Pearce and Israel, and prove in several cases that the renormalized
measure is not a Gibbs measure for any reasonable interaction. This means that
the RG map is ill-defined, and that the conventional RG description of
first-order phase transitions is not universally valid. For decimation or
Kadanoff transformations applied to the Ising model in dimension ,
these pathologies occur in a full neighborhood of the low-temperature part of the first-order
phase-transition surface. For block-averaging transformations applied to the
Ising model in dimension , the pathologies occur at low temperatures
for arbitrary magnetic-field strength. Pathologies may also occur in the
critical region for Ising models in dimension . We discuss in detail
the distinction between Gibbsian and non-Gibbsian measures, and give a rather
complete catalogue of the known examples. Finally, we discuss the heuristic and
numerical evidence on RG pathologies in the light of our rigorous theorems.Comment: 273 pages including 14 figures, Postscript, See also
ftp.scri.fsu.edu:hep-lat/papers/9210/9210032.ps.
Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters
Recent progress in studies of globular clusters has shown that they are not
simple stellar populations, being rather made of multiple generations. Evidence
stems both from photometry and spectroscopy. A new paradigm is then arising for
the formation of massive star clusters, which includes several episodes of star
formation. While this provides an explanation for several features of globular
clusters, including the second parameter problem, it also opens new
perspectives about the relation between globular clusters and the halo of our
Galaxy, and by extension of all populations with a high specific frequency of
globular clusters, such as, e.g., giant elliptical galaxies. We review progress
in this area, focusing on the most recent studies. Several points remain to be
properly understood, in particular those concerning the nature of the polluters
producing the abundance pattern in the clusters and the typical timescale, the
range of cluster masses where this phenomenon is active, and the relation
between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review
Blood transfusion in the critically ill: does storage age matter?
Morphologic and biochemical changes occur during red cell storage prior to product expiry, and these changes may hinder erythrocyte viability and function following transfusion. Despite a relatively large body of literature detailing the metabolic and structural deterioration that occurs during red cell storage, evidence for a significant detrimental clinical effect related to the transfusion of older blood is relatively less conclusive, limited primarily to observations in retrospective studies. Nonetheless, the implication that the transfusion of old, but not outdated blood may have negative clinical consequences demands attention. In this report, the current understanding of the biochemical and structural changes that occur during storage, known collectively as the storage lesion, is described, and the clinical evidence concerning the detrimental consequences associated with the transfusion of relatively older red cells is critically reviewed. Although the growing body of literature demonstrating the deleterious effects of relatively old blood is compelling, it is notable that all of these reports have been retrospective, and most of these studies have evaluated patients who received a mixture of red cell units of varying storage age. Until prospective studies have been completed and produce confirmative results, it would be premature to recommend any modification of current transfusion practice regarding storage age
Observation and study of baryonic B decays: B -> D(*) p pbar, D(*) p pbar pi, and D(*) p pbar pi pi
We present a study of ten B-meson decays to a D(*), a proton-antiproton pair,
and a system of up to two pions using BaBar's data set of 455x10^6 BBbar pairs.
Four of the modes (B0bar -> D0 p anti-p, B0bar -> D*0 p anti-p, B0bar -> D+ p
anti-p pi-, B0bar -> D*+ p anti-p pi-) are studied with improved statistics
compared to previous measurements; six of the modes (B- -> D0 p anti-p pi-, B-
-> D*0 p anti-p pi-, B0bar -> D0 p anti-p pi- pi+, B0bar -> D*0 p anti-p pi-
pi+, B- -> D+ p anti-p pi- pi-, B- -> D*+ p anti-p pi- pi-) are first
observations. The branching fractions for 3- and 5-body decays are suppressed
compared to 4-body decays. Kinematic distributions for 3-body decays show
non-overlapping threshold enhancements in m(p anti-p) and m(D(*)0 p) in the
Dalitz plots. For 4-body decays, m(p pi-) mass projections show a narrow peak
with mass and full width of (1497.4 +- 3.0 +- 0.9) MeV/c2, and (47 +- 12 +- 4)
MeV/c2, respectively, where the first (second) errors are statistical
(systematic). For 5-body decays, mass projections are similar to phase space
expectations. All results are preliminary.Comment: 28 pages, 90 postscript figures, submitted to LP0
Variance component estimation uncertainty for unbalanced data: Application to a continent-wide vertical datum
Variance component estimation (VCE) is used to update the stochastic model in least-squares adjustments, but the uncertainty associated with the VCE-derived weights is rarely considered. Unbalanced data is where there is an unequal number of observations in each heterogeneous dataset comprising the variance component groups. As a case study using highly unbalanced data, we redefine a continent-wide vertical datum from a combined least-squares adjustment using iterative VCE and its uncertainties to update weights for each data set. These are: (1) a continent-wide levelling network, (2) a model of the ocean’s mean dynamic topography and mean sea level observations, and (3) GPS-derived ellipsoidal heights minus a gravimetric quasigeoid model. VCE uncertainty differs for each observation group in the highly unbalanced data, being dependent on the number of observations in each group. It also changes within each group after each VCE iteration, depending on the magnitude of change for each observation group’s variances. It is recommended that VCE uncertainty is computed for VCE updates to the weight matrix for unbalanced data so that the quality of the updates for each group can be properly assessed. This is particularly important if some groups contain relatively small numbers of observations. VCE uncertainty can also be used as a threshold for ceasing iterations, as it is shown—for this data set at least—that it is not necessary to continue time-consuming iterations to fully converge to unity
Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes
BACKGROUND: A substantial body of research supports a genetic involvement in autism. Furthermore, results from various genomic screens implicate a region on chromosome 7q31 as harboring an autism susceptibility variant. We previously narrowed this 34 cM region to a 3 cM critical region (located between D7S496 and D7S2418) using the Collaborative Linkage Study of Autism (CLSA) chromosome 7 linked families. This interval encompasses about 4.5 Mb of genomic DNA and encodes over fifty known and predicted genes. Four candidate genes (NRCAM, LRRN3, KIAA0716, and LAMB1) in this region were chosen for examination based on their proximity to the marker most consistently cosegregating with autism in these families (D7S1817), their tissue expression patterns, and likely biological relevance to autism. METHODS: Thirty-six intronic and exonic single nucleotide polymorphisms (SNPs) and one microsatellite marker within and around these four candidate genes were genotyped in 30 chromosome 7q31 linked families. Multiple SNPs were used to provide as complete coverage as possible since linkage disequilibrium can vary dramatically across even very short distances within a gene. Analyses of these data used the Pedigree Disequilibrium Test for single markers and a multilocus likelihood ratio test. RESULTS: As expected, linkage disequilibrium occurred within each of these genes but we did not observe significant LD across genes. None of the polymorphisms in NRCAM, LRRN3, or KIAA0716 gave p < 0.05 suggesting that none of these genes is associated with autism susceptibility in this subset of chromosome 7-linked families. However, with LAMB1, the allelic association analysis revealed suggestive evidence for a positive association, including one individual SNP (p = 0.02) and three separate two-SNP haplotypes across the gene (p = 0.007, 0.012, and 0.012). CONCLUSIONS: NRCAM, LRRN3, KIAA0716 are unlikely to be involved in autism. There is some evidence that variation in or near the LAMB1 gene may be involved in autism
Search for rare quark-annihilation decays, B --> Ds(*) Phi
We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context
of the Standard Model, these decays are expected to be highly suppressed since
they proceed through annihilation of the b and u-bar quarks in the B- meson.
Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected
with the BABAR detector at SLAC. We find no evidence for these decays, and we
set Bayesian 90% confidence level upper limits on the branching fractions BF(B-
--> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results
are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid
Communications
Balanced Synaptic Input Shapes the Correlation between Neural Spike Trains
Stimulus properties, attention, and behavioral context influence correlations between the spike times produced by a pair of neurons. However, the biophysical mechanisms that modulate these correlations are poorly understood. With a combined theoretical and experimental approach, we show that the rate of balanced excitatory and inhibitory synaptic input modulates the magnitude and timescale of pairwise spike train correlation. High rate synaptic inputs promote spike time synchrony rather than long timescale spike rate correlations, while low rate synaptic inputs produce opposite results. This correlation shaping is due to a combination of enhanced high frequency input transfer and reduced firing rate gain in the high input rate state compared to the low state. Our study extends neural modulation from single neuron responses to population activity, a necessary step in understanding how the dynamics and processing of neural activity change across distinct brain states
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