212 research outputs found
On the size of the Fe II emitting region in the AGN Akn 120
We present a reverberation analysis of the strong, variable optical Fe II
emission bands in the spectrum of Akn 120, a low-redshift AGN which is one of
the best candidates for such a study. On time scales of several years the Fe II
line strengths follow the variations in the continuum strength. However, we are
unable to measure a clear reverberation lag time for these Fe II lines on any
time scale. This is due to the very broad and flat-topped nature of the Fe II
cross correlation functions, as compared to the H-beta response which is much
more sharply localized in time. Although there is some suggestion in the light
curve of a 300-day response time, our statistical analysis does not pick up
such a feature. We conclude that the optical Fe II emission does not come from
a photoionization-powered region similar in size to the H-beta emitting region,
but we cannot say for sure where it does come from. Our results are generally
consistent either with emission from a photoionized region several times larger
than the H-beta zone, or with emission from gas heated by some other means,
perhaps responding only indirectly to the continuum variations.Comment: Accepted for publication in the Ap
Disinhibition Bursting of Dopaminergic Neurons
Substantia nigra pars compacta (SNpc) dopaminergic neurons receive strong tonic inputs from GABAergic neurons in the substantia nigra pars reticulata (SNpr) and globus pallidus (GP), and glutamatergic neurons in the subthalamic nucleus. The presence of these tonic inputs raises the possibility that phasic disinhibition may trigger phasic bursts in dopaminergic neurons. We first applied constant NMDA and GABAA conductances onto a two-compartment single cell model of the dopaminergic neuron (Kuznetsov et al., 2006). The model exhibited disinhibition bursting upon stepwise removal of inhibition. A further bifurcation analysis suggests that disinhibition may be more robust than excitation alone in that for most levels of NMDA conductance, the cell remains capable of bursting even after a complete removal of inhibition, whereas too much excitatory input will drive the cell into depolarization block. To investigate the network dynamics of disinhibition, we used a modified version of an integrate-and-fire based model of the basal ganglia (Humphries et al., 2006). Synaptic activity generated in the network was delivered to the two-compartment single cell dopaminergic neuron. Phasic activation of the D1-expressing medium spiny neurons in the striatum (D1STR) produced disinhibition bursts in dopaminergic neurons through the direct pathway (D1STR to SNpr to SNpc). Anatomical studies have shown that D1STR neurons have collaterals that terminate in GP. Adding these collaterals to the model, we found that striatal activation increased the intra-burst firing frequency of the disinhibition burst as the weight of this connection was increased. Our studies suggest that striatal activation is a robust means by which disinhibition bursts can be generated by SNpc dopaminergic neurons, and that recruitment of the indirect pathway via collaterals may enhance disinhibition bursting
N-band Imaging of Seyfert Nuclei and the MIR-X-ray correlation
We present new mid-infrared (N-band) images of a sample of eight nearby
Seyfert galaxies. In all of our targets, we detect a central unresolved source,
which in some cases has been identified for the first time. In particular, we
have detected the mid-infrared emission from the active nucleus of NGC 4945,
which previously remained undetected at any wavelength but hard X-rays. We also
detect circumnuclear extended emission in the Circinus galaxy along its major
axis, and find marginal evidence for extended circumnuclear emission in NGC
3281.
The high spatial resolution (1.7") of our data allows us to separate the flux
of the nuclear point sources from the extended circumnuclear starburst (if
present). We complement our sample with literature data for a number of
non-active starburst galaxies, and relate the nuclear N-band flux to published
hard (2-10 kev) X-ray fluxes. We find tight and well-separated correlations
between nuclear N-band flux and X-ray flux for both Seyfert and starburst
nuclei which span over 3 orders of magnitude in luminosity. We demonstrate that
these correlations can be used as a powerful classification tool for galactic
nuclei.
For example, we find strong evidence against NGC 1808 currently harbouring an
active Seyfert nucleus based on its position in the mid-infrared-X-ray diagram.
On the other hand, we confirm that NGC 4945 is in fact a Seyfert 2 galaxy.Comment: 31 pages, incl. 4 figures, uses AASTex. Replaced with accepted
version after minor modifications. To appear in Ap
Face Recognition Is Affected by Similarity in Spatial Frequency Range to a Greater Degree Than Within-Category Object Recognition.
Regional and cellular gene expression changes in human Huntington's disease brain
Huntington's disease (HD) pathology is well understood at a histological level but a comprehensive molecular analysis of the effect of the disease in the human brain has not previously been available. To elucidate the molecular phenotype of HD on a genome-wide scale, we compared mRNA profiles from 44 human HD brains with those from 36 unaffected controls using microarray analysis. Four brain regions were analyzed: caudate nucleus, cerebellum, prefrontal association cortex [Brodmann's area 9 (BA9)] and motor cortex [Brodmann's area 4 (BA4)]. The greatest number and magnitude of differentially expressed mRNAs were detected in the caudate nucleus, followed by motor cortex, then cerebellum. Thus, the molecular phenotype of HD generally parallels established neuropathology. Surprisingly, no mRNA changes were detected in prefrontal association cortex, thereby revealing subtleties of pathology not previously disclosed by histological methods. To establish that the observed changes were not simply the result of cell loss, we examined mRNA levels in laser-capture microdissected neurons from Grade 1 HD caudate compared to control. These analyses confirmed changes in expression seen in tissue homogenates; we thus conclude that mRNA changes are not attributable to cell loss alone. These data from bona fide HD brains comprise an important reference for hypotheses related to HD and other neurodegenerative disease
Patterns of clinical presentation of adult coeliac disease in a rural setting
BACKGROUND: In recent years there has been increasing recognition that the pattern of presentation of coeliac disease may be changing. The classic sprue syndrome with diarrhoea and weight loss may be less common than the more subtle presentations of coeliac disease such as an isolated iron deficiency anaemia. As a result, the diagnosis of this treatable condition is often delayed or missed. Recent serologic screening tests allow non-invasive screening to identify most patients with the disease and can be applied in patients with even subtle symptoms indicative of coeliac disease. Both benign and malignant complications of coeliac disease can be avoided by early diagnosis and a strict compliance with a gluten free diet. AIM: The aim of this study is to evaluate the trends in clinical presentation of patients diagnosed with adult coeliac disease. In addition, we studied the biochemical and serological features and the prevalence of associated conditions in patients with adult coeliac disease. METHODS: This is an observational, retrospective, cross-sectional review of the medical notes of 32 adult patients attending the specialist coeliac clinic in a district general hospital. RESULTS: Anaemia was the most common mode of presentation accounting for 66% of patients. Less than half of the patients had any of the classical symptoms of coeliac disease and 25% had none of the classical symptoms at presentation. Anti-gliadin antibodies, anti-endomysial antibody and anti-tissue transglutaminase showed 75%, 68% and 90% sensitivity respectively. In combination, serology results were 100% sensitive as screening tests for adult coeliac disease. Fifty nine percent patients had either osteoporosis or osteopenia. There were no malignant complications observed during the follow up of our patients. CONCLUSION: Most adults with coeliac disease have a sub clinical form of the disease and iron deficiency anaemia may be its sole presenting symptom. Only a minority of adult coeliac disease patients present with classical mal-absorption symptoms of diarrhoea and weight loss. Patients with atypical form of disease often present initially to hospital specialists other than a gastro-enterologist. An awareness of the broad spectrum of presentations of adult coeliac disease, among doctors both in primary care and by the various hospital specialists in secondary care, is necessary to avoid delays in diagnosis. It is important to include serological screening tests for coeliac disease systematically in the evaluation of adult patients with unexplained iron deficiency anaemia or unexplained gastro-intestinal symptoms and in those who are considered to be at increased risk for coeliac disease
Utility of the Hebb–Williams maze paradigm for translational research in Fragile X syndrome: A direct comparison of mice and humans
To generate meaningful information, translational research must employ paradigms that allow extrapolation from animal models to humans. However, few studies have evaluated translational paradigms on the basis of defined validation criteria. We outline three criteria for validating translational paradigms. We then evaluate the Hebb–Williams maze paradigm (Hebb and Williams, 1946; Rabinovitch and Rosvold, 1951) on the basis of these criteria using Fragile X syndrome (FXS) as model disease. We focuse
Protein Structure along the Order–Disorder Continuum
Thermal fluctuations cause proteins to adopt an ensemble of conformations wherein the relative stability of the different ensemble members is determined by the topography of the underlying energy landscape. “Folded” proteins have relatively homogeneous ensembles, while “unfolded” proteins have heterogeneous ensembles. Hence, the labels “folded” and “unfolded” represent attempts to provide a qualitative characterization of the extent of structural heterogeneity within the underlying ensemble. In this work, we introduce an information-theoretic order parameter to quantify this conformational heterogeneity. We demonstrate that this order parameter can be estimated in a straightforward manner from an ensemble and is applicable to both unfolded and folded proteins. In addition, a simple formula for approximating the order parameter directly from crystallographic B factors is presented. By applying these metrics to a large sample of proteins, we show that proteins span the full range of the order–disorder axis.National Institutes of Health (U.S.) (NIH Grant 5R21NS063185-02
Modeling Intrinsically Disordered Proteins with Bayesian Statistics
The characterization of intrinsically disordered proteins is challenging because accurate models of these systems require a description of both their thermally accessible conformers and the associated relative stabilities or weights. These structures and weights are typically chosen such that calculated ensemble averages agree with some set of prespecified experimental measurements; however, the large number of degrees of freedom in these systems typically leads to multiple conformational ensembles that are degenerate with respect to any given set of experimental observables. In this work we demonstrate that estimates of the relative stabilities of conformers within an ensemble are often incorrect when one does not account for the underlying uncertainty in the estimates themselves. Therefore, we present a method for modeling the conformational properties of disordered proteins that estimates the uncertainty in the weights of each conformer. The Bayesian weighting (BW) formalism incorporates information from both experimental data and theoretical predictions to calculate a probability density over all possible ways of weighting the conformers in the ensemble. This probability density is then used to estimate the values of the weights. A unique and powerful feature of the approach is that it provides a built-in error measure that allows one to assess the accuracy of the ensemble. We validate the approach using reference ensembles constructed from the five-residue peptide met-enkephalin and then apply the BW method to construct an ensemble of the K18 isoform of the tau protein. Using this ensemble, we indentify a specific pattern of long-range contacts in K18 that correlates with the known aggregation properties of the sequence.National Institutes of Health (U.S.) (NIH Grant 5R21NS063185-02
Flight of the Bumblebee: the Early Excess Flux of Type Ia Supernova 2023bee revealed by , and Young Supernova Experiment Observations
We present high-cadence ultraviolet through near-infrared observations of the
Type Ia supernova (SN Ia) 2023bee in NGC~2708 ( Mpc), finding
excess flux in the first days after explosion relative to the expected
power-law rise from an expanding fireball. This deviation from typical behavior
for SNe Ia is particularly obvious in our 10-minute cadence light curve
and UV data. Compared to a few other normal SNe Ia with detected early
excess flux, the excess flux in SN 2023bee is redder in the UV and less
luminous. We present optical spectra of SN 2023bee, including two spectra
during the period where the flux excess is dominant. At this time, the spectra
are similar to those of other SNe Ia but with weaker Si II, C II and Ca II
absorption lines, perhaps because the excess flux creates a stronger continuum.
We compare the data to several theoretical models that have been proposed to
explain the early flux excess in SNe Ia. Interaction with either a nearby
companion star or close-in circumstellar material is expected to produce a
faster evolution than seen in the data. Radioactive material in the outer
layers of the ejecta, either from a double detonation explosion or simply an
explosion with a Ni clump near the surface, can not fully reproduce the
evolution either, likely due to the sensitivity of early UV observable to the
treatment of the outer part of ejecta in simulation. We conclude that no
current model can adequately explain the full set of observations. We find that
a relatively large fraction of nearby, bright SNe Ia with high-cadence
observations have some amount of excess flux within a few days of explosion.
Considering potential asymmetric emission, the physical cause of this excess
flux may be ubiquitous in normal SNe Ia.Comment: 21 pages, 12 figures. Accepted by the astrophysical journa
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