3,690 research outputs found
Lipase inhibition attenuates the acute inhibitory effects of oral fat on food intake in healthy subjects
The lipase inhibitor, orlistat, is used in the treatment of obesity and reduces fat absorption by about 30%. However, the mean weight loss induced by orlistat is less than expected for the degree of fat malabsorption. It was hypothesised that lipase inhibition with orlistat attenuates the suppressive effects of oral fat on subsequent energy intake in normal-weight subjects. Fourteen healthy, lean subjects (nine males, five females; aged 25 +/- 1.3 years) were studied twice, in a double-blind fashion. The subjects received a high-fat yoghurt 'preload' (males 400 g (2562 kJ); females 300 g (1923 kJ)), containing orlistat (120 mg) on one study day (and no orlistat on the other 'control' day), 30 min before ad libitum access to food and drinks; energy intake was assessed during the following 8 h. Blood samples were taken at regular intervals for the measurement of plasma cholecystokinin (CCK). Each subject performed a 3 d faecal fat collection following each study. Energy intake during the day was greater following orlistat (10,220 (SEM 928) kJ) v. control (9405 (SEM 824) kJ) (P=0.02). On both days plasma CCK increased (P<0.05) after the preload. Plasma CCK 20 min following ingestion of the preload was less after orlistat (4.1 (SEM 0.9) pmol/l) v. control (5.3 (SEM 0.9) pmol/l (P=0.028); however there was no difference in the area under the curve 0-510 min between the two study days. Fat excretion was greater following orlistat (1017 (SEM 168) kJ) v. control (484 (SEM 90) kJ) (P=0.004). In conclusion, in healthy, lean subjects the acute inhibitory effect of fat on subsequent energy intake is attenuated by orlistat and the increase in energy intake approximates the energy lost due to fat malabsorption.Deirdre O’Donovan, Christine Feinle-Bisset, Judith Wishart and Michael Horowit
Random Matrix approach to collective behavior and bulk universality in protein dynamics
Covariance matrices of amino acid displacements, commonly used to
characterize the large-scale movements of proteins, are investigated through
the prism of Random Matrix Theory. Bulk universality is detected in the local
spacing statistics of noise-dressed eigenmodes, which is well described by a
Brody distribution with parameter . This finding, supported by
other consistent indicators, implies a novel quantitative criterion to single
out the collective degrees of freedom of the protein from the majority of
high-energy, localized vibrations.Comment: 4 pages, 7 figure
An efficiency upper bound for inverse covariance estimation
We derive an upper bound for the efficiency of estimating entries in the
inverse covariance matrix of a high dimensional distribution. We show that in
order to approximate an off-diagonal entry of the density matrix of a
-dimensional Gaussian random vector, one needs at least a number of samples
proportional to . Furthermore, we show that with samples, the
hypothesis that two given coordinates are fully correlated, when all other
coordinates are conditioned to be zero, cannot be told apart from the
hypothesis that the two are uncorrelated.Comment: 7 Page
Random matrix approach in search for weak signals immersed in background noise
We present new, original and alternative method for searching signals coded
in noisy data. The method is based on the properties of random matrix
eigenvalue spectra. First, we describe general ideas and support them with
results of numerical simulations for basic periodic signals immersed in
artificial stochastic noise. Then, the main effort is put to examine the
strength of a new method in investigation of data content taken from the real
astrophysical NAUTILUS detector, searching for the presence of gravitational
waves. Our method discovers some previously unknown problems with data
aggregation in this experiment. We provide also the results of new method
applied to the entire respond signal from ground based detectors in future
experimental activities with reduced background noise level. We indicate good
performance of our method what makes it a positive predictor for further
applications in many areas.Comment: 15 pages, 16 figure
Crossover from Conserving to Lossy Transport in Circular Random Matrix Ensembles
In a quantum dot with three leads the transmission matrix t_{12} between two
of these leads is a truncation of a unitary scattering matrix S, which we treat
as random. As the number of channels in the third lead is increased, the
constraints from the symmetry of S become less stringent and t_{12} becomes
closer to a matrix of complex Gaussian random numbers with no constraints. We
consider the distribution of the singular values of t_{12}, which is related to
a number of physical quantities. Changing the number of channels in the third
lead corresponds to increasing the amount of loss in the system (and is
distinct from prior uses of a third lead to model dephasing)
Label-free proteomics identifies Calreticulin and GRP75/Mortalin as peripherally accessible protein biomarkers for spinal muscular atrophy
BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disease resulting from mutations in the survival motor neuron 1 (SMN1) gene. Recent breakthroughs in preclinical research have highlighted several potential novel therapies for SMA, increasing the need for robust and sensitive clinical trial platforms for evaluating their effectiveness in human patient cohorts. Given that most clinical trials for SMA are likely to involve young children, there is a need for validated molecular biomarkers to assist with monitoring disease progression and establishing the effectiveness of therapies being tested. Proteomics technologies have recently been highlighted as a potentially powerful tool for such biomarker discovery. METHODS: We utilized label-free proteomics to identify individual proteins in pathologically-affected skeletal muscle from SMA mice that report directly on disease status. Quantitative fluorescent western blotting was then used to assess whether protein biomarkers were robustly changed in muscle, skin and blood from another mouse model of SMA, as well as in a small cohort of human SMA patient muscle biopsies. RESULTS: By comparing the protein composition of skeletal muscle in SMA mice at a pre-symptomatic time-point with the muscle proteome at a late-symptomatic time-point we identified increased expression of both Calreticulin and GRP75/Mortalin as robust indicators of disease progression in SMA mice. We report that these protein biomarkers were consistently modified in different mouse models of SMA, as well as across multiple skeletal muscles, and were also measurable in skin biopsies. Furthermore, Calreticulin and GRP75/Mortalin were measurable in muscle biopsy samples from human SMA patients. CONCLUSIONS: We conclude that label-free proteomics technology provides a powerful platform for biomarker identification in SMA, revealing Calreticulin and GRP75/Mortalin as peripherally accessible protein biomarkers capable of reporting on disease progression in samples of muscle and skin
Compact smallest eigenvalue expressions in Wishart-Laguerre ensembles with or without fixed-trace
The degree of entanglement of random pure states in bipartite quantum systems
can be estimated from the distribution of the extreme Schmidt eigenvalues. For
a bipartition of size M\geq N, these are distributed according to a
Wishart-Laguerre ensemble (WL) of random matrices of size N x M, with a
fixed-trace constraint. We first compute the distribution and moments of the
smallest eigenvalue in the fixed trace orthogonal WL ensemble for arbitrary
M\geq N. Our method is based on a Laplace inversion of the recursive results
for the corresponding orthogonal WL ensemble by Edelman. Explicit examples are
given for fixed N and M, generalizing and simplifying earlier results. In the
microscopic large-N limit with M-N fixed, the orthogonal and unitary WL
distributions exhibit universality after a suitable rescaling and are therefore
independent of the constraint. We prove that very recent results given in terms
of hypergeometric functions of matrix argument are equivalent to more explicit
expressions in terms of a Pfaffian or determinant of Bessel functions. While
the latter were mostly known from the random matrix literature on the QCD Dirac
operator spectrum, we also derive some new results in the orthogonal symmetry
class.Comment: 25 pag., 4 fig - minor changes, typos fixed. To appear in JSTA
Spectral Density of Sparse Sample Covariance Matrices
Applying the replica method of statistical mechanics, we evaluate the
eigenvalue density of the large random matrix (sample covariance matrix) of the
form , where is an real sparse random matrix.
The difference from a dense random matrix is the most significant in the tail
region of the spectrum. We compare the results of several approximation
schemes, focusing on the behavior in the tail region.Comment: 22 pages, 4 figures, minor corrections mad
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