501 research outputs found
Fast stable direct fitting and smoothness selection for Generalized Additive Models
Existing computationally efficient methods for penalized likelihood GAM
fitting employ iterative smoothness selection on working linear models (or
working mixed models). Such schemes fail to converge for a non-negligible
proportion of models, with failure being particularly frequent in the presence
of concurvity. If smoothness selection is performed by optimizing `whole model'
criteria these problems disappear, but until now attempts to do this have
employed finite difference based optimization schemes which are computationally
inefficient, and can suffer from false convergence. This paper develops the
first computationally efficient method for direct GAM smoothness selection. It
is highly stable, but by careful structuring achieves a computational
efficiency that leads, in simulations, to lower mean computation times than the
schemes based on working-model smoothness selection. The method also offers a
reliable way of fitting generalized additive mixed models
Detecting Generalized Synchronization Between Chaotic Signals: A Kernel-based Approach
A unified framework for analyzing generalized synchronization in coupled
chaotic systems from data is proposed. The key of the proposed approach is the
use of the kernel methods recently developed in the field of machine learning.
Several successful applications are presented, which show the capability of the
kernel-based approach for detecting generalized synchronization. It is also
shown that the dynamical change of the coupling coefficient between two chaotic
systems can be captured by the proposed approach.Comment: 20 pages, 15 figures. massively revised as a full paper; issues on
the choice of parameters by cross validation, tests by surrogated data, etc.
are added as well as additional examples and figure
Splines and Wavelets on Geophysically Relevant Manifolds
Analysis on the unit sphere found many applications in
seismology, weather prediction, astrophysics, signal analysis, crystallography,
computer vision, computerized tomography, neuroscience, and statistics.
In the last two decades, the importance of these and other applications
triggered the development of various tools such as splines and wavelet bases
suitable for the unit spheres , and the
rotation group . Present paper is a summary of some of results of the
author and his collaborators on generalized (average) variational splines and
localized frames (wavelets) on compact Riemannian manifolds. The results are
illustrated by applications to Radon-type transforms on and
.Comment: The final publication is available at http://www.springerlink.co
Smoothing spline primordial power spectrum reconstruction
We reconstruct the shape of the primordial power spectrum (PPS) using a
smoothing spline. Our adapted smoothing spline technique provides a
complementary method to existing efforts to search for smooth features in the
PPS, such as a running spectral index. With this technique we find no
significant indication with WMAP first-year data that the PPS deviates from
Harrison-Zeldovich and no evidence for loss of power on large scales. We also
examine the effect on the cosmological parameters of the additional PPS
freedom. Smooth variations in the PPS are not significantly degenerate with
other cosmological parameters, but the spline reconstruction greatly increases
the errors on the optical depth and baryon fraction.Comment: 12 pages, 10 figures. Accepted to PR
Magnetic resonance imaging studies of spontaneous capillary water imbibition in aerated gypsum
Resolution of two-dimensional Currents in Superconductors from a two-dimensional magnetic field measurement by the method of regularization
The problem of reconstructing a two-dimensional (2D) current distribution in
a superconductor from a 2D magnetic field measurement is recognized as a
first-kind integral equation and resolved using the method of Regularization.
Regularization directly addresses the inherent instability of this inversion
problem for non-exact (noisy) data. Performance of the technique is evaluated
for different current distributions and for data with varying amounts of added
noise. Comparisons are made to other methods, and the present method is
demonstrated to achieve a better regularizing (noise filtering) effect while
also employing the generalized-cross validation (GCV) method to choose the
optimal regularization parameter from the data, without detailed knowledge of
the true (and generally unknown) solution. It is also shown that clean,
noiseless data is an ineffective test of an inversion algorithm.Comment: To appear in the Physical Review B. Some text/figure additions and
modification
<i>Trypanosoma brucei</i> DHRF-TS revisited:characterisation of a bifunctional and highly unstable recombinant dihydrofolate reductase-thymidylate synthase
<div><p>Bifunctional dihydrofolate reductase–thymidylate synthase (DHFR-TS) is a chemically and genetically validated target in African trypanosomes, causative agents of sleeping sickness in humans and nagana in cattle. Here we report the kinetic properties and sensitivity of recombinant enzyme to a range of lipophilic and classical antifolate drugs. The purified recombinant enzyme, expressed as a fusion protein with elongation factor Ts (Tsf) in ThyA<sup>-</sup> <i>Escherichia coli</i>, retains DHFR activity, but lacks any TS activity. TS activity was found to be extremely unstable (half-life of 28 s) following desalting of clarified bacterial lysates to remove small molecules. Stability could be improved 700-fold by inclusion of dUMP, but not by other pyrimidine or purine (deoxy)-nucleosides or nucleotides. Inclusion of dUMP during purification proved insufficient to prevent inactivation during the purification procedure. Methotrexate and trimetrexate were the most potent inhibitors of DHFR (<i>K</i><sub>i</sub> 0.1 and 0.6 nM, respectively) and FdUMP and nolatrexed of TS (<i>K</i><sub>i</sub> 14 and 39 nM, respectively). All inhibitors showed a marked drop-off in potency of 100- to 1,000-fold against trypanosomes grown in low folate medium lacking thymidine. The most potent inhibitors possessed a terminal glutamate moiety suggesting that transport or subsequent retention by polyglutamylation was important for biological activity. Supplementation of culture medium with folate markedly antagonised the potency of these folate-like inhibitors, as did thymidine in the case of the TS inhibitors raltitrexed and pemetrexed.</p></div
Anthropomorphic Measurements That Include Central Fat Distribution Are More Closely Related with Key Risk Factors than BMI in CKD Stage 3
Background: Body Mass Index (BMI) as a marker of obesity is an established risk factor for chronic kidney disease (CKD) and cardiovascular disease (CVD). However, BMI can overestimate obesity. Anthropomorphic measurements that include central fat deposition are emerging as a more important risk factor. We studied BMI, waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR) and conicity index (CI) in a cohort of patients with CKD stage 3 and compared the associations with other known risk factors for CKD progression and CVD. Methods: 1740 patients with CKD stage 3 were recruited from primary care for the Renal Risk in Derby study. Each participant underwent clinical assessment, including anthropomorphic measurements and pulse wave velocity (PWV), as well as urine and serum biochemistry tests. Results: The mean age of the cohort was 72.969 years with 60 % females. The mean eGFR was 52.5610.4 ml/min/1.73 m 2 and 16.9 % of the cohort had diabetes. With the cohort divided into normal and increased risk of morbidity and mortality using each anthropomorphic measurement, those measurements that included increased central fat distribution were significantly associated with more risk factors for CKD progression and CVD than increased BMI. Univariable analysis demonstrated central fat distribution was correlated with more risk factors than BMI. Subgroup analyses using recognised BMI cut-offs to define obesity and quartiles of WHR and CI demonstrated that increasing central fat distribution wa
Validated stability-indicating spectrofluorimetric methods for the determination of ebastine in pharmaceutical preparations
Two sensitive, selective, economic, and validated spectrofluorimetric methods were developed for the determination of ebastine (EBS) in pharmaceutical preparations depending on reaction with its tertiary amino group. Method I involves condensation of the drug with mixed anhydrides (citric and acetic anhydrides) producing a product with intense fluorescence, which was measured at 496 nm after excitation at 388 nm
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