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1.
J Magn Reson ; 355: 107541, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37688831

ABSTRACT

This study introduces a model selection technique based on Bayesian information criteria for estimating the number of components in a mixture during Diffusion-Ordered Spectroscopy (DOSY) Nuclear Magnetic Resonance (NMR) data analysis. As the accuracy of this technique is dependent on the efficiency of parameter estimators, we further investigate the performance of the Weighted Least Squares (WLS) and Maximum a Posteriori (MAP) estimators. The WLS method, enhanced with meticulously tuned L2-regularization, effectively detects components when the difference in self-diffusion coefficients is more than two-fold, especially when the component with the smaller coefficient has a larger weight ratio. The MAP method, strengthened by a substantial database of prior information, exhibits outstanding precision, decreasing this threshold to 1.5 times. Both estimators provide weight ratio estimates with standard deviations of approximately around 1 percentage point, although the MAP method tends to overestimate the component with a larger self-diffusion coefficient. Deviations from the expected values can exceed 10 percentage points, often due to inaccuracies in component detection. The error estimates are determined using data resampling techniques derived from a large-scale 1000-point experiment and an additional five measurements from a single-component mixture. This approach allowed us to thoroughly examine data distribution characteristics, thereby laying a robust groundwork for future refinement efforts.

2.
J Synchrotron Radiat ; 29(Pt 3): 644-653, 2022 May 01.
Article in English | MEDLINE | ID: mdl-35510997

ABSTRACT

A novel approach to the remote-control system for the compact multi-crystal energy-dispersive spectrometer for X-ray emission spectroscopy (XES) applications has been developed. This new approach is based on asynchronous communication between software components and on reactive design principles. In this paper, the challenges faced, their solutions, as well as the implementation and future development prospects are identified. The main motivation of this work was the development of a new holistic communication protocol that can be implemented to control various hardware components allowing both independent operation and easy integration into different SCADA systems.


Subject(s)
Software , Synchrotrons , Spectrometry, X-Ray Emission
3.
Methods Mol Biol ; 1687: 107-119, 2018.
Article in English | MEDLINE | ID: mdl-29067659

ABSTRACT

Investigations using mouse models have provided seminal insights into the pathogenesis of Duchenne muscular dystrophy and the development of novel therapeutics. Several important methods have been considered standard-in-the-field for analyses of skeletal muscle weakness, strength, endurance, and histopathology, as well as responses to therapeutics such as glucocorticoids, disease modifying drugs which are part of the current standard of care for patients with this disease. Here we describe optimized genetic, genomic, and physiologic assays to probe dystrophic pathobiology in the mdx mouse and related strains.


Subject(s)
Glucocorticoids/genetics , Muscle Contraction/genetics , Muscle, Skeletal/metabolism , Muscular Dystrophy, Duchenne/genetics , Animals , Disease Models, Animal , Glucocorticoids/metabolism , Humans , Mice , Mice, Inbred mdx/genetics , Muscle, Skeletal/pathology , Muscular Dystrophy, Duchenne/pathology
4.
Proc Natl Acad Sci U S A ; 112(49): E6780-9, 2015 Dec 08.
Article in English | MEDLINE | ID: mdl-26598680

ABSTRACT

Classic physiology studies dating to the 1930s demonstrate that moderate or transient glucocorticoid (GC) exposure improves muscle performance. The ergogenic properties of GCs are further evidenced by their surreptitious use as doping agents by endurance athletes and poorly understood efficacy in Duchenne muscular dystrophy (DMD), a genetic muscle-wasting disease. A defined molecular basis underlying these performance-enhancing properties of GCs in skeletal muscle remains obscure. Here, we demonstrate that ergogenic effects of GCs are mediated by direct induction of the metabolic transcription factor KLF15, defining a downstream pathway distinct from that resulting in GC-related muscle atrophy. Furthermore, we establish that KLF15 deficiency exacerbates dystrophic severity and muscle GC-KLF15 signaling mediates salutary therapeutic effects in the mdx mouse model of DMD. Thus, although glucocorticoid receptor (GR)-mediated transactivation is often associated with muscle atrophy and other adverse effects of pharmacologic GC administration, our data define a distinct GR-induced gene regulatory pathway that contributes to therapeutic effects of GCs in DMD through proergogenic metabolic programming.


Subject(s)
Glucocorticoids/pharmacology , Muscle, Skeletal/drug effects , Muscular Dystrophy, Duchenne/drug therapy , Animals , Female , Glucocorticoids/therapeutic use , Humans , Kruppel-Like Transcription Factors/physiology , Male , Mice , Mice, Inbred C57BL , Muscle, Skeletal/physiopathology , Nuclear Proteins/physiology , Receptors, Glucocorticoid/physiology
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