250 research outputs found
Data-driven efficient score tests for deconvolution problems
We consider testing statistical hypotheses about densities of signals in
deconvolution models. A new approach to this problem is proposed. We
constructed score tests for the deconvolution with the known noise density and
efficient score tests for the case of unknown density. The tests are
incorporated with model selection rules to choose reasonable model dimensions
automatically by the data. Consistency of the tests is proved
Born's rule from measurements of classical signals by threshold detectors which are properly calibrated
The very old problem of the statistical content of quantum mechanics (QM) is
studied in a novel framework. The Born's rule (one of the basic postulates of
QM) is derived from theory of classical random signals. We present a
measurement scheme which transforms continuous signals into discrete clicks and
reproduces the Born's rule. This is the sheme of threshold type detection.
Calibration of detectors plays a crucial role.Comment: The problem of double clicks is resolved; hence, one can proceed in
purely wave framework, i.e., the wave-partcile duality has been resolved in
favor of the wave picture of prequantum realit
Semiparametric Multivariate Accelerated Failure Time Model with Generalized Estimating Equations
The semiparametric accelerated failure time model is not as widely used as
the Cox relative risk model mainly due to computational difficulties. Recent
developments in least squares estimation and induced smoothing estimating
equations provide promising tools to make the accelerate failure time models
more attractive in practice. For semiparametric multivariate accelerated
failure time models, we propose a generalized estimating equation approach to
account for the multivariate dependence through working correlation structures.
The marginal error distributions can be either identical as in sequential event
settings or different as in parallel event settings. Some regression
coefficients can be shared across margins as needed. The initial estimator is a
rank-based estimator with Gehan's weight, but obtained from an induced
smoothing approach with computation ease. The resulting estimator is consistent
and asymptotically normal, with a variance estimated through a multiplier
resampling method. In a simulation study, our estimator was up to three times
as efficient as the initial estimator, especially with stronger multivariate
dependence and heavier censoring percentage. Two real examples demonstrate the
utility of the proposed method
Classical signal model reproducing quantum probabilities for single and coincidence detections
We present a simple classical (random) signal model reproducing Born's rule.
The crucial point of our approach is that the presence of detector's threshold
and calibration procedure have to be treated not as simply experimental
technicalities, but as the basic counterparts of the theoretical model. We call
this approach threshold signal detection model (TSD). The experiment on
coincidence detection which was done by Grangier in 1986 \cite{Grangier} played
a crucial role in rejection of (semi-)classical field models in favor of
quantum mechanics (QM): impossibility to resolve the wave-particle duality in
favor of a purely wave model. QM predicts that the relative probability of
coincidence detection, the coefficient is zero (for one photon
states), but in (semi-)classical models In TSD the
coefficient decreases as where is
the detection threshold. Hence, by increasing this threshold an experimenter
can make the coefficient essentially less than 1. The
TSD-prediction can be tested experimentally in new Grangier type experiments
presenting a detailed monitoring of dependence of the coefficient
on the detection threshold
Peroxisome Proliferator–Activated Receptor-γ Coactivator-1α Overexpression Increases Lipid Oxidation in Myocytes From Extremely Obese Individuals
Pigment Epithelium–Derived Factor Regulates Lipid Metabolism via Adipose Triglyceride Lipase
OBJECTIVE: Pigment epithelium-derived factor (PEDF) is an adipocyte-secreted factor involved in the development of insulin resistance in obesity. Previous studies have identified PEDF as a regulator of triacylglycerol metabolism in the liver that may act through adipose triglyceride lipase (ATGL). We used ATGL(-/-) mice to determine the role of PEDF in regulating lipid and glucose metabolism. RESEARCH DESIGN AND METHODS: Recombinant PEDF was administered to ATGL(-/-) and wild-type mice, and whole-body energy metabolism was studied by indirect calorimetry. Adipose tissue lipolysis and skeletal muscle fatty acid metabolism was determined in isolated tissue preparations. Muscle lipids were assessed by electrospray ionization-tandem mass spectrometry. Whole-body insulin sensitivity and skeletal muscle glucose uptake were assessed. RESULTS: PEDF impaired the capacity to adjust substrate selection, resulting in a delayed diurnal decline in the respiratory exchange ratio, and suppressed daily fatty acid oxidation. PEDF enhanced adipocyte lipolysis and triacylglycerol lipase activity in skeletal muscle. Muscle fatty acid uptake and storage were unaffected, whereas fatty acid oxidation was impaired. These changes in lipid metabolism were abrogated in ATGL(-/-) mice and were not attributable to hypothalamic actions. ATGL(-/-) mice were also refractory to PEDF-mediated insulin resistance, but this was not related to changes in lipid species in skeletal muscle. CONCLUSIONS: The results are the first direct demonstration that 1) PEDF influences systemic fatty acid metabolism by promoting lipolysis in an ATGL-dependent manner and reducing fatty acid oxidation and 2) ATGL is required for the negative effects of PEDF on insulin action
Inhibition of lipolysis in Type 2 diabetes normalizes glucose disposal without change in muscle glycogen synthesis rates
Suppression of lipolysis by acipimox is known to improve insulin-stimulated glucose disposal, and this is an important phenomenon. The mechanism has been assumed to be an enhancement of glucose storage as glycogen, but no direct measurement has tested this concept or its possible relationship to the reported impairment in insulin-stimulated muscle ATP production. Isoglycaemic–hyperinsulinaemic clamps with [13C]glucose infusion were performed on Type 2 diabetic subjects and matched controls with measurement of glycogen synthesis by 13C MRS (magnetic resonance spectroscopy) of muscle. 31P saturation transfer MRS was used to quantify muscle ATP turnover rates. Glucose disposal rates were restored to near normal in diabetic subjects after acipimox (6.2±0.8 compared with 4.8±0.6 mg·kgffm−1·min−1; P<0.01; control 6.6±0.5 mg·kgffm−1·min−1; where ffm, is fat-free mass). The increment in muscle glycogen concentration was 2-fold higher in controls compared with the diabetic group, and acipimox administration to the diabetic group did not increase this (2.0±0.8 compared with 1.9±1.1 mmol/l; P<0.05; control, 4.0±0.8 mmol/l). ATP turnover rates did not increase during insulin stimulation in any group, but a modest decrease in the diabetes group was prevented by lowering plasma NEFAs (non-esterified fatty acids; 8.4±0.7 compared with 7.1±0.5 μmol·g−1·min−1; P<0.05; controls 8.6±0.8 μmol·g−1·min−1). Suppression of lipolysis increases whole-body glucose uptake with no increase in the rate of glucose storage as glycogen but with increase in whole-body glucose oxidation rate. ATP turnover rate in muscle exhibits no relationship to the acute metabolic effect of insulin
Short-Term Exercise Training Does Not Stimulate Skeletal Muscle ATP Synthesis in Relatives of Humans With Type 2 Diabetes
OBJECTIVE-We tested the hypothesis that short-term exercise training improves hereditary insulin resistance by stimulating ATP synthesis and investigated associations With gene polymorphisms. RESEARCH DESIGN AND METHODS-We studied 24 nono-bese first-degree relatives of type 2 diabetic patients and 12 control subjects at rest, and 48 h after three bouts of exercise. In addition to measurements of oxygen uptake and insulin sensitivity (oral glucose tolerance test), ectopic lipids and mitochondrial ATP synthesis were assessed using H-1 and P-31 magnetic resonance spectroscopy, respectively. They were genotyped for polymorphisms in genes regulating mitochondrial function, PPARGC1A (rs8192678) and NDUFB6 (rs540467). RESULTS-Relatives had slightly lower (P = 0.012) insulin sensitivity than control subjects. In control subjects, ATP synthase flux rose by 18% (P = 0.0001), being 23% higher (P = 0.002) than that in relatives after exercise training. Relatives responding to exercise training with increased ATP synthesis (+19%, P = 0.009) showed improved insulin sensitivity (P = 0.009) compared with those whose insulin sensitivity did not improve. A polymorphism in the NDUFB6 gene from respiratory chain complex I related to ATP synthesis (P = 0.02) and insulin Sensitivity response to exercise training (P = 0.05). ATP synthase flux correlated with O-2 uptake and insulin sensitivity. CONCLUSIONS-The ability of short-term exercise to stimulate ATP production distinguished individuals with improved insulin sensitivity from those whose insulin sensitivity did not improve. lit addition, the NDUFB6 gene polymorphism appeared to modulate this adaptation. This finding suggests that genes involved in mitochondrial function contribute to the response of ATP synthesis to exercise training. Diabetes 58:1333-1341, 200
Proteomics Analysis of Human Skeletal Muscle Reveals Novel Abnormalities in Obesity and Type 2 Diabetes
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