40 research outputs found
Bayesian Estimation for Transport Equations for Nanocapacitors
No full textWe use and evaluate different Bayesian estimation methods to quantify uncertainties in model parameters in nanocapacitors. Here, randomness arises due to process variations; also, parameters that cannot be measured directly are to be determined. The methods include the direct approach, the Markov-chain Monte-Carlo (MCMC) method, and an iterative version of the latter that we have developed, where we use the calculated posterior distribution as the prior distribution for a new MCMC analysis. We investigate the influence of the number of samples in each Markov chain and the number of iterations on the total computational work and the error achieved. In addition, we discuss the methods for estimating the posterior distribution based on samples provided by the MCMC analysis. We apply our algorithms to the Poisson-Boltzmann and Poisson-Nernst-Planck equations which arise from modeling nanoelectrode biosensors, which have recently been used to detect minute concentrations of target particles. This technology has many applications in precision medicine. Numerical examples show the estimation of parameters such as ionic concentration, size of Stern layer, and the sizes of multiple electrodes (multilevel Bayesian estimation) of sensors for which experimental data are available
Calibration, Compensation, Parameter Estimation, and Uncertainty Quantification for Nanoelectrode Array Biosensors
No full textThis paper presents the use of a statistical approach to estimate physical/electrochemical parameters of impedance spectroscopy experiments performed with a realistic nanoelectrodes array biosensor platform. The Bayesian estimation methodology is based on the combination of nanobiosensor simulations, performed with the ENBIOS tool, with Markov-Chain Monte Carlo (MCMC) analyses. A simple 1D electrode-electrolyte geometry is first considered as a validation test case, allowing the accurate estimation of Stern layer permittivity and salt concentration, as set by a reference analytical model. Then, full 3D analyses of the nanoelectrodes’ array system are performed in order to estimate a number of relevant parameters for measurements in electrolyte. Furthermore, moving to more challenging test cases, size/permittivity of microparticles suspended in electrolyte will also be discussed. This methodology allows for the determination of impedance spectroscopy data parameters, and quantification of parameter uncertainties in these multi-variable detection problems. It is thus a very promising approach in order to improve the precision of biosensor measurement predictions, which are intrinsically affected by many parameters
Determination of Micro- and Nano-particle Properties by Multi-Frequency Bayesian Methods and Applications to Nanoelectrode Array Sensors
No full textWe demonstrate a new and robust Bayesian estimation method to extract properties of micro- and nano-scale analytes from measurements on advanced high-frequency impedance spectroscopy nanoelectrode array sensors. Firstly, the method is validated on model systems of a-priori known properties using accurate analytical and numerical models in place of actual measurements. Then, applications to real measurements with an advanced CMOS sensor demonstrate the usefulness of the methodology for robust and fast estimation of multi-dimensional parameters and parameter uncertainty in the context of biosensing and possibly sensor-fusion problems
Bayesian estimation of physical and geometrical parameters for nanocapacitor array biosensors
No full textMassively parallel nanosensor arrays fabricated with low-cost CMOS technology represent powerful platforms for biosensing in the Internet-of-Things (IoT) and Internet-of-Health (IoH) era. They can efficiently acquire “big data” sets of dependable calibrated measure-ments, representing a solid basis for statistical analysis and parameter estimation.
In this paper we propose Bayesian estimation methods to extract physical parameters and interpret the statistical variability in the measured outputs of a dense nanocapacitor array biosensor. Firstly, the physical and mathematical models are presented. Then, a simple 1D-symmetry structure is used as a validation test case where the estimated parameters are also known a-priori. Finally, we apply the methodology to the simultaneous extraction of multiple physical and geometrical parameters from measurements on a CMOS pixelated nanocapacitor biosensor platform
The role of kinase-coupled channel TRPM6 in cardiac automaticity
No full textTRPM6 and TRPM7 are unique proteins comprising an ion channel and kinase domain. The TRPM6 and TRPM7 channels are permeable for Mg2+ and play a crucial role in whole-body Mg2+ homeostasis. TRPM7 is expressed ubiquitously, while the expression of TRPM6 is limited to the kidney, intestine, lung, heart and testis. In humans, TRPM6 mutation causes Hypomagnesemia with Secondary Hypocalcemia (HSH). While HSH patients primarily present with seizures the symptoms also include cardiomyopathy and arrhythmia. Experiments with Trpm6 gene-deficient mice led to the hypothesis that hypomagnesemia in HSH patients was primarily caused by impaired intestinal transport of Mg2+. While the physiological role of TRPM6 in the intestine is relatively well defined, its function in the cardiovascular system remains to be established. In the present study, we used in situ hybridization (ISH) and qRT-PCR approaches to examine the expression of Trpm6 in the murine heart. We found that Trpm6 transcripts are abundantly present in cardiomyocytes of the embryonic heart and the heart of adult animals. To investigate the physiological role of TRPM6, we conducted non-invasive ECG measurements in freely moving mice. We observed that 4-week-old Trpm6 null mice develop sinus tachycardia and display a shortened heart rate corrected QT interval when compared to their control littermates. Furthermore, we found that dietary Mg2+ supplementation of pregnant females normalized both the elevated heart rate, as well as the shortened corrected QT interval in Trpm6 null pups. However, a delayed Mg2+-enriched diet provided only after the weaning stage was inefficient in normalizing the increased heart rate, suggesting that Mg2+ deficiency during prenatal development and weaning caused sinus tachycardia. Next, we analyzed the heart transcriptome using the gene microarray approach. We found that the expression levels of genes coding for G protein-coupled receptor kinase 2 (Grk2), myosin heavy chain 14 (Myh14) and Ras-Related Protein Rab-4A (Rab4A) were reduced in the heart of 8-week-old Trpm6 null mice, suggesting altered beta-adrenergic signaling within the sinus node as one potential mechanism behind the tachycardia. Collectively, our results suggest that Trpm6 is expressed in cardiomyocytes and that Trpm6 null mice develop a defect in the regulation of the heart rhythm caused by Mg2+ deficiency. Hence, ECG monitoring should be performed in human patients suffering from inherited or acquired forms of hypomagnesemia in order to find and treat accompanying cardiac arrhythmia
Bayessche inverse PDE Probleme
No full textIn this article we present algorithms to perform Bayesian inversion based on physical models, in particular based on partial differential equations. We are interested in identifying parameters of the PDEs that affect functionals of the solutions for which experimental data are available. Markov-chain Monte-Carlo methods like the Metropolis algorithm provide the algorithmic foundation. We present an adaptation and extension of this procedure to be able to perform multi-dimensional Bayesian inversion where not all measurements have to be present prior to the estimation, but become available in batches as time passes. Namely, based on the Delayed-Rejection Adaptive-Metropolis (DRAM) algorithm, we introduce an iterative approach, where we use the posterior of the last Metropolis run as the prior for the new run, where we use new measurements in each iteration. This allows to examine some information about the parameters already during the estimation process. Therefore a density estimator needs to be introduced. We make use of the Improved Fast Gauss Transform (IFGT) which allows us to perform a faster evaulation of the kernel density estimator, reducing the runtime from quadratic to nearly linear. Applications using a nano-capacitor sensor array are presented as well, where we estimate the radii of over 4000 nano-electrodes
Structural basis of G-quadruplex biochemical specificity
No full textTitle: Structural basis of G-qudruplex biochemical specificity Author: Ráchel Sgallová Department: Department of Low Temperature Physics Supervisor: Edward Arthur Curtis, Ph.D., Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Abstract: G-quadruplexes are noncanonical nucleic acid structures formed by stacked guanine tetrads. Despite their functional and structural diversity, a sin- gle consensus sequence is typically used to describe sequences with the potential to form G-quadruplex structures. We are interested in developing more specific sequence models for G-quadruplexes. In previous work, we functionally character- ized each sequence in a 496-member library of variants of a monomeric reference G-quadruplex for the ability to bind GTP, promote a model peroxidase reac- tion, generate intrinsic fluorescence, and to form multimers. In this study, we statistically characterized those results by PCA and identified some connections between primary sequence and biochemical function. Furthermore, we used NMR to obtain a broad overview of the structural features of this library. After deter- mining the 1 H NMR spectrum of each of these 496 sequences, spectra were sorted into multiple classes, most of which could be rationalized based on mutational patterns in the primary sequence...
On the Lyapunov spectrum of relative transfer operators
No full textWe analyze the Lyapunov spectrum of the relative Ruelle operator associated with a skew product whose base is an ergodic automorphism and whose fibers are full shifts. We prove that these operators can be approximated in the -topology by positive matrices with an associated dominated splitting.Whereas the second author has been supported in part by EU Marie-Curie IRSES BrazilianEuropean partnership in Dynamical Systems (FP7-PEOPLE-2012-IRSES 318999 BREUDS).info:eu-repo/semantics/publishedVersio
TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival
No full textZn2+, Mg2+, and Ca2+ are essential minerals required for a plethora of metabolic processes and signaling pathways. Different categories of cation-selective channels and transporters are therefore required to tightly control the cellular levels of individual metals in a cell-specific manner. However, the mechanisms responsible for the organismal balance of these essential minerals are poorly understood. Herein, we identify a central and indispensable role of the channel-kinase TRPM7 for organismal mineral homeostasis. The function of TRPM7 was assessed by single-channel analysis of TRPM7, phenotyping of TRPM7-deficient cells in conjunction with metabolic profiling of mice carrying kidney- and intestine-restricted null mutations in Trpm7 and animals with a global "kinase-dead" point mutation in the gene. The TRPM7 channel reconstituted in lipid bilayers displayed a similar permeability to Zn2+ and Mg2+. Consistently, we found that endogenous TRPM7 regulates the total content of Zn2+ and Mg2+ in cultured cells. Unexpectedly, genetic inactivation of intestinal rather than kidney TRPM7 caused profound deficiencies specifically of Zn2+, Mg2+, and Ca2+ at the organismal level, a scenario incompatible with early postnatal growth and survival. In contrast, global ablation of TRPM7 kinase activity did not affect mineral homeostasis, reinforcing the importance of the channel activity of TRPM7. Finally, dietary Zn2+ and Mg2+ fortifications significantly extended the survival of offspring lacking intestinal TRPM7. Hence, the organismal balance of divalent cations critically relies on one common gatekeeper, the intestinal TRPM7 channel
