Model-based prognosis using an explicit degradation model and Inverse FORM for uncertainty propagation

International audienceIn this paper, an analytical method issued from the field of reliability analysis is used for prognosis. The inverse first-order reliability method (Inverse FORM) is an uncertainty propagation method that can be adapted to remaining useful life (RUL) calculation. An extended Kalman filter (EKF) is first applied to estimate the current degradation state of the system, then the Inverse FORM allows to compute the probability density function (pdf) of the RUL. In the proposed Inverse FORM methodology, an analytical or numerical solution to the differential equation that describes the evolution of the system degradation is required to calculate the RUL model. In this work, the method is applied to a Paris fatigue crack growth model, and then compared to filter-based methods such as EKF and particle filter using performance evaluation metrics (precision, accuracy and timeliness). The main advantage of the Inverse FORM is its ability to compute the pdf of the RUL at a lower computational cost

Model-based prognosis of fatigue crack growth under variable amplitude loading

International audienceIn this paper, a model-based prognosis method using a particle filter that takes model uncertainty, measurement uncertainty and future loading uncertainty into account is proposed. A nonlinear analytical model of the degradation that depends on loading parameters is established, and then a particle filter is used to estimate and forecast these unknown inputs at the same time as the degradation state. Moreover, adding to this joint input-state estimation, a two-sided CUSUM algorithm is implemented to detect load variations. This would help the prognosis module to adapt to a change in the degradation state evolution, in order to correct the remaining useful life prediction. Real data from fatigue tests on fiber-reinforced metal matrix composite materials are used to demonstrate the efficiency of the proposed methodology for crack growth prognosis

Interval observer design for unknown input estimation of linear time-invariant discrete-time systems

International audienceIn this paper, the problem of joint state and unknown input estimation for linear time-invariant (LTI) discrete-time systems using interval observer is addressed. This problem has already been studied in the context of continuous-time systems. To the best of our knowledge, unknown input interval-based estimation for discrete-time systems has not been considered in the litterature. Assuming that the measurement noise and disturbances are bounded, lower and upper bounds are first computed for the unmeasured state and then for the unknown inputs. The results obtained with a numerical example highlight the efficiency of the method

The expansion of amino-acid repeats is not associated to adaptive evolution in mammalian genes

BACKGROUND: The expansion of amino acid repeats is determined by a high mutation rate and can be increased or limited by selection. It has been suggested that recent expansions could be associated with the potential of adaptation to new environments. In this work, we quantify the strength of this association, as well as the contribution of potential confounding factors. RESULTS: Mammalian positively selected genes have accumulated more recent amino acid repeats than other mammalian genes. However, we found little support for an accelerated evolutionary rate as the main driver for the expansion of amino acid repeats. The most significant predictors of amino acid repeats are gene function and GC content. There is no correlation with expression level. CONCLUSIONS: Our analyses show that amino acid repeat expansions are causally independent from protein adaptive evolution in mammalian genomes. Relaxed purifying selection or positive selection do not associate with more or more recent amino acid repeats. Their occurrence is slightly favoured by the sequence context but mainly determined by the molecular function of the gene

Comparative analysis of human and mouse expression data illuminates tissue-specific evolutionary patterns of miRNAs

MicroRNAs (miRNAs) constitute an important class of gene regulators. While models have been proposed to explain their appearance and expansion, the validation of these models has been difficult due to the lack of comparative studies. Here, we analyze miRNA evolutionary patterns in two mammals, human and mouse, in relation to the age of miRNA families. In this comparative framework, we confirm some predictions of previously advanced models of miRNA evolution, e.g. that miRNAs arise more frequently de novo than by duplication, or that the number of protein-coding gene targeted by miRNAs decreases with evolutionary time. We also corroborate that miRNAs display an increase in expression level with evolutionary time, however we show that this relation is largely tissue-dependent, and especially low in embryonic or nervous tissues. We identify a bias of tag-sequencing techniques regarding the assessment of breadth of expression, leading us, contrary to predictions, to find more tissue-specific expression of older miRNAs. Together, our results refine the models used so far to depict the evolution of miRNA genes. They underline the role of tissue-specific selective forces on the evolution of miRNAs, as well as the potential co-evolution patterns between miRNAs and the protein-coding genes they targe

Mass spectrometry captures off-target drug binding and provides mechanistic insights into the human metalloprotease ZMPSTE24.

Off-target binding of hydrophobic drugs can lead to unwanted side effects, either through specific or non-specific binding to unintended membrane protein targets. However, distinguishing the binding of drugs to membrane proteins from that of detergents, lipids and cofactors is challenging. Here, we use high-resolution mass spectrometry to study the effects of HIV protease inhibitors on the human zinc metalloprotease ZMPSTE24. This intramembrane protease plays a major role in converting prelamin A to mature lamin A. We monitored the proteolysis of farnesylated prelamin A peptide by ZMPSTE24 and unexpectedly found retention of the C-terminal peptide product with the enzyme. We also resolved binding of zinc, lipids and HIV protease inhibitors and showed that drug binding blocked prelamin A peptide cleavage and conferred stability to ZMPSTE24. Our results not only have relevance for the progeria-like side effects of certain HIV protease inhibitor drugs, but also highlight new approaches for documenting off-target drug binding

Comparative modular analysis of gene expression in vertebrate organs

ABSTRACT: BACKGROUND: The degree of conservation of gene expression between homologous organs largely remains an open question. Several recent studies reported some evidence in favor of such conservation. Most studies compute organs' similarity across all orthologous genes, whereas the expression level of many genes are not informative about organ specificity. RESULTS: Here, we use a modularization algorithm to overcome this limitation through the identification of inter-species co-modules of organs and genes. We identify such co-modules using mouse and human microarray expression data. They are functionally coherent both in terms of genes and of organs from both organisms. We show that a large proportion of genes belonging to the same co-module are orthologous between mouse and human. Moreover, their zebrafish orthologs also tend to be expressed in the corresponding homologous organs. Notable exceptions to the general pattern of conservation are the testis and the olfactory bulb. Interestingly, some co-modules consist of single organs, while others combine several functionally related organs. For instance, amygdala, cerebral cortex, hypothalamus and spinal cord form a clearly discernible unit of expression, both in mouse and human. CONCLUSIONS: Our study provides a new framework for comparative analysis which will be applicable also to other sets of large-scale phenotypic data collected across different species

vHOG, a multispecies vertebrate ontology of homologous organs groups

Motivation: Most anatomical ontologies are species-specific, whereas a framework for comparative studies is needed. We describe the vertebrate Homologous Organs Groups ontology, vHOG, used to compare expression patterns between species. Results: vHOG is a multispecies anatomical ontology for the vertebrate lineage. It is based on the HOGs used in the Bgee database of gene expression evolution. vHOG version 1.4 includes 1184 terms, follows OBO principles and is based on the Common Anatomy Reference Ontology (CARO). vHOG only describes structures with historical homology relations between model vertebrate species. The mapping to species-specific anatomical ontologies is provided as a separate file, so that no homology hypothesis is stated within the ontology itself. Each mapping has been manually reviewed, and we provide support codes and references when available. Availability and implementation: vHOG is available from the Bgee download site (http://bgee.unil.ch/), as well as from the OBO Foundry and the NCBO Bioportal websites. Contact: [email protected]; [email protected]

Influence of grain size, shape and compaction on georadar waves: example of an Aeolian dune

Many Ground Penetrating Radar (GPR) profiles acquired in dry aeolian environment have shown good reflectivity inside present-day dunes. We show that the origin of this reflectivity is related to changes in grain size distribution, packing and/or grain shape in a sandy material. We integrate these three parameters into analytical models for bulk permittivity in order to predict the reflections and the velocity of GPR waves. We consider two GPR cross-sections acquired over Aeolian dunes in the Chadian desert. The 2D migration of GPR data suggests that dunes contain different kinds of bounding surfaces. We discuss and model three kinds of reflections using reasonable geological hypothesis about Aeolian sedimentation processes. The propagation and the reflection of radar waves are calculated using the 1D wavelet modelling method in spectral domain. The results of the forward modelling are in good accordance with real observed data