Estimation rapide des paramètres d'un signal à phase polynomiale

National audiencePolynomial phase signals belong to a wide class of non-stationary signals used for modeling and engineering applications. In this paper, we take benefits of some advances in robust estimation in order to propose a new algorithm for estimating the parameters of a polynomial phase signal. The advantages of this algorithm are being fast and being robust to the shape of the noise

Parameter Estimation for Polynomial Phase Signals With a Fast and Robust Algorithm

International audiencePolynomial phase signals belong to a wide class of nonstationary signals used for modeling and engineering applications. In this paper, we take benefits of some advances in robust estimation in order to propose a new algorithm for estimating the parameters of a polynomial phase signal. This algorithm has the advantages to be fast and its structure is robust to the shape of the noise

A fast robust and simple algorithm for estimating parameters of polynomial phase signals

Polynomial phase signals belong to a wide class of signals used for modeling but processing associated to them are always difficult since they are non-stationary signals. In the method introduced in this paper, we take benefits of some advances in robust estimation in order to build a new algorithm for estimating the phasis parameters of polynomial phase signal. This algorithm has the advantages of being fast and being able to deal with signal whose phase is a polynomial of unknown order. The structure of this algorithm is robust to the shape of the noise.Les signaux à phase polynomiale constituent une vaste classe de signaux utilisés en modélisation mais leurs traitements se révèlent difficiles en raison de leur caractère non-stationnaire. Dans la méthode présentée dans cet article, nous mettons à profit de récents travaux en matière d’estimation robuste afin de réaliser un nouvel algorithme d’estimation des paramètres de la phase d’un signal. Cet algorithme présente les avantages d’être rapide et capable de traiter des signaux dont la phase est d’ordre inconnu. La structure de cet algorithme reste indépendante par le type de bruit car il est résistant à la forme de la distribution du bruit

A STAT3-decoy oligonucleotide induces cell death in a human colorectal carcinoma cell line by blocking nuclear transfer of STAT3 and STAT3-bound NF-κB

<p>Abstract</p> <p>Background</p> <p>The transcription factor STAT3 (signal transducer and activator of transcription 3) is frequently activated in tumor cells. Activated STAT3 forms homodimers, or heterodimers with other TFs such as NF-κB, which becomes activated. Cytoplasmic STAT3 dimers are activated by tyrosine phosphorylation; they interact with importins via a nuclear localization signal (NLS) one of which is located within the DNA-binding domain formed by the dimer. In the nucleus, STAT3 regulates target gene expression by binding a consensus sequence within the promoter. STAT3-specific decoy oligonucleotides (STAT3-decoy ODN) that contain this consensus sequence inhibit the transcriptional activity of STAT3, leading to cell death; however, their mechanism of action is unclear.</p> <p>Results</p> <p>The mechanism of action of a STAT3-decoy ODN was analyzed in the colon carcinoma cell line SW 480. These cells' dependence on activated STAT3 was verified by showing that cell death is induced by STAT3-specific siRNAs or Stattic. STAT3-decoy ODN was shown to bind activated STAT3 within the cytoplasm, and to prevent its translocation to the nucleus, as well as that of STAT3-associated NF-κB, but it did not prevent the nuclear transfer of STAT3 with mutations in its DNA-binding domain. The complex formed by STAT3 and the STAT3-decoy ODN did not associate with importin, while STAT3 alone was found to co-immunoprecipitate with importin. Leptomycin B and vanadate both trap STAT3 in the nucleus. They were found here to oppose the cytoplasmic trapping of STAT3 by the STAT3-decoy ODN. Control decoys consisting of either a mutated STAT3-decoy ODN or a NF-κB-specific decoy ODN had no effect on STAT3 nuclear translocation. Finally, blockage of STAT3 nuclear transfer correlated with the induction of SW 480 cell death.</p> <p>Conclusions</p> <p>The inhibition of STAT3 by a STAT3-decoy ODN, leading to cell death, involves the entrapment of activated STAT3 dimers in the cytoplasm. A mechanism is suggested whereby this entrapment is due to STAT3-decoy ODN's inhibition of active STAT3/importin interaction. These observations point to the high potential of STAT3-decoy ODN as a reagent and to STAT3 nucleo-cytoplasmic shuttling in tumor cells as a potential target for effective anti-cancer compounds.</p

The epigenetic regulator RINF (CXXC5) maintains SMAD7 expression in human immature erythroid cells and sustains red blood cells expansion

The gene CXXC5, encoding a Retinoid-Inducible Nuclear Factor (RINF), is located within a region at 5q31.2 commonly deleted in myelodysplastic syndrome (MDS) and adult acute myeloid leukemia (AML). RINF may act as an epigenetic regulator and has been proposed as a tumor suppressor in hematopoietic malignancies. However, functional studies in normal hematopoiesis are lacking, and its mechanism of action is unknow. Here, we evaluated the consequences of RINF silencing on cytokineinduced erythroid differentiation of human primary CD34+ progenitors. We found that RINF is expressed in immature erythroid cells and that RINF-knockdown accelerated erythropoietin-driven maturation, leading to a significant reduction (~45%) in the number of red blood cells (RBCs), without affecting cell viability. The phenotype induced by RINF-silencing was TGFβ-dependent and mediated by SMAD7, a TGFβ- signaling inhibitor. RINF upregulates SMAD7 expression by direct binding to its promoter and we found a close correlation between RINF and SMAD7 mRNA levels both in CD34+ cells isolated from bone marrow of healthy donors and MDS patients with del(5q). Importantly, RINF knockdown attenuated SMAD7 expression in primary cells and ectopic SMAD7 expression was sufficient to prevent the RINF knockdowndependent erythroid phenotype. Finally, RINF silencing affects 5’-hydroxymethylation of human erythroblasts, in agreement with its recently described role as a Tet2- anchoring platform in mouse. Altogether, our data bring insight into how the epigenetic factor RINF, as a transcriptional regulator of SMAD7, may fine-tune cell sensitivity to TGFβ superfamily cytokines and thus play an important role in both normal and pathological erythropoiesis

STAT5-and hypoxia-dependent upregulation of AXL

Internal tandem duplication in Fms-like tyrosine kinase 3 (FLT3-ITD) is the most frequent mutation observed in acute myeloid leukemia (AML) and correlates with poor prognosis. FLT3 tyrosine kinase inhibitors are promising for targeted therapy. Here, we investigated mechanisms dampening the response to the FLT3 inhibitor quizartinib, which is specific to the hematopoietic niche. Using AML primary samples and cell lines, we demonstrate that convergent signals from the hematopoietic microenvironment drive FLT3-ITD cell resistance to quizartinib through the expression and activation of the tyrosine kinase receptor AXL. Indeed, cytokines sustained phosphorylation of the transcription factor STAT5 in quizartinib-treated cells, which enhanced AXL expression by direct binding of a conserved motif in its genomic sequence. Likewise, hypoxia, another well-known hematopoietic niche hallmark, also enhanced AXL expression. Finally, in a xenograft mouse model, inhibition of AXL significantly increased the response of FLT3-ITD cells to quizartinib exclusively within a bone marrow environment. These data highlight a new bypass mechanism specific to the hematopoietic niche that hampers the response to quizartinib through combined upregulation of AXL activity. Targeting this signaling offers the prospect of a new therapy to eradicate resistant FLT3-ITD leukemic cells hidden within their specific microenvironment, thereby preventing relapses from FLT3-ITD clones

Une méthode rapide robuste et simple pour l'estimation des paramètres d'un signal à phase polynomiale

International audienceLes signaux a phase polynomiale constituent une vaste classe de signaux utilises en modelisation mais leurs traitements se revelent difficiles en raison de leur caractere non-stationnaire. Dans la methode presentee dans cet article, nous mettons a profit de recents travaux en matiere d'estimation robuste afin de realiser un nouvel algorithme d'estimation des parametres de la phase d'un signal. Cet algorithme presente les avantages d'etre rapide et capable de traiter des signaux dont la phase est d'ordre inconnu. La structure de cet algorithme reste independante par le type de bruit car il est resistant a la forme de la distribution du bruit

Rapid estimation of the parameters of a polynomial-phase signal

Les signaux à phase polynomiale forment une vaste classe de signaux non stationnaires utilisés entre autres pour la modélisation. Dans cet article, nous tirons partie de progrès en estimation robuste pour réaliser un algorithme pour l'estimation des paramètres d'un signal à phase polynomiale. Cet algorithme présente les avantages d'être rapide et d'avoir une structure robuste à la nature du bruit