147 research outputs found

    Dependency of the Finite-Impulse-Response-Based Head-Related Impulse Response Model on Filter Order

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    Various approaches have been reported on HRIR modeling to lighten the high computation cost of the 3-D audio systems without sacrificing the quality of the rendered sounds. The performance of these HRIR models have been widely evaluated usually in terms of the objective estimation errors between the original measured HRIRs and the modeled HRIRs. However, it is still unclear how much these objective evaluation results match the psychoacoustic evaluations. In this research, an efficient finite-impulse-response (FIR) model is studied as a case study which is essentially based on the concept of the minimum-phase modeling technique. The accuracy dependency of this modeling approach on the order of FIR filter is examined with the objective estimation errors and the psychoacoustic tests. In the psychoacoustic tests, the MIT HRIR database are exploited and evaluated in terms of sound source localization difference and sound quality difference by comparing the synthesized stimuli with the measured HRIRs and those with the FIR models of different orders. Results indicated that the measured hundred-sample-length HRIRs can be sufficiently modeled by the low-order FIR model from the perceptual point of view, and provided the relationship between perceptual sound localization/quality difference and the objective estimation results that should be useful for evaluating the other HRIR modeling approaches

    Genomic structure of human lysosomal glycosylasparaginase

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    AbstractThe gene structure of the human lysosomal enzyme glycosylasparaginase was determined. The gene spans 13 kb and consists of 9 exons. Both 5′ and 3′ untranslated regions of the gene are uninterrupted by introns. A number of transcriptional elements were identified in the 5′ upstream sequence that includes two putative CAAT boxes followed by TATA-like sequences together with two AP-2 binding sites and one for Sp1. A 100 bp CpG island and several ETF binding sites were also found. Additional AP-2 and Sp1 binding sites are present in the first intron. Two polyadenylation sites are present and appear to be functional. The major known glycosylasparaginase gene defect G488→C, which causes the lysosomal storage disease aspartylglycosaminuria (AGU) in Finland, is located in exon 4. Exon 5 encodes the post-translational cleavage site for the formation of the mature α/β subunits of the enzyme as well as a recently proposed active site threonine, Thr206

    Évaluation de polymorphismes de p22phox, RAGE et ALOX12 dans la survenue de la néphropathie diabétique chez le type 1 (projet NEPHRODIANOX)

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    Le stress oxydant est un des mécanismes clefs dans la physiopathologie de la néphropathie diabétique chez le patient type 1. Nous avons évalué l association de polymorphismes de trois gènes impliqués dans cette voie : C242T de CYBA (p22phox), -374T/A et -429T/C de RAGE, et Arg261Gln d ALOX12, dans le délai de survenue de la néphropathie microalbuminurique chez le patient diabétique de type 1. 162 patients type 1, ancienneté moyenne du diabète de 32,9 +/- 9 ans, inclus au CHU de Grenoble. 53 patients présentaient une microalbuminurie (> 30 mg/L) et 109 indemnes de néphropathie. Nous avons determiné pour chaque patient son statut vis-à-vis de chacun des polymorphysmes étudiés, et évalué leurs associations à la survenue de la microalbuminurie dans un modèle de cox. Le modèle de cox en analyse multi-variée retrouve quatre facteurs associés au délai de survenue de la néphroapthie diabétique : RAGE 374AA (HR 4.19 [1.84-9.58] (p=0.001)), p22phox TT+TC (HR 2.1 [1.16-3.8], p= 0.015), mais égalment le sexe masculin (HR 1.92 [1.07-3.43], p=0.028) et le diagnostique du diabète à l âge pédiatrique (HR 1.85 [1.03-3.32], p=0.039). Nous retrouvons également une association avec le délai de survenue de l IRCT (p= 0.028 pour p22phox TC+TT, et p=0.033 pour RAGE 374AA). Le polymorphisme C242T de p22phox semble indépendant de la rétinopathie. Conclusion : les polymorphismes C242T de p22phox et -374T/A de RAGE sont associés à une survenue plus précoce de la microalbuminurie dans une population de diabétiques de type 1 française. L indépendance de la rétinopathie ainsi que l association avec la survenue de l IRCT nous fournissent des arguments supplémentaires leur implication.Background: Oxidative stress is a key component of type 1 diabetic nephropathy. Therefore, we investigated the association between polymorphisms of three genes implicated in this pathway: C242T of CYBA (p22phox), -374T/A and -429T/C of RAGE, as Arg261Gln of ALOX 12, in the delay of microalbuminuria onset in type 1 diabetic patients. Methods: 162 diabetic type 1 patients with 32.9 +/- 9 years of diabetes duration were included at the Grenoble University Hospital. 53 presented a history of persistent microalbuminuria (> 30 mg/l) and 109 did not. Delay between microalbuminuria and diabetes diagnosis, as end stage renal disease (ESRD) onset and bio-clinical data, were recorded. Polymorphism status was determined and its association to microalbumuria was assessed with a Cox regression model. Results: All polymorphisms respect the Hardy Weinberg equilibrium. At univariate level, C242T dominant model (13.6% TT, 45.7% TC, 41.7% CC) and -374T/A (5.6% AA, 35.2% TA, 59% TT) were significantly correlated with microalbuminuria (p=0.038, 0.0021 respectively). The Cox regression model validated four significant variables: RAGE 374AA (HR 4.19 [1.84-9.58] (p=0.001)), p22phox TT+TC (HR 2.1 [1.16-3.8], p= 0.015), associated with male sex (HR 1.92 [1.07-3.43], p=0.028) and diabetes diagnosis at pediatric age (HR 1.85 [1.03-3.32], p=0.039). The same association was found with ESRD (p= 0.028 for p22phox TC+TT, and p=0.033 for RAGE 374AA). The C242T polymorphism was independent of retinopathy onset (66.7% of CC patients versus 63.6% of CT+TT p=0.6 for superiority and p=0.043 for non inferiority). Finally we suspected an increasing risk with polymorphism associations but it did not reach significant level. Conclusions: p22phox C242T, and RAGE-374T/A correlate with microalbuminuria onset in a type 1 diabetic French population. The same correlation with ESRD onset provides argument for the involvement of a genetic predisposition involving renal oxidative stress for diabetic nephropathy independently of retinopathy for C242T.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

    SRSF1 modulates PTPMT1 alternative splicing to regulate lung cancer cell radioresistance

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    Background Radioresistance is the major cause of cancer treatment failure. Additionally, splicing dysregulation plays critical roles in tumorigenesis. However, the involvement of alternative splicing in resistance of cancer cells to radiotherapy remains elusive. We sought to investigate the key role of the splicing factor SRSF1 in the radioresistance in lung cancer. Methods Lung cancer cell lines, xenograft mice models, and RNA-seq were employed to study the detailed mechanisms of SRSF1 in lung cancer radioresistance. Clinical tumor tissues and TCGA dataset were utilized to determine the expression levels of distinct SRSF1-regulated splicing isoforms. KM-plotter was applied to analyze the survival of cancer patients with various levels of SRSF1-regulated splicing isoforms. Findings Splicing factors were screened to identify their roles in radioresistance, and SRSF1 was found to be involved in radioresistance in cancer cells. The level of SRSF1 is elevated in irradiation treated lung cancer cells, whereas knockdown of SRSF1 sensitizes cancer cells to irradiation. Mechanistically, SRSF1 modulates various cancer-related splicing events, particularly the splicing of PTPMT1, a PTEN-like mitochondrial phosphatase. Reduced SRSF1 favors the production of short isoforms of PTPMT1 upon irradiation, which in turn promotes phosphorylation of AMPK, thereby inducing DNA double-strand break to sensitize cancer cells to irradiation. Additionally, the level of the short isoform of PTPMT1 is decreased in cancer samples, which is correlated to cancer patients' survival. Conclusions Our study provides mechanistic analyses of aberrant splicing in radioresistance in lung cancer cells, and establishes SRSF1 as a potential therapeutic target for sensitization of patients to radiotherapy

    Unreachable Peers Communication Scheme in Decentralized Networks Based on Peer-to-Peer Overlay Approaches

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    Decentralized networks bring us many benefits, but as networks evolve, many nodes either actively or passively become unreachable behind an NAT or a firewall. This has become a hindrance to the development of decentralized networks, where peer-to-peer communication data transfer between unreachable nodes cannot be accomplished, whether in decentralized file systems, decentralized social, or decentralized IoT. The existing scheme requires a series of centralized servers or requires network-wide flooding for consensus data, which can lead to the loss of decentralized nature of the network and cause flooding bottlenecks, contrary to the design concept of decentralization. In this paper, our proposed scheme uses a structured P2P overlay network to store the indexes of unreachable nodes in the whole network, so that the characteristics of a decentralized network are still maintained while ensuring the efficiency of lookup. When nodes communicate, the transmission channel is established so that both nodes continuously transmit data streams peer-to-peer without relying on the central server. Moreover, the scheme guarantees the security and privacy of nodes’ data transmission and the P2P overlay network without relying on centralized trusted institutions. Finally, we deploy a real cluster environment to verify the effectiveness of each module at different network sizes and prove the overall feasibility of the scheme. The scheme has certain advantages over existing solutions in terms of security, privacy, communication efficiency, device democracy, etc
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