Polymorphic variants of SCN1A and EPHX1 influence plasma carbamazepine concentration, metabolism and pharmacoresistance in a population of Kosovar Albanian epileptic patients

Aim The present study aimed to evaluate the effects of gene variants in key genes influencing pharmacokinetic and pharmacodynamic of carbamazepine (CBZ) on the response in patients with epilepsy. Materials & Methods Five SNPs in two candidate genes influencing CBZ transport and metabolism, namely ABCB1 or EPHX1, and CBZ response SCN1A (sodium channel) were genotyped in 145 epileptic patients treated with CBZ as monotherapy and 100 age and sex matched healthy controls. Plasma concentrations of CBZ, carbamazepine-10,11-epoxide (CBZE) and carbamazepine-10,11-trans dihydrodiol (CBZD) were determined by HPLC-UV-DAD and adjusted for CBZ dosage/kg of body weight. Results The presence of the SCN1A IVS5-91G>A variant allele is associated with increased epilepsy susceptibility. Furthermore, carriers of the SCN1A IVS5-91G>A variant or of EPHX1 c.337T>C variant presented significantly lower levels of plasma CBZ compared to carriers of the common alleles (0.71±0.28 vs 1.11±0.69 μg/mL per mg/Kg for SCN1A IVS5-91 AA vs GG and 0.76±0.16 vs 0.94±0.49 μg/mL per mg/Kg for EPHX1 c.337 CC vs TT; PG showed a reduced microsomal epoxide hydrolase activity as reflected by a significantly decreased ratio of CBZD to CBZ (0.13±0.08 to 0.26±0.17, pT SNP and SCN1A 3148A>G variants were not associated with significant changes in CBZ pharmacokinetic. Patients resistant to CBZ treatment showed increased dosage of CBZ (657±285 vs 489±231 mg/day; P<0.001) but also increased plasma levels of CBZ (9.84±4.37 vs 7.41±3.43 μg/mL; P<0.001) compared to patients responsive to CBZ treatment. CBZ resistance was not related to any of the SNPs investigated. Conclusions The SCN1A IVS5-91G>A SNP is associated with susceptibility to epilepsy. SNPs in EPHX1 gene are influencing CBZ metabolism and disposition. CBZ plasma levels are not an indicator of resistance to the therapy

Low Power oriented Hardware dependent Software Implementation in MPSoC Architectures

International audienceThis paper proposes a methodology for power aware hardware dependent software (HdS) generation for MPSoC architectures. The main contributions of this work are (1) a layered “power API” structure that spans across multiple HdS layers and (2) a power aware HdS generation flow that produces customized HdS implementation according to the application energy requirements and the platform power management capabilities. The major benefit of this methodology is to decouple the high level energy management strategies from the specific low level hardware implementation details, without sacrifying implementation efficiency

Parallel Programming of Multi-Processor SoC : A HW-SW Interface perspective

International audienceFor the design of classic computers the parallel programming concept is used to abstract HW/SW interfaces during high level specification of application software. The software is then adapted to existing multiprocessor platforms using a low level software layer that implements the programming model. Unlike classic computers, the design of heterogeneous MPSoC includes also building the processors and other kind of hardware components required to execute the software. In this case, the programming model hides both hardware and software refinements. This paper deals with parallel programming models to abstract both hardware and software interfaces in the case of heterogeneous MPSoC design. Different abstraction levels will be needed. For the long term, the use of higher level programming models will open new vistas for optimization and architecture exploration like CPU/RTOS tradeoffs

Service Based Component Design Approach for Flexible Hardware/Software Interface Modeling

ISSN: 1074-6005This paper describes a service-based model enabling systematic design and global simulation environments for SoC design. This model, called Service Dependency Graph (SDG) allows modeling of complex, customized (application-specific) interfaces. We also present a model generator that can automatically build hardware/software interfaces based on service and resource requirements described by the SDG. This approach has been applied successfully on the design of a Software Defined Radio application. The results show the effectiveness of the proposed approach in modeling complex interfaces. Additionally the SDG seems to be an excellent intermediate representation for the design automation of hardware software interfaces

Transcriptome assembly and abiotic related gene expression analysis of date palm reveal candidate genes involved in response to cadmium stress

Date palm in Tunisia is of major economic importance but are also factors of social, environmental and economic stability. An annotated assembly of the transcriptome of cultivar Deglet Nour was reported. RNA was isolated from plant Cd-contaminated leaves, and 37,049 unique Illumina RNA-seq reads were used in a transcriptome assembly. The draft transcriptome assembly consists of 6789 contigs and 17.285 singletons with a means length of 858 bp and 1.042 bp, respectively. The final assembly was functionally annotated using Blast2GO software, allowing the identification of putative genes controlling important agronomic traits. The annotated transcriptome data sets were used to query all known Kyoto Encyclopedia of Genes and Genomes pathways. The most represented molecular functions and biological processes were nucleotide binding and transcription, transport and response to stress and abiotic and biotic stimuli. A prediction of the genes interaction network was proposed by selecting corresponding functionally similar genes from Arabidopsis datasets, downloaded by GeneMANIA version 2.1. Several Cd-responsive genes expression was monitored in in vitro isolated explant of Cd stressed Deglet Nour. Some chelators encoding genes were upregulated confirming in silico findings. Genes encoding HMs transporters in date palm showed expression enhancement more pronounced after 20 days of exposure. P. dactylifera transcriptome provides a valuable resource for future functional analysis of candidate genes involved in metal stress response. - 2019 Elsevier Inc.Scopu

Flexible hardware/software interface modeling using high level service based component model

Complex systems-on-chip are designed by interconnecting pre-designed hardware and software components. During the design cycle, a global model of the SoC may be composed of hardware and software models at different abstraction levels. Designing hardware/software interfaces to interconnect SoC component is a source of design bottlenecks. This paper describes a service-based model enabling systematic design and co-simulation of hardware/software interfaces for SoC design. This model, called Service Dependency Graph (SDG) allows modeling of complex, customized (application-specific) interfaces. We also present a model generator that can automatically build hardware/software interfaces based on service and resource requirements described by the SDG. This approach has been applied successfully on the design of a Software Defined Radio application. The results show the effectiveness of the proposed approach in modeling complex interfaces