A constraint-based WCET computation framework

National audienceOTAWA is a tool dedicated to the WCET computation of critical real-time systems. The tool was enhanced in order to take into account modern micro-architecture features, through an ADL-based approach. Architecture constraints are expresses such that they can be solved by well known efficient constraint solvers. In this paper, we present how we could describe some complex architecture features using the Sim-nML language. We are also concerned by the validation and the animation point of views

Hardware architecture specification and constraint-based WCET computation

International audienceThe analysis of the worst-case execution times is necessary in the design of critical real-time systems. To get sound and precise times, the WCET analysis for these systems must be performed on binary code and based on static analysis. OTAWA, a tool providing WCET computation, uses the Sim-nML language to describe the instruction set and XML files to describe the microarchitecture. The latter information is usually inadequate to describe real architectures and, therefore, requires specific modifications, currently performed by hand, to allow correct time calculation. In this paper, we propose to extend Sim-nML in order to support the description of modern microarchitecture features along the instruction set description and to seamlessly derive the time calculation. This time computation is specified as a constraint solving problem that is automatically synthesized from the extended Sim-nML. Thanks to its declarative aspect, this approach makes easier and modular the description of complex features of microprocessors while maintaining a sound process to compute times

Répression transcriptionnelle du gène TRH

Les hormones thyroïdiennes (HT : T3, T4) exerçant des effets pléiotropes chez les vertébrés, leur synthèse et leur sécrétion doivent être finement contrôlées. Elles agissent elles-mêmes sur leur production, par un système de rétrocontrôle négatif de l’expression des gènes hypothalamique TRH et hypophysaire TSH. Les fondements moléculaires de cette répression transcriptionnelle des gènes TRH et TSH par l’hormone T3, forme biologiquement la plus active des HT, restent méconnus. Certaines caractéristiques de cette régulation commencent toutefois à être identifiées, notamment le rôle spécifique des isoformes TRβ (versus TRα) des récepteurs des HT. La spécificité fonctionnelle de ces isoformes résiderait principalement dans leur extrémité aminoterminale, qui permettrait une interaction différentielle avec certains comodulateurs. L’objectif, aujourd’hui, est de caractériser ces comodulateurs et d’analyser leur contribution à la régulation transcriptionnelle du gène TRH par l’hormone T3.The synthesis and secretion of thyroid hormones (TH: T3, T4) must be strictly regulated. TH act on their own production via a negative feedback system. The synthesis of thyrotropin-releasing hormone (TRH), produced in the hypothalamus, and thyrotropin (TSH) in the pituitary is inhibited at the transcriptional level by TH. TRH and TSH stimulate production of TH. An outstanding, still open, question is the molecular basis of T3-dependent transcription repression of TRH and TSH genes. However, some regulatory components have been identified, with the β-TH receptor (TRβ) playing a specific regulatory role (versus TRα) in the negative feedback effects of T3 on production of TRH and TSH. Moreover, the N-terminus of TRβ is known to be a key element in this regulation. A hypothesis to explain this isoform specificity could be that TRβ and TRα interact differentially with transcriptional comodulators. Thus, it is critical to characterize these comodulators and to analyse their contribution to the transcription regulation of TRH

Synthesis and characterization of biocompatible methacrylated Kefiran hydrogels: towards tissue engineering applications

Hydrogel application feasibility is still limited mainly due to their low mechanical strength and fragile nature. Therefore, several physical and chemical cross-linking modifications are being used to improve their properties. In this research, methacrylated Kefiran was synthesized by reacting Kefiran with methacrylic anhydride (MA). The developed MA-Kefiran was physicochemically characterized, and its biological properties evaluated by different techniques. Chemical modification of MA-Kefiran was confirmed by 1H-NMR and FTIR and GPC-SEC showed an average Mw of 793 kDa (PDI 1.3). The mechanical data obtained revealed MA-Kefiran to be a pseudoplastic fluid with an extrusion force of 11.21 ± 2.87 N. Moreover, MA-Kefiran 3D cryogels were successfully developed and fully characterized. Through micro-CT and SEM, the scaffolds revealed high porosity (85.53 ± 0.15%) and pore size (33.67 ± 3.13 μm), thick pore walls (11.92 ± 0.44 μm) and a homogeneous structure. Finally, MA-Kefiran revealed to be biocompatible by presenting no hemolytic activity and an improved cellular function of L929 cells observed through the AlamarBlue® assay. By incorporating methacrylate groups in the Kefiran polysaccharide chain, a MA-Kefiran product was developed with remarkable physical, mechanical, and biological properties, resulting in a promising hydrogel to be used in tissue engineering and regenerative medicine applications.H. Radhouani and C. Goncalveswere supported by the Foundation for Science and Technology (FCT) fromPortugal, with references CEECIND/00111/2017 and SFRH/BPD/94277/2013, respectively. S. Correia and this work were funded by the R&D Project KOAT-Kefiran Exopolysaccharide: Promising Biopolymer for Use in Regenerative Medicine and Tissue Engineering, with reference PTDC/BTMMAT/29760/2017 (POCI-01-0145-FEDER-029760), financed by FCT and co-financed by FEDER and POCI. We also thank Duarte N. Carvalho for input on the schematic representation of the process

Impact of kefiran exopolysaccharide extraction on its applicability for tissue engineering and regenerative medicine

Kefiran is an exopolysaccharide produced by the microflora of kefir grains used to produce the fermented milk beverage kefir. The health-promoting and physicochemical properties of kefiran led to its exploration for a range of applications, mainly in the food industry and biomedical fields. Aiming to explore its potential for tissue engineering and regenerative medicine (TERM) applications, the kefiran biopolymer obtained through three different extraction methodologies was fully characterized and compared. High-quality kefiran polysaccharides were recovered with suitable yield through different extraction protocols. The methods consisted of heating the kefir grains prior to recovering kefiran by centrifugation and differed mainly in the precipitation steps included before lyophilization. Then, kefiran scaffolds were successfully produced from each extract by cryogelation and freeze-drying. In all extracts, it was possible to identify the molecular structure of the kefiran polysaccharide through 1H-NMR and FTIR spectra. The kefiran from extraction 1 showed the highest molecular weight (~3000 kDa) and the best rheological properties, showing a pseudoplastic behavior; its scaffold presented the highest value of porosity (93.2% ± 2), and wall thickness (85.8 µm ± 16.3). All extracts showed thermal stability, good injectability and desirable viscoelastic properties; the developed scaffolds demonstrated mechanical stability, elastic behavior, and pore size comprised between 98â 94 µm. Additionally, all kefiran products proved to be non-cytotoxic over L929 cells. The interesting structural, physicochemical, and biological properties showed by the kefiran extracts and cryogels revealed their biomedical potential and suitability for TERM applications.H. Radhouani and C. Gonçalves were supported by the Foundation for Science and Technology (FCT) from Portugal, with references CEECIND/00111/2017 and SFRH/BPD/94277/ 2013, respectively. S. Correia and this work were funded by the R&D Project KOAT—Kefiran Exopolysaccharide: Promising Biopolymer for Use in Regenerative Medicine and Tissue Engineering, with reference PTDC/BTMMAT/29760/2017 (POCI-01-0145-FEDER-029760), financed by FCT and co-financed by FEDER and POCI, and by the Project “HEALTH-UNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological and infectious diseases”, ref. NORTE-01-0145-FEDER-000039 funded under the program NORTE-45-2020-20—Sistema de Apoio à Investigação Científica e Tecnológica— “Projetos Estruturados de I&D&I” UNorte. We also thank Duarte N. Carvalho for input on the schematic representation of the process