Caractérisation et modélisation des pièges par des mesures de dispersion basse-fréquence dans les technologies HEMT InAIN/GaN pour l'amplification de puissance en gamme millimétrique

Nowadays, High Electron Mobility Transistors (HEMTs) in Gallium Nitride (GaN) take the lead in power amplification at microwave frequencies. Most of the studies and developments on those HEMTs concern AlGaN/GaN structures but alternative transistors with an InAlN barrier, which reduces the strain in the crystal lattice of the whole structure, are investigated by few laboratories. This thesis presents some advanced studies on the new InAlN/GaN HEMT developed by the III-V Lab, focusing on the trapping phenomena induced by defects inside the crystal structure. A new method for the characterization of these defects, based on low-frequency S-Parameters measurements, is proposed. Furthermore, a non-linear electro thermal model including trapping effects for an InAlN/GaN HEMT is detailed and used to design a MMIC power amplifier for Ka-band applications.Les transistors à haute mobilité d’électrons (HEMTs) en Nitrure de Gallium (GaN) s’affirment aujourd’hui comme une technologie essentielle à l’amplification de puissance à haute fréquence. Les HEMTs GaN étudiées et développées reposent essentiellement sur une hétérostructure AlGaN/GaN mais une alternative à base d’une barrière composée en InAlN, réduisant les contraintes sur les mailles cristallographiques de l’ensemble, est étudiée par certains laboratoires. Ce manuscrit de thèse rapporte une étude des potentialités de la filière HEMT InAlN/GaN développée au III-V Lab, en s’intéressant tout particulièrement aux effets de pièges induits par des défauts présents au sein de la structure. Une méthode de détection de ces défauts est proposée, basée sur la mesure de paramètres [S] en basse fréquence. Un modèle de HEMT InAlN/GaN électrothermique comprenant la contribution des effets de pièges est rapporté et sert de base à la conception d’un amplificateur de puissance en technologie MMIC, fonctionnant en bande Ka, présenté au dernier chapitre

Monotone corrections for generic cell-centered Finite Volume approximations of anisotropic diffusion equations

We present a nonlinear technique to correct a general Finite Volume scheme for anisotropic diffusion problems, which provides a discrete maximum principle. We point out general properties satisfied by many Finite Volume schemes and prove the proposed corrections also preserve these properties. We then study two specific corrections proving, under numerical assumptions, that the corresponding solutions converge to the continuous one as the size of the mesh tends to 0. Finally we present numerical results showing these corrections suppress local minima produced by the initial Finite Volume scheme

Traps’ characterization and modeling by the study of the output conductance dispersion at low frequencies, in InAlN/GaN HEMT technologies for the amplification in millimetric range

Les transistors à haute mobilité d’électrons (HEMTs) en Nitrure de Gallium (GaN) s’affirment aujourd’hui comme une technologie essentielle à l’amplification de puissance à haute fréquence. Les HEMTs GaN étudiées et développées reposent essentiellement sur une hétérostructure AlGaN/GaN mais une alternative à base d’une barrière composée en InAlN, réduisant les contraintes sur les mailles cristallographiques de l’ensemble, est étudiée par certains laboratoires. Ce manuscrit de thèse rapporte une étude des potentialités de la filière HEMT InAlN/GaN développée au III-V Lab, en s’intéressant tout particulièrement aux effets de pièges induits par des défauts présents au sein de la structure. Une méthode de détection de ces défauts est proposée, basée sur la mesure de paramètres [S] en basse fréquence. Un modèle de HEMT InAlN/GaN électrothermique comprenant la contribution des effets de pièges est rapporté et sert de base à la conception d’un amplificateur de puissance en technologie MMIC, fonctionnant en bande Ka, présenté au dernier chapitre.Nowadays, High Electron Mobility Transistors (HEMTs) in Gallium Nitride (GaN) take the lead in power amplification at microwave frequencies. Most of the studies and developments on those HEMTs concern AlGaN/GaN structures but alternative transistors with an InAlN barrier, which reduces the strain in the crystal lattice of the whole structure, are investigated by few laboratories. This thesis presents some advanced studies on the new InAlN/GaN HEMT developed by the III-V Lab, focusing on the trapping phenomena induced by defects inside the crystal structure. A new method for the characterization of these defects, based on low-frequency S-Parameters measurements, is proposed. Furthermore, a non-linear electro thermal model including trapping effects for an InAlN/GaN HEMT is detailed and used to design a MMIC power amplifier for Ka-band applications

Transcriptomic Adjustments in a Freshwater Ectoparasite Reveal the Role of Molecular Plasticity for Parasite Host Shift

A parasite’s lifestyle is characterized by a critical dependency on its host for feeding, shelter and/or reproduction. The ability of parasites to exploit new host species can reduce the risk associated with host dependency. The number of host species that can be infected by parasites strongly affects their ecological and evolutionary dynamics along with their pathogenic effects on host communities. However, little is known about the processes and the pathways permitting parasites to successfully infect alternative host species, a process known as host shift. Here, we tested whether molecular plasticity changes in gene expression and in molecular pathways could favor host shift in parasites. Focusing on an invasive parasite, Tracheliastes polycolpus, infecting freshwater fish, we conducted a transcriptomic study to compare gene expression in parasites infecting their main host species and two alternative host species. We found 120 significant differentially expressed genes (DEGs) between parasites infecting the different host species. A total of 90% of the DEGs were identified between parasites using the main host species and those using the two alternative host species. Only a few significant DEGs (seven) were identified when comparing parasites from the two alternative host species. Molecular pathways enriched in DEGs and associated with the use of alternative host species were related to cellular machinery, energetic metabolism, muscle activity and oxidative stress. This study strongly suggests that molecular plasticity is an important mechanism sustaining the parasite’s ability to infect alternative hosts

Evolution and phenotypic characterization of HBV quasispecies in compliant patients experiencing unexplained entecavir treatment failure Running title: Entecavir, viral resistance & whole genome

International audienceEntecavir treatment failure can be observed in compliant patients despite an absence of detectable resistance mutations by Pol/RT Sanger sequencing. We hypothesized that these unexplained treatment failures could rely on other mechanisms of viral resistance, especially on mutations selected outside of the Pol/RT domain. Partial virological response to entecavir was observed in three patients treated with immunosuppressive drugs, without selection of Pol/RT resistance mutations. Mutations selected in the whole HBV genome during entecavir treatment and potentially associated with resistance were searched for using deep sequencing and characterized using a phenotypic resistance assay. Mutations Q206K (pre-core/core), Q120K (pre-S1/pre-S2, T-cell epitope) and A300E (spacer domain) were selected during entecavir treatment in patient #1 but were not associated with an increased level of resistance to entecavir or an increase in HBV replication capacity. Core promoter mutations T1753G, A1762T and G1764A were present before treatment in patient #1. HBs Ag immune escape mutations were present before treatment in patients #2 (sK122R, sT126I, sP127S and sG145R) and #3 (sM133I). These results provided a unique insight into the evolution of HBV quasispecies during entecavir treatment, addressing the whole HBV genome and not only the Pol/RT domain. Our results suggest that mutations selected outside of the Pol/RT domain could contribute to entecavir treatment failure, not by an increased level of resistance, but by an immune escape mechanism, in synergy with immunosuppressive drugs

Technologie InAlGaN/GaN/SiC à faibles effets mémoires délivrant 10W/mm à 30 GHz

International audienc

Modifications of the endosomal compartment in fibroblasts from sporadic Alzheimer’s disease patients are associated with cognitive impairment

International audienceAbstract Morphological alterations of the endosomal compartment have been widely described in post-mortem brains from Alzheimer’s disease (AD) patients and subjects with Down syndrome (DS) who are at high risk for AD. Immunostaining with antibodies against endosomal markers such as Early Endosome Antigen 1 (EEA1) revealed increased size of EEA1-positive puncta. In DS, peripheral cells such as peripheral blood mononuclear cells (PBMCs) and fibroblasts, share similar phenotype even in the absence of AD. We previously found that PBMCs from AD patients have larger EEA1-positive puncta, correlating with brain amyloid load. Here we analysed the endosomal compartment of fibroblasts from a very well characterised cohort of AD patients (IMABio3) who underwent thorough clinical, imaging and biomarkers assessments. Twenty-one subjects were included (7 AD with mild cognitive impairment (AD-MCI), 7 AD with dementia (AD-D) and 7 controls) who had amyloid-PET at baseline (PiB) and neuropsychological tests at baseline and close to skin biopsy. Fibroblasts isolated from skin biopsies were immunostained with anti-EEA1 antibody and imaged using a spinning disk microscope. Endosomal compartment ultrastructure was also analysed by electron microscopy. All fibroblast lines were genotyped and their AD risk factors identified. Our results show a trend to an increased EEA1-positive puncta volume in fibroblasts from AD-D as compared to controls (p.adj = 0.12) and reveal enhanced endosome area in fibroblasts from AD-MCI and AD-AD versus controls. Larger puncta size correlated with PiB retention in different brain areas and with worse cognitive scores at the time of biopsy as well as faster decline from baseline to the time of biopsy. Finally, we identified three genetic risk factors for AD ( ABCA1 , COX7C and MYO15A ) that were associated with larger EEA1 puncta volume. In conclusion, the endosomal compartment in fibroblasts could be used as cellular peripheral biomarker for both amyloid deposition and cognitive decline in AD patients

Modifications of the endosomal compartment in fibroblasts from sporadic Alzheimer’s disease patients are associated with cognitive impairment

International audienceAbstract Morphological alterations of the endosomal compartment have been widely described in post-mortem brains from Alzheimer’s disease (AD) patients and subjects with Down syndrome (DS) who are at high risk for AD. Immunostaining with antibodies against endosomal markers such as Early Endosome Antigen 1 (EEA1) revealed increased size of EEA1-positive puncta. In DS, peripheral cells such as peripheral blood mononuclear cells (PBMCs) and fibroblasts, share similar phenotype even in the absence of AD. We previously found that PBMCs from AD patients have larger EEA1-positive puncta, correlating with brain amyloid load. Here we analysed the endosomal compartment of fibroblasts from a very well characterised cohort of AD patients (IMABio3) who underwent thorough clinical, imaging and biomarkers assessments. Twenty-one subjects were included (7 AD with mild cognitive impairment (AD-MCI), 7 AD with dementia (AD-D) and 7 controls) who had amyloid-PET at baseline (PiB) and neuropsychological tests at baseline and close to skin biopsy. Fibroblasts isolated from skin biopsies were immunostained with anti-EEA1 antibody and imaged using a spinning disk microscope. Endosomal compartment ultrastructure was also analysed by electron microscopy. All fibroblast lines were genotyped and their AD risk factors identified. Our results show a trend to an increased EEA1-positive puncta volume in fibroblasts from AD-D as compared to controls (p.adj = 0.12) and reveal enhanced endosome area in fibroblasts from AD-MCI and AD-AD versus controls. Larger puncta size correlated with PiB retention in different brain areas and with worse cognitive scores at the time of biopsy as well as faster decline from baseline to the time of biopsy. Finally, we identified three genetic risk factors for AD ( ABCA1 , COX7C and MYO15A ) that were associated with larger EEA1 puncta volume. In conclusion, the endosomal compartment in fibroblasts could be used as cellular peripheral biomarker for both amyloid deposition and cognitive decline in AD patients

Protein Sci

Understanding the way how proteins interact with each other to form transient or stable protein complexes is a key aspect in structural biology. In this study, we combined chemical cross-linking with mass spectrometry to determine the binding stoichiometry and map the protein-protein interaction network of a human SAGA HAT subcomplex. MALDI-MS equipped with high mass detection was used to follow the cross-linking reaction using bis[sulfosuccinimidyl] suberate (BS3) and confirm the heterotetrameric stoichiometry of the specific stabilized subcomplex. Cross-linking with isotopically labeled BS3 d0-d4 followed by trypsin digestion allowed the identification of intra- and intercross-linked peptides using two dedicated search engines: pLink and xQuest. The identified interlinked peptides suggest a strong network of interaction between GCN5, ADA2B and ADA3 subunits; SGF29 is interacting with GCN5 and ADA3 but not with ADA2B. These restraint data were combined to molecular modeling and a low-resolution interacting model for the human SAGA HAT subcomplex could be proposed, illustrating the potential of an integrative strategy using cross-linking and mass spectrometry for addressing the structural architecture of multiprotein complexes