Etude et développement de procédés de gravure plasma de HfO2 pour l'élaboration de transistors CMOS sub-45nm

La miniaturisation des dispositifs CMOS impose d'introduire de nouveaux matériaux dans l'empilement de grille des transistors. Ainsi, l'empilement classique poly-silicium/SiO2 est remplacé par un empilement poly- silicium/métal/matériau à haute permittivité diélectrique. L'introduction de ces nouveaux matériaux nécessite le développement de nouveaux procédés de gravure plasma. L'objectif de ce travail est de proposer un procédé de gravure plasma capable de graver une fine couche de diélectrique (HfO2 dans notre cas) sélectivement par rapport au substrat de silicium sous-jacent. Cette étude montre que les plasmas à base de BCl3 sont très prometteurs dans ce domaine. En effet, les mécanismes de gravure en BCl3 reposent sur une compétition entre gravure et formation d'un dépôt de BCl sur la surface. La transition d'un régime à l'autre est contrôlée par l'énergie des ions du plasma. Comme le seuil de gravure en énergie est plus faible pour HfO2 que pour les substrats contenant du Si, il est possible d'obtenir une sélectivité de gravure infinie en ajustant l'énergie des ions judicieusement. De plus ce travail souligne le rôle important du conditionnement des parois du réacteur de gravure dans les mécanismes mis en jeu en plasma de BCl3. Enfin, des procédés de gravure répondant aux problèmes de sélectivité et d'anisotropie de gravure sont proposés pour graver la fine couche de HfO2 de grille.New materials have to be introduced in the gate stack in order to ensure the miniaturization of CMOS structures. Thus, the conventional poly-Si/SiO2 gate stack is going to be replaced by poly-Si/metal/high-k material stack. The introduction of these new materials requires the development of new plasma etching processes. The aim of this work was to develop plasma etching processes aimed to etch the thin high-k layer (HfO2 in our case) selectively towards the underlying silicon substrate. This work shows that BCL3 based plasmas are very promising to fulfill this goal. Indeed, the etching mechanisms in BCl3 plasmas rely on the competition of etching and BCl deposition on the surface. The transition from one regime to another is controlled by the plasma ion energy. As the ion energy threshold is lower for HfO2 than for Si containing substrates, infinite etch selectivity can be obtained by adjusting correctly the ion energy. Moreover, this study underlines the outstanding role of reactor wall conditioning in the etching mechanisms involved in BCl3 plasmas. Finally, etching processes in BCl3 plasmas addressing selectivity and anisotropy issues are proposed to etch thin HfO2 oxide gate.GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF

Organosilane-modified maghemite nanoparticles and their use as co-initiator in the ring-opening polymerization of epsilon-caprolactone.

Hydroxyl and amino groups were introduced on maghemite nanoparticles surface by grafting of (3-glycidoxypropyl)trimethoxysilane and N-(2-aminoethyl)-3-aminopropyltrimethoxy silane, in several solvents including water, toluene and N,N-dimethylformamide. Coating of maghemite particles by a biocompatible and biodegradable polyester, namely the poly(epsilon-caprolactone) was then achieved, by an aluminum isopropoxide-catalyzed ring-opening polymerization of var epsilon-caprolactone initiated ‘from' the maghemite particles surface. Silane and polymer coating were characterized by TGA and DRIFT spectroscopy. In this manner, nanocomposites containing up to 0.43 g of polymer per gram of maghemite were obtained

Contributions of thermokinetic calculations to the understanding of the microstructural evolutions of E-ATF Cr Coated Zr-based nuclear fuel claddings upon high temperature transients

International audienceChromium coated zirconium based nuclear fuel claddings are among the most promising evolutive concepts in the field of Enhanced Accident Tolerant Fuel (EATF) developments [1-2]. The development of these new claddings has been accelerated since 2011 and the Fukushima-DAICHI nuclear accident. Among some other objectives, one of the main ideas is to develop new concepts of nuclear fuel claddings able to delay the High Temperature (HT) steam oxidation kinetics and the associated hydrogen production (explosion risk) and to improve the resultant Post-Quenching (PQ) cladding strength and ductility upon and following hypothetical accident conditions such as Loss-of-Coolant-Accident (LOCA). In this context, Cr-coated Zr based alloys, with 10-20µm thick Cr coating (PVD deposition), show promising behaviour

Adult female acne treated with spironolactone: a retrospective data review of 70 cases

International audienceThe prevalence of acne in the adult population is increasing, particularly in women. Spironolactone regulates sebaceous gland activity by blocking androgen receptor. To evaluate retrospectively the efficacy of spironolactone in women with acne. Data from 70 women of at least 20 years, treated for their acne between 2010 and 2015 with low-dose spironolactone (≤150 mg/day), were analysed. Remission was defined by the number of retentional lesions inferior or equal to five and inflammatory lesions inferior or equal to two on the face. Variables influencing the response were studied using the Cox model. The mean age was 31.3 years; 39 (56%) women had prior courses of isotretinoin and 53 (76%) had an oral contraception prior to treatment. Remission data from a median treatment period of six months (95% CI: 4-9) were obtained from 47 (71%) women. Markers for a positive response to spironolactone were a high number of inflammatory lesions at inclusion (OR: 1.08; 95% CI: 1.03-1.13; p = 0.001) and relapse with previous isotretinoin (OR: 2.46; 95% CI: 1.09-5.54; p = 0.03). The marker for a negative response was an association with oral contraceptives containing first or second-generation progestin (OR: 2.77; 95% CI: 1.35-5.71; p = 0.005). This retrospective data analysis confirms that the use of low doses of spironolactone is a valuable alternative in women with acne in whom oral isotretinoin has failed. Moreover, the analysis shows that first and second-generation oral contraceptives decrease the efficacy of spironolactone, confirming the interest of using two third or fourth-generation oral contraceptives

Chronic dry eye induced corneal hypersensitivity, neuroinflammatory responses, and synaptic plasticity in the mouse trigeminal brainstem

International audienceBackground: Dry eye disease (DED) is a multifactorial disease associated with ocular surface inflammation, pain, and nerve abnormalities. We studied the peripheral and central neuroinflammatory responses that occur during persistent DED using molecular, cellular, behavioral, and electrophysiological approaches.Methods: A mouse model of DED was obtained by unilateral excision of the extraorbital lachrymal gland (ELG) and Harderian gland (HG) of adult female C57BL/6 mice. In vivo tests were conducted at 7, 14, and 21 days (d) after surgery. Tear production was measured by a phenol red test and corneal alterations and inflammation were assessed by fluorescein staining and in vivo confocal microscopy. Corneal nerve morphology was evaluated by nerve staining. Mechanical corneal sensitivity was monitored using von Frey filaments. Multi-unit extracellular recording of ciliary nerve fiber activity was used to monitor spontaneous corneal nerve activity. RT-qPCR and immunostaining were used to determine RNA and protein levels at d21.Results: We observed a marked reduction of tear production and the development of corneal inflammation at d7, d14, and d21 post-surgery in DED animals. Chronic DE induced a reduction of intraepithelial corneal nerve terminals. Behavioral and electrophysiological studies showed that the DED animals developed time-dependent mechanical corneal hypersensitivity accompanied by increased spontaneous ciliary nerve fiber electrical activity. Consistent with these findings, DED mice exhibited central presynaptic plasticity, demonstrated by a higher Piccolo immunoreactivity in the ipsilateral trigeminal brainstem sensory complex (TBSC). At d21 post-surgery, mRNA levels of pro-inflammatory (IL-6 and IL-1β), astrocyte (GFAP), and oxidative (iNOS2 and NOX4) markers increased significantly in the ipsilateral trigeminal ganglion (TG). This correlated with an increase in Iba1, GFAP, and ATF3 immunostaining in the ipsilateral TG of DED animals. Furthermore, pro-inflammatory cytokines (IL-6, TNFα, IL-1β, and CCL2), iNOS2, neuronal (ATF3 and FOS), and microglial (CD68 and Itgam) markers were also upregulated in the TBSC of DED animals at d21, along with increased immunoreactivity against GFAP and Iba1.Conclusions: Overall, these data highlight peripheral sensitization and neuroinflammatory responses that participate in the development and maintenance of dry eye-related pain. This model may be useful to identify new analgesic molecules to alleviate ocular pain

Etch process cleaning to improve wafer to wafer reproducibility

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Topical treatment with a mu opioid receptor agonist alleviates corneal allodynia and corneal nerve sensitization in mice

International audienceCorneal pain is considered to be a core symptom of ocular surface disruption and inflammation. The management of this debilitating condition is still a therapeutic challenge. Recent evidence supports a role of the opioid system in the management of corneal nociception. However, the functional involvement of the mu opioid receptor (MOR) underlying this analgesic effect is not known. We first investigated the expression of the MOR in corneal nerve fibers and trigeminal ganglion (TG) neurons in control mice and a mouse model of corneal inflammatory pain. We then evaluated the anti-nociceptive and electrophysiological effects of DAMGO ([D-Ala2,N-Me-Phe4,Gly5-ol] enkephalin), a MOR-selective ligand. MOR immunoreactivity was detected in corneal nerve fibers and primary afferent neurons of the ophthalmic branch of the TG of naive mice. MOR expression was significantly higher in both structures under conditions of inflammatory corneal pain. Topical ocular administration of DAMGO strongly reduced both the mechanical (von Frey) and chemical (capsaicin) corneal hypersensitivity associated with inflammatory ocular pain. Repeated instillations of DAMGO also markedly reversed the elevated spontaneous activity of the ciliary nerve and responsiveness of corneal polymodal nociceptors that were observed in mice with corneal pain. Finally, these DAMGO-induced behavioral and electrophysiological responses were totally blunted by the topical application of naloxone methiodide, an opioid receptor antagonist. Overall, these results provide evidence that topical pharmacological MOR activation may constitute a therapeutic target for the treatment of corneal pain and improve corneal nerve function to alleviate chronic pain

Expression of MT4-MMP, EGFR, and RB in Triple-Negative Breast Cancer Strongly Sensitizes Tumors to Erlotinib and Palbociclib Combination Therapy.

Abstract Purpose: Here, we investigated the clinical relevance of an unprecedented combination of three biomarkers in triple-negative breast cancer (TNBC), both in human samples and in patient-derived xenografts of TNBC (PDX-TNBC): EGFR, its recently identified partner (MT4-MMP), and retinoblastoma protein (RB).Experimental Design: IHC analyses were conducted on human and PDX-TNBC samples to evaluate the production of the three biomarkers. The sensitivity of cancer cells expressing or not MT4-MMP to anti-EGFR (erlotinib) or anti-CDK4/6 inhibitor (palbociclib) was evaluated in vitro in 2D and 3D proliferation assays and in vivo using xenografts and PDX-TNBC displaying different RB, MT4-MMP, and EGFR status after single (erlotinib or palbociclib) or combined (erlotinib + palbociclib) treatments.Results: EGFR and MT4-MMP were coexpressed in >70% of TNBC samples and PDX-TNBC, among which approximately 60% maintained RB expression. Notably, approximately 50% of all TNBC and PDX-TNBC expressed the three biomarkers. Single erlotinib and palbociclib treatments drastically reduced the in vitro proliferation of cells expressing EGFR and MT4-MMP when compared with control cells. Both TNBC xenografts and PDX expressing MT4-MMP, EGFR, and RB, but not PDX-TNBC with RB loss, were sensitive to erlotinib and palbociclib with an additive effect of combination therapy. Moreover, this combination was efficient in another PDX-TNBC expressing the three biomarkers and resistant to erlotinib alone.Conclusions: We defined a new association of three biomarkers (MT4-MMP/EGFR/RB) expressed together in 50% of TNBC and demonstrated its usefulness to predict the TNBC response to anti-EGFR and anti-CDK4/6 drugs used in single or combined therapy

Analysis of genomic and non-genomic signaling of estrogen receptor in PDX models of breast cancer treated with a combination of the PI3K inhibitor alpelisib (BYL719) and fulvestrant

International audienceAbstract Background Endocrine therapies targeting estrogen signaling have significantly improved breast cancer (BC) patient survival, although 40% of ERα-positive BCs do not respond to those therapies. Aside from genomic signaling, estrogen triggers non-genomic pathways by forming a complex containing methylERα/Src/PI3K, a hallmark of aggressiveness and resistance to tamoxifen. We aimed to confirm the prognostic value of this complex and investigated whether its targeting could improve tumor response in vivo. Methods The interaction of ERα/Src and ERα/PI3K was studied by proximity ligation assay (PLA) in a cohort of 440 BC patients. We then treated patient-derived BC xenografts (PDXs) with fulvestrant or the PI3K inhibitor alpelisib (BYL719) alone or in combination. We analyzed their anti-proliferative effects on 6 ERα+ and 3 ERα− PDX models. Genomic and non-genomic estrogen signaling were assessed by measuring ERα/PI3K interaction by PLA and the expression of estrogen target genes by RT-QPCR, respectively. Results We confirmed that ERα/Src and ERα/PI3K interactions were associated with a trend to poorer survival, the latter displaying the most significant effects. In ERα+ tumors, the combination of BYL719 and fulvestrant was more effective than fulvestrant alone in 3 models, irrespective of PI3K, PTEN status, or ERα/PI3K targeting. Remarkably, resistance to fulvestrant was associated with non-genomic ERα signaling, since genomic degradation of ERα was unaltered in these tumors, whereas the treatment did not diminish the level of ERα/PI3K interaction. Interestingly, in 2 ERα− models, fulvestrant alone impacted tumor growth, and this was associated with a decrease in ERα/PI3K interaction. Conclusions Our results demonstrate that ERα/PI3K may constitute a new prognostic marker, as well as a new target in BC. Indeed, resistance to fulvestrant in ERα+ tumors was associated with a lack of impairment of ERα/PI3K interaction in the cytoplasm. In addition, an efficient targeting of ERα/PI3K in ERα− tumors could constitute a promising therapeutic option