Characterization of the Transient Behavior of Gated/STI Diodes and their Associated BJT in the CDM Time Domain

International audienceA measurement setup for the characterization of very fast transient responses in the CDM time domain is described in this paper. Experimental results are demonstrated on STI and gated diodes with and without a guard ring implemented respectively in a 65nm and 130nm CMOS technology. The superior behavior of gated diodes during triggering is highlighted

Transit Time Extraction Method for ESD Protection Diodes Model

International audienceNowadays, even though ESD protection diodes are clearly the most used protection devices in I/O cells their behavior is a major problem during a very fast transient. In fact the forward and reverse recovery effects lead respectively to a high over voltage during their triggering and a sustained voltage during the turn-off. Those phenomena depend on the time needed by minority carriers to flow or evacuate the neutral region (the well). This time, which is the transit time of the diode, is also a key parameter of the diode transient behavior. In this presentation a simple extraction method is described in order to extract the transit time of an ESD protection diode. Then, the impact of the junction shape on the transit time will be demonstrated

STK11/LKB1 Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact

International audienceThe STK11/LKB1 gene codes for liver kinase B1 (STK11/LKB1), a highly conserved serine/threonine kinase involved in many energy-related cellular processes. The canonical tumor-suppressive role for STK11/LKB1 involves the activation of AMPK-related kinases, a master regulator of cell survival during stress conditions. In pre-clinical models, inactivation of STK11/LKB1 leads to the progression of lung cancer with the acquisition of metastatic properties. Moreover, preclinical and clinical data have shown that inactivation of STK11/LKB1 is associated with an inert tumor immune microenvironment, with a reduced density of infiltrating cytotoxic CD8+ T lymphocytes, a lower expression of PD-(L)1, and a neutrophil-enriched tumor microenvironment. In this review, we first describe the biological function of STK11/LKB1 and the role of its inactivation in cancer cells. We report descriptive epidemiology, co-occurring genomic alterations, and prognostic impact for lung cancer patients. Finally, we discuss recent data based on pre-clinical models and lung cancer cohorts analyzing the results of STK11/LKB1 alterations on the immune system and response or resistance to immune checkpoint inhibitors

A Physics-Based Compact Model for ESD Protection Diodes under Very Fast Transients

International audienceIn this paper, a complete analysis of the physical phenomena occurring in ESD protection diodes during very fast transients is investigated. Thanks to TCAD simulations and transient characterization, it is highlighted that the mobility degradation effect must be taken into account in addition to the conductivity modulation effect for modeling diode behavior during triggering. Finally, a new physics-based compact model of ESD protection diodes is proposed, demonstrated and validated under very fast transient events in the CDM time domain

Human adipose mesenchymal stem cells as potent anti-fibrosis therapy for systemic sclerosis

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A spliced antigenic peptide comprising a single spliced amino acid is produced in the proteasome by reverse splicing of a longer peptide fragment followed by trimming

Peptide splicing is a novel mechanism of production of peptides relying on the proteasome and involving the linkage of fragments originally distant in the parental protein. Peptides produced by splicing can be presented on class I molecules of the major histocompatibility complex and recognized by cytolytic T lymphocytes. Here, we describe a new antigenic peptide, which is presented by HLA-A3 and comprises two non-contiguous fragments of the melanoma differentiation antigen gp100PMEL17 spliced together in the reverse order to that in which they appear in the parental protein. Contrary to the previously described spliced peptides, which are produced by the association of fragments of 3 to 6 amino acids, the peptide described here results from the ultimate association of an 8-amino acid fragment with a single arginine residue. As described before, peptide splicing takes place in the proteasome by transpeptidation involving an acyl-enzyme intermediate linking one of the peptide fragment to a catalytic subunit of the proteasome. Interestingly, we observe that the peptide causing the nucleophilic attack on the acyl-enzyme intermediate must be at least three-amino acid long in order to give rise to a spliced peptide. The spliced peptide produced from this reaction therefore bears an extended C-terminus that needs to be further trimmed in order to produce the final antigenic peptide. We show that the proteasome is able to perform the final trimming step required to produce the antigenic peptide described here

Serum-Mediated Oxidative Stress from Systemic Sclerosis Patients Affects Mesenchymal Stem Cell Function

The Supplementary Material for this article can be found online at http://journal.frontiersin.org/article/10.3389/fimmu.2017.00988/full#supplementary-material.International audienceObjectives: Properties of mesenchymal stromal/stem cells (MSCs) from systemic sclerosis (SSc) patients have been reported to be altered. MSC-based therapy may therefore rely on the use of allogeneic MSCs from healthy subjects. Here, we investigated whether heterologous MSCs could exhibit altered properties following exposure to oxidative environment of SSc sera.Methods: Human bone marrow-derived MSCs were cultured in the presence of various sera: control human serum AB (SAB), SAB with HOCl-induced AOPPs at 400 or 1,000 µmol/L (SAB400 or SAB1000, respectively), or H2O2-induced AOPPs or SSc patient serum (PS). Proliferation, apoptosis, and senescence rates of MSCs were evaluated after 3, 6, and 10 days in culture. Reactive oxygen species and nitric oxide production were quantified at 24 h. Trilineage potential of differentiation was tested after 21 days in specific culture conditions and immunosuppressive function measured in a T lymphocyte proliferative assay.Results: In the presence of oxidative environment of PS, MSCs retained their proliferative potential and survived for at least the first 3 days of exposure, while the number of senescent MSCs increased at day 6 and apoptosis rate at day 10. Exposure to PS enhanced the antioxidant capacity of MSCs, notably the expression of SOD2 antioxidant gene. By contrast, the osteoblastic/adipogenic potential of MSCs was increased, whereas their immunosuppressive function was slightly reduced.Discussion: Although some functional properties of MSCs were affected upon culture with PS, evidence from preclinical studies and the present one suggested that MSCs can adapt to the oxidative environment and exert their therapeutic effect

Thin-body ESD protections in 28nm UTBB-FDSOI: From static to transient behavior

International audienceInnovative Ultra-Thin Body and Buried Oxide FDSOI protections (BBC-T and Z2-FET) are characterized and analyzed in order to assess the CDM time domain behavior. In addition to static (leakage and triggering) control, it is found that front and back gate coupling is a very efficient way to improve the transient responses of the proposed devices

Efficacy of composite versus ceramic inlays and onlays: study protocol for the CECOIA randomized controlled trial.

International audienceBACKGROUND: Dental caries is a common disease and affects many adults worldwide. Inlay or onlay restoration is widely used to treat the resulting tooth substance loss. Two esthetic materials can be used to manufacture an inlay/onlay restoration of the tooth: ceramic or composite. Here, we present the protocol of a multicenter randomized controlled trial (RCT) comparing the clinical efficacy of both materials for tooth restoration. Other objectives are analysis of overall quality, wear, restoration survival and prognosis. METHODS: The CEramic and COmposite Inlays Assessment (CECOIA) trial is an open-label, parallel-group, multicenter RCT involving two hospitals and five private practices. In all, 400 patients will be included. Inclusion criteria are adults who need an inlay/onlay restoration for one tooth (that can be isolated with use of a dental dam and has at least one intact cusp), can tolerate restorative procedures and do not have severe bruxism, periodontal or carious disease or poor oral hygiene. The decayed tissue will be evicted, the cavity will be prepared for receiving an inlay/onlay and the patient will be randomized by use of a centralized web-based interface to receive: 1) a ceramic or 2) composite inlay or onlay. Treatment allocation will be balanced (1:1). The inlay/onlay will be adhesively luted. Follow-up will be for 2 years and may be extended; two independent examiners will perform the evaluations. The primary outcome measure will be the score obtained with use of the consensus instrument of the Federation Dentaire Internationale (FDI) World Dental Federation. Secondary outcomes include this instrument's items, inlay/onlay wear, overall quality and survival of the inlay/onlay. Data will be analyzed by a statistician blinded to treatments and an adjusted ordinal logistic regression model will be used to compare the efficacy of both materials. DISCUSSION: For clinicians, the CECOIA trial results may help with evidence-based recommendations concerning the choice of materials for inlay/onlay restoration. For patients, the results may lead to improvement in long-term restoration. For researchers, the results may provide ideas for further research concerning inlay/onlay materials and prognosis.This trial is funded by a grant from the French Ministry of Health.Trial registration: ClinicalTrials.gov Identifier: NCT01724827