Méthode d'extraction fréquentielle de l'inductance de boucle pour la modélisation large bande des interconnexions de circuits numériques

4 pagesNational audienceDans le contexte des interconnexions de circuits numériques avancés, la modélisation de type RC actuelle n'est plus suffisamment précise face à l'augmentation des fréquences d'horloge, notamment en ce qui concerne les niveaux globaux. Les effets inductifs sont donc à prendre en compte et le concept de l'inductance de boucle semble être une solution intéressante pour ne pas complexifier de façon excessive les modèles. Nous décrivons dans ce papier une méthode d'extraction fréquentielle de l'inductance de boucle permettant de prendre en compte les effets de proximité dus à l'augmentation de la fréquence. Nous proposons, de plus, un modèle compact que nous validons par une analyse temporelle

Simulation, Measurement and Modeling of Orthogonal On-Chip Interconnects

International audienceThis paper explains the appearance of resonant frequency due to underlayer orthogonal metal grid in microstrip line structures. In the context of global interconnects, this resonant frequency may lead to noise and has to be estimate. A model, which allows one to approximate this resonant frequency, is validated by measurement

Frequency domain analysis of transmission zeroes on high-speed interconnects in the presence of an orthogonal metal grid underlayer

4 p.International audienceThis paper addresses high-speed interconnects in high density systems (Systems on Chip (SoC) in package (SiP) ...). These lines (of miscostrip or coplanar type) often have an underlayer of orthogonal metal grids which can affect transmission characteristics. We subsequently present a characterization through S-parameter measurements and electromagnetic simulations. Two kinds of grid are studied; grounded (CC) and floating grid (CO). In both cases, transmission zeroes appear. The position of these transmission zeroes in the frequency domain depends mainly on the grid length and, of course, on the grid charge CC or CO. In order to easily estimate it, we propose a simple equivalent circuit model which we validate by measurements and electromagnetic simulations. We then determine a set of expressions based on this model enabling us to analytically pinpoint the location transmission zero in the frequency domain, valid for any underlayer of orthogonal metal lines or grids

Nouvelles interconnexions globales à haut débit pour la réalisation de microsystèmes communicants de type SIP.

4 pagesNational audienceLes microsystèmes intégrés sur puces (SoC) ou en boîtier (SiP) sont actuellement en plein essor et nécessitent le développement de nouvelles structures d'interconnexions reliant les différents blocs fonctionnels entre eux. Nous proposons dans ce papier l'étude du concept d'interconnexion RF par couplage capacitif qui est une solution intéressante pour remplacer les interconnexions classiques. Dans un premier temps nous décrivons le principe de cette technique et montrons à l'aide de simulations circuits de type ADS, la faisabilité de ce concept. Nous présentons ensuite la caractérisation d'un canal de type microruban, réalisée sous HFSS ainsi que son comportement dans le domaine temporel. I. Introductio

Interrogation of Milk-Driven Changes to the Proteome of Intestinal Epithelial Cells by Integrated Proteomics and Glycomics

Bovine colostrum is a rich source of bioactive components which are important in the development of the intestine, in stimulating gut structure and function and in preparing the gut surface for subsequent colonization of microbes. What is not clear, however, is how colostrum may affect the repertoire of receptors and membrane proteins of the intestinal surface and the post-translational modifications associated with them. In the present work, we aimed to characterize the surface receptor and glycan profile of human HT-29 intestinal cells after exposure to a bovine colostrum fraction (BCF) by means of proteomic and glycomic analyses. Integration of label-free quantitative proteomic analysis and lectin array profiles confirmed that BCF exposure results in changes in the levels of glycoproteins present at the cell surface and also changes to their glycosylation pattern. This study contributes to our understanding of how milk components may regulate intestinal cells and prime them for bacterial interaction

Darolutamide and health-related quality of life in patients with non-metastatic castration-resistant prostate cancer : An analysis of the phase III ARAMIS trial

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.BACKGROUND: In the ARAMIS trial, darolutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT significantly improved metastasis-free survival (MFS), overall survival (OS) and time to pain progression in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Herein, we present analyses of patient-reported health-related quality of life (HRQoL) outcomes. PATIENTS AND METHODS: This double-blind, placebo-controlled, phase III trial randomised patients with nmCRPC and prostate-specific antigen doubling time ≤10 months to darolutamide 600 mg (n = 955) twice daily or matched placebo (n = 554) while continuing ADT. The primary end-point was MFS; the secondary end-points included OS and time to pain progression. In this analysis, HRQoL was assessed by the time to deterioration using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) prostate cancer subscale (PCS) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer Module (EORTC QLQ-PR25) subscales. RESULTS: Darolutamide significantly prolonged time to deterioration of FACT-P PCS versus placebo (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.70-0.91; P = 0.0005) at the primary analysis (cut-off date: 3rd September 2018). Time to deterioration of EORTC QLQ-PR25 outcomes showed statistically significant delays with darolutamide versus placebo for urinary (HR 0.64, 95% CI 0.54-0.76; P < 0.0001) and bowel (HR 0.78, 95% CI 0.66-0.92; P = 0.0027) symptoms. Time to worsening of hormonal treatment-related symptoms was similar between the two groups. CONCLUSION: In patients with nmCRPC who are generally asymptomatic, darolutamide maintained HRQoL by significantly delaying time to deterioration of prostate cancer-specific quality of life and disease-related symptoms versus placebo.publishersversionPeer reviewe

A new multiplex SARS-CoV-2 antigen microarray showed correlation of IgG, IgA, and IgM antibodies from patients with COVID-19 disease severity and maintenance of relative IgA and IgM antigen binding over time

Zoonotic spillover of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to humans in December 2019 caused the coronavirus disease 2019 (COVID-19) pandemic. Serological monitoring is critical for detailed understanding of individual immune responses to infection and protection to guide clinical therapeutic and vaccine strategies. We developed a high throughput multiplexed SARS-CoV-2 antigen microarray incorporating spike (S) and nucleocapsid protein (NP) and fragments expressed in various hosts which allowed simultaneous assessment of serum IgG, IgA, and IgM responses. Antigen glycosylation influenced antibody binding, with S glycosylation generally increasing and NP glycosylation decreasing binding. Purified antibody isotypes demonstrated a binding pattern and intensity different from the same isotype in whole serum, probably due to competition from the other isotypes present. Using purified antibody isotypes from naïve Irish COVID-19 patients, we correlated antibody isotype binding to different panels of antigens with disease severity, with binding to the S region S1 expressed in insect cells (S1 Sf21) significant for IgG, IgA, and IgM. Assessing longitudinal response for constant concentrations of purified antibody isotypes for a patient subset demonstrated that the relative proportion of antigen-specific IgGs decreased over time for severe disease, but the relative proportion of antigen-specific IgA binding remained at the same magnitude at 5 and 9 months post-first symptom onset. Further, the relative proportion of IgM binding decreased for S antigens but remained the same for NP antigens. This may support antigen-specific serum IgA and IgM playing a role in maintaining longer-term protection, important for developing and assessing vaccine strategies. Overall, these data demonstrate the multiplexed platform as a sensitive and useful platform for expanded humoral immunity studies, allowing detailed elucidation of antibody isotypes response against multiple antigens. This approach will be useful for monoclonal antibody therapeutic studies and screening of donor polyclonal antibodies for patient infusions

Arrangement of Kv1 α subunits dictates sensitivity to tetraethylammonium

Shaker-related Kv1 channels contain four channel-forming α subunits. Subfamily member Kv1.1 often occurs oligomerized with Kv1.2 α subunits in synaptic membranes, and so information was sought on the influence of their positions within tetramers on the channels’ properties. Kv1.1 and 1.2 α genes were tandem linked in various arrangements, followed by expression as single-chain proteins in mammalian cells. As some concatenations reported previously seemed not to reliably position Kv1 subunits in their assemblies, the identity of expressed channels was methodically evaluated. Surface protein, isolated by biotinylation of intact transiently transfected HEK-293 cells, gave Kv1.1/1.2 reactivity on immunoblots with electrophoretic mobilities corresponding to full-length concatenated tetramers. There was no evidence of protein degradation, indicating that concatemers were delivered intact to the plasmalemma. Constructs with like genes adjacent (Kv1.1-1.1-1.2-1.2 or Kv1.2-1.2-1.1-1.1) yielded delayed-rectifying, voltage-dependent K+ currents with activation parameters and inactivation kinetics slightly different from the diagonally positioned genes (Kv1.1-1.2-1.1-1.2 or 1.2–1.1-1.2-1.1). Pore-blocking petidergic toxins, α dendrotoxin, agitoxin-1, tityustoxin-Kα, and kaliotoxin, were unable to distinguish between the adjacent and diagonal concatamers. Unprecedentedly, external application of the pore-blocker tetraethylammonium (TEA) differentially inhibited the adjacent versus diagonal subunit arrangements, with diagonal constructs having enhanced susceptibility. Concatenation did not directly alter the sensitivities of homomeric Kv1.1 or 1.2 channels to TEA or the toxins. TEA inhibition of currents generated by channels made up from dimers (Kv1.1-1.2 and/or Kv1.2-1.1) was similar to the adjacently arranged constructs. These collective findings indicate that assembly of α subunits can be directed by this optimized concatenation, and that subunit arrangement in heteromeric Kv channels affects TEA affinity

Efficacy and Safety of Darolutamide in Patients with Nonmetastatic Castration-resistant Prostate Cancer Stratified by Prostate-specific Antigen Doubling Time : Planned Subgroup Analysis of the Phase 3 ARAMIS Trial

Background: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have a high risk of progression to metastatic disease, particularly if their prostate-specific antigen doubling time (PSADT) is ≤6 mo. However, patients remain at a high risk with a PSADT of >6 mo. Objective: To evaluate the efficacy and safety of darolutamide versus placebo in patients stratified by PSADT >6 or ≤6 mo. Design, setting, and participants: A planned subgroup analysis of a global multicenter, double-blind, randomized, phase 3 trial in men with nmCRPC and PSADT ≤10 mo was conducted. Intervention: Patients were randomized 2:1 to oral darolutamide 600 mg twice daily or placebo, while continuing androgen-deprivation therapy. Outcome measurements and statistical analysis: The primary endpoint was metastasis-free survival (MFS). Secondary endpoints were overall survival (OS) and times to pain progression, first cytotoxic chemotherapy, and symptomatic skeletal events. Quality of life (QoL) was measured using validated prostate-relevant tools. Safety was recorded throughout the study. Results and limitations: Of 1509 patients enrolled, 469 had PSADT >6 mo (darolutamide n = 286; placebo n = 183) and 1040 had PSADT ≤6 mo (darolutamide n = 669; placebo n = 371). Baseline characteristics were balanced between subgroups. Darolutamide significantly prolonged MFS versus placebo in both subgroups (unstratified hazard ratio [95% confidence interval]: PSADT >6 mo, 0.38 [0.26–0.55]; PSADT ≤6 mo, 0.41 [0.33–0.52]). OS and other efficacy and QoL endpoints favored darolutamide with significant improvement over placebo in both subgroups. The incidence of adverse events, including events commonly associated with androgen receptor inhibitors (fractures, falls, hypertension, and mental impairment), and discontinuations due to adverse events were low and similar to placebo. Limitations include small subgroup populations. Conclusions: In patients with nmCRPC and PSADT >6 mo (maximum 10 mo), darolutamide provided a favorable benefit/risk ratio, characterized by significant improvements in MFS, OS, and other clinically relevant endpoints; maintenance of QoL; and favorable tolerability. Patient summary: In patients with prostate cancer that has stopped responding to standard hormonal therapy (indicated by an increase in prostate-specific antigen [PSA] levels), there is a risk that the cancer will spread to other parts of the body. This risk is highest when the time it takes for the PSA level to double (ie, “PSA doubling time” [PSADT]) is less than 6 mo. However, there is still a risk that the cancer will spread even if the PSADT is longer than 6 mo. In a group of patients whose PSADT was more than 6 mo but no more than 10 mo, treatment with darolutamide slowed the cancer spread and allowed them to live longer than patients who received placebo (inactive drug). Darolutamide treatment did not cause many side effects and helped maintain patients’ quality of life without disruptions.publishedVersionPeer reviewe

Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study

AIMS/HYPOTHESIS: This is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19). METHODS: The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days. RESULTS: We included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th-75th percentile) 28.4 (25.0-32.4) kg/m(2). Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5-14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors. CONCLUSIONS/INTERPRETATION: In patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04324736