Analyse et caractérisation des couplages substrat et de la connectique dans les circuits 3D : Vers des modèles compacts

The 3D integration is the most promising technological solution to track the level of integration dictated by Moore's Law (see more than Moore, Moore versus more). It leads to important research for a dozen years. It can superimpose different circuits and components in one box. Its main advantage is to allow a combination of heterogeneous and highly specialized technologies for the establishment of a complete system, while maintaining a high level of performance with very short connections between the different circuits. The objective of this work is to provide consistent modeling via crossing, and / or contacts in the substrate, with various degrees of finesse / precision to allow the high-level designer to manage and especially to optimize the partitioning between the different strata. This modelization involves the development of multiple views at different levels of abstraction: the physical model to "high level" model. This would allow to address various issues faced in the design process: - The physical model using an electromagnetic simulation based on 2D or 3D ( finite element solver ) is used to optimize the via (materials, dimensions etc..) It determines the electrical performance of the via, including high frequency. Electromagnetic simulations also quantify the coupling between adjacent via. - The analytical compact of via their coupling model, based on a description of transmission line or Green cores is used for the simulations at the block level and Spice type simulations. Analytical models are often validated against measurements and / or physical models.L’intégration 3D est la solution technologique la plus prometteuse pour suivre le niveau d’intégration dictée par la loi de Moore (cf. more than Moore, versus more Moore). Elle entraine des travaux de recherche importants depuis une douzaine d’années. Elle permet de superposer différents circuits et composants dans un seul boitier. Son principal avantage est de permettre une association de technologies hétérogènes et très spécialisées pour la constitution d’un système complet, tout en préservant un très haut niveau de performance grâce à des connexions très courtes entre ces différents circuits. L’objectif de ce travail est de fournir des modélisations cohérentes de via traversant, ou/et de contacts dans le substrat, avec plusieurs degrés de finesse/précision, pour permettre au concepteur de haut niveau de gérer et surtout d’optimiser le partitionnement entre les différentes strates. Cette modélisation passe par le développement de plusieurs vues à différents niveaux d’abstraction: du modèle physique au modèle « haut niveau ». Elle devait permettre de répondre à différentes questions rencontrées dans le processus de conception :- le modèle physique de via basé sur une simulation électromagnétique 2D ou 3D (solveur « éléments finis ») est utilisé pour optimiser l’architecture du via (matériaux, dimensions etc.) Il permet de déterminer les performances électriques des via, notamment en haute fréquence. Les simulations électromagnétiques permettent également de quantifier le couplage entre via adjacents. - le modèle compact analytique de via et de leur couplage, basé sur une description de type ligne de transmission ou noyaux de Green, est utilisé pour les simulations au niveau bloc, ainsi que des simulations de type Spice. Les modèles analytiques sont souvent validés par rapport à des mesures et/ou des modèles physiques

Thyrotropin and CD40L Stimulate Interleukin-12 Expression in Fibrocytes: Implications for Pathogenesis of Thyroid-Associated Ophthalmopathy

Background: Increased numbers of bone marrow?derived progenitor cells, known as fibrocytes, populate the peripheral circulation, orbit, and thyroid of patients with Graves' disease (GD). These cells have been implicated in the development of thyroid-associated ophthalmopathy. They can differentiate into myofibroblasts or adipocytes, produce inflammatory cytokines, and remodel tissue. This study sought to determine whether thyrotropin (TSH) and CD40 ligand (CD40L), implicated in the pathogenesis of GD, induce interleukin-12 (IL-12) in human fibrocytes. Materials and Methods: IL-12 protein concentrations and mRNA levels were measured by Luminex and real-time polymerase chain reaction, respectively. Flow cytometry assessed intracellular IL-12 concentrations. Vector containing IL-12p40 promoter was transfected into cultured fibrocytes, and promoter activity was monitored using luciferase assay. Results: TSH and CD40L stimulated intracellular IL-12 protein accumulation in peripheral blood fibrocytes. Inhibiting Akt and nuclear factor-?B (NF-?B) activity diminished IL-12 expression in fibrocytes, while TSH did not induce promoter activity. TSH-mediated IL-12 production required de novo synthesized proteins and augmented IL-12 mRNA stability. IL-12 production mediated by CD40L required tumor necrosis factor receptor?associated factor 6. Conclusion: TSH and CD40L induce IL-12 expression in fibrocytes, and Akt and NF-?B mediate this activity. Given the importance of IL-12 in immune function, its production by fibrocytes may promote an inflammatory immune response and tissue remodeling in thyroid-associated ophthalmopathy.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140273/1/thy.2016.0243.pd

Bacteria derived extracellular vesicles in the pathogenesis and treatment of gastrointestinal tumours

Extracellular vesicles are fundamentally significant in the communication between cells. Outer Membrane Vesicles(OMVs) are a special kind of EVs produced by Gram-negative bacteria, which are minute exosome-like particles budding from the outer membrane, which have been found to play essential roles in diverse bacterial life events, including regulation of microbial interactions, pathogenesis promotion, stress responses and biofilm formation. Recently, and more researches have explored the substantial potentials of EVs as natural functional nanoparticles in the bioengineering applications in infectious diseases, cardiovascular diseases, autoimmune diseases and neurological diseases, such as antibacterial therapy, cancer drugs and immunoadjuvants, with several candidates in clinical trials showing promising efficacy. However, due to the poor understanding of sources, membrane structures and biogenesis mechanisms of EVs, progress in clinical applications still remains timid. In this review, we summarize the latest findings of EVs, especially in gastrointestinal tract tumours, to provide a comprehensive introduction of EVs in tumorigenesis and therapeutics

Characterization of a cuproptosis-related signature to evaluate immune features and predict prognosis in colorectal cancer

PurposeCuproptosis is a newly discovered type of cell death. Little is known about the roles that cuproptosis related genes (CRGs) play in colorectal cancer (CRC). The aim of this study is to evaluate the prognostic value of CRGs and their relationship with tumor immune microenvironment.MethodsTCGA-COAD dataset was used as the training cohort. Pearson correlation was employed to identify CRGs and paired tumor-normal samples were used to identify those CRGs with differential expression pattern. A risk score signature was constructed using LASSO regression and multivariate Cox stepwise regression methods. Two GEO datasets were used as validation cohorts for confirming predictive power and clinical significance of this model. Expression patterns of seven CRGs were evaluated in COAD tissues. In vitro experiments were conducted to validate the expression of the CRGs during cuproptosis.ResultsA total of 771 differentially expressed CRGs were identified in the training cohort. A predictive model termed riskScore was constructed consisting of 7 CRGs and two clinical parameters (age and stage). Survival analysis suggested that patients with higher riskScore showed shorter OS than those with lower (P<0.0001). ROC analysis revealed that AUC values of cases in the training cohort for 1-, 2-, and 3-year survival were 0.82, 0.80, 0.86 respectively, indicating its good predictive efficacy. Correlations with clinical features showed that higher riskScore was significantly associated with advanced TNM stages, which were further confirmed in two validation cohorts. Single sample gene set enrichment analysis (ssGSEA) showed that high-risk group presented with an immune-cold phenotype. Consistently, ESTIMATE algorithm analysis showed lower immune scores in riskScore-high group. Expressions of key molecules in riskScore model are strongly associated with TME infiltrating cells and immune checkpoint molecules. Patients with a lower riskScore exhibited a higher complete remission rate in CRCs. Finally, seven CRGs involved in riskScore were significantly altered between cancerous and paracancerous normal tissues. Elesclomol, a potent copper ionophore, significantly altered expressions of seven CRGs in CRCs, indicating their relationship with cuproptosis.ConclusionsThe cuproptosis-related gene signature could serve as a potential prognostic predictor for colorectal cancer patients and may offer novel insights into clinical cancer therapeutics

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Analysis and characterization of substrate and connection couplings in 3D circuits : Towards compact models

L’intégration 3D est la solution technologique la plus prometteuse pour suivre le niveau d’intégration dictée par la loi de Moore (cf. more than Moore, versus more Moore). Elle entraine des travaux de recherche importants depuis une douzaine d’années. Elle permet de superposer différents circuits et composants dans un seul boitier. Son principal avantage est de permettre une association de technologies hétérogènes et très spécialisées pour la constitution d’un système complet, tout en préservant un très haut niveau de performance grâce à des connexions très courtes entre ces différents circuits. L’objectif de ce travail est de fournir des modélisations cohérentes de via traversant, ou/et de contacts dans le substrat, avec plusieurs degrés de finesse/précision, pour permettre au concepteur de haut niveau de gérer et surtout d’optimiser le partitionnement entre les différentes strates. Cette modélisation passe par le développement de plusieurs vues à différents niveaux d’abstraction: du modèle physique au modèle « haut niveau ». Elle devait permettre de répondre à différentes questions rencontrées dans le processus de conception :- le modèle physique de via basé sur une simulation électromagnétique 2D ou 3D (solveur « éléments finis ») est utilisé pour optimiser l’architecture du via (matériaux, dimensions etc.) Il permet de déterminer les performances électriques des via, notamment en haute fréquence. Les simulations électromagnétiques permettent également de quantifier le couplage entre via adjacents. - le modèle compact analytique de via et de leur couplage, basé sur une description de type ligne de transmission ou noyaux de Green, est utilisé pour les simulations au niveau bloc, ainsi que des simulations de type Spice. Les modèles analytiques sont souvent validés par rapport à des mesures et/ou des modèles physiques.The 3D integration is the most promising technological solution to track the level of integration dictated by Moore's Law (see more than Moore, Moore versus more). It leads to important research for a dozen years. It can superimpose different circuits and components in one box. Its main advantage is to allow a combination of heterogeneous and highly specialized technologies for the establishment of a complete system, while maintaining a high level of performance with very short connections between the different circuits. The objective of this work is to provide consistent modeling via crossing, and / or contacts in the substrate, with various degrees of finesse / precision to allow the high-level designer to manage and especially to optimize the partitioning between the different strata. This modelization involves the development of multiple views at different levels of abstraction: the physical model to "high level" model. This would allow to address various issues faced in the design process: - The physical model using an electromagnetic simulation based on 2D or 3D ( finite element solver ) is used to optimize the via (materials, dimensions etc..) It determines the electrical performance of the via, including high frequency. Electromagnetic simulations also quantify the coupling between adjacent via. - The analytical compact of via their coupling model, based on a description of transmission line or Green cores is used for the simulations at the block level and Spice type simulations. Analytical models are often validated against measurements and / or physical models

Key variables identification and proactive assessment of real-time traffic flow accident risk on urban expressway

Based on accident data and detector data collected on two expressways in Shanghai, important variables for model construction were selected from the data of traffic flow within 5~10 min before the accident with random forest model. Then, the Bayesian network (BN) model based on the Gaussian mixture model and expected maximum algorithm was established for the analysis of real-time traffic flow state and accident risk. Meanwhile, the transferability of BN model was also assessed. The results show that BN model built with selected important variables is better than that with direct detection data, with the accident prediction accuracy rate of 82.78%. The results of the transferability show that the improved BN model is still better than the traditional model, though the accident prediction accuracy of BN model decreases

Clinical Analysis of Castleman’s Disease of the Lacrimal Gland

Objective. To explore the clinical manifestations, imaging characteristics, and pathological characteristics of Castleman’s disease of the lacrimal gland, enhance the knowledge of the disease, and improve the level of its diagnosis and treatment. Methods. In the retrospective study, the data of 5 patients diagnosed with Castleman’s disease of the lacrimal gland in Tianjin Medical University Eye Hospital from 2014 to 2018 were analyzed, and the relevant literature was reviewed. Results. All the 5 patients were confirmed by pathological examination. Clinical manifestations were characterized by mass occupying lesions in the lacrimal gland area, without obvious pain, accompanied by eyelid swelling and ptosis, as well as space-occupying symptoms. Imaging examination showed that there was a soft tissue mass in the enlarged lacrimal gland area, and the mass was rich in blood flows while showing no obvious specificity, which could invade the surrounding muscles. All patients underwent surgical resection. Pathological results showed that 1 case was of the hyaline-vascular type, 3 cases were of the plasma cell type, and 1 case showed malignant transformation to plasma cell tumor. Conclusion. Castleman’s disease of the lacrimal gland is a rare orbital lymphoproliferative disease lacking specificity in clinical manifestations and imaging examination. As there are difficulties in differentiating the disease from orbital inflammatory pseudotumor and orbital lymphoma, its diagnosis still depends on pathological examination. The disease is mainly treated with surgical resection, and the pathological type is determined postoperatively

Denoising Seismic Signal via Resampling Local Applicability Functions

We propose a novel seismic signal processing approach to efficiently and effectively attenuate seismic random noises. The proposed approach is a generalized seismic noise attenuation solution that can be applied to typical denoising operators. Our work has two main contributions. First, conventional filtering operators \u27regularize\u27 the denoised results through the operator design. However, as seismic data have strong nonstationarity, it is inevitable to remove certain signal components. The resampling mechanism alleviates the signal loss. Second, the resampling operation does not require a lot of parameter tuning, which improves the denoising efficiency. Using the proposed approach, compared with existing denoising operators, the intrinsic seismic signal components are better recovered since random noise has been suppressed. Synthetic example and field data applications quantitatively and qualitatively demonstrate excellent performances of the proposed approach