Seismic Response of Double Metro Tunnels Built in Deep Soft-Soil

Rapid development and urbanization have led to the use of underground structures along the world for a wide range of applications including tunnel for subways, railways, highways, material storage, sewage and water transport. The safety of these facilities during seismic events such as recent earthquake in Japan, Taiwan and Turkey becomes more and more problematic due to the complex soil-structure interaction (SSI). The major factor causing severe damages to metro structures is the large deformations imposed by surrounding soils. Thus, for a subway tunnel structure embedded in the soft soil, the study of nonlinear dynamic response of soil-structure interaction during earthquake is important. Nowadays, numerous tools of Finite Element (FE) analysis has been developed to simulate and analyse the tunnel behaviour in order to mitigate its damages during seismic events. In this paper, the displacement response of double metro tunnels under two different earthquake waves is investigate using a Finite Element program (ABAQUS) in 2D plane strain condition, by means of nonlinear dynamic behaviour of soil and tunnels in three different working conditions by varying the embedded depth of the tunnels in soil. The results show that the displacement response of double tunnels built in soft soil is related to the characteristics of the input ground motion, the nature of surrounding soil and the buried depth of the tunnel structures, the peak ground acceleration (PGA) and the SSI effect has an important influence on the displacement response of tunnel structures. Keywords: double metro tunnels, soft soil, nonlinear, dynamic analysis, ground motion, displacement response, SSI, FE, PGA, ABAQUS DOI: 10.7176/ISDE/12-2-04 Publication date: June 30th 202

Monocular Microscope to CT Registration using Pose Estimation of the Incus for Augmented Reality Cochlear Implant Surgery

For those experiencing severe-to-profound sensorineural hearing loss, the cochlear implant (CI) is the preferred treatment. Augmented reality (AR) aided surgery can potentially improve CI procedures and hearing outcomes. Typically, AR solutions for image-guided surgery rely on optical tracking systems to register pre-operative planning information to the display so that hidden anatomy or other important information can be overlayed and co-registered with the view of the surgical scene. In this paper, our goal is to develop a method that permits direct 2D-to-3D registration of the microscope video to the pre-operative Computed Tomography (CT) scan without the need for external tracking equipment. Our proposed solution involves using surface mapping of a portion of the incus in surgical recordings and determining the pose of this structure relative to the surgical microscope by performing pose estimation via the perspective-n-point (PnP) algorithm. This registration can then be applied to pre-operative segmentations of other anatomy-of-interest, as well as the planned electrode insertion trajectory to co-register this information for the AR display. Our results demonstrate the accuracy with an average rotation error of less than 25 degrees and a translation error of less than 2 mm, 3 mm, and 0.55% for the x, y, and z axes, respectively. Our proposed method has the potential to be applicable and generalized to other surgical procedures while only needing a monocular microscope during intra-operation

Contribution à l'ordonnancement d'ateliers avec ressources de transports

Nos travaux concernent l étude d une extension d un problème d ordonnancement bien connu sous l appellation job shop. Nous appelons cette extension le General Flexible Job Shop Scheduling Problem (GFJSSP). Celui-ci se rencontre dans différents types d ateliers ayant comme caractéristique commune d être soumis à des contraintes dues à des ressources de transport. Le GFJSSP se caractérise par l intégration de machines et robots flexibles. Le terme General induit par ailleurs la présence de robots dont la capacité est supposée unitaire dans notre étude, des temps opératoires bornés, et la possibilité de prise en compte d emplacements de stockage spécifiques. Après avoir défini l atelier et le problème correspondant à cette extension, nous avons proposé deux modélisations du GFJSSP ainsi défini : une première modélisation mathématique linéaire, et une modélisation graphique, qui correspond à une généralisation du graphe disjonctif couramment utilisé pour les problèmes de job shop. Nous avons ensuite abordé la résolution suivant deux étapes : tout d abord en nous focalisant sur l aspect séquencement des tâches de traitement et de transport, pour lequel nous avons élaboré deux méthodes heuristiques (de type Tabou et basée sur une procédure de shifting bottleneck améliorée) ; puis en intégrant dans un deuxième temps la problématique de l affectation induite par la flexibilité de certaines ressources. Pour cette dernière étape, nous avons combiné les méthodes précédentes avec un algorithme génétique. L algorithme hybride obtenu nous permet de résoudre des instances de la littérature correspondant à divers cas spécifiques, avec des résultats assez proches des meilleures méthodes dédiées. A termes, il pourrait être intégré dans un système d'aide à la décision général qui s affranchirait de la phase d identification préalable du type de job shop considéré, et serait adapté à la résolution de nombreux cas (avec ou sans problème d'affectation, temps de traitement fixes ou bornés, avec ou sans stockage, etc..).Our work focuses on an extension of the well known job shop scheduling problem. We call this extension the General Flexible Job Shop Scheduling Problem (GFJSSP). It occurs in various kinds of workshops which are particularly constrained by one or several transportation resources (called robots). GFJSSP is characterized by the flexibility of both machines and robots. In the studied problem, the term General involves unitary capacity transportation resources, bounded processing times, and possible input/output buffers for machines. After defining the workshop and the corresponding problem, we proposed two kinds of model for the GFJSSP: a mathematical model, and a graphical one. This last one is a generalization of the disjunctive graph commonly used for job shop problems. We then addressed the resolution in two steps: firstly, by focusing on the sequencing of processing and transportation tasks. For this purpose we have developed two heuristics (Tabu search and an improved shifting bottleneck procedure). Secondly, we have considered the assignment problem involved by the flexibility of some resources. For this last step, we combined the above methods with a genetic algorithm. This hybrid algorithm allowed us to solve various specific cases of instances in the literature, with performance rather close to the best dedicated methods. In the future, it could be integrated within a general decision support system which could emancipate from the initial identification phase of the considered type of job shop, and which would be suitable for solving many cases (with or without assignment problem, fixed or bounded processing times, with or without storage, and so on).BELFORT-UTBM-SEVENANS (900942101) / SudocSudocFranceF

Effect of NETs/COX-2 pathway on immune microenvironment and metastasis in gastric cancer

BackgroundNeutrophil extracellular traps (NETs) are crucial in the progression of several cancers. The formation of NETs is closely related to reactive oxygen species (ROS), and the granule proteins involved in nucleosome depolymerization under the action of ROS together with the loosened DNA compose the basic structure of NETs. This study aims to investigate the specific mechanisms of NETs promoting gastric cancer metastasis in order to perfect the existing immunotherapy strategies.MethodsIn this study, the cells and tumor tissues of gastric cancer were detected by immunological experiments, real-time polymerase chain reaction and cytology experiments. Besides, bioinformatics analysis was used to analyze the correlation between cyclooxygenase-2 (COX-2) and the immune microenvironment of gastric cancer, as well as its effect on immunotherapy.ResultsExamination of clinical specimens showed that NETs were deposited in tumor tissues of patients with gastric cancer and their expression was significantly correlated with tumor staging. Bioinformatics analysis showed that COX-2 was involved in gastric cancer progression and was associated with immune cell infiltration as well as immunotherapy. In vitro experiments, we demonstrated that NETs could activate COX-2 through Toll-like receptor 2 (TLR2) and thus enhance the metastatic ability of gastric cancer cells. In addition, in a liver metastasis model of nude mice we also demonstrated the critical role of NETs and COX-2 in the distant metastasis of gastric cancer.ConclusionNETs can promote gastric cancer metastasis by initiating COX-2 through TLR2, and COX-2 may become a target for gastric cancer immunotherapy

Structural Analysis of Heparin-Derived 3- O -Sulfated Tetrasaccharides: Antithrombin Binding Site Variants

Heparin is a polysaccharide that is widely used as an anticoagulant drug. The mechanism for heparin’s anticoagulant activity is primarily through its interaction with a serine protease inhibitor, antithrombin III (AT), that enhances its ability to inactivate blood coagulation serine proteases, including thrombin (factor IIa) and factor Xa. The AT-binding site in the heparin is one of the most well-studied carbohydrate-protein binding sites and its structure is the basis for the synthesis of the heparin pentasaccharide drug, fondaparinux. Despite our understanding of the structural requirements for the heparin pentasaccharide AT-binding site, there is a lack of data on the natural variability of these binding sites in heparins extracted from animal tissues. The present work provides a detailed study on the structural variants of the tetrasaccharide fragments of this binding site afforded following treatment of a heparin with heparin lyase II. The 5 most commonly observed tetrasaccharide fragments of the AT-binding site are fully characterized, and a method for their quantification in heparin and low-molecular-weight heparin products is described

Deciphering the genome structure and paleohistory of _Theobroma cacao_

We sequenced and assembled the genome of _Theobroma cacao_, an economically important tropical fruit tree crop that is the source of chocolate. The assembly corresponds to 76% of the estimated genome size and contains almost all previously described genes, with 82% of them anchored on the 10 _T. cacao_ chromosomes. Analysis of this sequence information highlighted specific expansion of some gene families during evolution, for example flavonoid-related genes. It also provides a major source of candidate genes for _T. cacao_ disease resistance and quality improvement. Based on the inferred paleohistory of the T. cacao genome, we propose an evolutionary scenario whereby the ten _T. cacao_ chromosomes were shaped from an ancestor through eleven chromosome fusions. The _T. cacao_ genome can be considered as a simple living relic of higher plant evolution

CERT1 mutations perturb human development by disrupting sphingolipid homeostasis

Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are associated with intellectual disability, but the pathogenic mechanism remains obscure. Here, we characterize 31 individuals with de novo missense variants in CERT1. Several variants fall into a previously uncharacterized dimeric helical domain that enables CERT homeostatic inactivation, without which sphingolipid production goes unchecked. The clinical severity reflects the degree to which CERT autoregulation is disrupted, and inhibiting CERT pharmacologically corrects morphological and motor abnormalities in a Drosophila model of the disease, which we call ceramide transporter (CerTra) syndrome. These findings uncover a central role for CERT autoregulation in the control of sphingolipid biosynthetic flux, provide unexpected insight into the structural organization of CERT, and suggest a possible therapeutic approach for patients with CerTra syndrome.This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS), NIH (R01NS109858, to VAG); the Paul A. Marks Scholar Program at the Columbia University Vagelos College of Physicians and Surgeons (to VAG); a TIGER grant from the TAUB Institute at the Columbia Vagelos College of Physicians and Scientists (to VAG); the Swiss National Science Foundation (SNF 31003A-179371, to TH); the European Joint Program on Rare Diseases (EJP RD+SNF 32ER30-187505, to TH); the Swiss Cancer League (KFS-4999-02-2020, to GD); the EPFL institutional fund (to GD); the Kristian Gerhard Jebsen Foundation (to GD); the Swiss National Science Foundation (SNSF) (310030_184926, to GD); the Swiss Foundation for Research on Muscle Disease (FSRMM, to MAL); the Natural Science and Engineering Research Council of Canada (Discovery Grant 2020-04241, to JEB); the Italian Ministry of Health Young Investigator Grant (GR-2011-02347754, to EL); the Fondazione Istituto di Ricerca Pediatrica – Città della Speranza (18-04, to EL); the Wroclaw Medical University (SUB.E160.21.004, to RS); the National Science Centre, Poland (2017/27/B/NZ5/0222, to RS); Telethon Undiagnosed Diseases Program (TUDP) (GSP15001); the Temple Street Foundation/Children’s Health Foundation Ireland (RPAC 19-02, to IK); the Deutsche Forschungsgemeinschaft (DFG) (PO2366/2–1, to BP); the Instituto de Salud Carlos III, Spain (to ELM, EBS, and BMD); the National Natural Science Foundation of China (81871079 and 81730036, to HG and KX); and the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH (R01 DK115574, to SSC).The DEFIDIAG study is funded by grants from the French Ministry of Health in the framewok of the national French initiative for genomic medicine. The funders were not involved in the study design, data acquisition, analysis, or writing of the manuscript. Funding for the DECIPHER project was provided by Wellcome. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between Wellcome and the Department of Health, and the Wellcome Sanger Institute (grant number WT098051). The views expressed in this publication are those of the author(s) and not necessarily those of Wellcome or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12, granted by the Republic of Ireland REC). The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network.S