942 research outputs found

    FEM Analysis of Spring-backs in Age Forming of Aluminum Alloy Plates

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    AbstractThe age forming technology, characterized by huge spring-backs, has been developed to manufacture large integral wing-skin panel parts, which necessitates devising a method of predicting spring-backs. A 7B04-T7451 aluminum alloy creep test in tension is accomplished at 155 °C, and the creep curves are obtained. The material constants of the mechanism-based creep constitutive equations are determined through experiments. The age forming process and the spring-backs of 7B04 aluminum alloy plates are analyzed using the commercial finite element software ABAQUS. The effects of plate thickness and forming time on spring-backs are researched. The spring-backs decrease with the increase of plate thickness and forming time. The test results verify the reliability of the finite element method (FEM) analysis

    Mode-Multiplexed Transmission over Conventional Graded-Index Multimode Fibers

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    We present experimental results for combined mode-multiplexed and wavelength multiplexed transmission over conventional graded-index multimode fibers. We use mode-selective photonic lanterns as mode couplers to precisely excite a subset of the modes of the multimode fiber and additionally to compensate for the differential group delay between the excited modes. Spatial mode filters are added to suppress undesired higher order modes. We transmit 30-Gbaud QPSK signals over 60 WDM channels, 3 spatial modes, and 2 polarizations, reaching a distance of 310 km based on a 44.3 km long span. We also report about transmission experiments over 6 spatial modes for a 17-km single-span experiment. The results indicate that multimode fibers support scalable mode-division multiplexing approaches, where modes can be added over time if desired. Also the results indicate that mode-multiplexed transmission distance over 300 km are possible in conventional multimode fibers

    Hierarchical multi-class segmentation of glioma images using networks with multi-level activation function

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    For many segmentation tasks, especially for the biomedical image, the topological prior is vital information which is useful to exploit. The containment/nesting is a typical inter-class geometric relationship. In the MICCAI Brain tumor segmentation challenge, with its three hierarchically nested classes 'whole tumor', 'tumor core', 'active tumor', the nested classes relationship is introduced into the 3D-residual-Unet architecture. The network comprises a context aggregation pathway and a localization pathway, which encodes increasingly abstract representation of the input as going deeper into the network, and then recombines these representations with shallower features to precisely localize the interest domain via a localization path. The nested-class-prior is combined by proposing the multi-class activation function and its corresponding loss function. The model is trained on the training dataset of Brats2018, and 20% of the dataset is regarded as the validation dataset to determine parameters. When the parameters are fixed, we retrain the model on the whole training dataset. The performance achieved on the validation leaderboard is 86%, 77% and 72% Dice scores for the whole tumor, enhancing tumor and tumor core classes without relying on ensembles or complicated post-processing steps. Based on the same start-of-the-art network architecture, the accuracy of nested-class (enhancing tumor) is reasonably improved from 69% to 72% compared with the traditional Softmax-based method which blind to topological prior.Comment: 12pages first versio

    Two females with mutations in USP9X highlight the variable expressivity of the intellectual disability syndrome

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    The genetic causes of intellectual disability (ID) are heterogeneous and include both chromosomal and monogenic etiologies. The X-chromosome is known to contain many ID-related genes and males show a marked predominance for intellectual disability. Here we report two females with syndromic intellectual disability. The first individual was relatively mild in her presentation with mild-moderate intellectual disability, hydronephrosis and altered pigmentation along the lines of Blaschko without additional congenital anomalies. A second female presented shortly after birth with dysmorphic facial features, post-axial polydactyly and, on follow-up assessment, demonstrated moderate intellectual disability. Chromosomal studies for Individual 1 identified an X-chromosome deletion due to a de novo pericentric inversion; the inversion breakpoint was associated with deletion of the 5′UTR of the USP9X, a gene which has been implicated in a syndromic intellectual disability affecting females. The second individual had a de novo frameshift mutation detected by whole-exome sequencing that was predicted to be deleterious, NM_001039590.2 (USP9X): c.4104_4105del (p.(Arg1368Serfs*2)). Haploinsufficiency of USP9X in females has been associated with ID and congenital malformations that include heart defects, scoliosis, dental abnormalities, anal atresia, polydactyly, Dandy Walker malformation and hypoplastic corpus callosum. The extent of the congenital malformations observed in Individual 1 was less striking than Individual 2 and other individuals previously reported in the literature, and suggests that USP9X mutations in females can have a wider spectrum of presentation than previously appreciated

    Measurements of Correlated Insulator Gaps in a Transition Metal Dichalcogenide Moir\'e Superlattice

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    Moir\'e superlattices of transitional metal dichalcogenides exhibit strong electron-electron interaction that has led to experimental observations of Mott insulators and generalized Wigner crystals. In this letter, we report direct measurements of the thermodynamic gaps of these correlated insulating states in a dual-gate WS2/WSe2 moir\'e bilayer. We employ the microwave impedance microscopy to probe the electronic features in both the graphene top gate and the moir\'e bilayer, from which we extract the doping dependence of the chemical potential of the moir\'e bilayer and the energy gaps for various correlated insulating states utilizing the Landau quantization of graphene. These gaps are relatively insensitive to the application of an external electric field to the WS2/WSe2 moir\'e bilayer

    β1 integrin mediates an alternative survival pathway in breast cancer cells resistant to lapatinib

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    Abstract Introduction The overexpression of human epidermal growth factor receptor (HER)-2 in 20% of human breast cancers and its association with aggressive growth has led to widespread use of HER2-targeted therapies, such as trastuzumab (T) and lapatinib (L). Despite the success of these drugs, their efficacy is limited in patients whose tumors demonstrate de novo or acquired resistance to treatment. The β1 integrin resides on the membrane of the breast cancer cell, activating several elements of breast tumor progression including proliferation and survival. Methods We developed a panel of HER2-overexpressing cell lines resistant to L, T, and the potent LT combination through long-term exposure and validated these models in 3D culture. Parental and L/T/LT-resistant cells were subject to HER2 and β1 integrin inhibitors in 3D and monitored for 12 days, followed by quantification of colony number. Parallel experiments were conducted where cells were either stained for Ki-67 and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) or harvested for protein and analyzed by immunoblot. Results were subjected to statistical testing using analysis of variance and linear contrasts, followed by adjustment with the Sidak method. Results Using multiple cell lines including BT474 and HCC1954, we reveal that in L and LT resistance, where phosphorylation of EGFR/HER1, HER2, and HER3 are strongly inhibited, kinases downstream of β1 integrin--including focal adhesion kinase (FAK) and Src--are up-regulated. Blockade of β1 by the antibody AIIB2 abrogates this up-regulation and functionally achieves significant growth inhibition of L and LT resistant cells in 3D, without dramatically affecting the parental cells. SiRNA against β1 as well as pharmacologic inhibition of FAK achieve the same growth inhibitory effect. In contrast, trastuzumab-resistant cells, which retain high levels of phosphorylated EGFR/HER1, HER2, and HER3, are only modestly growth-inhibited by AIIB2. Conclusions Our data suggest that HER2 activity, which is suppressed in resistance involving L but not T alone, dictates whether β1 mediates an alternative pathway driving resistance. Our findings justify clinical studies investigating the inhibition of β1 or its downstream signaling moieties as strategies to overcome acquired L and LT resistance

    HRS/EHRA/APHRS/LAHRS/ACC/AHA worldwide practice update for telehealth and arrhythmia monitoring during and after a pandemic

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    Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), started in the city of Wuhan late in 2019. Within a few months, the disease spread toward all parts of the world and was declared a pandemic on March 11, 2020. The current health care dilemma worldwide is how to sustain the capacity for quality services not only for those suffering from COVID-19 but also for non-COVID-19 patients, all while protecting physicians, nurses, and other allied health care workers

    RNA biomarkers in colorectal cancer

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    Colorectal cancer (CRC) develops and progresses through a systematic selection for (epi) genetic alterations that drive the transformation from normal colon epithelium to adenocarcinoma. These changes affect both noncoding RNAs and mRNAs and so define the clinical behaviour of cancer cells within a distinctive host genetic and environmental context. Although earlier diagnosis and more effective treatment modalities have decreased mortality from CRC, prognostic stratification and adjuvant therapy selection after surgery remain dependent on broad descriptive classifications, opportune histological markers of poor prognosis and chemotherapy efficacy data derived from diverse CRC populations. Crucially, there is significant inter- and intra-individual variability in response to, and tolerance of, chemotherapy treatments. These limitations explain the small clinical benefit of new agents studied in contemporary phase III trials. Molecular assays have the potential to address these constraints and there has been intense interest in the identification of clinically relevant molecular biomarkers. These must be easy to obtain and quantify and ideally represent steps in well-understood carcinogenic pathways or host-response mechanisms. Although some biomarkers can provide broad prognostic information based on CRC subtype (e.g. MSI status) or can somewhat predict response to targeted therapies (e.g. KRAS), no RNA-based biomarkers have entered routine clinical practice. This is due, in part, to the genetic heterogeneity of both patients and CRC. In addition, serious underlying issues with regards to study design, poor technical protocols, inadequate quality controls and inappropriate data analysis prevent successful translation of research results. Consequently, the identification of clinically relevant panels of biomarkers will depend not just on further advances in our understanding of CRC biology, but will need to be coupled with appropriate study designs and more suitable, standardised and transparent techniques
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