A motion mesh approach for fluid.structure interaction of spatial structures

p. 2600-2610Mesh motion strategy is one of the key problems in fluid-structure interaction analysis (FSI). One popular technique which often used to solve this problem is known as the spring analogy method. In this paper a new mesh update approach based on the spring analogy method is presented for the effective treatment of mesh moving boundary problem,which can avoid the generation of squashed invalid elements and maintain mesh quality by considering each element shape and grid scale in the definition of the spring stiffness. Meanwhile, the approach is applied to several 2D and 3D boundary correction problems for fully unstructured meshes and evaluated by a mesh quality indicator. With this application, it is demonstrated that the present approach can keep good mesh quality even under large motion of bodie.s. Finally, the computational robustness of the present approach on is highlightedZhang, X.; Zhou, D.; Chen, X. (2009). A motion mesh approach for fluid.structure interaction of spatial structures. Editorial Universitat Politècnica de València. http://hdl.handle.net/10251/659

Tuning electronic properties of epitaxial multilayer-graphene/4H–SiC(0001) by Joule heating decomposition in hydrogen

Abstract(#br)On the semi-insulating 4H–SiC (0001) surface, hydrogenated multilayers graphene (MLG) were epitaxially prepared by the method of Joule heating decomposition in the hydrogen atmosphere. The structural and chemical characteristics of multilayers graphene have been elaborately analyzed by the X-ray photoelectron and Raman spectroscopies, showing the level of hydrogenation being promoted with the increase of hydrogen pressure. Then, diodes with MLG/4H–SiC contact were fabricated and studied, proving that the Schottky barrier height (SBH) of MLG/4H–SiC junction was enhanced by the hydrogenation. By studying the typical current-voltage characteristics, the SBH was observed to be heightened from 0.84 eV to 1.0 eV along with the hydrogen pressure increasing from 10 −2 mbar to 10 2 mbar. Finally, graphene-semiconductor-graphene photodetectors were fabricated, showing peak responsivity as high as~ 0.9 A/W and external quantum efficiency of 345%, under the 324 nm illumination and biased at 3V

The potential diagnostic accuracy of urine formaldehyde levels in Alzheimer’s disease: A systematic review and meta-analysis

BackgroundFormaldehyde (FA), a toxic aldehyde, has been shown to be associated with a variety of cognitive disorders, including Alzheimer’s disease (AD). There is increasing evidence that FA levels are significantly increased in AD patients and may be involved in the pathological process of AD. The aim of this study was to assess the potential diagnostic value of urine FA levels in AD using meta-analysis techniques.MethodsOriginal reports of morning urine FA levels in AD patients and healthy controls (HCs) were included in the meta-analysis. Standardized mean differences (SMD) were calculated using a random-effects model, heterogeneity was explored using methodological, age, sex difference and sensitivity analyses, and receiver operating characteristic (ROC) curves were constructed to assess the diagnostic value of urine FA levels in AD.ResultsA total of 12 studies were included, and the urine FA levels of 874 AD patients and 577 HCs were reviewed. Compared with those in HCs, the FA levels were significantly increased in AD patients. The heterogeneity of the results did not affect their robustness, and results of the area under the curve (AUC) suggested that urine FA levels had good potential diagnostic value.ConclusionUrine FA levels are involved in AD disease progression and are likely to be useful as a potential biomarker for clinical auxiliary diagnosis. However, further studies are needed to validate the results of this study

Integrated RNA and DNA sequencing reveals early drivers of metastatic breast cancer

Breast cancer metastasis remains a clinical challenge, even within a single patient across multiple sites of the disease. Genome-wide comparisons of both the DNA and gene expression of primary tumors and metastases in multiple patients could help elucidate the underlying mechanisms that cause breast cancer metastasis. To address this issue, we performed DNA exome and RNA sequencing of matched primary tumors and multiple metastases from 16 patients, totaling 83 distinct specimens. We identified tumor-specific drivers by integrating known protein-protein network information with RNA expression and somatic DNA alterations and found that genetic drivers were predominantly established in the primary tumor and maintained through metastatic spreading. In addition, our analyses revealed that most genetic drivers were DNA copy number changes, the TP53 mutation was a recurrent founding mutation regardless of subtype, and that multiclonal seeding of metastases was frequent and occurred in multiple subtypes. Genetic drivers unique to metastasis were identified as somatic mutations in the estrogen and androgen receptor genes. These results highlight the complexity of metastatic spreading, be it monoclonal or multiclonal, and suggest that most metastatic drivers are established in the primary tumor, despite the substantial heterogeneity seen in the metastases

Enhancer Remodeling during Adaptive Bypass to MEK Inhibition Is Attenuated by Pharmacologic Targeting of the P-TEFb Complex

Targeting the dysregulated BRaf-MEK-ERK pathway in cancer has increasingly emerged in clinical trial design. Despite clinical responses in specific cancers using inhibitors targeting BRaf and MEK, resistance develops often involving non-genomic adaptive bypass mechanisms. Inhibition of MEK1/2 by trametinib in triple negative breast cancer (TNBC) patients induced dramatic transcriptional responses, including upregulation of receptor tyrosine kinases (RTKs) comparing tumor samples before and after one week of treatment. In preclinical models MEK inhibition induced genome-wide enhancer formation involving the seeding of BRD4, MED1, H3K27 acetylation and p300 that drives transcriptional adaptation. Inhibition of P-TEFb associated proteins BRD4 and CBP/p300 arrested enhancer seeding and RTK upregulation. BRD4 bromodomain inhibitors overcame trametinib resistance, producing sustained growth inhibition in cells, xenografts and syngeneic mouse TNBC models. Pharmacological targeting of P-TEFb members in conjunction with MEK inhibition by trametinib is an effective strategy to durably inhibit epigenomic remodeling required for adaptive resistance

Dynamic Reprogramming of the Kinome in Response to Targeted MEK Inhibition in Triple-Negative Breast Cancer

Kinase inhibitors have limited success in cancer treatment because tumors circumvent their action. Using a quantitative proteomics approach, we assessed kinome activity in response to MEK inhibition in triple negative breast cancer (TNBC) cells and genetically engineered mice (GEMMs). MEK inhibition caused acute ERK activity loss, resulting in rapid c-Myc degradation that induced expression and activation of several receptor tyrosine kinases (RTKs). RNAi knockdown of ERK or c-Myc mimicked RTK induction by MEK inhibitors, whereas prevention of proteasomal c-Myc degradation blocked kinome reprogramming. MEK inhibitor-induced RTK stimulation overcame MEK2 but not MEK1 inhibition, reactivating ERK and producing drug resistance. The C3Tag GEMM for TNBC similarly induced RTKs in response to MEK inhibition. The inhibitor-induced RTK profile suggested a kinase inhibitor combination therapy that produced GEMM tumor apoptosis and regression where single agents were ineffective. This approach defines mechanisms of drug resistance, allowing rational design of combination therapies for cancer

FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036

Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2+ cell line responses to inhibition with lapatinib were analyzed by RNAseq and ChIPseq to characterize transcriptional and epigenetic changes. Motif analysis of lapatinib-responsive genomic regions implicated the pioneer transcription factor FOXA1 as a mediator of adaptive responses. Lapatinib in combination with FOXA1 depletion led to dysregulation of enhancers, impaired adaptive upregulation of HER3, and decreased proliferation. HER2-directed therapy using clinically relevant drugs (trastuzumab with or without lapatinib or pertuzumab) in a 7-day clinical trial designed to examine early pharmacodynamic response to antibody-based anti-HER2 therapy showed reduced FOXA1 expression was coincident with decreased HER2 and HER3 levels, decreased proliferation gene signatures, and increased immune gene signatures. This highlights the importance of the immune response to anti-HER2 antibodies and suggests that inhibiting FOXA1-mediated adaptive responses in combination with HER2 targeting is a potential therapeutic strategy

High-performance 4H-SiC-based ultraviolet p-i-n photodetector

A high-performance 4H-SiC p-i-n photodetector for visible-blind ultraviolet (UV) applications has been designed and fabricated. The electrical and optical characteristics were measured at room temperature. The photodetector suffered from significant dark current of 2.5 pA/mm(2) at reverse bias of 5 V, and the UV light photocurrent was larger than four orders of magnitude higher than the dark current. The built-in potential and the unintentional i-layer doping concentration were obtained from capacitance-voltage (C-V) measurements. The spectral peak responsivity of the detector reached 0.13 A/W at a wavelength of 270 nm, corresponding to a maximum external quantum efficiency of similar to 61%. And the ratio of responsivity at 270 nm to that at 380 nm was > 10(3). The characteristics imply that the photodetector has a great improved ultraviolet-visible rejection ratio which is needed for ultraviolet signal detection

4H-SiC ultraviolet avalanche photodetectors with low breakdown voltage and high gain

Xiamen Science and Technology Plan Foundation of Fujian Province [350Z20031076]The separate absorption and multiplication (SAM) 4H-SiC ultraviolet (UV) avalanche photodetectors (APDs) have been designed, fabricated and characterized. A gain higher than 1.8 x 10(4) was achieved at 90% breakdown voltage of similar to 55 V. At 0 V, the peak absolute responsivity was estimated to be larger than 0.078 A/W at 270 nm, corresponding to a peak external quantum efficiency of over 35.8%. The long-wavelength cutoff was about 380 nm. In addition, the UV-to-visible rejection ratio of around three orders of magnitude was extracted from the spectra response. When the reverse bias was larger than 35 V, the spectral responsivity enhanced distinctly. At the reverse bias of 42 V, the peak responsivity increased to 0.203 A/W at 270 nm, corresponding to a maximum external quantum efficiency of similar to 93%, which showed a distinct avalanche behavior. Furthermore, the ideality factor around 1.65 and the spectral detectivity about 3.1 X 10(13) cm Hz(1/2) W(-1) were estimated. in conclusion, the 4H-SiC APD have excellent performance for UV detection. (C) 2008 Elsevier Ltd. All rights reserved