342 research outputs found

    Lamb Wave Mode Selection for Increased Sensitivity ot Interfacial Weaknesses of Adhesive Bonds

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    Interface quality between layers in a layered structure is critical in fracture and fatigue analysis. A theoretical and quantitative solution to the problem from a NDE point of view would be desirable in both manufacturing and for in-service investigation of a variety of different structures. For example a great need exists to develop a reliable and efficient inspection program of adhesive bond delamination and interfacial weakness detection in aging aircraft noting that the bond degradation generally preceeds cracking in the aluminum skin, starting at the rivet holes

    Mechanochemical Solvent-Free Catalytic C—H Methylation

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    The mechanochemical, solvent-free, highly regioselective, rhodium-catalyzed C-H methylation of (hetero)arenes is reported. The reaction shows excellent functional-group compatibility and is demonstrated to work for the late-stage C-H methylation of biologically active compounds. The method requires no external heating and benefits from considerably shorter reaction times than previous solution-based C-H methylation protocols. Additionally, the mechanochemical approach is shown to enable the efficient synthesis of organometallic complexes that are difficult to generate conventionally

    Phenotypic Detection of Clonotypic B Cells in Multiple Myeloma by Specific Immunoglobulin Ligands Reveals their Rarity in Multiple Myeloma

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    In multiple myeloma, circulating “clonotypic” B cells, that express the immunoglobulin rearrangement of the malignant plasma cell clone, can be indirectly detected by PCR. Their role as potential “feeder” cells for the malignant plasma cell pool remains controversial. Here we established for the first time an approach that allows direct tracking of such clonotypic cells by labeling with patient-specific immunoglobulin ligands in 15 patients with myeloma. Fifty percent of patients showed evidence of clonotypic B cells in blood or bone marrow by PCR. Epitope-mimicking peptides from random libraries were selected on each patient's individual immunoglobulin and used as ligands to trace cells expressing the idiotypic immunoglobulin on their surface. We established a flow cytometry and immunofluorescence protocol to track clonotypic B cells and validated it in two independent monoclonal B cell systems. Using this method, we found clonotypic B cells in only one out of 15 myeloma patients. In view of the assay's validated sensitivity level of 10−3, this surprising data suggests that the abundance of such cells has been vastly overestimated in the past and that they apparently represent a very rare population in myeloma. Our novel tracing approach may open perspectives to isolate and analyze clonotypic B cells and determine their role in myeloma pathobiology

    Characterization of Adhesive Bonding Using Leaky Lamb Waves

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    The performance of adhesive bonds in primary structures strongly depends on the quality of adhesion. Many NDE methods are presently used to detect unbonded areas; however, these methods cannot be used to determine bond properties. In standard ultrasonic techniques, the velocity of bulk wave propagation through the specimen is measured by time-offlight. Unfortunately, the waves reflected from the bonded region cannot be easily identified or analyzed to determine the properties of the adhesive layer

    An enclosed in-gel PCR amplification cassette with multi-target, multi-sample detection for platform molecular diagnostics

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    This work describes a self-contained, simple, disposable, and inexpensive gel capillary cassette for DNA amplification in near point of care settings. The cassette avoids the need for pumps or valves during raw sample delivery or polymerase chain reaction (PCR) amplification steps. The cassette contains capillary reaction units that can be stored at room temperature for up to 3 months. The current cassette configuration format can simultaneously tests up to 16 patients for two or more targets, accommodates different sample types on the same cassette, has integrated positive and negative controls and allows flexibility for multiple geometries. PCR reagents in the cassette are desiccated to allow storage at room temperature with rehydration by raw sample at the time of testing. The sample is introduced to the cassette via a transfer pipette simply by capillary force. DNA amplification was carried out in a portable prototype instrument for PCR thermal cycling with fluorescence detection of amplified products by melt curve analysis. To demonstrate performance, raw genital swabs and urine were introduced to the same cassette to simultaneously detect four sexually transmitted infections. Herpes Simplex Viruses (HSV-1 and HSV-2) were detected from raw genital swabs. Ureaplasma Urealyticum (UU) and Mycoplasma Homonis (MH) were detected from raw urine. Results for multiple patients were obtained in as little as 50'. This platform allows multiparameter clinical testing with a pre-assembled cassette that requires only the introduction of raw sample. Modification of the prototype device to accommodate larger cassettes will ultimately provide high throughput simultaneous testing of even larger numbers of samples for many different targets, as is required for most clinical applications. Combinations of wax and/or polymer cassettes holding capillary reaction units are feasible. The components of the cassette are suited to mass production and robotic assembly to produce a readily manufactured disposable reaction cassette that can be configured for disease-specific testing panels. Rapid testing with a disposable reaction cassette on an inexpensive instrument will permit on the spot evaluation of patients in the clinic for faster medical decision-making and more informed therapeutic choices

    Sanidade.

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    Introdução. Comportamento e sinais clínicos. Doenças virais. Varíola da carpa. Herpevírus da necrose hematopoiética do kinguio. Herpevírus da carpa. Viremia-primaveril da carpa. Linfocistose. Doenças bacterianas. Infecções por Aeromonas spp. Infecções por Flavobacterium columnare. Infecções por Edwardsiella spp. Infecções por Vibrio spp. Infecções por Streptococcus spp. Infecções por Mycobacterium spp. Infecções por Francisella spp. Doenças parasitárias causadas por protozoários: Doença do buraco na cabeça. Tricodiníase. Tetrahymenose ou doença dos guppies. Ictioftiríase ou doença dos pontos brancos. Piscinoodiníase ou doença do veludo. Doenças parasitárias causadas por helmintos: Monogenea. Digenea. Cestoda. Nematoda. Acantocephala. Doenças parasitárias causadas por crustáceos: Copépodes. Branquiúros. Isópodes. Doenças causadas por fungos: Saprolegniose. Doenças causadas por microsporídeos: Microsporídeos. Profilaxia. Aclimatação. Quarentena. Tratamento com quimioterápicos. Cuidados na aplicação de produtos e medicamentos. Seleção do método de aplicação. Considerações finais.bitstream/item/225453/1/pl-cap4.pd

    An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

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    For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
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