988 research outputs found

    Integrated AlGaN quadruple-band ultraviolet photodetectors

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    Cataloged from PDF version of article.Monolithically integrated quadruple back-illuminated ultraviolet metalsemiconductormetal photodetectors with four different spectral responsivity bands were demonstrated on each of two different Al xGa 1-xN heterostructures. The average of the full-width at half-maximum (FWHM) of the quantum efficiency peaks was 18.15nm for sample A, which incorporated five 1000nm thick epitaxial layers. In comparison, the average FWHM for sample B was 9.98 nm, which incorporated nine 500nm thick epitaxial layers. © 2012 IOP Publishing Ltd

    The chemotherapeutic agent DMXAA as a unique IRF3-dependent type-2 vaccine adjuvant

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    5,6-Dimethylxanthenone-4-acetic acid (DMXAA), a potent type I interferon (IFN) inducer, was evaluated as a chemotherapeutic agent in mouse cancer models and proved to be well tolerated in human cancer clinical trials. Despite its multiple biological functions, DMXAA has not been fully characterized for the potential application as a vaccine adjuvant. In this report, we show that DMXAA does act as an adjuvant due to its unique property as a soluble innate immune activator. Using OVA as a model antigen, DMXAA was demonstrated to improve on the antigen specific immune responses and induce a preferential Th2 (Type-2) response. The adjuvant effect was directly dependent on the IRF3-mediated production of type-I-interferon, but not IL-33. DMXAA could also enhance the immunogenicity of influenza split vaccine which led to significant increase in protective responses against live influenza virus challenge in mice compared to split vaccine alone. We propose that DMXAA can be used as an adjuvant that targets a specific innate immune signaling pathway via IRF3 for potential applications including vaccines against influenza which requires a high safety profile

    Search For Heavy Pointlike Dirac Monopoles

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    We have searched for central production of a pair of photons with high transverse energies in ppˉp\bar p collisions at s=1.8\sqrt{s} = 1.8 TeV using 70pb170 pb^{-1} of data collected with the D\O detector at the Fermilab Tevatron in 1994--1996. If they exist, virtual heavy pointlike Dirac monopoles could rescatter pairs of nearly real photons into this final state via a box diagram. We observe no excess of events above background, and set lower 95% C.L. limits of 610,870,or1580GeV/c2610, 870, or 1580 GeV/c^2 on the mass of a spin 0, 1/2, or 1 Dirac monopole.Comment: 12 pages, 4 figure

    Accounting Problems Under the Excess Profits Tax

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    DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.Funding Agencies|Research Council of Norway; Odd Fellow</p

    Biallelic mutations in IRF8 impair human NK cell maturation and function

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    Human NK cell deficiencies are rare yet result in severe and often fatal disease, particularly as a result of viral susceptibility. NK cells develop from hematopoietic stem cells, and few monogenic errors that specifically interrupt NK cell development have been reported. Here we have described biallelic mutations in IRF8, which encodes an interferon regulatory factor, as a cause of familial NK cell deficiency that results in fatal and severe viral disease. Compound heterozygous or homozygous mutations in IRF8 in 3 unrelated families resulted in a paucity of mature CD56dim NK cells and an increase in the frequency of the immature CD56bright NK cells, and this impairment in terminal maturation was also observed in Irf8–/–, but not Irf8+/–, mice. We then determined that impaired maturation was NK cell intrinsic, and gene expression analysis of human NK cell developmental subsets showed that multiple genes were dysregulated by IRF8 mutation. The phenotype was accompanied by deficient NK cell function and was stable over time. Together, these data indicate that human NK cells require IRF8 for development and functional maturation and that dysregulation of this function results in severe human disease, thereby emphasizing a critical role for NK cells in human antiviral defense

    A comparative study on the abundance and elemental composition of POM in three interconnected basins: the Black, the Marmara and the Mediterranean Seas

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    The abundance and elemental composition of suspended particulate organic matter in the upper layers of the interconnected Mediterranean, Marmara and Black Seas having different ecosystems were determined in 1990-1998. The aim was principally to compare the C:N:P ratio of seston and understand factors controlling the seston composition in near- and off-shore waters of these seas. In the Marmara Sea, euphotic zone average particulate concentrations varied regionally and seasonally between 10-35 ìM for POC, 0.4-4.5 ìM for PON and 0.05-0.45 ìM for PP. These concentrations are mostly above the off-shore Black Sea values but much greater than those measured in the open waters of the north-eastern Mediterranean whose near-shore data are comparable with the seston content of the deep Black Sea. Comparison of C:N:P ratios of seston reveals that atmospheric and land-based phosphorus input influences the C:P and N:P ratios in the near-shore waters. Apparent nutrient deficiencies observed in the water column were not as remarkable in the elemental composition of seston. Unexpectedly, in the NE Mediterranean, N:P ratios from regression analyses of particulate data are very low (7-9) in the coastal region but slightly increase to levels of 10-15 in the open sea. In the Sea of Marmara, the N:P ratios (7-12) of seston are as low as in the Mediterranean, being consistent with the particulate ratios of the Black Sea inflow and NO3:PO4 ratios of the Marmara sub-halocline water. The Black Sea seston is relatively rich in carbonaceous compounds with N:P ratio ranging merely between 15-17 in the open sea but 9-27 in coastal waters where riverine discharges markedly influence the stoichiometry of seston

    Identification of a RAI1-associated disease network through integration of exome sequencing, transcriptomics, and 3D genomics.

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    Smith-Magenis syndrome (SMS) is a developmental disability/multiple congenital anomaly disorder resulting from haploinsufficiency of RAI1. It is characterized by distinctive facial features, brachydactyly, sleep disturbances, and stereotypic behaviors. We investigated a cohort of 15 individuals with a clinical suspicion of SMS who showed neither deletion in the SMS critical region nor damaging variants in RAI1 using whole exome sequencing. A combination of network analysis (co-expression and biomedical text mining), transcriptomics, and circularized chromatin conformation capture (4C-seq) was applied to verify whether modified genes are part of the same disease network as known SMS-causing genes. Potentially deleterious variants were identified in nine of these individuals using whole-exome sequencing. Eight of these changes affect KMT2D, ZEB2, MAP2K2, GLDC, CASK, MECP2, KDM5C, and POGZ, known to be associated with Kabuki syndrome 1, Mowat-Wilson syndrome, cardiofaciocutaneous syndrome, glycine encephalopathy, mental retardation and microcephaly with pontine and cerebellar hypoplasia, X-linked mental retardation 13, X-linked mental retardation Claes-Jensen type, and White-Sutton syndrome, respectively. The ninth individual carries a de novo variant in JAKMIP1, a regulator of neuronal translation that was recently found deleted in a patient with autism spectrum disorder. Analyses of co-expression and biomedical text mining suggest that these pathologies and SMS are part of the same disease network. Further support for this hypothesis was obtained from transcriptome profiling that showed that the expression levels of both Zeb2 and Map2k2 are perturbed in Rai1 (-/-) mice. As an orthogonal approach to potentially contributory disease gene variants, we used chromatin conformation capture to reveal chromatin contacts between RAI1 and the loci flanking ZEB2 and GLDC, as well as between RAI1 and human orthologs of the genes that show perturbed expression in our Rai1 (-/-) mouse model. These holistic studies of RAI1 and its interactions allow insights into SMS and other disorders associated with intellectual disability and behavioral abnormalities. Our findings support a pan-genomic approach to the molecular diagnosis of a distinctive disorder

    Powder sheets additive manufacturing: Principles and capabilities for multi-material printing

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    In this work, a novel Metal Additive Manufacturing using Powder sheets (MAPS) method for printing multimaterial composites in one process is proposed. MAPS employs powder sheets (i.e. metal powder-polymer matrix flexible films) as the feedstock material. Its key advantages include a relatively rapid change from one material to another and a minimum wastage of materials due to the elimination of the powder bed. The powder sheets were fabricated using a 'solvent casting' method. They were then employed in a commercialised metal printer for printing metal multi-material composites. To prove the disruptive concept of MAPS, a 60-layer trimetallic multi-material composite (304 L stainless steel, In718 and CoCrFeMnNi high entropy alloy) was additively manufactured using three different types of powder sheet material in the same manufacturing system for the first time. Experimental results indicate a high density (99.80 %) multi-material composites was printed by MAPS. EDX and SEM observations of the multi-material composites revealed variations of chemical composition and microstructure along the build direction. The newly proposed MAPS manufacturing method and results of this study provide insights into a new avenue for multi-material metallic parts
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