97 research outputs found

    Automated Phase Mapping with AgileFD and its Application to Light Absorber Discovery in the V-Mn-Nb Oxide System

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    Rapid construction of phase diagrams is a central tenet of combinatorial materials science with accelerated materials discovery efforts often hampered by challenges in interpreting combinatorial x-ray diffraction datasets, which we address by developing AgileFD, an artificial intelligence algorithm that enables rapid phase mapping from a combinatorial library of x-ray diffraction patterns. AgileFD models alloying-based peak shifting through a novel expansion of convolutional nonnegative matrix factorization, which not only improves the identification of constituent phases but also maps their concentration and lattice parameter as a function of composition. By incorporating Gibbs’ phase rule into the algorithm, physically meaningful phase maps are obtained with unsupervised operation, and more refined solutions are attained by injecting expert knowledge of the system. The algorithm is demonstrated through investigation of the V-Mn-Nb oxide system where decomposition of eight oxide phases, including two with substantial alloying, provides the first phase map for this pseudo-ternary system. This phase map enables interpretation of high-throughput band gap data, leading to the discovery of new solar light absorbers and the alloying-based tuning of the direct-allowed band-gap energy of MnV2O6. The open-source family of AgileFD algorithms can be implemented into a broad range of high throughput workflows to accelerate materials discovery

    A promyelocytic leukemia protein-thrombospondin 2 axis and the risk of relapse in neuroblastoma

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    Purpose. Neuroblastoma is a childhood malignancy originating from the sympathetic nervous system with a complex biology, prone to metastasize and relapse. High-risk, metastatic cases are explained in part by amplification or mutation of oncogenes such as MYCN and ALK and loss of tumour suppressor genes in chromosome band 1p. However, it is fundamental to identify other pathways responsible for the large portion of neuroblastomas with no obvious molecular alterations. Experimental design. Neuroblastoma cell lines were used for assessment of tumour growth in vivo and in vitro. Protein expression in tissues and cells was assessed using immunofluorescence and immunohistochemistry. The association of PML expression with neuroblastoma outcome and relapse was calculated using log-rank and Mann-Whitney tests, respectively. Gene expression was assessed using chip microarrays. Results: PML is detected in the developing and adult sympathetic nervous system, whereas it is not expressed or low in metastatic neuroblastoma tumours. Reduced PML expression in patients with low-risk cancers - i.e. localized and negative for the MYCN protooncogene - is strongly associated with tumour recurrence. PML-I, but not PML-IV, isoform suppresses angiogenesis via upregulation of thrombospondin-2 (TSP-2), a key inhibitor of angiogenesis. Finally, PML-I and TSP-2 expression inversely correlates with tumour angiogenesis and recurrence in localized neuroblastomas. Dvorkina et al. A promyelocytic leukaemia protein-thrombospondin 2 axis and the risk of relapse in neuroblastoma 3 Conclusions: Our work reveals a novel PML-I-TSP2 axis for regulation of angiogenesis and cancer relapse, which could be used to identify patients with low-risk, localized tumours that might benefit from chemotherapy

    Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome

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    Autosomal dominant hyper-IgE syndrome (AD-HIES) is typically caused by dominant-negative (DN) STAT3 mutations. Patients suffer from cold staphylococcal lesions and mucocutaneous candidiasis, severe allergy, and skeletal abnormalities. We report 12 patients from 8 unrelated kindreds with AD-HIES due to DN IL6ST mutations. We identified seven different truncating mutations, one of which was recurrent. The mutant alleles encode GP130 receptors bearing the transmembrane domain but lacking both the recycling motif and all four STAT3-recruiting tyrosine residues. Upon overexpression, the mutant proteins accumulate at the cell surface and are loss of function and DN for cellular responses to IL-6, IL-11, LIF, and OSM. Moreover, the patients’ heterozygous leukocytes and fibroblasts respond poorly to IL-6 and IL-11. Consistently, patients with STAT3 and IL6ST mutations display infectious and allergic manifestations of IL-6R deficiency, and some of the skeletal abnormalities of IL-11R deficiency. DN STAT3 and IL6ST mutations thus appear to underlie clinical phenocopies through impairment of the IL-6 and IL-11 response pathways

    Large signal design method of distributed power amplifiers applied to a 2-18GHz GaAs chip exhibiting high power density performances

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    International audienceA suitable large signal design method of distributed power amplifiers, based on the optimum FET load requirement for high power operation, is proposed in this article. The gate and drain line characteristic admittances are determined, providing both the initial values and right directions for an optimum design. To validate the proposed design method, a FET amplifier demonstrator with a gate periphery of 1.2 mm has been manufactured at the Texas Instruments foundry. The MMIC distributed amplifier demonstrated an improved power density performance of 340 mW/mm over the 2-18-GHz frequency band associated with a minimum of 13% power-added efficiency and 24% drain efficiency at 1-dB compression in CW operatio

    Optimum design method of distributed power-FET amplifiers. Application to 2-18GHz MMIC exhibiting improved power performances

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    International audienceA suitable and effective design method of distributed power amplifiers, based on the optimum FET load requirement for power operation, is proposed in this paper. An analytical determination of the gate and drain line characteristic admittances provides both the initial values and right directions for an optimum design. The best trade-offs between wide band and high power operation have been investigated. To validate the method, a FET amplifier demonstrator with a gate periphery of 1.2 mm has been manufactured at the Texas Instruments foundry. The MMIC amplifier demonstrated state of the art power density performance of 340 mW/mm over the 2-18 GHz band associated with 14.2% power added efficiency, 26.5% drain efficiency and 26.1 dBm output power at 1 dB compression in CW operation

    Truth Behind Thames: Archaeological and Historical Investigations of the “Missionary Whaleship”

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    Transporting the second detachment of American missionaries to the Hawaiian Islands earned Thames its novel moniker, but this was only one of several unique distinctions it earned during its sailing career. It was the largest vessel ever constructed at Potapaug, Connecticut (today's Essex) upon its launch in 1818, and the first four-years of Thames' employment involved competing for freight and cargo against the famed "packets" of the Black Ball Line. While Thames did not adhere to a sailing schedule, it completed more crossings per-year than the early packets and its crossings were almost invariably shorter. Thames' merchant service ended in 1822 and it was subsequently acquired by a newly-formed investment firm out of New Haven, Connecticut. There Thames was converted for an arguably more demanding role: whaling. Its maiden voyage as a whaleship facilitated the aforementioned mission group to their destination without incident and Thames finally returned with some 1,900 barrels of sperm whale oil after a three-year cruise. Despite achieving a full cargo, however, Thames' owners were dissatisfied with its outcome. They opted to sell the ship rather than outfit it for a second voyage, and Thames entered into the Sag Harbor, New York (Long Island) whaling fleet. Thames was altogether a "greasy" (lucky) Sag Harbor whaler until 1838, when it was deemed unfit for further use, condemned, and purposefully scuttled as a breakwater and barrier against erosion in the harbor's near shore area. The ship's decaying hull gradually receded from view and memory until the late-1960s, when a significant quantity of its remains were removed during a marina construction project. Today, the reconstructed keel and disarticulated structural members of the merchant vessel-turned-whaleship Thames are permanently exhibited at Mystic Seaport in Mystic, Connecticut. As the construction characteristics of repurposed vessels and the processes of merchant vessel-to-whaleship conversion have seemingly escaped archaeological and historic research, alike, the social and historical contexts and the broader significance of converted vessels has been understudied--to say the least. In truth, conversions were far more popular than purpose-built whaleships throughout the majority of the "Golden Age" of American whaling (roughly 1820-1850) and "recycled" vessels played an important role in the industry's unprecedented resurgence following the War of 1812. Furthermore, these vessels provided a chance to experiment with emerging designs and construction methods that later appear in the forms of purpose-built whaleships. This thesis informs upon these topics by examining the history and archaeology of Thames, an unparalleled example of a converted vessel whose documentary and physical evidence have yet been carefully considered. A combined theoretical approach involving aspects of object biography and a recent development known as object itinerary orient this study. As such, the extensive, dynamic, and socially-meaningful "entanglements" that Thames may be said to have experienced during its 203 year existence are considered critical aspects for generating a better understanding of its various roles, as are the present and future entanglements it experiences as a museum object at Mystic Seaport
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