531 research outputs found

    Enhanced Shot Noise in Tunneling through a Stack of Coupled Quantum Dots

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    We have investigated the noise properties of the tunneling current through vertically coupled self-assembled InAs quantum dots. We observe super-Poissonian shot noise at low temperatures. For increased temperature this effect is suppressed. The super-Poissonian noise is explained by capacitive coupling between different stacks of quantum dots

    Macroeconomic Modeling of Tax Policy: A Comparison of Current Methodologies

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    The macroeconomic effects of tax reform are a subject of significant discussion and controversy. In 2015, the House of Representatives adopted a new “dynamic scoring” rule requiring a point estimate within the budget window of the deficit effect due to the macroeconomic response to certain proposed tax legislation. The revenue estimates provided by the staff of the Joint Committee on Taxation (JCT) for major tax bills often play a critical role in Congressional deliberations and public discussion of those bills. The JCT has long had macroeconomic analytic capability, and in recent years, responding to Congress’ interest in macrodynamic estimates for purposes of scoring legislation, outside think tank groups — notably the Tax Policy Center and the Tax Foundation — have also developed macrodynamic estimation models. The May 2017 National Tax Association (NTA) Spring Symposium brought together the JCT with the Tax Foundation and the Tax Policy Center for a panel discussion regarding their respective macrodynamic estimating approaches. This paper reports on that discussion. Below each organization provides a general description of their macrodynamic modeling methodology and answers five questions posed by the convening authors

    Infection of Mice with the Agent of Human Granulocytic Ehrlichiosis after Different Routes of Inoculation

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    Population kinetics of the agent of human granulocytic ehrlichiosis (aoHGE) were examined after needle and tickborne inoculation of C3H mice. Blood, skin, lung, spleen, liver, kidney, brain, lymph node, and bone marrow samples were analyzed by using real-time polymerase chain reaction (PCR) at various intervals after inoculation, using a p44 gene target. The highest number of copies of the p44 gene target occurred in blood and bone marrow samples, emphasizing aoHGE leukocytotropism. Numbers of copies of the p44 gene target in other tissues reflected vascular perfusion rather than replication. Needle-inoculated infected mice had earlier dissemination, but kinetics of infection in both groups were parallel, with declining rates of infection by day 20 and recovery in some mice on days 20-60 after inoculation. On the basis of an aoHGE lysate ELISA, mice seroconverted by day 10 after inoculation. Therefore, real-time PCR is useful for quantitative studies with the aoHGE in experimental infections, and results showed that needle inoculation can be used to study the aoHGE infection because of its similarity to tickborne inoculatio

    Lymphoadenopathy during Lyme Borreliosis Is Caused by Spirochete Migration-Induced Specific B Cell Activation

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    Lymphadenopathy is a hallmark of acute infection with Borrelia burgdorferi, a tick-borne spirochete and causative agent of Lyme borreliosis, but the underlying causes and the functional consequences of this lymph node enlargement have not been revealed. The present study demonstrates that extracellular, live spirochetes accumulate in the cortical areas of lymph nodes following infection of mice with either host-adapted, or tick-borne B. burgdorferi and that they, but not inactivated spirochetes, drive the lymphadenopathy. The ensuing lymph node response is characterized by strong, rapid extrafollicular B cell proliferation and differentiation to plasma cells, as assessed by immunohistochemistry, flow cytometry and ELISPOT analysis, while germinal center reactions were not consistently observed. The extrafollicular nature of this B cell response and its strongly IgM-skewed isotype profile bear the hallmarks of a T-independent response. The induced B cell response does appear, however, to be largely antigen-specific. Use of a cocktail of recombinant, in vivo-expressed B. burgdorferi-antigens revealed the robust induction of borrelia-specific antibody-secreting cells by ELISPOT. Furthermore, nearly a quarter of hybridomas generated from regional lymph nodes during acute infection showed reactivity against a small number of recombinant Borrelia-antigens. Finally, neither the quality nor the magnitude of the B cell responses was altered in mice lacking the Toll-like receptor adaptor molecule MyD88. Together, these findings suggest a novel evasion strategy for B. burgdorferi: subversion of the quality of a strongly induced, potentially protective borrelia-specific antibody response via B. burdorferi's accumulation in lymph nodes

    The Early Dissemination Defect Attributed to Disruption of Decorin-Binding Proteins is Abolished in Chronic Murine Lyme Borreliosis

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    The laboratory mouse model of Lyme disease has revealed that Borrelia burgdorferi differentially expresses numerous outer surface proteins that influence different stages of infection (tick-borne transmission, tissue colonization, dissemination, persistence, and tick acquisition). Deletion of two such outer surface proteins, decorin-binding proteins A and B (DbpA/B), has been documented to decrease infectivity, impede early dissemination, and, possibly, prevent persistence. In this study, DbpA/B-deficient spirochetes were confirmed to exhibit an early dissemination defect in immunocompetent, but not immunodeficient, mice, and the defect was found to resolve with chronicity. Development of disease (arthritis and carditis) was attenuated only in the early stage of infection with DbpA/B-deficient spirochetes in both types of mice. Persistence of the DbpA/B-deficient spirochetes occurred in both immunocompetent and immunodeficient mice in a manner indistinguishable from that of wild-type spirochetes. Dissemination through the lymphatic system was evaluated as an underlying mechanism for the early dissemination defect. At 12 h, 3 days, 7 days, and 14 days postinoculation, DbpA/B-deficient spirochetes were significantly less prevalent and in lower numbers in lymph nodes than wild-type spirochetes. However, in immunodeficient mice, deficiency of DbpA/B did not significantly decrease the prevalence or spirochete numbers in lymph nodes. Complementation of DbpA/B restored a wild-type phenotype. Thus, the results indicated that deficiency of DbpA/B allows the acquired immune response to restrict early dissemination of spirochetes, which appears to be at least partially mediated through the lymphatic system

    Borrelia burgdorferi OspA is an arthropod-specific transmission-blocking Lyme disease vaccine

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    Borrelia burgdorferi, the spirochetal agent of Lyme disease, is transmitted by Ixodes ticks. A vaccine based on B. burgdorferi outer surface protein (Osp) A protects mice from spirochete infection. Here we report on the expression of OspA on spirochetes inside engorging ticks and relate OspA expression to antispirochetal immunity. Spirochetes in the gut of unfed nymphal ticks were stained by an OspA antibody, whereas in feeding ticks, the majority of spirochetes in the gut and salivary glands did not stain with the antibody. Thus, OspA was not expressed on most spirochetes during transmission from the vector to the vertebrate host. To examine the mechanism of protection afforded by OspA antibody, mice were passively immunized with OspA antibody at different times relative to tick attachment. When OspA antibody was administered to mice before or at the time of tick attachment, spirochetal development events in the vector, such as growth and salivary gland invasion, were blocked and the mice were protected from B. burgdorferi infection. When OspA antibody was administered to mice 48 h after tick attachment, spirochetes persisted in the nymphs and the mice were not protected despite the presence of circulating antibodies in the host as well as in the tick blood meal. Thus, OspA immunity appears to be effective only during a narrow window time at the beginning of the blood meal when antibodies bind to OspA-expressing spirochetes in the tick gut and block transmission from the vector to the host
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