200 research outputs found

    User's guide to a system of finite-element supersonic panel flutter programs

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    The utilization and operation of a set of six computer programs for the prediction of panel flutter at supersonic speeds by finite element methods are described. The programs run individually to determine the flutter behavior of a flat panel where the finite elements which model the panel each have four degrees of freedom (DOF), a curved panel where the finite elements each have four DOF, and a curved panel where the finite elements each have six DOF. The panels are assumed to be of infinite aspect ratio and are subjected to either simply-supported or clamped boundary conditions. The aerodynamics used by these programs are based on piston theory. Application of the program is illustrated by sample cases where the number of beam finite elements equals four, the in-plane tension parameter is 0.0, the maximum camber to panel length ratio for a curved panel case is 0.05, and the Mach number is 2.0. This memorandum provides a user's guide for these programs, describes the parameters that are used, and contains sample output from each of the programs

    Effects of Picrotoxin Application on the Cardiac Ganglion of the American Lobster, \u3ci\u3eHomarus americanus\u3c/i\u3e

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    Picrotoxin (PTX) has been employed extensively as a tool within the crustacean stomatogastric nervous system (STNS) for its efficacy in blocking K+ and Cl+ currents gated by both GABA and glutamate. Through blocking some currents in the STNS, PTX allows for examination of other components without their presence. However, effects of PTX are relatively unknown within the lobster’s cardiac ganglion (CG). As an incredibly small nervous system of only nine neurons, the lobster CG presents an excellent model system for studying neural circuits. Given that the chemical synapses in the CG are mediated by glutamate, the present study aimed to investigate the action of PTX in the lobster CG with the intent of better understanding its pharmacological impacts as a potential tool for studying the system. Therefore, this study aimed to establish the effects of PTX on CG responses to the application of exogenous GABA or glutamate. When data from both modulators were pooled, PTX applied at a concentration of 10-5M had significant effects on burst duration but not duty cycle or burst frequency of the CG. PTX did suppress GABA (5x10-5M) mediated inhibition of burst duration and duty cycle. PTX did not have any significant effects on burst duration, duty cycle, or frequency compared to exogenous glutamate application. These results indicate that glutamatergic inhibitory synapses are not present in the CG and PTX partially suppresses only GABAergic responses in this system

    In Fed meetings, decision making is free – but not equal.

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    With its ability to influence interest rates globally, the Federal Open Market Committee (FOMC) of the US Federal Reserve is arguably one of the most important decision making bodies on the planet. But how does it come to its decisions? In new research which analyses transcripts of FOMC deliberations over nearly 30 years, Joseph Gardner and John T. Woolley find that women speak less than men for nearly their entire tenure on the FOMC. While women are free to speak, they write, they do not participate equally in FOMC deliberations, and this could be influencing policy choices

    Enhancing the Fed’s transparency didn’t hurt its deliberations

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    For more than two decades, transcripts of the US Federal Reserve’s Open Market Committee meetings have been made available to the public. But has the move to greater transparency about monetary policymaking hurt committee deliberations? In new research which examines committee meeting transcripts from 1978 to 2007, Joseph Gardner and John T. Woolley find that leadership – not transparency – had the greatest effect on how members deliberated during meetings

    The Epidemiology of Staphylococcus aureus and Panton-Valentine Leucocidin (pvl) in Central Australia, 2006-2010

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    Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: The Central Australian Indigenous population has a high incidence of Staphylococcus aureus bacteremia (SAB) but little is known about the local molecular epidemiology. Methods: Prospective observational study of bacteremic and nasal colonizing S.aureus isolates between June 2006 to June 2010. All isolates underwent single nucleotide polymorphism (SNP) genotyping and testing for the presence of the Panton-Valentine Leucocidin (pvl) gene. Results: Invasive isolates (n = 97) were predominantly ST93 (26.6 %) and pvl positive (54.3 %), which was associated with skin and soft tissue infections (OR 4.35, 95 % CI 1.16, 16.31). Non-multiresistant MRSA accounted for 31.9 % of bacteremic samples and showed a trend to being healthcare associated (OR 2.16, 95 % CI 0.86, 5.40). Non-invasive isolates (n = 54) were rarely ST93 (1.9 %) or pvl positive (7.4 %). Conclusions: In Central Australia, ST93 was the dominant S.aureus clone, and was frequently pvl positive and associated with an aggressive clinical phenotype. Whether non-nasal carriage is more important with invasive clones or whether colonization occurs only transiently remains to be elucidated

    Neuroblastoma: an ongoing cold front for cancer immunotherapy.

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    Neuroblastoma is the most frequent extracranial childhood tumour but effective treatment with current immunotherapies is challenging due to its immunosuppressive microenvironment. Efforts to date have focused on using immunotherapy to increase tumour immunogenicity and enhance anticancer immune responses, including anti-GD2 antibodies; immune checkpoint inhibitors; drugs which enhance macrophage and natural killer T (NKT) cell function; modulation of the cyclic GMP-AMP synthase-stimulator of interferon genes pathway; and engineering neuroblastoma-targeting chimeric-antigen receptor-T cells. Some of these strategies have strong preclinical foundation and are being tested clinically, although none have demonstrated notable success in treating paediatric neuroblastoma to date. Recently, approaches to overcome heterogeneity of neuroblastoma tumours and treatment resistance are being explored. These include rational combination strategies with the aim of achieving synergy, such as dual targeting of GD2 and tumour-associated macrophages or natural killer cells; GD2 and the B7-H3 immune checkpoint; GD2 and enhancer of zeste-2 methyltransferase inhibitors. Such combination strategies provide opportunities to overcome primary resistance to and maximize the benefits of immunotherapy in neuroblastoma

    BK virus-specific T-cell immune reconstitution after allogeneic hematopoietic cell transplantation

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    © 2020 by The American Society of HematologyClinical disease caused by BK virus reactivation is a frequent complication of allogeneic hematopoietic cell transplantation (HCT). Because of the lack of effective antiviral agents, BK virus-specific T cells are emerging as a potential therapy for BK virus disease, but the immune response to BK virus after allogeneic HCT has not been well characterized. Our study describes reconstitution of BK virus-specific T-cell immunity in 77 adult patients after HCT. All patients had urinary symptoms, and urine was tested for BK virus replication; 33 patients were positive for BK virus (cases), and 44 were negative (controls). In BK virus cases, the median time to first positive test was 75 days (range, 2-511). BK virus cases had lower CD4 T-cell counts 3 to 9 months after transplant, but CD8 T-cell counts were similar in cases and controls. BK virus-specific T cells were identified by cytokine flow cytometry in cryopreserved samples collected prospectively. BK virus-specific CD4 T cells producing T helper 1 (Th1) cytokines recovered quickly after HCT. BK virus-specific T cells were detected more frequently in patients with BK virus reactivation at most time points, and CD4 T cells producing Th1 cytokines were more frequent than BK virus-specific cytolytic CD8 T cells. Early detection of interferon-Îł+ and cytolytic BK virus-specific CD4 T cells was associated with lower rates of hematuria among cases. Overall, our study describes recovery of BK virus-specific T cells after HCT and the distinct roles for BK virus-specific T cells in the development and resolution of clinical symptoms.This work was supported by a Collaborative Research Grant from the Harvard Medical School–Portugal Program in Translational Research HMSP-ICT/0001/201, National Institutes of Health, National Cancer Institute grants CA183559, CA183560, and CA229092, and the Pasquarello Tissue Bank in Hematologic Malignancies. E.E. is a PhD candidate at Universidade de Lisboa, and this work is submitted in partial fulfillment of the requirement for a PhD and was supported by a grant for medical fellows enrolled in a PhD program (SubsĂ­dios aos Internos Doutorandos–SINTD) from Fundação para a CiĂȘncia e Tecnologia, number SFRH/SINTD/135312/2017info:eu-repo/semantics/publishedVersio

    The Chalcidoidea bush of life: evolutionary history of a massive radiation of minute wasps.

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    Chalcidoidea are mostly parasitoid wasps that include as many as 500 000 estimated species. Capturing phylogenetic signal from such a massive radiation can be daunting. Chalcidoidea is an excellent example of a hyperdiverse group that has remained recalcitrant to phylogenetic resolution. We combined 1007 exons obtained with Anchored Hybrid Enrichment with 1048 ultra-conserved elements (UCEs) for 433 taxa including all extant families, >95% of all subfamilies, and 356 genera chosen to represent the vast diversity of the superfamily. Going back and forth between the molecular results and our collective knowledge of morphology and biology, we detected bias in the analyses that was driven by the saturation of nucleotide data. Our final results are based on a concatenated analysis of the least saturated exons and UCE datasets (2054 loci, 284 106 sites). Our analyses support an expected sister relationship with Mymarommatoidea. Seven previously recognized families were not monophyletic, so support for a new classification is discussed. Natural history in some cases would appear to be more informative than morphology, as illustrated by the elucidation of a clade of plant gall associates and a clade of taxa with planidial first-instar larvae. The phylogeny suggests a transition from smaller soft-bodied wasps to larger and more heavily sclerotized wasps, with egg parasitism as potentially ancestral for the entire superfamily. Deep divergences in Chalcidoidea coincide with an increase in insect families in the fossil record, and an early shift to phytophagy corresponds with the beginning of the "Angiosperm Terrestrial Revolution". Our dating analyses suggest a middle Jurassic origin of 174 Ma (167.3-180.5 Ma) and a crown age of 162.2 Ma (153.9-169.8 Ma) for Chalcidoidea. During the Cretaceous, Chalcidoidea may have undergone a rapid radiation in southern Gondwana with subsequent dispersals to the Northern Hemisphere. This scenario is discussed with regard to knowledge about the host taxa of chalcid wasps, their fossil record and Earth's palaeogeographic history

    Taking a more nuanced look at behavior change for demand reduction in the illegal wildlife trade

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    The illegal wildlife trade threatens the future of many species, and undermines economies and livelihoods. Conservationists have largely responded with supply‐side interventions, such as antipoaching patrols, but these often fail to stem the tide of wildlife trafficking. There is now increasing interest in demand‐side interventions, which seek to lower poaching pressure on sought‐after species by reducing consumer's desire for, and purchase of, specific wildlife products. Individual behavior change approaches, from environmental education to social marketing, have been widely advocated by academics, practitioners, and policy makers. However, this is an emerging field and we lack the breadth of evidence needed to understand and predict the potential outcomes of demand reduction interventions. To help us gain broader insights, we examine the literature from public health and international development on the effectiveness of behavior change interventions, and critique the current conceptualization of strategies for reducing consumer demand in the illegal wildlife trade. We show that behavior change is difficult to achieve and interventions may have unintended and undesirable consequences because of unaddressed systemic, cultural and environmental drivers, and limited resourcing. We conclude that some sections of the conservation community are advocating a shift from one reductionist approach based on limiting supply, to another based on limiting demand, and argue that conservationists should learn from the public health and international development projects that have integrated systems thinking. By accounting for the multiple interactions and synergies between different factors in the wildlife trade, we can develop more strategic approaches to protecting endangered species

    Protecting Wild Land from Wind Farms in a Post-EU Scotland

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    Scotland is one of the places in Europe to have experienced significant wind farm development over recent years. Concern about impacts on wild land has resulted in legal challenges based on European Union (EU) law. This article analyses whether wild land can be protected from wind farms and the differences that the United Kingdom (UK) departure from the EU will make. It considers the concept of 'wild land' compared with 'wilderness', analyses the legal basis (if any) for wild land protection, and examines potential impacts from wind farms. It highlights the significance of EU environmental law, particularly nature conservation and environmental assessment law, and analyses recent Scottish jurisprudence that has applied this. The role of the European Commission and Court of Justice of the EU (CJEU) is emphasised as a key part of EU environmental law. The article asks whether relevant global and regional environmental agreements can effectively replace the content of the substantive law and context of the Commission and CJEU. Four environmental agreements and two related compliance procedures are briefly evaluated. The conclusion is that while EU law does not directly provide protection for wild land, it is considerably stronger than the international environmental agreements that may replace it
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