526 research outputs found
SciTokens: Capability-Based Secure Access to Remote Scientific Data
The management of security credentials (e.g., passwords, secret keys) for
computational science workflows is a burden for scientists and information
security officers. Problems with credentials (e.g., expiration, privilege
mismatch) cause workflows to fail to fetch needed input data or store valuable
scientific results, distracting scientists from their research by requiring
them to diagnose the problems, re-run their computations, and wait longer for
their results. In this paper, we introduce SciTokens, open source software to
help scientists manage their security credentials more reliably and securely.
We describe the SciTokens system architecture, design, and implementation
addressing use cases from the Laser Interferometer Gravitational-Wave
Observatory (LIGO) Scientific Collaboration and the Large Synoptic Survey
Telescope (LSST) projects. We also present our integration with widely-used
software that supports distributed scientific computing, including HTCondor,
CVMFS, and XrootD. SciTokens uses IETF-standard OAuth tokens for
capability-based secure access to remote scientific data. The access tokens
convey the specific authorizations needed by the workflows, rather than
general-purpose authentication impersonation credentials, to address the risks
of scientific workflows running on distributed infrastructure including NSF
resources (e.g., LIGO Data Grid, Open Science Grid, XSEDE) and public clouds
(e.g., Amazon Web Services, Google Cloud, Microsoft Azure). By improving the
interoperability and security of scientific workflows, SciTokens 1) enables use
of distributed computing for scientific domains that require greater data
protection and 2) enables use of more widely distributed computing resources by
reducing the risk of credential abuse on remote systems.Comment: 8 pages, 6 figures, PEARC '18: Practice and Experience in Advanced
Research Computing, July 22--26, 2018, Pittsburgh, PA, US
PyMT-Maclow: A novel, inducible, murine model for determining the role of CD68 positive cells in breast tumor development
CD68+ tumor-associated macrophages (TAMs) are pro-tumorigenic, pro-angiogenic and are associated with decreased survival rates in patients with cancer, including breast cancer. Non-specific models of macrophage ablation reduce the number of TAMs and limit the development of mammary tumors. However, the lack of specificity and side effects associated with these models compromise their reliability. We hypothesized that specific and controlled macrophage depletion would provide precise data on the effects of reducing TAM numbers on tumor development. In this study, the MacLow mouse model of doxycycline-inducible and selective CD68+ macrophage depletion was crossed with the murine mammary tumor virus (MMTV)-Polyoma virus middle T antigen (PyMT) mouse model of spontaneous ductal breast adenocarcinoma to generate the PyMT-MacLow line. In doxycycline-treated PyMT-MacLow mice, macrophage numbers were decreased in areas surrounding tumors by 43%. Reducing the number of macrophages by this level delayed tumor progression, generated less proliferative tumors, decreased the vascularization of carcinomas and down-regulated the expression of many pro-angiogenic genes. These results demonstrate that depleting CD68+ macrophages in an inducible and selective manner delays the development of mammary tumors and that the PyMT-MacLow model is a useful and unique tool for studying the role of TAMs in breast cancer
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Leadership as sustainability: context and primary school principals in Jamaica
School leadership is as challenging as it is rewarding. And, in a fast paced educational policy environment, school leaders sometimes are having to play catchup with the latest government mandate. This challenge is exacerbated in environments where economic and social problems and lack of parental engagement in education are a daily occurrence and a significant risk to the effectiveness of schools. While we recognize the notion of sustainable school leadership is continuing its evolution, we also acknowledge it is not a single act and nor is it enacted by a single individual. Reporting findings from a qualitative study of primary school leaders in Jamaica, we argue that sustainable school leadership is not a new form of leadership, but rather a type of leadership that combines multiple practices to produce long-term impacts on members of a school community that are “now” and “futures” oriented
Cloned cattle derived from a novel zona-free embryo reconstruction system
As the demand for cloned embryos and offspring increases, the need arises for the development of nuclear transfer procedures that are improved in both efficiency and ease of operation. Here, we describe a novel zona-free cloning method that doubles the throughput in cloned bovine embryo production over current procedures and generates viable offspring with the same efficiency. Elements of the procedure include zona-free enucleation without a holding pipette, automated fusion of 5-10 oocyte-donor cell pairs and microdrop in vitro culture. Using this system, zona-free embryos were reconstructed from five independent primary cell lines and cultured either singularly (single-IVC) or as aggregates of three (triple-IVC). Blastocysts of transferable quality were obtained at similar rates from zona-free single-IVC, triple-IVC, and control zona-intact embryos (33%, 25%, and 29%, respectively). In a direct comparison, there was no significant difference in development to live calves at term between single-IVC, triple-IVC, and zona-intact embryos derived from the same adult fibroblast line (10%, 13%, and 15%, respectively). This zona-free cloning method could be straightforward for users of conventional cloning procedures to adopt and may prove a simple, fast, and efficient alternative for nuclear cloning of other species as well
ENU Mutagenesis Reveals a Novel Phenotype of Reduced Limb Strength in Mice Lacking Fibrillin 2
Background: Fibrillins 1 (FBN1) and 2 (FBN2) are components of microfibrils, microfilaments that are present in many connective tissues, either alone or in association with elastin. Marfan's syndrome and congenital contractural arachnodactyly (CCA) result from dominant mutations in the genes FBN1 and FBN2 respectively. Patients with both conditions often present with specific muscle atrophy or weakness, yet this has not been reported in the mouse models. In the case of Fbn1, this is due to perinatal lethality of the homozygous null mice making measurements of strength difficult. In the case of Fbn2, four different mutant alleles have been described in the mouse and in all cases syndactyly was reported as the defining phenotypic feature of homozygotes.Methodology/Principal Findings: As part of a large-scale N-ethyl-N-nitrosourea (ENU) mutagenesis screen, we identified a mouse mutant, Mariusz, which exhibited muscle weakness along with hindlimb syndactyly. We identified an amber nonsense mutation in Fbn2 in this mouse mutant. Examination of a previously characterised Fbn2-null mutant, Fbn2(fp), identified a similar muscle weakness phenotype. The two Fbn2 mutant alleles complement each other confirming that the weakness is the result of a lack of Fbn2 activity. Skeletal muscle from mutants proved to be abnormal with higher than average numbers of fibres with centrally placed nuclei, an indicator that there are some regenerating muscle fibres. Physiological tests indicated that the mutant muscle produces significantly less maximal force, possibly as a result of the muscles being relatively smaller in Mariusz mice.Conclusions: These findings indicate that Fbn2 is involved in integrity of structures required for strength in limb movement. As human patients with mutations in the fibrillin genes FBN1 and FBN2 often present with muscle weakness and atrophy as a symptom, Fbn2-null mice will be a useful model for examining this aspect of the disease process further
Preventing phosphorylation of dystroglycan ameliorates the dystrophic phenotype in mdx mouse
Loss of dystrophin protein due to mutations in the DMD gene causes Duchenne muscular dystrophy. Dystrophin loss also leads to the loss of the dystrophin glycoprotein complex (DGC) from the sarcolemma which contributes to the dystrophic phenotype. Tyrosine phosphorylation of dystroglycan has been identified as a possible signal to promote the proteasomal degradation of the DGC. In order to test the role of tyrosine phosphorylation of dystroglycan in the aetiology of DMD, we generated a knock-in mouse with a phenylalanine substitution at a key tyrosine phosphorylation site in dystroglycan, Y890. Dystroglycan knock-in mice (Dag1Y890F/Y890F) had no overt phenotype. In order to examine the consequence of blocking dystroglycan phosphorylation on the aetiology of dystrophin-deficient muscular dystrophy, the Y890F mice were crossed with mdx mice an established model of muscular dystrophy. Dag1Y890F/Y890F/mdx mice showed a significant improvement in several parameters of muscle pathophysiology associated with muscular dystrophy, including a reduction in centrally nucleated fibres, less Evans blue dye infiltration and lower serum creatine kinase levels. With the exception of dystrophin, other DGC components were restored to the sarcolemma including α-sarcoglycan, α-/β-dystroglycan and sarcospan. Furthermore, Dag1Y890F/Y890F/mdx showed a significant resistance to muscle damage and force loss following repeated eccentric contractions when compared with mdx mice. While the Y890F substitution may prevent dystroglycan from proteasomal degradation, an increase in sarcolemmal plectin appeared to confer protection on Dag1Y890F/Y890F/mdx mouse muscle. This new model confirms dystroglycan phosphorylation as an important pathway in the aetiology of DMD and provides novel targets for therapeutic intervention
‘PRi special edition: The intersections between public relations and neoliberalism’ – The road to nowhere: Re-examining activists’ role in civil societies
The French sociologist Pierre Bourdieu (1977) argued that the presence of critical counter-voices and powers is a fundamental element of any genuine democracy. However, in Australia these counter-voices are increasingly marginalized and threatened by controversial laws that would limit the legal standing of conservation groups and the use of overseas donations for advocacy purposes based on the argument that “systematic, well-funded” environmental campaigns are threatening the nation’s economic prosperity.
Drawing on social movement theory and Bourdieu’s theory of practice, this case study details the final months of the Save Beeliar Wetlands campaign in the lead up to the 2017 West Australian state election. The author challenges three common assumptions in the extant PR activism literature: The existence of activists in opposition to organizations and governments, the presence of a ‘zone of compromise’ between activists and the organizations or governments whose actions they are opposing and the conceptualization of activists as homogenous entity.
Evolving into a colorful collective of over 35 local groups, five local councils and thousands of individuals, Beeliar Wetland Defenders successfully created an alternative narrative to the State and Federal Governments’ neoliberal agenda. Activists thereby contributed significantly to a change in leadership and the termination of a $1.9billion infrastructure project. This paper argues that activist groups’ interventions in public debate perform a valuable societal voice as critical counter-voices in challenging established hierarchies and power relationships. However, in mounting and framing their arguments within the neoliberal framework, activist groups may also inadvertently reinforce this worldview
Infrequent Detection of KI, WU and MC Polyomaviruses in Immunosuppressed Individuals with or without Progressive Multifocal Leukoencephalopathy
Conflicting prevalence of newly identified KI(KIPyV), WU(WUPyV) and Merkel Cell Carcinoma(MCPyV) polyomaviruses have been reported in progressive multifocal leukoencephalopathy(PML) patient samples, ranging from 0 to 14.3%. We analyzed the prevalence of these polyomaviruses in cerebrospinal fluid(CSF), peripheral blood mononuclear cells(PBMC), and bone marrow samples from PML patients, immunosuppressed individuals with or without HIV, and multiple sclerosis(MS) patients. Distinct PCR tests for KIPyV, WUPyV and MCPyV DNA performed in two independent laboratories detected low levels of MCPyV DNA only in 1/269 samples. The infrequent detections of these viruses in multiple samples from immunosuppressed individuals including those with PML suggest that their reactivation mechanisms may be different from that of JC polyomavirus (JCPyV) and that they do not play a role in the pathogenesis of PML
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