1,687 research outputs found

    Computing the eigenvalues of symmetric H2-matrices by slicing the spectrum

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    The computation of eigenvalues of large-scale matrices arising from finite element discretizations has gained significant interest in the last decade. Here we present a new algorithm based on slicing the spectrum that takes advantage of the rank structure of resolvent matrices in order to compute m eigenvalues of the generalized symmetric eigenvalue problem in O(nmlogαn)\mathcal{O}(n m \log^\alpha n) operations, where α>0\alpha>0 is a small constant

    Long-term complete remission with belinostat in a patient with chemotherapy refractory peripheral t-cell lymphoma

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    Peripheral T/NK-cell lymphomas (PTCL) are rare malignancies with a poor prognosis. Due to the lack of randomised studies, standard therapy has not been established. First-line treatment with anthracycline-based polychemotherapy followed by consolidation with high-dose therapy and autologous stem cell transplant in responding patients has demonstrated good feasibility with low toxicity in prospective studies and is widely used in eligible patients. In relapsed and refractory patients, who are not candidates for transplant approaches, therapeutic options are limited and are usually palliative. Several new agents are currently under investigation to improve the outcome of PTCL in the first line and salvage settings. Belinostat, a histone deacetylase (HDAC) inhibitor, has demonstrated broad antineoplastic activity in preclinical studies, and promising results in advanced relapsed/refractory lymphomas. Here, we report the case of a 73 year old patient with heavily pre-treated refractory PTCL in complete remission with belinostat for 39 months

    MR angiography with blood pool contrast agents

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    Contrast-enhanced magnetic resonance angiography (CE-MRA) with standard extracellular contrast material is well established for vascular imaging. Recently, the first blood pool contrast agent (BPA) has become clinically available. This paper reviews characteristics and classification of BPA as well as first clinical experience in various vascular territories. BPAs comprise gadolinium-based compounds, synthetic compounds, and ultrasmall superparamagnetic iron-oxide (USPIO) particles. Such BPAs are retained in blood with a prolonged time-window of enhancement as compared to extracellular gadolinium chelates. Promising results from USPIO at first-pass and steady-state angiography have been published, but no USPIO is approved yet. Gadofosveset is the first clinically approved BPA. After bolus injection, gadofosveset binds noncovalently to serum-albumine, thus enhancing relaxivity. First published results from carotid, coronary, renal, and peripheral angiography are encouraging; particularly helpful is prolonged enhancement during steady state. More BPAs have been clinically evaluated, but no approval has been granted. Bolus-injectable BPAs allow for first-pass CE-MRA similar to standard extracellular contrast media, but with higher relaxivity, allowing lower doses and reduced injection rates. An additional feature of BPA is the steady-state phase with a broad time window enabling high-resolution angiography or double-gated angiography of coronary arteries to compensate for the complex motion patter

    Measuring the Size, Scope & Scale of the Social Enterprise Sector in Manitoba

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    This project surveyed social enterprises in Manitoba during the spring and summer of 2011 to develop clear indicators of their size, market activities, and socio‐economic contributions. In this study, a social enterprise is defined as a business venture, owned or operated by a nonprofit organization that sells goods or provides services in the market to create a blended return on investment; financial, social, environmental, and cultural. Using this definition, researchers identified 266 operating social enterprises in Manitoba. Of the 266 social enterprises that received the survey, 118 responded. Indicators of socio‐economic contribution included sales and revenue, expenditures, employment, volunteer engagement, and clients served and trained. Respondents were asked to report results of the 2010 financial year. The following report is a summary of the survey findings. Prior to revealing the survey findings, this paper provides a brief history of the innovative approaches to community economic development that have been used in Manitoba. The province’s roots in community‐based economic models laid the foundation for Manitoba’s current social enterprises, which are found to be a diverse sector, composed of businesses meeting a range of poverty reduction, social, cultural or environmental goals. The survey results suggest that in 2010, the 118 responding social enterprises generated at least 55.4millionincumulativerevenue,includingatleast55.4 million in cumulative revenue, including at least 41.5 million generated through sales. Responding social enterprises paid at least 25.3millioninsalariesandwagesto3,752people,ofwhom3,450wereemployedaspartofthemissionoftheorganization.WeestimatethatManitobasocialenterprisespaid,onaverage,justover25.3 million in salaries and wages to 3,752 people, of whom 3,450 were employed as part of the mission of the organization. We estimate that Manitoba social enterprises paid, on average, just over 20,000 in wages and salary per full‐time equivalent employee. Additionally, social enterprises trained 6,890 individuals, generated 5,870 volunteer opportunities, and provided services to an average of 4,200 people. This paper builds a strong case for stakeholders, community, funder, and government, to collaboratively value these distinct contributions and to support hospitable environments for social enterprises.BC‐Alberta Social Economy Research Alliance (BALTA), Canadian Community Economic Development Network (CCEDNet), Manitoba Social Enterprise Working Group, Assiniboine Credit Union, United Way of Winnipeg, Social Sciences and Humanities Research Council of Canada, Mount Royal Universit

    Unbiased Characterization of Anopheles Mosquito Blood Meals by Targeted High-Throughput Sequencing

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    Understanding mosquito host choice is important for assessing vector competence or identifying disease reservoirs. Unfortunately, the availability of an unbiased method for comprehensively evaluating the composition of insect blood meals is very limited, as most current molecular assays only test for the presence of a few pre-selected species. These approaches also have limited ability to identify the presence of multiple mammalian hosts in a single blood meal. Here, we describe a novel high-throughput sequencing method that enables analysis of 96 mosquitoes simultaneously and provides a comprehensive and quantitative perspective on the composition of each blood meal. We validated in silico that universal primers targeting the mammalian mitochondrial 16S ribosomal RNA genes (16S rRNA) should amplify more than 95% of the mammalian 16S rRNA sequences present in the NCBI nucleotide database. We applied this method to 442 female Anopheles punctulatus s. l. mosquitoes collected in Papua New Guinea (PNG). While human (52.9%), dog (15.8%) and pig (29.2%) were the most common hosts identified in our study, we also detected DNA from mice, one marsupial species and two bat species. Our analyses also revealed that 16.3% of the mosquitoes fed on more than one host. Analysis of the human mitochondrial hypervariable region I in 102 human blood meals showed that 5 (4.9%) of the mosquitoes unambiguously fed on more than one person. Overall, analysis of PNG mosquitoes illustrates the potential of this approach to identify unsuspected hosts and characterize mixed blood meals, and shows how this approach can be adapted to evaluate inter-individual variations among human blood meals. Furthermore, this approach can be applied to any disease-transmitting arthropod and can be easily customized to investigate non-mammalian host sources

    Impact of Autologous and Allogeneic Stem Cell Transplantation in Peripheral T-Cell Lymphomas

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    Peripheral T/NK-cell lymphomas (PTCLs) are rare malignancies characterized by poor prognosis. So far, no standard therapy has been established, due to the lack of randomised studies. High-dose therapy and autologous stem cell transplantation (HDT-autoSCT) have shown good feasibility with low toxicity in retrospective studies. In relapsing and refractory PTCL several comparison analyses suggest similar efficacy for PTCL when compared with aggressive B-cell lymphoma. In the upfront setting, prospective data show promising results with a long-lasting overall survival in a relevant subset of patients. Achieving a complete remission at transplantation seems to be the most important prognostic factor. Allogeneic stem cell transplantation (alloSCT) has been investigated only as salvage treatment. Especially when using reduced intensity conditioning regimen, eligible patients seem to benefit from this approach. To define the role for upfront stem cell transplantation a randomised trial by the German High-Grade Non-Hodgkin Lymphoma Study Group comparing HDT-autoSCT and alloSCT will be initiated this year

    Fast neutron induced reactions leading to activation products: selected cases relevant to development of low activation materials, transmutation and hazard assessment of nuclear wastes

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    Neutron induced cross sections are of interest for practical applications and for testing nuclear models. In this work(n,p),(n,np),(n,α\alpha),(n,nα\alpha),(n,n'γ\gamma), (n,2n) and (n,3n) reactions on vanadium, molybdenum, technetium and lead have been measured in the energy range of 0.5 to 20.6 MeV using the activation technique. The radioactive reaction products with half-lives between 58 seconds and 20300 years have been measured offline via high-resolution γ\gamma-ray-spectrometry and Liquid Scintillation Counting, the latter in combination with radiochemical separation. Irradiations with neutron energies in the range of 0.5 to 6 MeV were done using the 3^{3}H(p,n)3^{3}He reaction with a solid-state Ti/T target while energies between 7.4 and 12.5 MeV were covered with the 2^{2}H(d,n)3^{3}He reaction utilizing a D2_{2} gas target. Irradiations in the energy range from 13.4 to 20.6 MeV were performed using the 3^{3}H(d,n)4^{4}He reaction, again with a solid Ti/T target. Most of the reactions were investigated using a light mass setup to minimise scattering effects, but for short half-lives a pneumatic sample transport system was used as well. A special sample holder was developed for the measurement of the nat^{nat}Mo(n,x)94^{94}Nb reaction. All cross sections were measured relative to the 27^{27}Al(n,α\alpha)24^{24}Na standard cross section and all necesarry corrections due to their radiation process and the measurement of the induced activity have been applied. Nuclear model calculations were performed for all investigated reactions. For reactions on 99^{99}Tc and Pb the original STAPRE code was used, while for reactions on V and Mo a modified version STAPRE-H was employed. As a result of this thesis work an extended database for neutron induced cross sections on four elements was obtained. It was possible to establish first excitation functions for reactions on a radioactive target nucleus, one very long-lived product and one purely β\beta^{-} emitting product. It was found that existing evaluations are not always reliable in the prediction of unknown cross sections. Although the experimental results of this work helped to considerably improve the calculations, some deficiencies still exist in case of complex particle emission (like d,t,α\alpha) and second chance emission (n,np) or (n,pn) etc

    Investigations on the Usefulness of CEACAMs as Potential Imaging Targets for Molecular Imaging Purposes

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    Members of the carcinoembryonic antigen cell adhesion molecules (CEACAMs) family are the prototype of tumour markers. Classically they are used as serum markers, however, CEACAMs could serve as targets for molecular imaging as well. In order to test the anti CEACAM monoclonal antibody T84.1 for imaging purposes, CEACAM expression was analysed using this antibody. Twelve human cancer cell lines from different entities were screened for their CEACAM expression using qPCR, Western Blot and FACS analysis. In addition, CEACAM expression was analyzed in primary tumour xenografts of these cells. Nine of 12 tumour cell lines expressed CEACAM mRNA and protein when grown in vitro. Pancreatic and colon cancer cell lines showed the highest expression levels with good correlation of mRNA and protein level. However, when grown in vivo, the CEACAM expression was generally downregulated except for the melanoma cell lines. As the CEACAM expression showed pronounced expression in FemX-1 primary tumours, this model system was used for further experiments. As the accessibility of the antibody after i.v. application is critical for its use in molecular imaging, the binding of the T84.1 monoclonal antibody was assessed after i.v. injection into SCID mice harbouring a FemX-1 primary tumour. When applied i.v., the CEACAM specific T84.1 antibody bound to tumour cells in the vicinity of blood vessels. This binding pattern was particularly pronounced in the periphery of the tumour xenograft, however, some antibody binding was also observed in the central areas of the tumour around blood vessels. Still, a general penetration of the tumour by i.v. application of the anti CEACAM antibody could not be achieved despite homogenous CEACAM expression of all melanoma cells when analysed in tissue sections. This lack of penetration is probably due to the increased interstitial fluid pressure in tumours caused by the absence of functional lymphatic vessels.Germany. Bundesministerium für Bildung und Forschung (TOMCAT, grant number 01EZ0824
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