43 research outputs found

    Magnetic Resonance Angiography Visualization of Abnormal Tumor Vasculature in Genetically Engineered Mice

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    Previous research on the vasculature of tumor-bearing animals has focused upon the microvasculature. Magnetic resonance angiography (MRA) offers a noninvasive, complementary approach that provides information about larger vessels. Quantitative analysis of MRA images of spontaneous preclinical tumor models has not been previously reported. Eleven Tg

    Malignancy-Associated Vessel Tortuosity: A Computer-Assisted, MRA Study of Choroid Plexus Carcinoma in Genetically Engineered Mice

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    Background and Purpose—The ability to assess tumor malignancy and to monitor treatment response non-invasively would be of value to both clinicians and animal investigators. This report describes the MR imaging characteristics of a genetically engineered mouse model of choroid plexus carcinoma (CPC) during tumor growth and progression to malignancy. We assess the ability of vessel tortuosity measurements, as calculated from high-resolution MRA images, to detect emerging CPC cancers. Methods—MR images were analyzed of 9 healthy mice and of 20 CPC mice with precancerous choroid dysplasia or with cancer over a wide range of sizes. Two vessel tortuosity measures and a measure of vessel density (vessel count) were calculated from MRA images. Malignancy assessment was based upon a statistical analysis of vessel tortuosity, using an equation derived from an earlier study of human brain tumor patients. Results—Choroid dysplasia was correctly judged non-malignant. On the basis of vessel count, neoangiogenesis could not be detected until cancers were full-blown and had reached a volume of approximately 80mm3. Vessel tortuosity measurements, however, correctly identified emerging malignancy in lesions larger than 0.3mm3. Conclusion—This report provides the first description of in vivo, MR imaging characteristics of genetically engineered CPC mice during the progression from dysplasia to cancer. Vessel tortuosity measurements offer promise of correctly defining even tiny tumors as malignant

    Novel Genetic Tools for Diaminopimelic Acid Selection in Virulence Studies of Yersinia pestis

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    Molecular studies of bacterial virulence are enhanced by expression of recombinant DNA during infection to allow complementation of mutants and expression of reporter proteins in vivo. For highly pathogenic bacteria, such as Yersinia pestis, these studies are currently limited because deliberate introduction of antibiotic resistance is restricted to those few which are not human treatment options. In this work, we report the development of alternatives to antibiotics as tools for host-pathogen research during Yersinia pestis infections focusing on the diaminopimelic acid (DAP) pathway, a requirement for cell wall synthesis in eubacteria. We generated a mutation in the dapA-nlpB(dapX) operon of Yersinia pestis KIM D27 and CO92 which eliminated the expression of both genes. The resulting strains were auxotrophic for diaminopimelic acid and this phenotype was complemented in trans by expressing dapA in single and multi-copy. In vivo, we found that plasmids derived from the p15a replicon were cured without selection, while selection for DAP enhanced stability without detectable loss of any of the three resident virulence plasmids. The dapAX mutation rendered Y. pestis avirulent in mouse models of bubonic and septicemic plague which could be complemented when dapAX was inserted in single or multi-copy, restoring development of disease that was indistinguishable from the wild type parent strain. We further identified a high level, constitutive promoter in Y. pestis that could be used to drive expression of fluorescent reporters in dapAX strains that had minimal impact to virulence in mouse models while enabling sensitive detection of bacteria during infection. Thus, diaminopimelic acid selection for single or multi-copy genetic systems in Yersinia pestis offers an improved alternative to antibiotics for in vivo studies that causes minimal disruption to virulence

    On a Completely Residual-Based Method for Computer Code Verification

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    OneButton: A Link Resolving Application to Guide Users to Optimal Fulfillment Options

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    Like many consortia, institutional members of the Private Academic Library Network of Indiana (PALNI) provide multiple fulfillment options to obtain requested items for their users. Users can place on shelf holds on items, or they can request material that isn’t held by their institution through a group circulation resource sharing network (dubbed PALShare) or through traditional InterLibrary Loan (ILL) (through WorldShare ILL or ILLiad). All of these options can be confusing to users who may not understand the best or fastest way to get access to needed materials. A PHP application, OneButton, was developed that replaces multiple fulfillment buttons in institutional discovery interfaces with a single OpenURL link. OneButton looks up holdings and availability at a user’s home institution and across the consortium and routes the user to the optimal fulfillment option for them. If an item is held by and available at their institution, the user can be shown a stack map to help guide them to the item on the shelf; if an item is held by and available at the consortium, the user is routed to a group circulation request form; otherwise, the user is routed to an ILL request form. All routing and processing are handled by the OneButton application – the user doesn’t need to think about what the ‘best’ fulfillment option is. This article will discuss the experiences of one institution using OneButton in production since fall 2017, analytics data gathered, and how other institutions can adopt the application (freely available on GitHub: https://github.com/PALNI/onebutton)
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