211 research outputs found

    Knox v. United States Department of Labor: The Potentially Risky Business of Interpreting Asbestos Statutes

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    Hypermaskulinitet - It's a man's world

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    Hypermaskulinitet är en förklaringsfaktor till konflikter inom studiet av internationella relationer. Feministiska teoretiker har på senare år forskat allt mer kring fenomenet och denna uppsats är ett steg i ledet att applicera feministisk teori i praktiken. Problemställningen i uppsatsen avser att urskilja hypermaskulinitet i studieobjektet USA:s kommunikation i utvalda konflikter. Uppsatsen är av longitudinell karaktär och urvalet har begränsats till fem presidenttal per konflikt från sammanlagt fem konflikter där USA varit en närvarande kraft. Om hypermaskulinitet går att urskilja avser uppsatsen vidare att finna vilket uttryck diskursen tar sig och dess förändring över tid. Syftet med undersökningen är att via applicering av hypermaskulina teorier bredda spektret av förklaringsfaktorer till konflikter. Operationaliseringen bygger på tidigare forskning och valda analysmetoder är frekvens- och diskursanalys vilka ger arbetet en kvantitativ samt kvalitativ karaktär. Resultat av analyserna är samstämmiga även om diskursanalysen ger tydligare utslag av hypermaskulinitet

    Targeting small molecule drugs to T cells with antibody-directed cell-penetrating gold nanoparticles

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    We sought to develop a nanoparticle vehicle that could efficiently deliver small molecule drugs to target lymphocyte populations. The synthesized amphiphilic organic ligand-protected gold nanoparticles (amph-NPs) were capable of sequestering large payloads of small molecule drugs within hydrophobic pockets of their ligand shells. These particles exhibit membrane-penetrating activity in mammalian cells, and thus enhanced uptake of a small molecule TGF-β inhibitor in T cells in cell culture. By conjugating amph-NPs with targeting antibodies or camelid-derived nanobodies, the particles' cell-penetrating properties could be temporarily suppressed, allowing targeted uptake in specific lymphocyte subpopulations. Degradation of the protein targeting moieties following particle endocytosis allowed the NPs to recover their cell-penetrating activity in situ to enter the cytoplasm of T cells. In vivo, targeted amph-NPs showed 40-fold enhanced uptake in CD8+ T cells relative to untargeted particles, and delivery of TGF-β inhibitor-loaded particles to T cells enhanced their cytokine polyfunctionality in a cancer vaccine model. Thus, this system provides a facile approach to concentrate small molecule compounds in target lymphocyte populations of interest for immunotherapy in cancer and other diseases.Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Contract W911NF-13-D-0001)Melanoma Research AllianceNational Cancer Institute (U.S.) (David H. Koch Institute for Integrative Cancer Research at MIT. (Support (Core) Grant P30-CA14051)National Institutes of Health (U.S.) (Grant CA174795)National Institutes of Health (U.S.) (Grant CA172164)Horizon 2020 Framework Programme (European Commission). FutureNanoNeeds Projec

    Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts

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    Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multiregion samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host.</p

    Sheridan School of Architectural Technology Volume 2 [S2017]

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    Welcome to Sheridan’s School of Architectural Technician/Technology printed portfolio volume 2. A combination of student work as well as faculty research has once again been been amalgamated into a print and digital portfolio showing the academic excellence of our program. Student work in the book is largely from the course CADD 39788 Architectural Computer Visualisation with a few projects from other courses making guest appearances. Our faculty research section near the back of the book offers insights into the professional interests and engagements of Sheridan professors.https://source.sheridancollege.ca/fast_books/1002/thumbnail.jp

    A non-destructive sugar-feeding assay for parasite detection and estimating the extrinsic incubation period of Plasmodium falciparum in individual mosquito vectors

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    Despite its epidemiological importance, the time Plasmodium parasites take to achieve development in the vector mosquito (the extrinsic incubation period, EIP) remains poorly characterized. A novel non-destructive assay designed to estimate EIP in single mosquitoes, and more broadly to study Plasmodium–Anopheles vectors interactions, is presented. The assay uses small pieces of cotton wool soaked in sugar solution to collect malaria sporozoites from individual mosquitoes during sugar feeding to monitor infection status over time. This technique has been tested across four natural malaria mosquito species of Africa and Asia, infected with Plasmodium falciparum (six field isolates from gametocyte-infected patients in Burkina Faso and the NF54 strain) and across a range of temperatures relevant to malaria transmission in field conditions. Monitoring individual infectious mosquitoes was feasible. The estimated median EIP of P. falciparum at 27 °C was 11 to 14 days depending on mosquito species and parasite isolate. Long-term individual tracking revealed that sporozoites transfer onto cotton wool can occur at least until day 40 post-infection. Short individual EIP were associated with short mosquito lifespan. Correlations between mosquito/parasite traits often reveal trade-offs and constraints and have important implications for understanding the evolution of parasite transmission strategies
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