1,721,077 research outputs found
Antibodies against endogenous retroviruses promote lung cancer immunotherapy
No full textB cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response.sponsorship: [
"We are grateful for assistance from the Advanced Light Microscopy, Advanced Sequencing, Experimental Histopathology, Biological Research, Cell Services, Proteomics, Flow Cytometry and Scientific Computing facilities at the Francis Crick Institute. The TRACERx study (ClinicaTtrials.gov: NCT01888601) is sponsored by University College London (UCL/12/0279) and has been approved by an independent research ethics committee (13/LO/1546). TRACERx is funded by Cancer Research UK (C11496/A17786) and is coordinated through the Cancer Research UK and University College London Cancer Trials Centre, which has a core grant from CRUK (C444/A15953). We gratefully acknowledge the patients and relatives who participated in the TRACERx study. We thank all site personnel, investigators, funders and industry partners who supported the generation of the data within this study. The results shown here are in whole or part based on data generated by the TCGA Research Network (http://cancergenome.nih.gov). The GTEx Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health and by NCI, NHGRI, NHLBI, NIDA, NIMH and NINDS. This work was supported by the Francis Crick Institute (CC2097, CC2088, CC2041 and CC2044), which receives its core funding from Cancer Research UK, the UK Medical Research Council and the Wellcome Trust. For the purpose of open access, the author has applied a CC BY public copyright licence to any author accepted manuscript version arising from this submission. This work was also supported by the Cancer Research UK Lung Cancer Centre of Excellence and the CRUK City of London Centre Award (C7893/A26233) as well as by the University College London Experimental Cancer Medicine Centre. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 101018670). C.S. is a Royal Society Napier Research Professor (RSRP\\R\\210001). C.S. is funded by Cancer Research UK (TRACERx (C11496/A17786), PEACE (C416/A21999) and CRUK Cancer Immunotherapy Catalyst Network); the Cancer Research UK Lung Cancer Centre of Excellence (C11496/A30025); the Rosetrees Trust and the Butterfield and Stoneygate Trusts; the Novo Nordisk Foundation (ID16584); the Royal Society Professorship Enhancement Award (RP/EA/180007); the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre; the Cancer Research UK-University College London Centre; the Experimental Cancer Medicine Centre; the Breast Cancer Research Foundation (US); and the Mark Foundation for Cancer Research Aspire Award (grant no. 21-029-ASP). This work was supported by a Stand Up To Cancer-LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational Research Grant (grant no. SU2C-AACR-DT23-17 to S. M. Dubinett and A. E. Spira). Stand Up To Cancer is a division of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the scientific partner of SU2C. C.S. is in receipt of an ERC Advanced Grant (PROTEUS) from the ERC under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 835297). K.S.S.E. was supported by the European Union's Horizon 2020 research and innovation programme under Marie Sklodowska-Curie grant agreement no. 838540 and the Royal Society (RF\\ERE\\210216). A.F.",
"has received funding from the European Union's Horizon 2020 research and innovation programme under Marie Sklodowska-Curie grant agreement no. 892360. S.d.C.T. was funded in part by a Marie Sklodowska-Curie Individual Fellowship from the European Union (MSCA-IF-2015-EF-ST 703228-iGEMMdev). T.K. is supported by the JSPS Overseas Research Fellowships Program (202060447). S.-H.L. is supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant no. HR20C0025), and a National Research Foundation of Korea (NRF) grant funded by the Korean government (Ministry of Science and ICT) (grant no. 2020R1A2C3006535). C.M.-R. is supported by the Rosetrees Trust (M630) and by the Wellcome Trust. A.M.F. is supported by Stand Up To Cancer (SU2C-AACR-DT23-17). M.A.B. is supported by Cancer Research UK and the Rosetrees Trust. K.L. is funded by the UK Medical Research Council (MR/P014712/1 and MR/V033077/1), the Rosetrees Trust and Cotswold Trust (A2437), and Cancer Research UK (C69256/A30194). N.J.B. is a fellow of the Lundbeck Foundation (R272-2017-4040) and acknowledges funding from the Aarhus University Research Foundation (AUFF-E-2018-7-14) and the Novo Nordisk Foundation (NNF21OC0071483). N. McGranahan is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (grant no. 211179/Z/18/Z), and also receives funding from Cancer Research UK, Rosetrees and the NIHR BRC at University College London Hospitals, and the Cancer Research UK-University College London Experimental Cancer Medicine Centre. M.J.-H. is a CRUK Career Establishment Awardee and has received funding from CRUK, the IASLC International Lung Cancer Foundation, the Lung Cancer Research Foundation, the Rosetrees Trust, UKI NETs, the NIHR and the NIHR UCLH Biomedical Research Centre."
] (University College London|UCL/12/0279, University College London|13/LO/1546, Cancer Research UK, University College London Cancer Trials Centre, CRUK, Common Fund of the Office of the Director of the National Institutes of Health, NCI, NHGRI, NHLBI, NIDA, NIMH, NINDS, Francis Crick Institute|CC2097, Francis Crick Institute|CC2088, Francis Crick Institute|CC2041, Francis Crick Institute|CC2044, UK Medical Research Council, Wellcome Trust, Cancer Research UK Lung Cancer Centre of Excellence|C11496/A30025, CRUK City of London Centre Award|C7893/A26233, University College London Experimental Cancer Medicine Centre, European Research Council (ERC) under the European Union|101018670, European Research Council (ERC) under the European Union|RSRP\R\210001, (CRUK Cancer Immunotherapy Catalyst Network), Rosetrees Trust, Stoneygate Trusts, Novo Nordisk Foundation|NNF21OC0071483, Royal Society Professorship Enhancement Award|RP/EA/180007, National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, Experimental Cancer Medicine Centre, Breast Cancer Research Foundation (US), Mark Foundation for Cancer Research Aspire Award|21-029-ASP, Stand Up To Cancer-LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational Research Grant|835297, Stand Up To Cancer is a division of the Entertainment Industry Foundation, scientific partner of SU2C, ERC Advanced Grant (PROTEUS) from the ERC under the European Union|MSCA-IF-2015-EF-ST 703228-iGEMMdev, European Union|211179/Z/18/Z, Royal Society|202060447, JSPS Overseas Research Fellowships Program|HR20C0025, Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea|2020R1A2C3006535, National Research Foundation of Korea (NRF) - Korean government (Ministry of Science and ICT)|MR/P014712/1, Stand Up To Cancer, Rosetrees Trust - UK Medical Research Council|MR/V033077/1, Rosetrees Trust - UK Medical Research Council|A2437, Rosetrees Trust and Cotswold Trust|AUFF-E-2018-7-14, Aarhus University Research Foundation, Rosetrees, NIHR BRC at University College London Hospitals, Cancer Research UK-University College London Experimental Cancer Medicine Centre, CRUK Career Establishment Awardee, IASLC International Lung Cancer Foundation, Lung Cancer Research Foundation, NIHR, NIHR UCLH Biomedical Research Centre, European Research Council (ERC)|101018670)status: Publishe
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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