59 research outputs found

    Dissent and the Future of the Church

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    Sidney Callahan has held visiting chairs of interdisciplinary studies and moral theology at Georgetown University and St. John\u27s University. This talk was presented at Sacred Heart University on September 29, 2004, as part of a year-long series of symposia on The Church and the Contemporary World, sponsored by the Center for Catholic Thought, Ethics, and Culture

    In Conversation: Ruth Macklin, Alison Reiheld, Robyn Bluhm, Sidney Callahan, and Frances Kissling Discuss the Marlise Munoz Case, Advance Directives, and Pregnant Women

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    Feminist bioethicists of a variety of persuasions discuss the 2013 case of Marlise Munoz, a pregnant woman whose medical care was in dispute after she became brain dead

    LSST: from Science Drivers to Reference Design and Anticipated Data Products

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    (Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg2^2 field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5σ\sigma point-source depth in a single visit in rr will be 24.5\sim 24.5 (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg2^2 with δ<+34.5\delta<+34.5^\circ, and will be imaged multiple times in six bands, ugrizyugrizy, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg2^2 region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to r27.5r\sim27.5. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Comment on Confucian Family Love from a Christian Perspective

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    OBSERVATIONS OF THE SOLAR-WIND TURBULENCE NEAR THE SUN

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    I have morethan the usual number of people to thank for their assistance during my stay at Caltech-and for my staying here at all. We all remember the War, the Draft, and the Great Draft Lottery of 1969: I lost the lottery, but (as most of the white, educated middle class did) avoided the War. Prof. M. Cohen, my first mentor, assisted me in getting a job at JPL. Prof. Ward Whaling has spent the last four years bending rules in my favor so I could keep the job. To both I am grateful. Many people at J7L have helped me in the course of this work. I would especially like to thank Don Trask and Pete MxcDoran for theirs assistance and encouragement.The data for this thesis would not have existed without the hard work of Warren Martin and Art Zygielbaum. I also thank Jack Lorell of the Mariner Mars 1971 Celestial Mechanics Experiment for assisting me in obtaining the data from that mission. I am indebted to Dorothe Horttor of JPL who has worked beyond the call of duty typing the thesis for me. I have benefitted greatly from my association with my advisor Prof. J. R. Jokipii. His comments on this manuscript were extremely valuable in making it coherent and readable. I aFso thank Prof. D. 0. Muhlemn for his comments. Profs. James Gunn and PeterGoldreich have done much to stimulate my learning about astrophysics; I thank them for their patience, Many friends have made my stay at Caltech more pleasant. I especially thank Paul Schechter for his companionship and for taking a date to the prty where I met my wife, Judy. She deserves specialcredit for keeping me sane and happy enough to finish this endeavor. During the course of my graduate study I have been supporte
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