50 research outputs found
ArtMaps: A Technology for Looking at Tate’s Collection
This article presents ArtMaps, a crowdsourcing web-based app for desktop and mobile use that allows users to locate, move and annotate artworks in the Tate collection in relation to one or more sets of locations. Here the authors show that ArtMaps extends the ‘space’ of the museum and facilitates a new, pluriperspectival, way of looking at art
ArtMaps: interpreting the spatial footprints of artworks
Creating and utilizing simple links between items and locations in map-based systems has become a mainstream component of modern computing. In this paper, we explore support for ‘art mapping’, an activity that requires consideration of more complex interpretations of spatial relationships as users engage with identifying locations of relevance to artworks. Through a user study of the ArtMaps platform, and an exploratory study with professional artists, we identify diverse interpretations of spatial meaning in relation to art. We find that art mapping highlights potential for more active engagement with art through technology, but challenges existing systems for spatial representation. Through connecting our findings with work on designing for interpretation, and on space and place in HCI, we contribute new understanding of creating engagement through the spatial interpretation of art, and define potential characteristics and uses of holistic ‘footprints’ for artworks
Different prion disease phenotypes result from inoculation of cattle with two temporally separated sources of sheep scrapie from Great Britain
BACKGROUND: Given the theoretical proposal that bovine spongiform encephalopathy (BSE) could have originated from sheep scrapie, this study investigated the pathogenicity for cattle, by intracerebral (i.c.) inoculation, of two pools of scrapie agents sourced in Great Britain before and during the BSE epidemic. Two groups of ten cattle were each inoculated with pools of brain material from sheep scrapie cases collected prior to 1975 and after 1990. Control groups comprised five cattle inoculated with sheep brain free from scrapie, five cattle inoculated with saline, and for comparison with BSE, naturally infected cattle and cattle i.c. inoculated with BSE brainstem homogenate from a parallel study. Phenotypic characterisation of the disease forms transmitted to cattle was conducted by morphological, immunohistochemical, biochemical and biological methods. RESULTS: Disease occurred in 16 cattle, nine inoculated with the pre-1975 inoculum and seven inoculated with the post-1990 inoculum, with four cattle still alive at 83 months post challenge (as at June 2006). The different inocula produced predominantly two different disease phenotypes as determined by histopathological, immunohistochemical and Western immunoblotting methods and biological characterisation on transmission to mice, neither of which was identical to BSE. Whilst the disease presentation was uniform in all scrapie-affected cattle of the pre-1975 group, the post-1990 inoculum produced a more variable disease, with two animals sharing immunohistochemical and molecular profile characteristics with animals in the pre-1975 group. CONCLUSION: The study has demonstrated that cattle inoculated with different pooled scrapie sources can develop different prion disease phenotypes, which were not consistent with the phenotype of BSE of cattle and whose isolates did not have the strain typing characteristics of the BSE agent on transmission to mice
Reflections on Seminole Rock: The Past, Present, and Future of Deference to Agency Regulatory Interpretations
Seminole Rock (or Auer) deference has captured the attention of scholars, policymakers, and the judiciary. That is why Notice & Comment, the blog of the Yale Journal on Regulation and the American Bar Association’s Section of Administrative Law & Regulatory Practice, hosted an online symposium from September 12 to September 23, 2016 on the subject. This symposium contains over 20 contributions addressing different aspects of Seminole Rock deference.
Topics include: History of Seminole Rock Empirical Examinations of Seminole Rock Understanding Seminole Rock Within Agencies Understanding Seminole Rock as Applied to Tax, Environmental Law, and Criminal Sentencing Why Seminole Rock Matters Should the Supreme Court Overrule Seminole Rock? Would Overruling Seminole Rock Have Unintended Consequences? What Might the Supreme Court Do? What Might Congress Do? The Future of Seminole Roc
Viral Protein Fragmentation May Broaden T-Cell Responses to HIV Vaccines
High mutation rates of human immunodeficiency virus (HIV) allows escape from T cell recognition preventing development of effective T cell vaccines. Vaccines that induce diverse T cell immune responses would help overcome this problem. Using SIV gag as a model vaccine, we investigated two approaches to increase the breadth of the CD8 T cell response. Namely, fusion of vaccine genes to ubiquitin to target the proteasome and increase levels of MHC class I peptide complexes and gene fragmentation to overcome competition between epitopes for presentation and recognition.three vaccines were compared: full-length unmodified SIV-mac239 gag, full-length gag fused at the N-terminus to ubiquitin and 7 gag fragments of equal size spanning the whole of gag with ubiquitin-fused to the N-terminus of each fragment. Genes were cloned into a replication defective adenovirus vector and immunogenicity assessed in an in vitro human priming system. The breadth of the CD8 T cell response, defined by the number of distinct epitopes, was assessed by IFN-γ-ELISPOT and memory phenotype and cytokine production evaluated by flow cytometry. We observed an increase of two- to six-fold in the number of epitopes recognised in the ubiquitin-fused fragments compared to the ubiquitin-fused full-length gag. In contrast, although proteasomal targeting was achieved, there was a marked reduction in the number of epitopes recognised in the ubiquitin-fused full-length gag compared to the full-length unmodified gene, but there were no differences in the number of epitope responses induced by non-ubiquitinated full-length gag and the ubiquitin-fused mini genes. Fragmentation and ubiquitination did not affect T cell memory differentiation and polyfunctionality, though most responses were directed against the Ad5 vector.Fragmentation but not fusion with ubiquitin increases the breadth of the CD8 T vaccine response against SIV-mac239 gag. Thus gene fragmentation of HIV vaccines may maximise responses
The ABC130 barrel module prototyping programme for the ATLAS strip tracker
For the Phase-II Upgrade of the ATLAS Detector, its Inner Detector,
consisting of silicon pixel, silicon strip and transition radiation
sub-detectors, will be replaced with an all new 100 % silicon tracker, composed
of a pixel tracker at inner radii and a strip tracker at outer radii. The
future ATLAS strip tracker will include 11,000 silicon sensor modules in the
central region (barrel) and 7,000 modules in the forward region (end-caps),
which are foreseen to be constructed over a period of 3.5 years. The
construction of each module consists of a series of assembly and quality
control steps, which were engineered to be identical for all production sites.
In order to develop the tooling and procedures for assembly and testing of
these modules, two series of major prototyping programs were conducted: an
early program using readout chips designed using a 250 nm fabrication process
(ABCN-25) and a subsequent program using a follow-up chip set made using 130 nm
processing (ABC130 and HCC130 chips). This second generation of readout chips
was used for an extensive prototyping program that produced around 100
barrel-type modules and contributed significantly to the development of the
final module layout. This paper gives an overview of the components used in
ABC130 barrel modules, their assembly procedure and findings resulting from
their tests.Comment: 82 pages, 66 figure
Global urban environmental change drives adaptation in white clover
Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
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
Ten simple rules for creating a scientific web application
The use of scientific web applications (SWApps) across biological and environmental sciences has grown exponentially over the past decades or so. Although quantitative evidence for such increased use in practice is scant, collectively, we have observed that these tools become more commonplace in teaching, outreach, and in science coproduction (e.g., as decision support tools). Despite the increased popularity of SWApps, researchers often receive little or no training in creating such tools. Although rolling out SWApps can be a relatively simple and quick process using modern, popular platforms like R shiny apps or Tableau dashboards, making them useful, usable, and sustainable is not. These 10 simple rules for creating a SWApp provide a foundation upon which researchers with little to no experience in web application design and development can consider, plan, and carry out SWApp projects