98 research outputs found
The Open Linguistics Working Group: developing the Linguistic Linked Open Data cloud
The Open Linguistics Working Group (OWLG) brings together researchers from various fields of linguistics, natural language processing, and information technology to present and discuss principles, case studies, and best practices for representing, publishing and linking linguistic data collections. A major outcome of our work is the Linguistic Linked Open Data (LLOD) cloud, an LOD (sub-)cloud of linguistic resources, which covers various linguistic databases, lexicons, corpora, terminologies, and metadata repositories. We present and summarize five years of progress on the development of the cloud and of advancements in open data in linguistics, and we describe recent community activities. The paper aims to serve as a guideline to orient and involve researchers with the community and/or Linguistic Linked Open Data
Canonical path integral measures for Holst and Plebanski gravity. I. Reduced Phase Space Derivation
An important aspect in defining a path integral quantum theory is the
determination of the correct measure. For interacting theories and theories
with constraints, this is non-trivial, and is normally not the heuristic
"Lebesgue measure" usually used. There have been many determinations of a
measure for gravity in the literature, but none for the Palatini or Holst
formulations of gravity. Furthermore, the relations between different resulting
measures for different formulations of gravity are usually not discussed.
In this paper we use the reduced phase technique in order to derive the
path-integral measure for the Palatini and Holst formulation of gravity, which
is different from the Lebesgue measure up to local measure factors which depend
on the spacetime volume element and spatial volume element.
From this path integral for the Holst formulation of GR we can also give a
new derivation of the Plebanski path integral and discover a discrepancy with
the result due to Buffenoir, Henneaux, Noui and Roche (BHNR) whose origin we
resolve. This paper is the first in a series that aims at better understanding
the relation between canonical LQG and the spin foam approach.Comment: 27 pages, minor correction
An imbalance between specialized pro-resolving lipid mediators and pro-inflammatory leukotrienes promotes instability of atherosclerotic plaques
Chronic unresolved inflammation plays a causal role in the development of advanced atherosclerosis, but the mechanisms that prevent resolution in atherosclerosis remain unclear. Here, we use targeted mass spectrometry to identify specialized pro-resolving lipid mediators (SPM) in histologically-defined stable and vulnerable regions of human carotid atherosclerotic plaques. The levels of SPMs, particularly resolvin D1 (RvD1), and the ratio of SPMs to pro-inflammatory leukotriene B4 (LTB₄), are significantly decreased in the vulnerable regions. SPMs are also decreased in advanced plaques of fat-fed Ldlr⁻/⁻ mice. Administration of RvD1 to these mice during plaque progression restores the RvD1:LTB₄ ratio to that of less advanced lesions and promotes plaque stability, including decreased lesional oxidative stress and necrosis, improved lesional efferocytosis, and thicker fibrous caps. These findings provide molecular support for the concept that defective inflammation resolution contributes to the formation of clinically dangerous plaques and offer a mechanistic rationale for SPM therapy to promote plaque stability
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
Introduction into Land Aquisition
This discussion will give an overview of the laws on land acquisition, what the typical process looks like, and one community’s perspective on communication related to the process
An Exploratory Study of Automated GUI Testing: Goals, Issues, and Best Practices
Manually testing GUIs can be expensive and complex, so the creation of automated GUI test suites has been an area of significant interest. However, to our knowledge, the motivations of testers and the problems they encounter when attempting to create and use automated GUI tests have not been explored. We used Grounded Theory to investigate the goals motivating automated GUI testing, the issues testers encounter, and the best practices applied to overcome these issues. Through this study, we demonstrate that automated GUI test suite evolution and architecture are extremely important to the success of automated GUI testing and describe techniques that can be of use to practitioners. In addition to these best practices, this study identifies additional areas in which future research should be concentrated.N
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Siderophile element constraints on the thermal history of the H chondrite parent body.
The abundances of highly siderophile elements (HSE: Re, Os, Ir, Ru, Pt, Pd), as well as 187Re-187Os and 182Hf-182W isotopic systematics were determined for separated metal, slightly magnetic, and nonmagnetic fractions from seven H4 to H6 ordinary chondrites. The HSE are too abundant in nonmagnetic fractions to reflect metal-silicate equilibration. The disequilibrium was likely a primary feature, as 187Re-187Os data indicate only minor open-system behavior of the HSE in the slightly and non-magnetic fractions. 182Hf-182W data for slightly magnetic and nonmagnetic fractions define precise isochrons for most meteorites that range from 5.2 ± 1.6 Ma to 15.2 ± 1.0 Ma after calcium aluminum inclusion (CAI) formation. By contrast, 182W model ages for the metal fractions are typically 2-5 Ma older than the slope-derived isochron ages for their respective, slightly magnetic and nonmagnetic fractions, with model ages ranging from 1.4 ± 0.8 Ma to 12.6 ± 0.9 Ma after CAI formation. This indicates that the W present in the silicates and oxides was not fully equilibrated with the metal when diffusive transport among components ceased, consistent with the HSE data. Further, the W isotopic compositions of size-sorted metal fractions from some of the H chondrites also differ, indicating disequilibrium among some metal grains. The chemical/isotopic disequilibrium of siderophile elements among H chondrite components is likely the result of inefficient diffusion of siderophile elements from silicates and oxides to some metal and/or localized equilibration as H chondrites cooled towards their respective Hf-W closure temperatures. The tendency of 182Hf-182W isochron ages to young from H5 to H6 chondrites may indicate derivation of these meteorites from a slowly cooled, undisturbed, concentrically-zoned parent body, consistent with models that have been commonly invoked for H chondrites. Overlap of isochron ages for H4 and H5 chondrites, by contrast, appear to be more consistent with shallow impact disruption models. The W isotopic composition of metal from one CR chondrite was examined to compare with H chondrite metals. In contrast to the H chondrites, the CR chondrite metal is characterized by an enrichment in 183W that is consistent with nucleosynthetic s-process depletion. Once corrected for the correlative nucleosynthetic effect on 182W, the 182W model age for this meteorite of 7.0 ± 3.6 Ma is within the range of model ages of most metal fractions from H chondrites. The metal is therefore too young to be a direct nebular condensate, as proposed by some prior studies
Recommended from our members
Siderophile element constraints on the thermal history of the H chondrite parent body.
The abundances of highly siderophile elements (HSE: Re, Os, Ir, Ru, Pt, Pd), as well as 187Re-187Os and 182Hf-182W isotopic systematics were determined for separated metal, slightly magnetic, and nonmagnetic fractions from seven H4 to H6 ordinary chondrites. The HSE are too abundant in nonmagnetic fractions to reflect metal-silicate equilibration. The disequilibrium was likely a primary feature, as 187Re-187Os data indicate only minor open-system behavior of the HSE in the slightly and non-magnetic fractions. 182Hf-182W data for slightly magnetic and nonmagnetic fractions define precise isochrons for most meteorites that range from 5.2 ± 1.6 Ma to 15.2 ± 1.0 Ma after calcium aluminum inclusion (CAI) formation. By contrast, 182W model ages for the metal fractions are typically 2-5 Ma older than the slope-derived isochron ages for their respective, slightly magnetic and nonmagnetic fractions, with model ages ranging from 1.4 ± 0.8 Ma to 12.6 ± 0.9 Ma after CAI formation. This indicates that the W present in the silicates and oxides was not fully equilibrated with the metal when diffusive transport among components ceased, consistent with the HSE data. Further, the W isotopic compositions of size-sorted metal fractions from some of the H chondrites also differ, indicating disequilibrium among some metal grains. The chemical/isotopic disequilibrium of siderophile elements among H chondrite components is likely the result of inefficient diffusion of siderophile elements from silicates and oxides to some metal and/or localized equilibration as H chondrites cooled towards their respective Hf-W closure temperatures. The tendency of 182Hf-182W isochron ages to young from H5 to H6 chondrites may indicate derivation of these meteorites from a slowly cooled, undisturbed, concentrically-zoned parent body, consistent with models that have been commonly invoked for H chondrites. Overlap of isochron ages for H4 and H5 chondrites, by contrast, appear to be more consistent with shallow impact disruption models. The W isotopic composition of metal from one CR chondrite was examined to compare with H chondrite metals. In contrast to the H chondrites, the CR chondrite metal is characterized by an enrichment in 183W that is consistent with nucleosynthetic s-process depletion. Once corrected for the correlative nucleosynthetic effect on 182W, the 182W model age for this meteorite of 7.0 ± 3.6 Ma is within the range of model ages of most metal fractions from H chondrites. The metal is therefore too young to be a direct nebular condensate, as proposed by some prior studies
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