100,403 research outputs found
Digital technology in mathematics education: Why it works (or doesn't)
No full textThe integration of digital technology confronts teachers, educators and researchers with many questions. What is the potential of ICT for learning and teaching, and which factors are decisive in making it work in the mathematics classroom? To investigate these questions, six cases from leading studies in the field are described, and decisive success factors are identified. This leads to the conclusion that crucial factors for the success of digital technology in mathematics education include the design of the digital tool and corresponding tasks exploiting the tool's pedagogical potential, the role of the teacher and the educational context
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
Handwritten biographical information on Paulina T. McClung Merritt
No full textA handwritten biography of Paulina T. McClung Merritt by an unknown author, 1892.
Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
No full textIFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
Dispelling the Myths Behind First-author Citation Counts
No full textWe 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
Pelevin’s Trinity in the novel “t”: author – protagonist – reader
No full textThe article attempts to interpret Pelevin's artistic strategy in the novel "T" by exploring its subject organization and addressing the key problems of the author, the protagonist, and the reader as they are seen by the researcher. The article analyzes the peculiarities of constructing the narrative reality in the novel "T", and goes on to discuss Pelevin's philosophic models of the development of the humankind, and the emergence of his new anthropology
Measuring industry-science links through inventor-author relations: A profiling method
No full textIn this pilot study we examine the performance of text-based profiling in recovering a set of validated inventor-author links. In a first step we match patents and publications solely based on their similarity in content. Next, we compare inventor and author names on the highest ranked matches for the occurrence of name matches. Finally, we compare these candidate matches with the names listed in a validated set of inventor-author names. Our text-based profile methodology performs significantly better than a random matching of patents and publications, suggesting that text-based profiling is a valuable complementary tool to the name searches used in previous studies.innovation; industry-science links; text-based profiling;
Wave turbulence of a rotating array of quantized vortices in the T → 0 temperature limit
No full textThe dynamics of quantized vortices in the zero temperature limit is currently of great interest, particularly in the case of the Fermi superfluid He-B. Here we study wave turbulence, generated by the librating motion of a rotating cylindrical container filled with He-B, in the limit of vanishing viscous forces at temperatures . The polarization of the quantized vortices with respect to the axis of rotation is measured using non-invasive NMR techniques. We observe a decrease of the polarization when the librating motion is started, and a two-stage relaxation process when the modulation of the rotation velocity is stopped. The first relaxation process is associated with the dissipation of large-scale flow stored in inertial waves and the solid body rotation of the vortex array. From the decay of these energy reservoirs we determine the rate of energy dissipation of large-scale flow. The later second process is related to the relaxation of Kelvin waves on individual vortices. This process is monitored by the recovery of the polarization. The existence of a Kelvin wave cascade at the lowest temperatures is currently a central open question. We supply some evidence for the cascade
DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire
No full textThe majority of known human tumor-associated antigens derive from non-mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate tolerance-breaking CD4+ T cell help. Candidate MHC class Ibinding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia-associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitopederived from Friend murine leukemia virus gag protein (FMuLVgag) and vaccinated tolerant FMuLVgag-transgenic (gag-Tg) mice. Vaccination with the construct induced epitopespecificIFN-c-producing CD8+ T cells in normal and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag-Tg mice, and no autoimmune injury resulted. However, these CD8+ T cells did exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific CTL killed FBL-3 leukemia cells expressing endogenous FMuLVgag antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti-microbial T cell help to activate epitope-specific polyclonal CD8+ T cell responses from a residual tolerized repertoire
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Metabolic regulation of anti-tumor CD8+ T cell responses
No full textCancer immunotherapies have revolutionized the cancer therapy landscape, but many patients do not yet benefit. Methods to increase the applicability and response rates of cancer immunotherapy are therefore warranted. CD8+ T cells are key effectors of the anti-tumor immune response, but their function is often hampered in cancer. Both systemic metabolic conditions, such as aging and obesity, and tumor-specific metabolic barriers impair the anti-tumor T cell response.
To identify distinct cell-intrinsic metabolic vulnerabilities of CD8+ T cells and cancer cells, aiming to enable the specific therapeutic targeting of either population, we conducted an in vitro pharmacologic screen. We found that CD8+ T cells are highly sensitive to ferroptosis, a lipid peroxidation-triggered cell death pathway, induced by inhibitors of glutathione peroxidase 4 (GPX4). Optimal CD8+ T cell-mediated anti-tumor immunity depends on acyl-CoA synthetase long chain family member 4 (ACSL4), which promotes ferroptosis sensitivity. Moreover, we determined that overexpression of GPX4 or ferroptosis suppressor protein 1 (FSP1) generates ferroptosis-resistant CD8+ T cells, which may be valuable when systemic ferroptosis-inducing cancer therapies become available.
To study how systemic metabolism impacts anti-tumor immunity, we modeled human obesity by feeding mice a high-fat diet (HFD). We demonstrated that HFD impairs CD8+ T cell function in the tumor microenvironment (TME) and accelerates tumor growth. MC38 tumor cells and CD8+ T cells display distinct metabolic adaptations with diet-induced obesity. The cancer cells increase fat uptake, resulting in depletion of fatty acids and fewer CD8+ T cells in HFD tumors. Accordingly, disabling cancer cell-intrinsic metabolic reprogramming with HFD improves anti-tumor immunity. Bioinformatic analyses revealed that similar metabolic rewiring correlates with reduced CD8+ T cell infiltration in human cancers. A further characterization of CD8+ T cells with HFD demonstrated more frequent antigen-experienced phenotypes systemically but reduced activation in the TME. This dysfunction depends on the HFD environment and can be rescued by anti-PD-1 therapy.
Together, our studies have highlighted how anti-tumor immunity is impacted by T cell-intrinsic and systemic metabolism. Specifically, our results suggest that the handling of fats, both intracellularly, in the TME, and systemically, is a critical regulator of the anti-tumor CD8+ T cell response.Medical SciencesMedical Science
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