1,007 research outputs found
Multidimensional rasch models for partial credit scoring
Rasch models for partial-credit scoring are discussed
and a multidimensional version of the model is formulated.
A model may be specified in which consecutive
item responses depend on an underlying latent trait. In
the multidimensional partial-credit model, different responses
may be explained by different latent traits. Data
from van Kuyk’s (1988) size concept test and the Raven
Progressive Matrices test were analyzed. Maximum
likelihood estimation and goodness-of-fit testing are discussed
and applied to these datasets. Goodness-of-fit
statistics show that for both tests, multidimensional partial-credit models were more appropriate than the unidimensional
partial-credit model. Index terms: X2 testing,
exponential family model, multidimensional item response
theory, multidimensional Rasch model, partial-credit
models, Progressive Matrices test, Rasch model
Intertumoral differences dictate the outcome of TGF-β blockade on the efficacy of viro-immunotherapy
The absence of T cells in the tumor microenvironment of solid tumors is a major barrier to cancer immunotherapy efficacy. Oncolytic viruses, including reovirus type 3 Dearing (Reo), can recruit CD8+ T cells to the tumor and thereby enhance the efficacy of immunotherapeutic strategies that depend on high T-cell density, such as CD3-bispecific antibody (bsAb) therapy. TGF-β signaling might represent another barrier to effective Reo&CD3-bsAb therapy due to its immunoinhibitory characteristics. Here, we investigated the effect of TGF-β blockade on the antitumor efficacy of Reo&CD3-bsAb therapy in the preclinical pancreatic KPC3 and colon MC38 tumor models, where TGF-β signaling is active. TGF-β blockade impaired tumor growth in both KPC3 and MC38 tumors. Furthermore, TGF-β blockade did not affect reovirus replication in both models and significantly enhanced the Reo-induced T-cell influx in MC38 colon tumors. Reo administration decreased TGF-β signaling in MC38 tumors but instead increased TGF-β activity in KPC3 tumors, resulting in the accumulation of α-smooth muscle actin (αSMA+) fibroblasts. In KPC3 tumors, TGF-β blockade antagonized the antitumor effect of Reo&CD3-bsAb therapy, even though T-cell influx and activity were not impaired. Moreover, genetic loss of TGF-β signaling in CD8+ T cells had no effect on therapeutic responses. In contrast, TGF-β blockade significantly improved therapeutic efficacy of Reo&CD3-bsAb in mice bearing MC38 colon tumors, resulting in a 100% complete response. Further understanding of the factors that determine this intertumor dichotomy is required before TGF-β inhibition can be exploited as part of viroimmunotherapeutic combination strategies to improve their clinical benefit.Significance:Blockade of the pleiotropic molecule TGF-β can both improve and impair the efficacy of viro-immunotherapy, depending on the tumor model. While TGF-β blockade antagonized Reo&CD3-bsAb combination therapy in the KPC3 model for pancreatic cancer, it resulted in 100% complete responses in the MC38 colon model. Understanding factors underlying this contrast is required to guide therapeutic application.Cancer Signaling networks and Molecular Therapeutic
Search for the Standard Model Higgs boson produced in association with top quarks and decaying into bb¯ in pp collisions at √s = 8 TeV with the ATLAS detector
Measurement of the top quark mass in the tt bar → lepton+jets and tt bar → dilepton channels using √s = 7 TeV ATLAS data
Search for high-mass diphoton resonances in pp collisions at √s = 8 TeV with the ATLAS detector
Measurement of the correlation between flow harmonics of different order in lead-lead collisions at √sNN = 2.76 TeV with the ATLAS detector
Observation and measurements of the production of prompt and non-prompt Jψ mesons in association with Z boson in pp collisions at √s = 8 TeV with the ATLAS detector
Search for massive supersymmetric particles decaying to many jets using the ATLAS detector in pp collisions at √s = 8 TeV
Search for type-III seesaw heavy leptons in pp collisions at √s = 8 TeV with the ATLAS detector
Combined measurement of the Higgs boson mass in pp collisions at √s = 7 and 8 TeV with the ATLAS and CMS experiments
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