706 research outputs found
Contributions to the theory of rank order statistics: computation rules for probabilities of rank orders
1 online resource (PDF, 4 pages
Contributions to the theory of rank order statistics: applications of lattice theory
1 online resource (PDF, 20 pages
Contributions to the Theory of Rank Order Statistics. The Two Sample Case: Fine Structure Of the Ordering Of Probabilities of Rank Orders
1 online resource (PDF, 30 pages
Survelliance Problems: Wiener Processes
1 online resource (PDF, 24 pages
Understanding the dynamics of segregation bands of simulated granular material in a rotating drum
Axial segregation of a binary mixture of grains in a rotating drum is studied
using Molecular Dynamics (MD) simulations. A force scheme leading to a constant
restitution coefficient is used and shows that axial segregation is possible
between two species of grains made of identical material differing by size.
Oscillatory motion of bands is investigated and the influence of the frictional
properties elucidated. The mechanism of bands merging is explained using direct
imaging of individual grains
Test of peak values in physiopathologic time series
1 online resource (PDF, 17 pages
Book reviews
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45702/1/11336_2005_Article_BF02289852.pd
Activation of STING-Dependent Innate Immune Signaling By S-Phase-Specific DNA Damage in Breast Cancer
Background: Previously we identified a DNA damage response–deficient (DDRD) molecular subtype within breast cancer. A 44-gene assay identifying this subtype was validated as predicting benefit from DNA-damaging chemotherapy. This subtype was defined by interferon signaling. In this study, we address the mechanism of this immune response and its possible clinical significance.
Methods: We used immunohistochemistry (IHC) to characterize immune infiltration in 184 breast cancer samples, of which 65 were within the DDRD subtype. Isogenic cell lines, which represent DDRD-positive and -negative, were used to study the effects of chemokine release on peripheral blood mononuclear cell (PBMC) migration and the mechanism of immune signaling activation. Finally, we studied the association between the DDRD subtype and expression of the immune-checkpoint protein PD-L1 as detected by IHC. All statistical tests were two-sided.
Results: We found that DDRD breast tumors were associated with CD4+ and CD8+ lymphocytic infiltration (Fisher’s exact test P < .001) and that DDRD cells expressed the chemokines CXCL10 and CCL5 3.5- to 11.9-fold more than DNA damage response–proficient cells (P < .01). Conditioned medium from DDRD cells statistically significantly attracted PBMCs when compared with medium from DNA damage response–proficient cells (P < .05), and this was dependent on CXCL10 and CCL5. DDRD cells demonstrated increased cytosolic DNA and constitutive activation of the viral response cGAS/STING/TBK1/IRF3 pathway. Importantly, this pathway was activated in a cell cycle–specific manner. Finally, we demonstrated that S-phase DNA damage activated expression of PD-L1 in a STING-dependent manner.
Conclusions: We propose a novel mechanism of immune infiltration in DDRD tumors, independent of neoantigen production. Activation of this pathway and associated PD-L1 expression may explain the paradoxical lack of T-cell-mediated cytotoxicity observed in DDRD tumors. We provide a rationale for exploration of DDRD in the stratification of patients for immune checkpoint–based therapies
The Molonglo Reference Catalog 1-Jy radio source survey IV. Optical spectroscopy of a complete quasar sample
Optical spectroscopic data are presented here for quasars from the Molonglo
Quasar Sample (MQS), which forms part of a complete survey of 1-Jy radio
sources from the Molonglo Reference Catalogue. The combination of low-frequency
selection and complete identifications means that the MQS is relatively free
from the orientation biases which affect most other quasar samples. To date,
the sample includes 105 quasars and 6 BL Lac objects, 106 of which have now
been confirmed spectroscopically. This paper presents a homogenous set of
low-resolution optical spectra for 79 MQS quasars, the majority of which have
been obtained at the Anglo-Australian Telescope. Full observational details are
given and redshifts, continuum and emission-line data tabulated for all
confirmed quasars.Comment: 40 pages, ApJS in pres
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