Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.

The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair-deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers\u27 tissue of origin

Comparison of the Models of the Air Gauge Static Characteristics

In the article, the authors analyze and discuss several models used to the calculation of air gauge characteristics. The model based on the actual mass flow (which is smaller than the theoretical one) was proposed, too. Calculations have been performed with a dedicated software with the second critical parameters included. The air gauge static characteristics calculated with 6 different models were compared with the experimental data. It appeared that the second critical parameters model (SCP) provided the characteristics close to the experimental ones, with an error of ca. 3% within the air gauge measuring range

Mathematical Model of Dynamic Work Conditions in the Measuring Chamber of an Air Gauge

The goal of the proposed computational model was to evaluate the dynamical properties of air gauges in order to exploit them in such industrial applications as in-process control, form deviation measurement, dynamical measurement. The model is based on Reynolds equations complemented by the k-ε turbulence model. The boundary conditions were set in different areas (axis of the chamber, side surfaces, inlet pipeline and outlet cross-section) as Dirichlet's and Neumann's ones. The TDMA method was applied and the efficiency of the calculations was increased due to the "line-by-line" procedure. The proposed model proved to be accurate and useful for non-stationary two-dimensional flow through the air gauge measuring chamber