Molecular Classification and Biomarkers of Outcome With Immunotherapy in Extensive-Stage Small-Cell Lung Cancer: Analyses of the CASPIAN Phase 3 Study

BACKGROUND: We explored potential predictive biomarkers of immunotherapy response in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with durvalumab (D) + tremelimumab (T) + etoposide-platinum (EP), D + EP, or EP in the randomized phase 3 CASPIAN trial. METHODS: 805 treatment-naïve patients with ES-SCLC were randomized (1:1:1) to receive D + T + EP, D + EP, or EP. The primary endpoint was overall survival (OS). Patients were required to provide an archived tumor tissue block (or ≥ 15 newly cut unstained slides) at screening, if these samples existed. After assessment for programmed cell death ligand-1 expression and tissue tumor mutational burden, residual tissue was used for additional molecular profiling including by RNA sequencing and immunohistochemistry. RESULTS: In 182 patients with transcriptional molecular subtyping, OS with D ± T + EP was numerically highest in the SCLC-inflamed subtype (n = 10, median 24.0 months). Patients derived benefit from immunotherapy across subtypes; thus, additional biomarkers were investigated. OS benefit with D ± T + EP versus EP was greater with high versus low CD8A expression/CD8 cell density by immunohistochemistry, but with no additional benefit with D + T + EP versus D + EP. OS benefit with D + T + EP versus D + EP was associated with high expression of CD4 (median 25.9 vs. 11.4 months) and antigen-presenting and processing machinery (25.9 vs. 14.6 months) and MHC I and II (23.6 vs. 17.3 months) gene signatures, and with higher MHC I expression by immunohistochemistry. CONCLUSIONS: These findings demonstrate the tumor microenvironment is important in mediating better outcomes with D ± T + EP in ES-SCLC, with canonical immune markers associated with hypothesized immunotherapy mechanisms of action defining patient subsets that respond to D ± T. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03043872

The R2R3-MYB Transcription Factor Gene Family in Maize

MYB proteins comprise a large family of plant transcription factors, members of which perform a variety of functions in plant biological processes. To date, no genome-wide characterization of this gene family has been conducted in maize (Zea mays). In the present study, we performed a comprehensive computational analysis, to yield a complete overview of the R2R3-MYB gene family in maize, including the phylogeny, expression patterns, and also its structural and functional characteristics. The MYB gene structure in maize and Arabidopsis were highly conserved, indicating that they were originally compact in size. Subgroup-specific conserved motifs outside the MYB domain may reflect functional conservation. The genome distribution strongly supports the hypothesis that segmental and tandem duplication contribute to the expansion of maize MYB genes. We also performed an updated and comprehensive classification of the R2R3-MYB gene families in maize and other plant species. The result revealed that the functions were conserved between maize MYB genes and their putative orthologs, demonstrating the origin and evolutionary diversification of plant MYB genes. Species-specific groups/subgroups may evolve or be lost during evolution, resulting in functional divergence. Expression profile study indicated that maize R2R3-MYB genes exhibit a variety of expression patterns, suggesting diverse functions. Furthermore, computational prediction potential targets of maize microRNAs (miRNAs) revealed that miR159, miR319, and miR160 may be implicated in regulating maize R2R3-MYB genes, suggesting roles of these miRNAs in post-transcriptional regulation and transcription networks. Our comparative analysis of R2R3-MYB genes in maize confirm and extend the sequence and functional characteristics of this gene family, and will facilitate future functional analysis of the MYB gene family in maize

A hybrid approach for the optimal synthesis of pencil beams through array antennas

A hybrid approach to the synthesis of the excitations and locations of non-uniformly spaced arrays, in order to achieve optimal focusing in any given direction, is proposed and discussed. The approach takes definite advantage from the convexity of the problem with respect to the excitation variables, and exploits a simulated annealing procedure as far as the location variables are concerned. The corresponding synthesized patterns outperform previously known results in standard benchmark problems

A study of vapor CdCl2 treatment by CSS in CdS/CdTe solar cells

We report the effect of CdCl2 vapor treatment on the photovoltaic parameters of CdS/CdTe solar cells. Vapor treatment allows combining CdCl2 exposure time and annealing in one step. In this alternative treatment, the CdS/CdTe substrates were treated with CdCl2 vapor in a close spaced sublimation (CSS) configuration. The substrate temperature and CdCl2, powder source temperature were 400 degrees C. The treatment was done by varying the treatment time (t) from 15 to 90 min. Such solar cells are examined by measuring their current density versus voltage (J-V) characteristics. The open-circuit voltage V-oc), short circuit current density (J(sc)) and fill factor (FF) of our best cell, fabricated and normalized to the area of 1 cm(2), were V-oc = 663 mV, J(sc) = 18.5 mA/cm(2) and FF = 40%, respectively, corresponding to a total area conversion efficiency of n = 5%. In cells of minor area (0.1 cm(2)) efficiencies of 8% have been obtained. (C) 2010 Elsevier Ltd. All rights reserved