Integrative molecular characterization of malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune-checkpoint gene VISTA in epithelioid MPM, strikingly higher than in other solid cancers, with implications for the immune response to MPM and for its immunotherapy. Our findings highlight new avenues for further investigation of MPM biology and novel therapeutic options. SIGNIFICANCE: Through a comprehensive integrated genomic study of 74 MPMs, we provide a deeper understanding of histology-independent determinants of aggressive behavior, define a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity, and discovered strong expresssion of the immune-checkpoint gene VISTA in epithelioid MPM

Comparative genome analysis of the yellow fever mosquito Aedes aegypti with Drosophila melanogaster and the malaria vector mosquito Anopheles gambiae

An in silico comparative genomics approach was used to identify putative orthologs to genetically mapped genes from the mosquito, Aedes aegypti, in the Drosophila melanogaster and Anopheles gambiae genome databases. Comparative chromosome positions of 73 D. melanogaster orthologs indicated significant deviations from a random distribution across each of the five A. aegypti chromosomal regions, suggesting that some ancestral chromosome elements have been conserved. However, the two genomes also reflect extensive reshuffling within and between chromosomal regions. Comparative chromosome positions of A. gambiae orthologs indicate unequivocally that A. aegypti chromosome regions share extensive homology to the five A. gambiae chromosome arms. Whole-arm or near-whole-arm homology was contradicted with only two genes among the 75 A. aegypti genes for which orthologs to A. gambiae were identified. The two genomes contain large conserved chromosome segments that generally correspond to break/fusion events and a reciprocal translocation with extensive paracentric inversions evident within. Only very tightly linked genes are likely to retain conserved linear orders within chromosome segments. The D. melanogaster and A. gambiae genome databases therefore offer limited potential for comparative positional gene determinations among even closely related dipterans, indicating the necessity for additional genome sequencing projects with other dipteran species

Absolute X-ray yields from laser-irradiated, Ge-doped aerogel targets

We have measured the production of $h\nu$ $\geq$ 10 keV x rays from low-density, Ge-doped aerogel targets at the OMEGA laser (Laboratory for Laser Energetics, University of Rochester). The targets were 1.2mm long by 1.5mm diameter beryllium cylinders filled with Ge-doped (20 atomic percent) SiO$_2$ aerogel. The doped-aerogel density was 4.8 or 6.5 mg/cm$^3$. Forty beams of the OMEGA laser ($\lambda$ = 351 nm) illuminated the two cylindrical faces of the target with a total power of $\gtrsim$18 TW. Ge K-shell x-ray emission was spectrally resolved with a two-channel crystal spectrometer and recorded with temporal resolution with a set of calibrated photoconductive devices (PCDs)

Teacher Leaders as Equity-Centered Change Agents: Exploring the Conditions that Influence Navigating Change to Promote Educational Equity

As inequities continue to be present for students of color, for English-language learners, for students from low-income households, for LGBTQ students and for students with disabilities, schools must find ways to increase achievement and high expectations for all students. Although not explored thoroughly in the research literature, teacher leaders (TLs) can be key change agents in developing more equitable schools. The purpose of this qualitative study was to examine the work of equity-centered TLs who facilitated professional learning on their campuses in relation to equity issues. Particularly, this study looked at the facilitators and inhibitors for TLs spearheading change and how they navigate these conditions. Data sources included reflection journals, class assignments and interviews. Findings indicate that TLs facilitating change for equity in schools with unsupportive conditions (i.e. fear, lack of principal support) found these conditions served as barriers for teachers to address inequities. These TLs had to put equity on hold and focus on building more supportive conditions. Teacher leaders in schools with supportive conditions (i.e. collegiality, principal support) found that these conditions promoted a focus on equity and led to teacher empowerment and greater educational equity. This study has implications for leadership preparation, professional development and educational change