Scientist Spotlights in Secondary Schools: Student Shifts in Multiple Measures Related to Science Identity after Receiving Written Assignments.

Based on theoretical frameworks of scientist stereotypes, possible selves, and science identity, written assignments were developed to teach science content through biographies and research of counter-stereotypical scientists-Scientist Spotlights (www.scientistspotlights.org). Previous studies on Scientist Spotlight assignments showed significant shifts in how college-level biology students relate to and describe scientists and in their performance in biology courses. However, the outcomes of Scientist Spotlight assignments in secondary schools were yet to be explored. In collaboration with 18 science teachers from 12 schools, this study assessed the impacts of Scientist Spotlight assignments for secondary school students. We used published assessment tools: Relatability prompt; Stereotypes prompt; and Performance/Competence, Interest, and Recognition (PCIR) instrument. Statistical analyses compared students' responses before and after receiving at least three Scientist Spotlight assignments. We observed significant shifts in students' relatability to and descriptions of scientists as well as other science identity measures. Importantly, disaggregating classes by implementation strategies revealed that students' relatability shifts were significant for teachers reporting in-class discussions and not significant for teachers reporting no discussions. Our findings raise questions about contextual and pedagogical influences shaping student outcomes with Scientist Spotlight assignments, like how noncontent Instructor Talk might foster student shifts in aspects of science identity.

SAR studies around a series of triazolopyridines as potent and selective PI3Kγ inhibitors.

Herein we describe the SAR of a novel series of 6-aryl-2-amino-triazolopyridines as potent and selective PI3Kγ inhibitors. The 6-aryl-triazolopyridine core was identified by chemoproteomic screening of a kinase focused library. Rapid chemical expansion around a bi-functional core identified the key features required for PI3Kγ activity and selectivity. The series was optimized to afford 43 (CZC19945), a potent PI3Kγ inhibitor with high oral bioavailability and selectivity over PI3Kα and PI3Kδ. Modification to the core afforded 53 (CZC24832) which showed increased selectivity over the entire kinome in particular over PI3Kß.

Preparation of kinase-biased compounds in the search for lead inhibitors of kinase targets.

This work describes the preparation of approximately 13,000 compounds for rapid identification of hits in high-throughput screening (HTS). These compounds were designed as potential serine/threonine or tyrosine kinase inhibitors. The library consists of various scaffolds, e.g., purines, oxindoles, and imidazoles, whereby each core scaffold generally includes the hydrogen bond acceptor/donor properties known to be important for kinase binding. Several of these are based upon literature kinase templates, or adaptations of them to provide novelty. The routes to their preparation are outlined. A variety of automation techniques were used to prepare >500 compounds per scaffold. Where applicable, scavenger resins were employed to remove excess reagents and when necessary, preparative high performance liquid chromatography (HPLC) was used for purification. These compounds were screened against an 'in-house' kinase panel. The success rate in HTS was significantly higher than the corporate compound collection.