Juicio de límites entre el Perú y Bolivia prueba peruana presentada al Gobierno de la Republica Argentina

T. 2. Organización audiencial -- t. 4. Virreinato de Buenos Aires -- t. 5. Gobernaciones diversas -- t. 6 Gobernaciones de Álvarez Maldonado -- t. 8. Chunchos -- t. 9. Mojo

An Unbiased Functional Genetics Screen Identifies Rare Activating ERBB4 Mutations

Despite the relatively high frequency of somatic ERBB4 mutations in various cancer types, only a few activating ERBB4 mutations have been characterized, primarily due to lack of mutational hotspots in the ERBB4 gene. Here, we utilized our previously published pipeline, an in vitro screen for activating mutations, to perform an unbiased functional screen to identify potential activating ERBB4 mutations from a randomly mutated ERBB4 expression library. Ten potentially activating ERBB4 mutations were identified and subjected to validation by functional and structural analyses. Two of the 10 ERBB4 mutants, E715K and R687K, demonstrated hyperactivity in all tested cell models and promoted cellular growth under two-dimensional and three-dimensional culture conditions. ERBB4 E715K also promoted tumor growth in in vivo Ba/F3 cell mouse allografts. Importantly, all tested ERBB4 mutants were sensitive to the pan-ERBB tyrosine kinase inhibitors afatinib, neratinib, and dacomitinib. Our data indicate that rare ERBB4 mutations are potential candidates for ERBB4-targeted therapy with pan-ERBB inhibitors.Statement of Significance:ERBB4 is a member of the ERBB family of oncogenes that is frequently mutated in different cancer types but the functional impact of its somatic mutations remains unknown. Here, we have analyzed the function of over 8,000 randomly mutated ERBB4 variants in an unbiased functional genetics screen. The data indicate the presence of rare activating ERBB4 mutations in cancer, with potential to be targeted with clinically approved pan-ERBB inhibitors.</p

Equation of state of stishovite and interpretation of SiO 2 shock‐compression data

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95606/1/jgrb13349.pd

Combining the reasoned action approach and habit formation to reduce sitting time in classrooms : Outcome and process evaluation of the Let’s Move It teacher intervention

Creating active classroom environments and reducing excessive student sitting requires changes in teachers' behaviours. This study examines a teacher training intervention, which aimed to increase the extent to which teachers use strategies to interrupt prolonged periods of students' sitting, as well as strategies to reduce total sitting time. The training was part of the Let's Move It (LMI) multi-level school-based intervention that aimed to reduce sedentary behaviour and increase physical activity among older adolescents, drawing on insights from social psychological theories, such as the reasoned action approach, self-regulation approaches and habit formation. We explore (1) whether the intervention increased teachers' use of sitting reduction strategies, (2) whether theoretical mechanisms mediated these changes, and (3) how teachers utilized habit formation. This pragmatic experimental study of vocational school teachers (n = 234) was embedded within a cluster-randomized controlled trial evaluating LMI, in which schools were randomized to intervention or no-treatment control arms. Three intervention workshops targeted skills and motivation to use sitting reduction strategies in class (e.g., active teaching methods, activity breaks). Participants self-reported sitting reduction activities, theoretical mediators, and use of behaviour change techniques (BCTs) at baseline and 8-weeks follow-up. Compared to controls, intervention schools' teachers increased breaks to interrupt sitting, but not their outcome expectations, perceived behavioural control or intentions - potentially due to ceiling effects. Effects were mediated by BCT use and perceived behavioural control. Descriptive norms mediated the effects of the intervention on intention, which in turn mediated the intervention effects on BCT use. BCT use and intention were positively related to reducing students' sitting.Peer reviewe