Tumor recurrence following treatment is the major cause of mortality for glioblastoma multiforme (GBM) patients. Thus, insights on the evolutionary process at recurrence are critical for improved patient care. Here, we describe our genomic analyses of the initial and recurrent tumor specimens from each of 38 GBM patients. A substantial divergence in the landscape of driver alterations was associated with distant appearance of a recurrent tumor from the initial tumor, suggesting that the genomic profile of the initial tumor can mislead targeted therapies for the distally recurred tumor. In addition, in contrast to IDH1-mutated gliomas, IDH1-wild-type primary GBMs rarely developed hypermutation following temozolomide (TMZ) treatment, indicating low risk for TMZ-induced hypermutation for these tumors under the standard regimen.

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Teaching and learning are highly social activities. Seminal psychologists such as Vygotsky, Piaget, and Bandura have theorized that social interaction is a key mechanism in the process of learning and development. In particular, the benefits of peer interaction for learning and motivation in classrooms have been broadly demonstrated through empirical studies. Hence, it would be valuable if computer-based environments could support a mechanism for a peer interaction. Though no claim of peer equivalence is made, pedagogical agents as learning companions (PALs)-animated digital characters functioning to simulate human-peer-like interaction-might provide an opportunity to simulate such social interaction in computer-based learning. In this article we ground the instructional potential of PALs in several social-cognitive theories, including distributed cognition, social interaction, and Bandura's social-cognitive theory. We discuss how specific concepts of the theories might support various instructional functions of PALs, acknowledging concepts that PALs cannot address. Based on the theoretical perspectives, we suggest key constituents for designing PALs that in human-peer interactions have proven significant. Finally, we review the current status of PAL research with respect to these constituents and suggest where further empirical research is necessary.Keywords: pedagogical agents, learning companions, social interaction, computer-based learning environment, advanced technology for learning Advances in computer and communication technology are providing opportunities to augment human cognition, interaction, and even social rela-

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The potential of emotional interaction between human and computer has recently interested researchers in human-computer interaction. The instructional impact of this interaction in learning environments has not been established, however. This study examined the impact of emotion and gender of a pedagogical agent as a learning companion (PAL) on social judgements, interest, self-efficacy, and learning. Two experiments investigated separately the effects of a PAL's emotional expression and empathetic response. Experiment 1 focused on emotional expression (positive vs. negative vs. neutral) and gender (male vs. female) with a sample of 142 male and female college students in a computer literacy course. Experiment 2 investigated the impact of empathetic response (responsive vs. non-responsive) and gender with 56 pre-service teachers. Overall, the results yielded main and interaction effects of PAL emotion and gender on the dependent variables. In particular, the PAL's empathetic response had a positive impact on learner interest and self-efficacy; PAL gender had a positive impact on recall. The findings imply that the emotion and the gender of the digital learning companion could be utilized to optimize college students' motivation and learning.