Reverse Engineering of Modified Genes by Bayesian Network Analysis Defines Molecular Determinants Critical to the Development of Glioblastoma

In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I–IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated). These 10 genes were able to predict tumor status with 96–100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential ‘hubs of activity’. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several ‘key genes’ may be required for the development of glioblastoma. Further studies are needed to validate these ‘key genes’ as useful tools for early detection and novel therapeutic options for these tumors.

The Next Generation of Scientists: Examining the Experiences of Graduate Students in Network-Level Social-Ecological Science

By integrating the research and resources of hundreds of scientists from dozens of institutions, network-level science is fast becoming one scientific model of choice to address complex problems. In the pursuit to confront pressing environmental issues such as climate change, many scientists, practitioners, policy makers, and institutions are promoting network-level research that integrates the social and ecological sciences. To understand how this scientific trend is unfolding among rising scientists, we examined how graduate students experienced one such emergent social-ecological research initiative, Integrated Science for Society and Environment, within the large-scale, geographically distributed Long Term Ecological Research (LTER) Network. Through workshops, surveys, and interviews, we found that graduate students faced challenges in how they conceptualized and practiced social-ecological research within the LTER Network. We have presented these conceptual challenges at three scales: the individual/project, the LTER site, and the LTER Network. The level of student engagement with and knowledge of the LTER Network was varied, and students faced different institutional, cultural, and logistic barriers to practicing social-ecological research. These types of challenges are unlikely to be unique to LTER graduate students; thus, our findings are relevant to other scientific networks implementing new social-ecological research initiatives.

Background traffic modeling for large-scale network simulation

Network simulation is an indispensable tool for studying Internet-scale networks due to the heterogeneous structure, immense size and changing properties. It is crucial for network simulators to generate representative traffic, which is necessary for effectively evaluating next-generation network protocols and applications. With network simulation, we can make a distinction between foreground traffic, which is generated by the target applications the researchers intend to study and therefore must be simulated with high fidelity, and background traffic, which represents the network traffic that is generated by other applications and does not require significant accuracy. The background traffic has a significant impact on the foreground traffic, since it competes with the foreground traffic for network resources and therefore can drastically affect the behavior of the applications that produce the foreground traffic. This dissertation aims to provide a solution to meaningfully generate background traffic in three aspects. First is realism. Realistic traffic characterization plays an important role in determining the correct outcome of the simulation studies. This work starts from enhancing an existing fluid background traffic model by removing its two unrealistic assumptions. The improved model can correctly reflect the network conditions in the reverse direction of the data traffic and can reproduce the traffic burstiness observed from measurements. Second is scalability. The trade-off between accuracy and scalability is a constant theme in background traffic modeling. This work presents a fast rate-based TCP (RTCP) traffic model, which originally used analytical models to represent TCP congestion control behavior. This model outperforms other existing traffic models in that it can correctly capture the overall TCP behavior and achieve a speedup of more than two orders of magnitude over the corresponding packet-oriented simulation. Third is network-wide traffic generation. Regardless of how detailed or scalable the models are, they mainly focus on how to generate traffic on one single link, which cannot be extended easily to studies of more complicated network scenarios. This work presents a cluster-based spatio-temporal background traffic generation model that considers spatial and temporal traffic characteristics as well as their correlations. The resulting model can be used effectively for the evaluation work in network studies.

Background Traffic Modeling for Large-Scale Network Simulation

Network simulation is an indispensable tool for studying Internet-scale networks due to the heterogeneous structure, immense size and changing properties. It is crucial for network simulators to generate representative traffic, which is necessary for effectively evaluating next-generation network protocols and applications. With network simulation, we can make a distinction between foreground traffic, which is generated by the target applications the researchers intend to study and therefore must be simulated with high fidelity, and background traffic, which represents the network traffic that is generated by other applications and does not require significant accuracy. The background traffic has a significant impact on the foreground traffic, since it competes with the foreground traffic for network resources and therefore can drastically affect the behavior of the applications that produce the foreground traffic. This dissertation aims to provide a solution to meaningfully generate background traffic in three aspects. First is realism. Realistic traffic characterization plays an important role in determining the correct outcome of the simulation studies. This work starts from enhancing an existing fluid background traffic model by removing its two unrealistic assumptions. The improved model can correctly reflect the network conditions in the reverse direction of the data traffic and can reproduce the traffic burstiness observed from measurements. Second is scalability. The trade-off between accuracy and scalability is a constant theme in background traffic modeling. This work presents a fast rate-based TCP (RTCP) traffic model, which originally used analytical models to represent TCP congestion control behavior. This model outperforms other existing traffic models in that it can correctly capture the overall TCP behavior and achieve a speedup of more than two orders of magnitude over the corresponding packet-oriented simulation. Third is network-wide traffic generation. Regardless of how detailed or scalable the models are, they mainly focus on how to generate traffic on one single link, which cannot be extended easily to studies of more complicated network scenarios. This work presents a cluster-based spatio-temporal background traffic generation model that considers spatial and temporal traffic characteristics as well as their correlations. The resulting model can be used effectively for the evaluation work in network studies.