An integrative approach to characterize disease-specific pathways and their coordination: a case study in cancer

BACKGROUND: The most common application of microarray technology in disease research is to identify genes differentially expressed in disease versus normal tissues. However, it is known that, in complex diseases, phenotypes are determined not only by genes, but also by the underlying structure of genetic networks. Often, it is the interaction of many genes that causes phenotypic variations. RESULTS: In this work, using cancer as an example, we develop graph-based methods to integrate multiple microarray datasets to discover disease-related co-expression network modules. We propose an unsupervised method that take into account both co-expression dynamics and network topological information to simultaneously infer network modules and phenotype conditions in which they are activated or de-activated. Using our method, we have discovered network modules specific to cancer or subtypes of cancers. Many of these modules are consistent with or supported by their functional annotations or their previously known involvement in cancer. In particular, we identified a module that is predominately activated in breast cancer and is involved in tumor suppression. While individual components of this module have been suggested to be associated with tumor suppression, their coordinated function has never been elucidated. Here by adopting a network perspective, we have identified their interrelationships and, particularly, a hub gene PDGFRL that may play an important role in this tumor suppressor network. CONCLUSION: Using a network-based approach, our method provides new insights into the complex cellular mechanisms that characterize cancer and cancer subtypes. By incorporating co-expression dynamics information, our approach can not only extract more functionally homogeneous modules than those based solely on network topology, but also reveal pathway coordination beyond co-expression

Validation in Fusion Research: Towards Guidelines and Best Practices

Because experiment/model comparisons in magnetic confinement fusion have not yet satisfied the requirements for validation as understood broadly, a set of approaches to validating mathematical models and numerical algorithms are recommended as good practices. Previously identified procedures, such as verification, qualification, and analysis of error and uncertainty, remain important. However, particular challenges intrinsic to fusion plasmas and physical measurement therein lead to identification of new or less familiar concepts that are also critical in validation. These include the primacy hierarchy, which tracks the integration of measurable quantities, and sensitivity analysis, which assesses how model output is apportioned to different sources of variation. The use of validation metrics for individual measurements is extended to multiple measurements, with provisions for the primacy hierarchy and sensitivity. This composite validation metric is essential for quantitatively evaluating comparisons with experiments. To mount successful and credible validation in magnetic fusion, a new culture of validation is envisaged.Comment: 27 pages, 1 table, 6 figure

Asymptotics and local constancy of characters of p-adic groups

In this paper we study quantitative aspects of trace characters $\Theta_\pi$ of reductive $p$-adic groups when the representation $\pi$ varies. Our approach is based on the local constancy of characters and we survey some other related results. We formulate a conjecture on the behavior of $\Theta_\pi$ relative to the formal degree of $\pi$, which we are able to prove in the case where $\pi$ is a tame supercuspidal. The proof builds on J.-K.~Yu's construction and the structure of Moy-Prasad subgroups.Comment: Proceedings of Simons symposium on the trace formul

Strong "quantum" chaos in the global ballooning mode spectrum of three-dimensional plasmas

The spectrum of ideal magnetohydrodynamic (MHD) pressure-driven (ballooning) modes in strongly nonaxisymmetric toroidal systems is difficult to analyze numerically owing to the singular nature of ideal MHD caused by lack of an inherent scale length. In this paper, ideal MHD is regularized by using a $k$-space cutoff, making the ray tracing for the WKB ballooning formalism a chaotic Hamiltonian billiard problem. The minimum width of the toroidal Fourier spectrum needed for resolving toroidally localized ballooning modes with a global eigenvalue code is estimated from the Weyl formula. This phase-space-volume estimation method is applied to two stellarator cases.Comment: 4 pages typeset, including 2 figures. Paper accepted for publication in Phys. Rev. Letter

Simulation and real-time optimal scheduling: a framework for integration

Traditional scheduling and simulation models of the same system differ in several fundamental respects. These include the definition of a schedule, the existence of an objective function which orders schedules and indicates the performance of a given schedule according to specific criteria, and the level of fidelity at which the items are represented and processed through he system. This paper presents a conceptual, object-oriented, architecture for combining a traditional, high-level, scheduling system with a detailed, process- level, discrete-event simulation. A multi-echelon planning framework is established in the context of modeling end-to-end military deployments with the focus on detailed seaport operations

Orthodontic tooth movement enhancing bony apposition in alveolar bony defect: a case report

Introduction: Prevalence of complications from orthognathic surgery is relatively low but if it happens it is vital to manage the post complication bony defect appropriately. Case Presentation: This case report describes a 20-year-old gentleman who suffered from a complication from a bimaxillary orthognathic surgery. A bone grafting was carried out to repair the bony defect from the surgery but it was unsuccessful. A non-invasive technique employing the use of very light orthodontic force with a laceback stainless steel ligature is described and a successful space closure with an improvement in the periodontal condition and bone apposition has been shown. Conclusion: This technique can be considered if orthodontic tooth movement is needed across a deficient alveolar ridge. © 2009 Hibino and Wong; licensee BioMed Central Ltd.published_or_final_versio

Stochastic E2F Activation and Reconciliation of Phenomenological Cell-Cycle Models

A new, stochastic model of entry into the mammalian cell cycle provides a mechanistic understanding of the temporal variability observed across populations of cells and reconciles previously proposed phenomenological cell-cycle models