Slug-based epithelial-mesenchymal transition gene signature is associated with prolonged time to recurrence in glioblastoma

Background
We previously identified a precise stage-associated gene expression signature of coordinately expressed genes, including the transcription factor Slug (SNAI2) and other epithelial mesenchymal transition (EMT) markers, present in samples from publicly available gene expression datasets in multiple cancer types. The expression levels of the co-expressed genes vary in a continuous and coordinate manner across the samples, ranging from absence of expression to strong co-expression of all genes. These data suggest that tumor cells may pass through an EMT like process of mesenchymal transition to varying degrees. 

Findings
Here we show that this signature in glioblastoma multiforme (GBM) is associated with time to recurrence following initial treatment. By analyzing data from The Cancer Genome Atlas (TCGA), we found that GBM patients who responded to therapy and had long time to recurrence had low levels of the signature in their tumor samples (P = 3x10^-7^). We also found that the signature is strongly correlated in gliomas with the putative stem cell marker CD44, and is highly enriched among the differentially expressed genes in glioblastomas vs. lower grade gliomas. 

Conclusions 
Our results suggest that long delay before tumor recurrence is associated with absence of the mesenchymal transition signature, raising the possibility that inhibiting this transition might improve the durability of therapy in glioma patients

Current-Induced Step Bending Instability on Vicinal Surfaces

We model an apparent instability seen in recent experiments on current induced step bunching on Si(111) surfaces using a generalized 2D BCF model, where adatoms have a diffusion bias parallel to the step edges and there is an attachment barrier at the step edge. We find a new linear instability with novel step patterns. Monte Carlo simulations on a solid-on-solid model are used to study the instability beyond the linear regime.Comment: 4 pages, 4 figure

Dual Monte Carlo and Cluster Algorithms

We discuss the development of cluster algorithms from the viewpoint of probability theory and not from the usual viewpoint of a particular model. By using the perspective of probability theory, we detail the nature of a cluster algorithm, make explicit the assumptions embodied in all clusters of which we are aware, and define the construction of free cluster algorithms. We also illustrate these procedures by rederiving the Swendsen-Wang algorithm, presenting the details of the loop algorithm for a worldline simulation of a quantum $S=$ 1/2 model, and proposing a free cluster version of the Swendsen-Wang replica method for the random Ising model. How the principle of maximum entropy might be used to aid the construction of cluster algorithms is also discussed.Comment: 25 pages, 4 figures, to appear in Phys.Rev.

On generalized cluster algorithms for frustrated spin models

Standard Monte Carlo cluster algorithms have proven to be very effective for many different spin models, however they fail for frustrated spin systems. Recently a generalized cluster algorithm was introduced that works extremely well for the fully frustrated Ising model on a square lattice, by placing bonds between sites based on information from plaquettes rather than links of the lattice. Here we study some properties of this algorithm and some variants of it. We introduce a practical methodology for constructing a generalized cluster algorithm for a given spin model, and investigate apply this method to some other frustrated Ising models. We find that such algorithms work well for simple fully frustrated Ising models in two dimensions, but appear to work poorly or not at all for more complex models such as spin glasses.Comment: 34 pages in RevTeX. No figures included. A compressed postscript file for the paper with figures can be obtained via anonymous ftp to minerva.npac.syr.edu in users/paulc/papers/SCCS-527.ps.Z. Syracuse University NPAC technical report SCCS-52

Safe Zero-Shot Model-Based Learning and Control: A Wasserstein Distributionally Robust Approach

This paper explores distributionally robust zero-shot model-based learning and control using Wasserstein ambiguity sets. Conventional model-based reinforcement learning algorithms struggle to guarantee feasibility throughout the online learning process. We address this open challenge with the following approach. Using a stochastic model-predictive control (MPC) strategy, we augment safety constraints with affine random variables corresponding to the instantaneous empirical distributions of modeling error. We obtain these distributions by evaluating model residuals in real time throughout the online learning process. By optimizing over the worst case modeling error distribution defined within a Wasserstein ambiguity set centered about our empirical distributions, we can approach the nominal constraint boundary in a provably safe way. We validate the performance of our approach using a case study of lithium-ion battery fast charging, a relevant and safety-critical energy systems control application. Our results demonstrate marked improvements in safety compared to a basic learning model-predictive controller, with constraints satisfied at every instance during online learning and control.Comment: In review for CDC2

Synchronization and Redundancy: Implications for Robustness of Neural Learning and Decision Making

Learning and decision making in the brain are key processes critical to survival, and yet are processes implemented by non-ideal biological building blocks which can impose significant error. We explore quantitatively how the brain might cope with this inherent source of error by taking advantage of two ubiquitous mechanisms, redundancy and synchronization. In particular we consider a neural process whose goal is to learn a decision function by implementing a nonlinear gradient dynamics. The dynamics, however, are assumed to be corrupted by perturbations modeling the error which might be incurred due to limitations of the biology, intrinsic neuronal noise, and imperfect measurements. We show that error, and the associated uncertainty surrounding a learned solution, can be controlled in large part by trading off synchronization strength among multiple redundant neural systems against the noise amplitude. The impact of the coupling between such redundant systems is quantified by the spectrum of the network Laplacian, and we discuss the role of network topology in synchronization and in reducing the effect of noise. A range of situations in which the mechanisms we model arise in brain science are discussed, and we draw attention to experimental evidence suggesting that cortical circuits capable of implementing the computations of interest here can be found on several scales. Finally, simulations comparing theoretical bounds to the relevant empirical quantities show that the theoretical estimates we derive can be tight.Comment: Preprint, accepted for publication in Neural Computatio