Understanding complexity in the HIF signaling pathway using systems biology and mathematical modeling

Hypoxia is a common micro-environmental stress which is experienced by cells during a range of physiologic and pathophysiologic processes. The identification of the hypoxia-inducible factor (HIF) as the master regulator of the transcriptional response to hypoxia transformed our understanding of the mechanism underpinning the hypoxic response at the molecular level and identified HIF as a potentially important new therapeutic target. It has recently become clear that multiple levels of regulatory control exert influence on the HIF pathway giving the response a complex and dynamic activity profile. These include positive and negative feedback loops within the HIF pathway as well as multiple levels of crosstalk with other signaling pathways. The emerging model reflects a multi-level regulatory network that affects multiple aspects of the physiologic response to hypoxia including proliferation, apoptosis, and differentiation. Understanding the interplay between the molecular mechanisms involved in the dynamic regulation of the HIF pathway at a systems level is critically important in defining new appropriate therapeutic targets for human diseases including ischemia, cancer, and chronic inflammation. Here, we review our current knowledge of the regulatory circuits which exert influence over the HIF response and give examples of in silico model-based predictions of the dynamic behaviour of this system

A Point Matching Algorithm for Automatic Generation of Groundtruth for Document Images

Geometric groundtruth at character, word, and line level is crucial for developing and evaluating optical character recognition (OCR) algorithms. Kanungo and Haralick [ICPR ’96] proposed a closed loop methodology for generating character level groundtruth for rescanned image. In this article we present a robust version of their methodology. We grouped the feature points and used branch and bound algorithm on the grouped feature point set to estimate the transformation. Euclidean distance between character centroids was used as the error metric. We performed experiments on a randomly selected subset of the University of Washington dataset.

THE BIBLE AND OPTICAL CHAR RECOGNITION The Bible—an unlikely resource for language technology research—

proves ideal for evaluating OCR techniques. As global online access to information becomes more common, the technology of multilingual optical character recognition (OCR) increases in importance as a way to convert paper documents into electronic, searchable, text. In OCR, as in any evolving technology, careful evaluation is an integral part of research and development. OCR evaluation is done by comparing a system’s output for a dataset of document test images with the corresponding correct symbolic text, known as ground truth. Unfortunately, the usual way of obtaining ground truth is by manual data entry by humans, which is labor-intensive, time-consuming, expensive, and prone to errors. Worse, because no single set of ground truth evaluation data can be used in more than one language, there has until now been no way to conduct carefully controlled OCR experiments in a multilingual setting

Containment Domains: A Scalable, Efficient and Flexible Resilience Scheme for Exascale Systems

This paper describes and evaluates a scalable and efficient resilience scheme based on the concept of containment domains. Containment domains are a programming construct that enable applications to express resilience needs and to interact with the system to tune and specialize error detection, state preservation and restoration, and recovery schemes. Containment domains have weak transactional semantics and are nested to take advantage of the machine and application hierarchies and to enable hierarchical state preservation, restoration and recovery. We evaluate the scalability and efficiency of containment domains using generalized trace-driven simulation and analytical analysis and show that containment domains are superior to both checkpoint restart and redundant execution approaches