The application of machine learning algorithms to healthcare data can enhance patient care while also reducing healthcare worker cognitive load. These algorithms can be used to detect anomalous physiological readings, potentially leading to expedited emergency response or new knowledge about the development of a health condition. However, while there has been much research conducted in assessing the performance of anomaly detection algorithms on well-known public datasets, there is less conceptual comparison across unsupervised and supervised performance on physiological data. Moreover, while (...) heart rate data are both ubiquitous and noninvasive, there has been little research specifically for anomaly detection of this type of data. Considering that heart rate data are indicative of both potential health complications and an individual’s physical activity, this is a rich source of largely overlooked data. To this end, we employed and evaluated five machine learning algorithms, two of which are unsupervised and the remaining three supervised, in their ability to detect anomalies in heart rate data. These algorithms were then evaluated on real heart rate data. Findings supported the effectiveness of local outlier factor and random forests algorithms in the task of heart rate anomaly detection, as each model generalized well from their training on simulated heart rate data to real world heart rate data. Furthermore, results support that simulated data can help configure algorithms to a degree of performance when real labeled data are not available and that this type of learning might be especially helpful in initial deployment of a system without prior data. (shrink)

Iron uptake and storage in mammalian cells is at least partly regulated at a posttranscriptional level by the iron regulatory proteins (IRP‐1 and IRP‐2). These cytoplasmic regulators share 79% similarity in protein sequence and bind tightly to conserved mRNA stem‐loops, named iron‐responsive elements (IREs). The IRP:IRE interaction underlies the regulation of translation and stability of several mRNAs central to iron metabolism. The question of why the cell requires two such closely related regulatory proteins may be resloved as we learn more (...) about the expression and regulation of these proteins. It is evident so far that, despite similarities, the IRPs differ in several important respects. They are coordinately regulated by cellular iron, but whereas IRP‐1 is inactivated by high iron levels, IRP‐2 is rapidly degraded. Further differences arise in their expression and RNA‐binding specificity. The two proteins each recognise a large repertoire of IRE‐like sequences, including a small group of exclusive RNA targets. These findings hint that IRP‐1 and IRP‐2 may bind preferenitially to certain mRNAs in vivo, possibly extending their known functions beyond the regulation of intracellular iron homeostasis. (shrink)

The subcellular location and function of many proteins are regulated by nuclear–cytoplasmic shuttling. BRCA1 and BARD1 provide an interesting model system for understanding the influence of protein dimerization on nuclear transport and localization. These proteins function predominantly in the nucleus to regulate cell cycle progression, DNA repair/recombination and gene transcription, and their export to the cytoplasm has been linked to apoptosis. Germ‐line mutations in the BRCA1/BRCA2 and BARD1 genes predispose to risk of breast/ovarian cancer, and certain mutations impair protein function (...) and nuclear accumulation. BRCA1 and BARD1 shuttle between the nucleus and cytoplasm; however heterodimerization masks the nuclear export signals located within each protein, causing nuclear retention of the BRCA1–BARD1 complex and potentially influencing its role in DNA repair, cell survival and regulation of centrosome duplication. This review discusses BRCA1, BRCA2 and BARD1 subcellular localization with emphasis on regulation of transport by protein dimerization and its functional implications. BioEssays 27:884–893, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

In the wake of life-changing events—whether as global in reach as the terrorist attacks on September 11 or as personal as the death of a child—the first question that springs to mind is “Why?” Why do good people suffer pain and loss? Why does God allow these things to happen? In this simple, straightforward book, Bruce Henderson tackles some of the most difficult questions that people of faith face in their lives. Drawing from the wisdom of visionary Emanuel Swedenborg, who (...) wrestled with these same questions more than two hundred years ago, Henderson describes a universe in which God allows us free will and choice, subtly guiding the course of our lives with an insight no mortal can comprehend. Pain and suffering ultimately lead to good, and as we walk the path, we draw ever closer to heaven. In the end, the question is not why these things happen, but what good can come of them, and how we can use our gift of free will to create a better world for ourselves and others. In this, Henderson says, God is our partner and guiding hand, turning pain to hope and trust. (shrink)

What happens to us when we die? Is there really a heaven and hell? Are there angels watching over us? These questions follow us from early childhood to old age, particularly in moments when we’re confronted with the loss of a loved one. In _Window to Eternity,_ Bruce Henderson draws from the teachings of visionary Emanuel Swedenborg to paint a vivid picture of heaven and hell, where the souls of the departed become angels and demons and indescribable wonders await. But (...) far from being a distant destination, Henderson shows that heaven is a choice that each of us makes every day—ours to have or to turn away from, regardless of our background or religious upbringing. (shrink)