7 research outputs found

    The Physics of the B Factories

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    Ergonomic Design of a Mechanical Device for Increasing the Rate of Union in Open Fractures of the Tibia

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    Open fractures of the tibia resulting from motor vehicle accidents often take a long time to unite and sometimes do not unite at all. The patients are usually treated with rigid external fixators and immobilized for long periods. Without adequate physiological use, the bone and soft tissue takes longer to heal. This paper reports the development of a mechanical device, based on a hierarchical design approach. The process involves identification of functional requirements from both the expert and user population, which are then mapped on to design parameters. The outcome is a device that allows patients to mobilize their injured limb while they are still bed-bound. The device is being tested for usability and reliability in an on-going study, which is aimed at comparing the treatment of two groups of patients: one using the device in the course of their rehabilitation, while the other does not.</jats:p

    A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-\u3b2 Superfamily

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    We present an integromic analysis of gene alterations that modulate transforming growth factor \u3b2 (TGF-\u3b2)-Smad-mediated signaling in 9,125 tumor samples across 33 cancer types in The Cancer Genome Atlas (TCGA). Focusing on genes that encode mediators and regulators of TGF-\u3b2 signaling, we found at least one genomic alteration (mutation, homozygous deletion, or amplification) in 39% of samples, with highest frequencies in gastrointestinal cancers. We identified mutation hotspots in genes that encode TGF-\u3b2 ligands (BMP5), receptors (TGFBR2, AVCR2A, and BMPR2), and Smads (SMAD2 and SMAD4). Alterations in the TGF-\u3b2 superfamily correlated positively with expression of metastasis-associated genes and with decreased survival. Correlation analyses showed the contributions of mutation, amplification, deletion, DNA methylation, and miRNA expression to transcriptional activity of TGF-\u3b2 signaling in each cancer type. This study provides a broad molecular perspective relevant for future functional and therapeutic studies of the diverse cancer pathways mediated by the TGF-\u3b2 superfamily. To date, there are no studies of the TGF-\u3b2 superfamily of signaling pathways across multiple cancers. This study represents a key starting point for unraveling the role of this complex superfamily in 33 divergent cancer types from over 9,000 patients
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