Altitude alerter

This project designed and constructed an altitude alerter. The device reported deviations of 50, 100 and 150 feet above and below a set altitude. The design was implemented using a pressure sensor, which output a voltage to a PIC microprocessor and was translated into a deviation through software. The design was tested as a protoboard prototype and as a PC Board product. The design was found to work properly with a deviation accuracy of twenty feet

Use of proposed technologies at the Worcester EcoTarium

The objective of this project was to develop effective ways for the EcoTarium in Worcester to use its new Telecommunications Theater. This report discusses ideas we formulated or expanded upon to make use of the facility and its technologically advanced capabilities. Our most important ideas revolved around the usage of digital cameras by patrons and staff, with the Telecommunications Theater as a means to combine the new technology with existing presentation practices

National trends in the diagnosis and repair of SLAP lesions in the United States

BACKGROUND: Since superior labrum anterior-to-posterior (SLAP) tear was introduced as an International Classification of Diseases-Ninth Revision, Clinical Modification diagnosis in 1994, awareness, diagnosis, and surgical treatment of this disorder has increased. Here, we aim to clarify trends in the frequency of SLAP tear diagnosis and arthroscopic SLAP repair surgery in the United States. METHODS: Using private insurance claims from 2003 to 2013 in MarketScan (approximately 55 million Americans), we identified patients with SLAP tear diagnosis or arthroscopic SLAP repair surgery. Population-based rates of SLAP diagnosis and related shoulder procedures were calculated. RESULTS: A total of 329,643 patients in the MarketScan database received a SLAP tear diagnosis. In all, 62.8% underwent some form of shoulder surgery after diagnosis. SLAP diagnosis increased from 28.0 per 100,000 in 2003 to 142.4 per 100,000 in 2013 (p \u3c 0.0001); the rate of shoulder surgery in these patients increased from 20.1 per 100,000 in 2003 to 74.1 per 100,000 in 2013 (p \u3c 0.0001). However, the percentage of patients with SLAP tears who got shoulder surgery decreased (p \u3c 0.0001). In 2003, almost no patient got biceps tenodesis for SLAP tears; by 2013, 18.1% of surgeries for SLAP tear were biceps tenodesis. Isolated arthroscopic SLAP repairs peaked in 2009 at 28.4 per 100,000 and stabilized thereafter. CONCLUSION: We confirmed prior reports that SLAP diagnosis increased from 2003 to 2013, although the percentage of these patients who underwent surgery decreased over this period. Arthroscopic SLAP repair doubled but then plateaued after 2009. Biceps tenodesis now accounts for a substantial portion of surgeries for SLAP tear. This may reflect an improved understanding of superior labrum anatomy and biomechanics

The microbial genotoxin colibactin exacerbates mismatch repair mutations in colorectal tumors

Certain Enterobacteriaceae strains contain a 54-kb biosynthetic gene cluster referred to as “pks” encoding the biosynthesis of a secondary metabolite, colibactin. Colibactin-producing E. coli promote colorectal cancer (CRC) in preclinical models, and in vitro induce a specific mutational signature that is also detected in human CRC genomes. Yet, how colibactin exposure affects the mutational landscape of CRC in vivo remains unclear. Here we show that colibactin-producing E. coli-driven colonic tumors in mice have a significantly higher SBS burden and a larger percentage of these mutations can be attributed to a signature associated with mismatch repair deficiency (MMRd; SBS15), compared to tumors developed in the presence of colibactin-deficient E. coli. We found that the synthetic colibactin 742 but not an inactive analog 746 causes DNA damage and induces transcriptional activation of p53 and senescence signaling pathways in non-transformed human colonic epithelial cells. In MMRd colon cancer cells (HCT 116), chronic exposure to 742 resulted in the upregulation of BRCA1, Fanconi anemia, and MMR signaling pathways as revealed by global transcriptomic analysis. This was accompanied by increased T>N single-base substitutions (SBS) attributed to the proposed pks+ E. coli signature (SBS88), reactive oxygen species (SBS17), and mismatch-repair deficiency (SBS44). A significant co-occurrence between MMRd SBS44 and pks-associated SBS88 signature was observed in a large cohort of human CRC patients (n=2,945), and significantly more SBS44 mutations were found when SBS88 was also detected. Collectively, these findings reveal the host response mechanisms underlying colibactin genotoxic activity and suggest that colibactin may exacerbate MMRd-associated mutations

Quantifying the local tissue volume and composition in individual brains with magnetic resonance imaging

We describe a quantitative neuroimaging method to estimate the macromolecular tissue volume (MTV), a fundamental measure of brain anatomy. By making measurements over a range of field strengths and scan parameters, we tested the key assumptions and the robustness of the method. The measurements confirm that a consistent, quantitative estimate of macromolecular volume can be obtained across a range of scanners. MTV estimates are sufficiently precise to enable a comparison between data obtained from an individual subject with control population data. We describe two applications. First, we show that MTV estimates can be combined with T1 and diffusion measurements to augment our understanding of the tissue properties. Second we show that MTV provides a sensitive measure of disease status in individual patients with multiple sclerosis. The MTV maps are obtained using short clinically appropriate scans that can reveal how tissue changes influence behavior and cognition

A human ciliopathy reveals essential functions for NEK10 in airway mucociliary clearance

© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Mucociliary clearance, the physiological process by which mammalian conducting airways expel pathogens and unwanted surface materials from the respiratory tract, depends on the coordinated function of multiple specialized cell types, including basal stem cells, mucus-secreting goblet cells, motile ciliated cells, cystic fibrosis transmembrane conductance regulator (CFTR)-rich ionocytes, and immune cells1,2. Bronchiectasis, a syndrome of pathological airway dilation associated with impaired mucociliary clearance, may occur sporadically or as a consequence of Mendelian inheritance, for example in cystic fibrosis, primary ciliary dyskinesia (PCD), and select immunodeficiencies3. Previous studies have identified mutations that affect ciliary structure and nucleation in PCD4, but the regulation of mucociliary transport remains incompletely understood, and therapeutic targets for its modulation are lacking. Here we identify a bronchiectasis syndrome caused by mutations that inactivate NIMA-related kinase 10 (NEK10), a protein kinase with previously unknown in vivo functions in mammals. Genetically modified primary human airway cultures establish NEK10 as a ciliated-cell-specific kinase whose activity regulates the motile ciliary proteome to promote ciliary length and mucociliary transport but which is dispensable for normal ciliary number, radial structure, and beat frequency. Together, these data identify a novel and likely targetable signaling axis that controls motile ciliary function in humans and has potential implications for other respiratory disorders that are characterized by impaired mucociliary clearance