GPS Position and Heading Circuitry for Ships

Circuit boards that contain radio-frequency (RF) and digital circuitry have been developed by NASA to satisfy a requirement of the Port of Houston Authority for relatively inexpensive Global Positioning System (GPS) receivers that indicate the azimuthal headings as well as the positions of ships. The receiver design utilizes the unique architecture of the Mitel commercial chip-set, which provides for an accurate GPS-based heading-determination device. The major components include two RF front ends (each connected to a separate antenna), a surface-acoustic-wave intermediate-frequency filter between second- and third-stage mixers, a correlator, and a reduced-instruction- set computer. One of the RF front ends operates as a master, the other as a slave. Both RF front ends share a 10-MHz sinusoidal clock oscillator, which provides for more accurate carrier phase measurements between the two antennas. The outputs of the RF front ends are subjected to conventional GPS processing. The commercial-based chip-set design approach provides an inexpensive open architecture GPS platform, which can be used in developing and implementing unique GPS-heading and attitude-determination algorithms for specific applications. The heading is estimated from the GPS position solutions of the two antennas by an algorithm developed specifically for this application. If a third (and preferably a fourth) antenna were added, it would be possible to estimate the attitude of the GPS receiver in three dimensions instead of only its heading in a horizontal plane

Book Reviews

Book Reviews: Unconquerable Rebel: Robert W. Wilcox And Hawaiian Politics, 1880 - 1903 by Ernest Andrade, Jr.; Women And Children First: the Life And Times of Elsie Wilcox of Kaua'i by Judith Dean Gething Hughes; the Shipmans of East Hawai'i by Emmett Cahill; Shaping History: the Role of Newspapers In Hawai'i by Helen Geracimos Chapin; Waikiki 100 B.C. To 1900 A.D.: An Untold Story by George S. Kanahele; Surveying the Mahele: Mapping the Hawaiian Land Revolution by Riley M. Moffat And Gary L. Fitzpatrick; the Filipino Piecemeal Sugar Strike of 1924-1925 by John E. Reinecke; Sugar Water: Hawaii's Plantation Ditches by Carol Wilcox; Who Runs the University? the Politics of Higher Education In Hawaii, 1985 - 1992 by David Youn

Localization of IFN-γ-Activated Stat1 and IFN Regulatory Factors 1 and 2 in Breast Cancer Cells

The aim of the present work was to evaluate the induction and localization of Stat1, interferon (IFN) regulatory factor-1 (IRF-1), and IRF-2 after IFN-γ exposure of human breast cancer cell lines, SKBR3, MDA468, MCF7, and BT20. Results from growth assays, Western staining, electrophoretic mobility shift assay (EMSA), and immunohistochemical staining were collated to test our hypothesis that immunohistochemical analysis of Stat1, IRF-1, and IRF-2 would provide additional information about the functionality of the IFN-γ signaling pathway in human tumor lines. EMSA results showed that in each of four cell lines, Stat1 expression was increased and demonstrated functional activity after IFN-γ stimulation. Western and EMSA analysis showed upregulation of IRF-1 but not IRF-2 in each cell line. Confocal microscopy of cells stained for Stat1, IRF-1, and IRF-2 confirmed the results and also provided novel information about the intracellular localization of proteins and intercellular variations in responses. The proportion of cells with IRF-1 stimulation and translocation was positively correlated with the IFN-γ growth suppression in vitro. In conclusion, using four independent assays, we have demonstrated that heterogeneity in IFN-γ-mediated upregulation of signal transduction proteins can be detected in vitro and that these differences can explain distinct cellular growth effects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63148/1/107999003322558755.pd

Blood-brain barrier permeability in survivors of immune-mediated thrombotic thrombocytopenic purpura: A pilot study

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening disorder of systemic microthrombosis and organ ischemia. The etiology of chronic cerebrovascular outcomes in iTTP survivors is largely unknown. In this pilot study, we measured blood-brain barrier (BBB) permeability in patients with iTTP at the start of remission and 6 months later. This prospective pilot study included 7 adult patients with incident iTTP. Eligibility criteria included ADAMTS13 activity, 10% and detectable inhibitor at diagnosis. Patients were recruited from London Health Sciences Centre in Canada (2017-2019) within 3 days of hospital admission and followed for 6 months after remission (defined as normalization of platelet count and lactate dehydrogenase with no clinical signs or symptoms of microvascular injury for more than 30 days after the last plasma exchange). All patients had cerebral computed tomography perfusion scans with BBB permeability surface product measurements. Patients (5 women, 2 men) had a mean age of 48 years (range, 21-77 years). At diagnosis, patients had a mean platelet count of 22 (standard deviation [SD], 25) 3 109/L. At the start of remission, mean BBB permeability surface product was 0.91 (0.30) mL/min/100 g. Six months later, the mean permeability surface product was 0.56 (0.22) mL/min/100 g, with a mean difference of 20.312 mL/min/100 g (95% confidence interval: 20.4729 to 20.1510; P 5.0032). In this pilot study of patients with iTTP, pathologically increased BBB permeability was evident, and although there was some improvement, this persisted 6 months after remission. Future work will explore the chronicity of these findings and their clinical implications

Chronic Hepatitis B Virus Infection: The Relation between Hepatitis B Antigen Expression, Telomere Length, Senescence, Inflammation and Fibrosis.

BACKGROUND: Chronic Hepatitis B virus (HBV) infection can lead to the development of chronic hepatitis, cirrhosis and hepatocellular carcinoma. We hypothesized that HBV might accelerate hepatocyte ageing and investigated the effect of HBV on hepatocyte cell cycle state and biological age. We also investigated the relation between inflammation, fibrosis and cell cycle phase. METHODS: Liver samples from patients with chronic HBV (n = 91), normal liver (n = 55) and regenerating liver (n = 15) were studied. Immunohistochemistry for cell cycle phase markers and HBV antigens was used to determine host cell cycle phase. Hepatocyte-specific telomere length was evaluated by quantitative fluorescent in-situ hybridization (Q-FISH) in conjunction with hepatocyte nuclear area and HBV antigen expression. The effects of induced cell cycle arrest and induced cellular senescence on HBV production were assessed in vitro. RESULTS: 13.7% hepatocytes in chronic HBV had entered cell cycle, but expression of markers for S, G2 and M phase was low compared with regenerating liver. Hepatocyte p21 expression was increased (10.9%) in chronic HBV and correlated with liver fibrosis. Mean telomere length was reduced in chronic HBV compared to normal. However, within HBV-affected livers, hepatocytes expressing HBV antigens had longer telomeres. Telomere length declined and hepatocyte nuclear size increased as HBV core antigen (HBcAg) expression shifted from the nucleus to cytoplasm. Nuclear co-expression of HBcAg and p21 was not observed. Cell cycle arrest induced in vitro was associated with increased HBV production, in contrast to in vitro induction of cellular senescence, which had no effect. CONCLUSION: Chronic HBV infection was associated with hepatocyte G1 cell cycle arrest and accelerated hepatocyte ageing, implying that HBV induced cellular senescence. However, HBV replication was confined to biologically younger hepatocytes. Changes in the cellular location of HBcAg may be related to the onset of cellular senescence

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Translational pharmacology of an inhaled small molecule αvβ6 integrin inhibitor for idiopathic pulmonary fibrosis

The αvβ6 integrin plays a key role in the activation of transforming growth factor-β (TGFβ), a pro-fibrotic mediator that is pivotal to the development of idiopathic pulmonary fibrosis (IPF). We identified a selective small molecule αvβ6 RGD-mimetic, GSK3008348, and profiled it in a range of disease relevant pre-clinical systems. To understand the relationship between target engagement and inhibition of fibrosis, we measured pharmacodynamic and diseaserelated end points. Here we report, GSK3008348 binds to αvβ6 with high affinity in human IPF lung and reduces downstream pro-fibrotic TGFβ signaling to normal levels. In human lung epithelial cells, GSK3008348 induces rapid internalization and lysosomal degradation of the αvβ6 integrin. In the murine bleomycin-induced lung fibrosis model, GSK3008348 engages αvβ6, induces prolonged inhibition of TGFβ signaling and reduces lung collagen deposition and serum C3M, a marker of IPF disease progression. These studies highlight the potential of inhaled GSK3008348 as an anti-fibrotic therapy

Carbon Meets Silicon II

The exhibition was part of the seventh International Conference on Internet Technologies and Applications (ITA17), held at Wrexham Glyndwr University from Tuesday 12 to Friday 15 September in 2017. The exhibition bought the work of fifteen diverse artists, scientists and technologists working in a range of media who have all in some way collaborated via ideas with specialist outside of their immediate field of enquiry. International artists from Chicago, Italy and Denmark met with UK artists from Wales, Salford and Bristol to reflect on the global nature of ‘Carbon Meets Silicon’. All of the artworks in the exhibition were about making connections and every artist involved had collaborated in some way. The exhibition theme uses carbon and silicon as metaphors for the changing face of art practice in the digital age. Carbon references the materiality of the art object and silicon references how an artworks physical presence is questioned in the light of new media, resulting in the digital or virtual bringing artists closer to scientists and engineers. The focus for this year is Arts/Science/Technology Collaborations and the exhibition brings together the work of sixteen diverse artists, scientists and technologists working in a range of media who have all in some way collaborated via ideas with specialist outside of their immediate field of enquiry. To understand the complexity of the world we need to utilise the cognitive evolutionary tools developed through both scientific and artistic thinking. Science allows us to understand causality, predictions and rationality; art gives us expression, surprise and has the capacity to change minds. Collaborations between the arts and sciences has a long history of interdependence, but also tension and antipathy. Acknowledging the things we don’t know we don’t know; to quote Rumsfeld ‘the unknown unknowns’ [1] is as important as knowing the as the known unknowns and Crew’s approach to knowledge sums it up nicely. He said that we should follow: “the ethic of respecting that which is known, acknowledging what is still unknown and acting as if one cared about the difference” [2] Today we must re-frame our perceptions to ensure this dualism does not set artists and scientists apart. Global Challenges are better understood with a diverse team of researchers from both the arts and sciences working on solutions together. Collaboration can results in new approaches to core issues that may underlie developmental problems. "Third culture starts when artists become scientists, when science paints the future, when systems are predictive and when politicians become poets." [3] In 1963 the influential scientist and novelist C.P Snow’s book The Two Cultures and the Scientific Revolution was published outlining an optimistic view of the sometimes difficult relationship that exists between science and the arts [4]. Scneiderman (2016) advances the case for combining applied and basic research work to put the arts on an equal footing with science. Holzbaur (2012) recognised new paradigms for multi-disciplinary, inter-disciplinary and trans-disciplinary collaboration with an understanding that if you think beyond traditional disciplines you can impact societal change [5]. The generation of new knowledge often arises on the boundaries of disciplines rather than within them. This exhibition and symposium explores the well-established discourse that exists between artists, scientist and technologists and how this symbiotic relationship has brought new understandings to the world. References [1] Rumsfeld, D (2002) "Defense.gov News Transcript: DoD News Briefing – Secretary Rumsfeld and Gen. Myers, United States Department of Defense (defense.gov)" [2] Crews, F. (2006). Follies of the Wise, Shoemaker and Hoard. Emeryville, CA. [3] Matthias Horx (2012) Keynote Speaker ELIA Biennial Conference: Art, Science and Society 8-12 Nov, Hosted by the University of Applied Arts, Vienna. [4] Snow, C. P. (1959) The Two Cultures. Cambridge University Press, Cambridge, UK. ISBN 0-521-45730-0 [5] Earnshaw R.A (2017). Holzbaur, U.D. (2012) and Scneiderman (2016) cited in: Art Design and Technology: Collaboration and Implementation, Springer, Switzerland, Chapter 2 Independent Working, Collaboration and Team Activity. p 9-1

Natural History of Liver Disease in a Large International Cohort of Children with Alagille syndrome:Results from The GALA Study

BACKGROUND: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international, cohort of children with ALGS.METHODS: Multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born Jan-1997 - Aug-2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS.RESULTS: 1433 children (57% male) from 67 centers in 29 countries were included. 10 and 18-years NLS rates were 54.4% and 40.3%. By 10 and 18-years, 51.5% and 66.0% of ALGS children experienced ≥1 adverse liver-related event (CEPH, transplant or death). Children (&gt;6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and &lt;10.0 mg/dL had a 4.1-fold (95% CI 1.6 - 10.8) and those ≥10.0 mg/dL had an 8.0-fold (95% CI 3.4 - 18.4) increased risk of developing CEPH compared with those &lt;5.0 mg/dL. Median TB levels between ≥5.0 and &lt;10.0 mg/dL and &gt;10.0 mg/dL were associated with a 4.8 (95% CI 2.4 - 9.7) and 15.6 (95% CI 8.7 - 28.2) increased risk of transplantation relative to &lt;5.0 mg/dL. Median TB &lt;5.0 mg/dL were associated with higher NLS rates relative to ≥5.0 mg/dL, with 79% reaching adulthood with native liver (p&lt;0.001).CONCLUSIONS: In this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB &lt;5.0 mg/dL between 6-and-12-months of age is associated with better hepatic outcomes. These thresholds provide clinicians with an objective tool to assist with clinical decision-making and in the evaluation of novel therapies.</p

Characteristics of Adults in the Hepatitis B Research Network in North America Reflect Their Country of Origin and Hepatitis B Virus Genotype

Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the US and Canada might be disproportionately affected. The Hepatitis B Research Network (HBRN) is a cooperative network of investigators from the United States and Canada, created to facilitate clinical, therapeutic, and translational research in adults and children with hepatitis B. We describe the structure of the network and baseline characteristics of adults with hepatitis B enrolled in the network