452 research outputs found

    Guidance, Navigation, and Control for Agile Small Spacecraft with Articulating Solar Arrays

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    Payload operations for small satellites are often impacted by the need to allocate time for modifying the attitude to perform power generation or orbit maneuvering. A typical small satellite design would consist of a single rigid body with body-mounted solar cells, making the power generation subject to the spacecraft’s attitude. Often to achieve the high power generation that is required to enable the payload function, the attitude must be specifically set to maximize the solar cell area facing the Sun, which typically means diverting it from an attitude that is useful for payload operations for some period of time. At the scale of modern global constellations, these downtimes in the payload operation schedule can greatly reduce the overall capability of the system. By including deployable, articulating solar arrays in the design of small spacecraft, array pointing can be decoupled from the mainpayload pointing operations. With these pieces decoupled, payload operations can proceed uninterrupted while the articulating arrays ensure sufficient power generation. In this paper, the dynamic equations of the multibody system are derived, and guidance, navigation, and control (GNC) considerations are presented for achieving decoupled attitude and articulation objectives. Results from simulation of a sample mission show that agile target tracking attitude maneuvers can be performed together with array solar tracking with negligible impact on overall payload pointing performance

    Flight Results of the Attitude Determination and Control System for the NEMO-HD Earth Observation Microsatellite

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    NEMO-HD is an Earth observation microsatellite designed and built at the Space Flight Laboratory at the University of Toronto Institute for Aerospace Studies (SFL) in collaboration with the Slovenian Centre of Excellence for Space Sciences and Technologies (SPACE-SI) who owns and operates the spacecraft. The mission was launched successfully into a circular Sun-synchronous orbit with 10:30 LTDN at an altitude of 535 km, aboard the VEGA VV16 mission from French Guiana on September 2, 2020. The primary payload is an optical imager, providing still imagery on its panchromatic (PAN) channel with 2.8 m ground sample distance (GSD), 5.6 m GSD on its four multi-spectral channels (R,G,B,NIR), and high definition video with 1920x1080 resolution. To achieve the precise pointing and stability requirements required for high quality optical imagery, the spacecraft is three-axis stabilized using reaction wheels for attitude control, and dual star trackers for attitude determination. The spacecraft has three targeting modes for imaging: inertial pointing, nadir-pointing, and ground target tracking; the exact mode selection depends upon the type of imagery desired. In this paper we discuss spacecraft attitude determination and control system design, and present the detailed attitude determination and control system pointing performance results for the mission in each of the primary operational modes, using one of the two star trackers as the “true” reference attitude

    Application and clinical impact of the RESIST-4 O.K.N.V. rapid diagnostic test for carbapenemase detection in blood cultures and clinical samples

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    Invasive infections caused by carbapenemase-producing bacteria are associated with excess mortality. We applied a rapid diagnostic test (RDT) on clinical samples with an elevated likelihood of carbapenemase-producing bacteria and documented its impact on antibiotic treatment decisions. Among 38 patients, twelve tested positive for infections caused by carbapenemase-producing bacteria (31.6%), mainly in blood cultures. KPC (n = 10) was more frequent than OXA-48 (n = 2). RDT-based carbapenemase detection led to a treatment modification to ceftazidime/avibactam-containing regimens in all patients before detailed antibiotic testing results became available. Eleven patients (92%) survived the acute infection, whereas one patient with a ceftazidime/avibactam- and colistin-resistant OXA-48-positive isolate died

    Studies Needed to Address Public Health Challenges of the 2009 H1N1 Influenza Pandemic: Insights from Modeling

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    In light of the 2009 influenza pandemic and potential future pandemics, Maria Van Kerkhove and colleagues anticipate six public health challenges and the data needed to support sound public health decision making.The authors acknowledge support from the Bill & Melinda Gates Foundation (MDVK, CF, NMF); Royal Society (CF); Medical Research Council (MDVK, CF, PJW, NMF); EU FP7 programme (NMF); UK Health Protection Agency (PJW); US National Institutes of Health Models of Infectious Disease Agent Study program through cooperative agreement 1U54GM088588 (ML); NIH Director's Pioneer Award, DP1-OD000490-01 (DS); EU FP7 grant EMPERIE 223498 (DS); the Wellcome Trust (DS); 3R01TW008246-01S1 from Fogerty International Center and RAPIDD program from Fogerty International Center with the Science & Technology Directorate, Department of Homeland Security (SR); and the Institut de Veille Sanitaire Sanitaire funded by the French Ministry of Health (J-CD). The funders played no role in the decision to submit the article or in its preparation

    HTS and Rational Drug Design [RDD] to Generate a Class of 5-HT2C-Selective Ligands for Possible Use in Schizophrenia

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    (Chemical Equation Presented) Treating neurological conditions: Optimization of a previously identified lead 5-HT2C agonist (left) led to the discovery of a highly selective 5-HT2C agonist (right). Importantly, this compound is a 5-HT2B receptor antagonist. Because of its selective 5-HT2C receptor activity, the compound was further evaluated in the phencyclidine model of disrupted prepulse inhibition, and found to exhibit normalizing effects comparable to those shown by the 5-HT 2C agonist vabicaserin, a drug currently in phase II clinical studies for schizophrenia

    Isoquinoline Alkaloids Isolated from Corydalis yanhusuo and Their Binding Affinities at the Dopamine D1 Receptor

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    Bioactivity-guided fractionation of Corydalis yanhusuo has resulted in the isolation of eight known isoquinoline alkaloids - tetrahydropalmatine, isocorypalmine, stylopine, corydaline, columbamine, coptisin, 13-methylpalmatine, and dehydrocorybulbine. The tertiary alkaloids were further analyzed by chiral HPLC to determine the ratios of d-and l-isomers. The isolated compounds were screened for their binding affinities at the dopamine D(1) receptor. Isocorypalmine had the highest affinity (K(i) = 83 nM). The structure-affinity relationships of these alkaloids are discussed

    Rational Drug Design Leading to the Identification of a Potent 5-HT 2C Agonist Lacking 5-HT 2B Activity

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    The 5-HT2C receptor is an attractive drug target in the quest for new therapeutics to treat a variety of human disorders. We have previously undertaken a structural optimization campaign that has led to some potent and moderately selective 5-HT2C receptor agonists. After expanding our structure–function library, we were able to combine our data sets so as to allow the design of compounds of improved selectivity and potency. We disclose herein the structural optimization of our previously reported 5-HT2B/5-HT2C agonists, which has led to the identification of a highly selective 5-HT2C agonist, (+)-trans-[2-(2-cyclopropylmethoxyphenyl)cyclopropyl]methylamine hydrochloride, with an EC50 of 55 nM and no detectable agonism at the 5-HT2B receptor

    Assessing serotonin receptor mRNA editing frequency by a novel ultra high-throughput sequencing method

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    RNA editing is a post-transcriptional modification of pre-mRNA that results in increased diversity in transcriptomes and proteomes. It occurs in a wide variety of eukaryotic organisms and in some viruses. One of the most common forms of pre-mRNA editing is A-to-I editing, in which adenosine is deaminated to inosine, which is read as guanosine during translation. This phenomenon has been observed in numerous transcripts, including the mammalian 5-HT2C receptor, which can be edited at five distinct sites. Methods used to date to quantify 5-HT2C receptor editing are labor-intensive, expensive and provide limited information regarding the relative abundance of 5-HT2C receptor editing variants. Here, we present a novel, ultra high-throughput method to quantify 5-HT2C receptor editing, compare it to a more conventional method, and use it to assess the effect of a range of genetic and pharmacologic manipulations on 5-HT2C editing. We conclude that this new method is powerful and economical, and we provide evidence that alterations in 5-HT2C editing appear to be a result of regional changes in brain activity, rather than a mechanism to normalize 5-HT2C signaling

    Establishment and characterization of models of chemotherapy resistance in colorectal cancer: Towards a predictive signature of chemoresistance

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    Current standard treatments for metastatic colorectal cancer (CRC) are based on combination regimens with one of the two chemotherapeutic drugs, irinotecan or oxaliplatin. However, drug resistance frequently limits the clinical efficacy of these therapies. In order to gain new insights into mechanisms associated with chemoresistance, and departing from three distinct CRC cell models, we generated a panel of human colorectal cancer cell lines with acquired resistance to either oxaliplatin or irinotecan. We characterized the resistant cell line variants with regards to their drug resistance profile and transcriptome, and matched our results with datasets generated from relevant clinical material to derive putative resistance biomarkers. We found that the chemoresistant cell line variants had distinctive irinotecan- or oxaliplatin-specific resistance profiles, with non-reciprocal cross-resistance. Furthermore, we could identify several new, as well as some previously described, drug resistance-associated genes for each resistant cell line variant. Each chemoresistant cell line variant acquired a unique set of changes that may represent distinct functional subtypes of chemotherapy resistance. In addition, and given the potential implications for selection of subsequent treatment, we also performed an exploratory analysis, in relevant patient cohorts, of the predictive value of each of the specific genes identified in our cellular models
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