172 research outputs found

    Searching for Hyperspectral Optical Proxies to Aid Chesapeake Bay Resource Managers in the Detection of Poor Water Quality

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    Shellfish aquaculture is a growing industry in the Chesapeake Bay. As population grows near the coast, extreme weather events cause a greater volume of pollutant runoff from impervious surfaces and agricultural lands. Resource managers who monitor shellfish beds need reliable information on a variety of water quality indicators at higher frequency than is possible through field monitoring programs and at a higher level of detail than current satellite products can provide. Although many factors causing degraded water quality that can impact human health are not currently discernable by traditional multispectral techniques, hyperspectral imagery offers a new opportunity to detect phytoplankton communities associated with harmful algal blooms and biotoxin production. Together with resource managers in their routine monitoring of sites around the bay from small boats, we have been exploring remotely sensed optical proxies for the detection of harmful algal blooms and sewage. Early warning by remote sensing could guide sampling and improve the efficiency of shellfish bed closures, ultimately improving health outcomes for humans and animals. An extensive network of routine sampling by Chesapeake Bay Program managers makes this is an ideal location to develop and test future satellite data products to support management decisions. Next generation hyperspectral measurements from the future Plankton Aerosol Cloud ocean Ecosystem (PACE) mission at nearly daily frequency, combined with the potential of higher spatial resolution from the Surface Biology and Geology (SBG) observing system recommended in the recent Decadal Survey, along with high frequency observations from the newly selected Geostationary Littoral Imaging and Monitoring Radiometer (GLIMR) Earth Venture Instrument make this a critical time for defining the needs of the aquaculture and resource management community to save lives, time, and money

    Isocost Lines Describe the Cellular Economy of Genetic Circuits

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    Genetic circuits in living cells share transcriptional and translational resources that are available in limited amounts. This leads to unexpected couplings among seemingly unconnected modules, which result in poorly predictable circuit behavior. In this study, we determine these interdependencies between products of different genes by characterizing the economy of how transcriptional and translational resources are allocated to the production of proteins in genetic circuits. We discover that, when expressed from the same plasmid, the combinations of attainable protein concentrations are constrained by a linear relationship, which can be interpreted as an isocost line, a concept used in microeconomics. We created a library of circuits with two reporter genes, one constitutive and the other inducible in the same plasmid, without a regulatory path between them. In agreement with the model predictions, experiments reveal that the isocost line rotates when changing the ribosome binding site strength of the inducible gene and shifts when modifying the plasmid copy number. These results demonstrate that isocost lines can be employed to predict how genetic circuits become coupled when sharing resources and provide design guidelines for minimizing the effects of such couplings.United States. Air Force Office of Scientific Research (Grant FA9550-14-1-0060)United States. Defense Advanced Research Projects Agency (Contract W911NF-12-1-0540)National Institutes of Health (U.S.) (Grant P50 GM098792

    Design of Driver-Assist Systems Under Probabilistic Safety Specifications Near Stop Signs

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    In this paper, we consider the problem of designing in-vehicle driver-assist systems that warn or override the driver to prevent collisions with a guaranteed probability. The probabilistic nature of the problem naturally arises from many sources of uncertainty, among which the behavior of the surrounding vehicles and the response of the driver to on-board warnings. We formulate this problem as a control problem for uncertain systems under probabilistic safety specifications and leverage the structure of the application domain to reach computationally efficient implementations. Simulations using a naturalistic data set show that the empirical probability of safety is always within 5% of the theoretical value in the case of direct driver override. In the case of on-board warnings, the empirical value is more conservative due primarily to drivers decelerating more strongly than requested. However, the empirical value is greater than or equal to the theoretical value, demonstrating a clear safety benefit

    Safety Control of a Class of Stochastic Order Preserving Systems with Application to Collision Avoidance near Stop Signs

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    Abstract-In this paper, we consider the problem of keeping the state of a system outside of an undesired set of states with probability at least P. We focus on a class of order preserving systems with a constant input disturbance that is extracted from a known probability distribution. Leveraging the structure of the system, we construct an explicit supervisor that guarantees the system state to be kept outside the undesired set with at least probability P. We apply this supervisor to a collision avoidance problem, where a semi-autonomous vehicle is engaged in preventing a rear-end collision with a preceding human-driven vehicle, while stopping at a stop sign. We apply the designed supervisor in simulations in which the preceding vehicle trajectories are taken from a test data set. Using this data, we demonstrate experimentally that the probability of preventing a rear-end collision while stopping at the stop sign is at least P, as expected from theory. The simulation results further show that this probability is very close to P, indicating that the supervisor is not conservative

    Intelligent Assistant Language Understanding On Device

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    It has recently become feasible to run personal digital assistants on phones and other personal devices. In this paper we describe a design for a natural language understanding system that runs on device. In comparison to a server-based assistant, this system is more private, more reliable, faster, more expressive, and more accurate. We describe what led to key choices about architecture and technologies. For example, some approaches in the dialog systems literature are difficult to maintain over time in a deployment setting. We hope that sharing learnings from our practical experiences may help inform future work in the research community

    Effects of three low-volume, high-intensity exercise conditions on affective valence

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    © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. A common barrier to exercise is “lack of time”. Accordingly, interest in low-volume, high-intensity training has grown exponentially since this activity is considered time-efficient. However, the high-intensity nature of this exercise may frequently result in feelings of displeasure creating another barrier for many people. The purpose of this study was to compare affective (pleasure-displeasure) responses to three low-volume, high-intensity exercise conditions, including a novel shortened-sprint protocol. Using a within-subjects, randomised crossover experiment, healthy participants (N = 36) undertook a single bout of: 1) traditional reduced-exertion, high-intensity interval training (TREHIT), 2) a novel, shortened-sprint REHIT (SSREHIT) protocol, and 3) sprint continuous training (SCT). Affect and perceived efforts were recorded throughout exercise using the Feeling Scale (FS) and the 15-point Borg Rating of Perceived Exertion (RPE) scale, respectively. Enjoyment was recorded 5 min post-exercise using the Exercise Enjoyment Scale (EES). Differences were found for FS (condition by time interaction: P = 0.01GG, η2 = 0.26), RPE (P = 0.01GG, η2 = 0.23), and enjoyment (P < 0.01) with all outcomes favouring SSREHIT. Shortened-sprint protocols may diminish feelings of displeasure and might be a time-efficient yet tolerable exercise choice to help motivate some people to increase their physical activity and fitness

    ClustScan: an integrated program package for the semi-automatic annotation of modular biosynthetic gene clusters and in silico prediction of novel chemical structures

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    The program package ‘ClustScan’ (Cluster Scanner) is designed for rapid, semi-automatic, annotation of DNA sequences encoding modular biosynthetic enzymes including polyketide synthases (PKS), non-ribosomal peptide synthetases (NRPS) and hybrid (PKS/NRPS) enzymes. The program displays the predicted chemical structures of products as well as allowing export of the structures in a standard format for analyses with other programs. Recent advances in understanding of enzyme function are incorporated to make knowledge-based predictions about the stereochemistry of products. The program structure allows easy incorporation of additional knowledge about domain specificities and function. The results of analyses are presented to the user in a graphical interface, which also allows easy editing of the predictions to incorporate user experience. The versatility of this program package has been demonstrated by annotating biochemical pathways in microbial, invertebrate animal and metagenomic datasets. The speed and convenience of the package allows the annotation of all PKS and NRPS clusters in a complete Actinobacteria genome in 2–3 man hours. The open architecture of ClustScan allows easy integration with other programs, facilitating further analyses of results, which is useful for a broad range of researchers in the chemical and biological sciences

    Adjuvant pembrolizumab versus placebo in resected high-risk stage II melanoma: Health-related quality of life from the randomized phase 3 KEYNOTE-716 study

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    Background: Adjuvant pembrolizumab significantly improved recurrence-free survival (RFS) versus placebo in resected stage IIB and IIC melanoma in the phase 3 KEYNOTE-716 study. Health-related quality of life (HRQoL) results are reported. Methods: Patients were randomly assigned 1:1 to pembrolizumab 200 mg (2 mg/kg, patients ≥ 12 to \u3c 18 years) Q3W or placebo for ≤ 17 cycles or until disease recurrence, unacceptable toxicity, or withdrawal. Change from baseline in EORTC QLQ-C30 global health status (GHS)/quality of life (QoL) was a prespecified exploratory end point. Change in EORTC QLQ-C30 functioning, symptom, and single-item scales, and EQ-5D-5L visual analog scale (VAS) were also summarized. Primary analyses were performed at week 48 to ensure adequate completion/compliance. The HRQoL population comprised patients who received ≥ 1 dose of treatment and completed ≥ 1 assessment. Results: The HRQoL population included 969 patients (pembrolizumab, n = 483; placebo, n = 486). Compliance at week 48 was ≥ 80 % for both instruments. EORTC QLQ-C30 GHS/QoL, physical functioning, role functioning, and EQ-5D-5L VAS scores were stable from baseline to week 48 in both arms, with no clinically meaningful decline observed. Scores did not differ significantly between pembrolizumab and placebo. EORTC QLQ-C30 GHS/QoL, physical functioning, role functioning, and EQ-5D-5L VAS scores remained stable through week 96 in both arms. Conclusions: HRQoL was stable with adjuvant pembrolizumab, with no clinically meaningful decline observed. Change from baseline in HRQoL was similar between arms. These results, in conjunction with the improved RFS and manageable safety previously reported, support the use of adjuvant pembrolizumab for high-risk stage II melanoma

    Targeting of Aberrant αvβ6 Integrin Expression in Solid Tumors Using Chimeric Antigen Receptor-Engineered T Cells.

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    Expression of the αvβ6 integrin is upregulated in several solid tumors. In contrast, physiologic expression of this epithelial-specific integrin is restricted to development and epithelial re-modeling. Here, we describe, for the first time, the development of a chimeric antigen receptor (CAR) that couples the recognition of this integrin to the delivery of potent therapeutic activity in a diverse repertoire of solid tumor models. Highly selective targeting αvβ6 was achieved using a foot and mouth disease virus-derived A20 peptide, coupled to a fused CD28+CD3 endodomain. To achieve selective expansion of CAR T cells ex vivo, an IL-4-responsive fusion gene (4αβ) was co-expressed, which delivers a selective mitogenic signal to engineered T cells only. In vivo efficacy was demonstrated in mice with established ovarian, breast, and pancreatic tumor xenografts, all of which express αvβ6 at intermediate to high levels. SCID beige mice were used for these studies because they are susceptible to cytokine release syndrome, unlike more immune-compromised strains. Nonetheless, although the CAR also engages mouse αvβ6, mild and reversible toxicity was only observed when supra-therapeutic doses of CAR T cells were administered parenterally. These data support the clinical evaluation of αvβ6 re-targeted CAR T cell immunotherapy in solid tumors that express this integrin

    Preliminary surface charging analysis of Ariel payload dielectrics in early transfer orbit and L2-relevant space environment

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    Ariel [1] is the M4 mission of the ESA’s Cosmic Vision Program 2015-2025, whose aim is to characterize by lowresolution transit spectroscopy the atmospheres of over one thousand warm and hot exoplanets orbiting nearby stars. The operational orbit of the spacecraft is baselined as a large amplitude halo orbit around the Sun-Earth L2 Lagrangian point, as it offers the possibility of long uninterrupted observations in a fairly stable radiative and thermo-mechanical environment. A direct escape injection with a single passage through the Earth radiation belts and no eclipses is foreseen. The space environment around Earth and L2 presents significant design challenges to all spacecraft, including the effects of interactions with Sun radiation and charged particles owning to the surrounding plasma environment, potentially leading to dielectrics charging and unwanted electrostatic discharge (ESD) phenomena endangering the Payload operations and its data integrity. Here, we present some preliminary simulations and analyses about the Ariel Payload dielectrics and semiconductors charging along the transfer orbit from launch to L2 include