887 research outputs found

    Model-based spacecraft and mission design for the evaluation of technology

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    In order to meet the future vision of robotic missions, engineers will face intricate mission concepts, new operational approaches, and technologies that have yet to be developed. The concept of smaller, model driven projects helps this transition by including life-cycle cost as part of the decision making process. For example, since planetary exploration missions have cost ceilings and short development periods, heritage flight hardware is utilized. However, conceptual designs that rely solely on heritage technology will result in estimates that may not be truly representative of the actual mission being designed and built. The Laboratory for Spacecraft and Mission Design (LSMD) at the California Institute of Technology is developing integrated concurrent models for mass and cost estimations. The purpose of this project is to quantify the infusion of specific technologies where the data would be useful in guiding technology developments leading up to a mission. This paper introduces the design-to-cost model to determine the implications of various technologies on the spacecraft system in a collaborative engineering environment. In addition, comparisons of the benefits of new or advanced technologies for future deep space missions are examined

    Climatic niche and flowering and fruiting phenology of an epiphytic plant

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    Species have geographic distributions constrained by combinations of abiotic factors, biotic factors and dispersal-related factors. Abiotic requirements vary across the life stages for a species; for plant species, a particularly important life stage is when the plant flowers and develops seeds. A previous year-long experiment showed that ambient temperature of 5–35 °C, relative humidity of >50 % and ≤15 consecutive rainless days are crucial abiotic conditions for Spanish moss (Tillandsia usneoides L.). Here, we explore whether these optimal physiological intervals relate to the timing of the flowering and fruiting periods of Spanish moss across its range. As Spanish moss has a broad geographic range, we examined herbarium specimens to detect and characterize flowering/fruiting periods for the species across the Americas; we used high-temporal-resolution climatic data to assess the availability of optimal conditions for Spanish moss populations during each population's flowering period. We explored how long populations experience suboptimal conditions and found that most populations experience suboptimal conditions in at least one environmental dimension. Flowering and fruiting periods of Spanish moss populations are either being optimized for one or a few parameters or may be adjusted such that all parameters are suboptimal. Spanish moss populations appear to be constrained most closely by minimum temperature during this period

    Experiences of Middle-Level Students, Teachers, and Parents in the Do the Write Thing Violence Prevention Program

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    We examined experiences of participants in Do the Write Thing national violence prevention program for middle-level students. Using mixed methods, we conducted surveys and focus groups with students, parents, and teachers who attended the program’s National Recognition Week in Washington, DC. Results revealed important affective, behavioral, and cognitive impacts on participants, including improved relationships, increased understanding of violence, and commitment to reduce violence. Participants from cities where insufficient time and resources were devoted to the project did not experience significant change. Teachers reported developing greater empathy for their students and making substantial changes in their teaching, providing support for students and infusing activities addressing violence into their curriculum. Recommendations are made for increased program support and future research

    Lethal Mutagenesis of Picornaviruses with N-6-Modified Purine Nucleoside Analogues

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    RNA viruses exhibit extraordinarily high mutation rates during genome replication. Nonnatural ribonucleosides that can increase the mutation rate of RNA viruses by acting as ambiguous substrates during replication have been explored as antiviral agents acting through lethal mutagenesis. We have synthesized novel N-6-substituted purine analogues with ambiguous incorporation characteristics due to tautomerization of the nucleobase. The most potent of these analogues reduced the titer of poliovirus (PV) and coxsackievirus (CVB3) over 1,000-fold during a single passage in HeLa cell culture, with an increase in transition mutation frequency up to 65-fold. Kinetic analysis of incorporation by the PV polymerase indicated that these analogues were templated ambiguously with increased efficiency compared to the known mutagenic nucleoside ribavirin. Notably, these nucleosides were not efficient substrates for cellular ribonucleotide reductase in vitro, suggesting that conversion to the deoxyriboucleoside may be hindered, potentially limiting genetic damage to the host cell. Furthermore, a high-fidelity PV variant (G64S) displayed resistance to the antiviral effect and mutagenic potential of these analogues. These purine nucleoside analogues represent promising lead compounds in the development of clinically useful antiviral therapies based on the strategy of lethal mutagenesis

    Lethal Mutagenesis of Poliovirus Mediated by a Mutagenic Pyrimidine Analogue

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    Lethal mutagenesis is the mechanism of action of ribavirin against poliovirus (PV) and numerous other RNA viruses. However, there is still considerable debate regarding the mechanism of action of ribavirin against a variety of RNA viruses. Here we show by using T7 RNA polymerase mediated production of PV genomic RNA, PV polymerase-catalyzed primer extension and cell-free PV synthesis that a pyrimidine ribonucleoside triphosphate analogue (rPTP) with ambiguous basepairing capacity is an efficient mutagen of the PV genome. The in vitro incorporation properties of rPTP are superior to ribavirin triphosphate. We observed a log-linear relationship between virus titer reduction and the number of rPMP molecules incorporated. A PV genome encoding a high-fidelity polymerase was more sensitive to rPMP incorporation, consistent with diminished mutational robustness of high-fidelity PV. The nucleoside (rP) did not exhibit antiviral activity in cell culture owing to the inability of rP to be converted to rPMP by cellular nucleotide kinases. rP was also a poor substrate for herpes simplex virus thymidine kinase. The block to nucleoside phosphorylation could be bypassed by treatment with the P nucleobase, which exhibited both antiviral activity and mutagenesis, presumably a reflection of rP nucleotide formation by a nucleotide salvage pathway. These studies provide additional support for lethal mutagenesis as an antiviral strategy, suggest that rPMP prodrugs may be highly efficacious antiviral agents, and provide a new tool to determine the sensitivity of RNA virus genomes to mutagenesis as well as interrogation of the impact of mutational load on the population dynamics of these viruses

    Synthesis of a 6-Methyl-7-Deaza Analogue of Adenosine that Potently Inhibits Replication of Polio and Dengue Viruses

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    Bioisosteric deaza analogues of 6-methyl-9-β-D-ribofuranosylpurine, a hydrophobic analogue of adenosine, were synthesized and evaluated for antiviral activity. Whereas the 1-deaza and 3-deaza analogues were essentially inactive in plaque assays of infectivity, a novel 7-deaza-6-methyl-9-β-D-ribofuranosylpurine analogue, structurally related to the natural product tubercidin, potently inhibited replication of poliovirus (PV) in HeLa cells (IC50 = 11 nM) and dengue virus (DENV) in Vero cells (IC50 = 62 nM). Selectivity against PV over cytotoxic effects to HeLa cells was >100-fold after incubation for 7 h. Mechanistic studies of the 5'-triphosphate of 7-deaza-6-methyl-9-β-D-ribofuranosylpurine revealed that this compound is an efficient substrate of PV RNA-dependent RNA polymerase (RdRP) and is incorporated into RNA mimicking both ATP and GTP

    IMPaCT - Integration of Missions, Programs, and Core Technologies

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    IMPaCT enables comprehensive information on current NASA missions, prospective future missions, and the technologies that NASA is investing in, or considering investing in, to be accessed from a common Web-based interface. It allows dependencies to be established between missions and technology, and from this, the benefits of investing in individual technologies can be determined. The software also allows various scenarios for future missions to be explored against resource constraints, and the nominal cost and schedule of each mission to be modified in an effort to fit within a prescribed budget

    A Once and Future Gulf of Mexico Ecosystem: Restoration Recommendations of an Expert Working Group

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    The Deepwater Horizon (DWH) well blowout released more petroleum hydrocarbons into the marine environment than any previous U.S. oil spill (4.9 million barrels), fouling marine life, damaging deep sea and shoreline habitats and causing closures of economically valuable fisheries in the Gulf of Mexico. A suite of pollutants — liquid and gaseous petroleum compounds plus chemical dispersants — poured into ecosystems that had already been stressed by overfishing, development and global climate change. Beyond the direct effects that were captured in dramatic photographs of oiled birds in the media, it is likely that there are subtle, delayed, indirect and potentially synergistic impacts of these widely dispersed, highly bioavailable and toxic hydrocarbons and chemical dispersants on marine life from pelicans to salt marsh grasses and to deep-sea animals. As tragic as the DWH blowout was, it has stimulated public interest in protecting this economically, socially and environmentally critical region. The 2010 Mabus Report, commissioned by President Barack Obama and written by the secretary of the Navy, provides a blueprint for restoring the Gulf that is bold, visionary and strategic. It is clear that we need not only to repair the damage left behind by the oil but also to go well beyond that to restore the anthropogenically stressed and declining Gulf ecosystems to prosperity-sustaining levels of historic productivity. For this report, we assembled a team of leading scientists with expertise in coastal and marine ecosystems and with experience in their restoration to identify strategies and specific actions that will revitalize and sustain the Gulf coastal economy. Because the DWH spill intervened in ecosystems that are intimately interconnected and already under stress, and will remain stressed from global climate change, we argue that restoration of the Gulf must go beyond the traditional “in-place, in-kind” restoration approach that targets specific damaged habitats or species. A sustainable restoration of the Gulf of Mexico after DWH must: 1. Recognize that ecosystem resilience has been compromised by multiple human interventions predating the DWH spill; 2. Acknowledge that significant future environmental change is inevitable and must be factored into restoration plans and actions for them to be durable; 3. Treat the Gulf as a complex and interconnected network of ecosystems from shoreline to deep sea; and 4. Recognize that human and ecosystem productivity in the Gulf are interdependent, and that human needs from and effects on the Gulf must be integral to restoration planning. With these principles in mind, we provide the scientific basis for a sustainable restoration program along three themes: 1. Assess and repair damage from DWH and other stresses on the Gulf; 2. Protect existing habitats and populations; and 3. Integrate sustainable human use with ecological processes in the Gulf of Mexico. Under these themes, 15 historically informed, adaptive, ecosystem-based restoration actions are presented to recover Gulf resources and rebuild the resilience of its ecosystem. The vision that guides our recommendations fundamentally imbeds the restoration actions within the context of the changing environment so as to achieve resilience of resources, human communities and the economy into the indefinite future

    Once and Future Gulf of Mexico Ecosystem: Restoration Recommendations of an Expert Working Group

    Get PDF
    The Deepwater Horizon (DWH) well blowout released more petroleum hydrocarbons into the marine environment than any previous U.S. oil spill (4.9 million barrels), fouling marine life, damaging deep sea and shoreline habitats and causing closures of economically valuable fisheries in the Gulf of Mexico. A suite of pollutants—liquid and gaseous petroleum compounds plus chemical dispersants—poured into ecosystems that had already been stressed by overfishing, development and global climate change. Beyond the direct effects that were captured in dramatic photographs of oiled birds in the media, it is likely that there are subtle, delayed, indirect and potentially synergistic impacts of these widely dispersed, highly bioavailable and toxic hydrocarbons and chemical dispersants on marine life from pelicans to salt marsh grasses and to deep-sea animals. As tragic as the DWH blowout was, it has stimulated public interest in protecting this economically, socially and environmentally critical region. The 2010 Mabus Report, commissioned by President Barack Obama and written by the secretary of the Navy, provides a blueprint for restoring the Gulf that is bold, visionary and strategic. It is clear that we need not only to repair the damage left behind by the oil but also to go well beyond that to restore the anthropogenically stressed and declining Gulf ecosystems to prosperity-sustaining levels of historic productivity. For this report, we assembled a team of leading scientists with expertise in coastal and marine ecosystems and with experience in their restoration to identify strategies and specific actions that will revitalize and sustain the Gulf coastal economy. Because the DWH spill intervened in ecosystems that are intimately interconnected and already under stress, and will remain stressed from global climate change, we argue that restoration of the Gulf must go beyond the traditional "in-place, in-kind" restoration approach that targets specific damaged habitats or species. A sustainable restoration of the Gulf of Mexico after DWH must: 1. Recognize that ecosystem resilience has been compromised by multiple human interventions predating the DWH spill; 2. Acknowledge that significant future environmental change is inevitable and must be factored into restoration plans and actions for them to be durable; 3. Treat the Gulf as a complex and interconnected network of ecosystems from shoreline to deep sea; and 4. Recognize that human and ecosystem productivity in the Gulf are interdependent, and that human needs from and effects on the Gulf must be integral to restoration planning. With these principles in mind, the authors provide the scientific basis for a sustainable restoration program along three themes: 1. Assess and repair damage from DWH and other stresses on the Gulf; 2. Protect existing habitats and populations; and 3. Integrate sustainable human use with ecological processes in the Gulf of Mexico. Under these themes, 15 historically informed, adaptive, ecosystem-based restoration actions are presented to recover Gulf resources and rebuild the resilience of its ecosystem. The vision that guides our recommendations fundamentally imbeds the restoration actions within the context of the changing environment so as to achieve resilience of resources, human communities and the economy into the indefinite future
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