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At least 37 records · Page 2

3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV–infected mice

Pathogenic coronaviruses are a major threat to global public health, as exemplified by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emerged SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). We describe herein the structure-guided optimization of a series of inhibitors of the coronavirus 3C-like protease (3CLpro), an enzyme essential for viral replication. The optimized compounds were effective against several human coronaviruses including MERS-CoV, SARS-CoV, and SARS-CoV-2 in an enzyme assay and in cell-based assays using Huh-7 and Vero E6 cell lines. Two selected compounds showed antiviral effects against SARS-CoV-2 in cultured primary human airway epithelial cells. In a mouse model of MERS-CoV infection, administration of a lead compound 1 day after virus infection increased survival from 0 to 100% and reduced lung viral titers and lung histopathology. These results suggest that this series of compounds has the potential to be developed further as antiviral drugs against human coronaviruses.

60 APPLIED LIFE SCIENCES↗

A quantitative model used to compare within-host SARS-CoV-2, MERS-CoV, and SARS-CoV dynamics provides insights into the pathogenesis and treatment of SARS-CoV-2

The scientific community is focused on developing antiviral therapies to mitigate the impacts of the ongoing novel coronavirus disease 2019 (COVID-19) outbreak. This will be facilitated by improved understanding of viral dynamics within infected hosts. Here, using a mathematical model in combination with published viral load data, we compare within-host viral dynamics of SARS-CoV-2 with analogous dynamics of MERS-CoV and SARS-CoV. Our quantitative analyses using a mathematical model revealed that the within-host reproduction number at symptom onset of SARS-CoV-2 was statistically significantly larger than that of MERS-CoV and similar to that of SARS-CoV. In addition, the time from symptom onset to the viral load peak for SARS-CoV-2 infection was shorter than those of MERS-CoV and SARS-CoV. These findings suggest the difficulty of controlling SARS-CoV-2 infection by antivirals. We further used the viral dynamics model to predict the efficacy of potential antiviral drugs that have different modes of action. The efficacy was measured by the reduction in the viral load area under the curve (AUC). Our results indicate that therapies that block de novo infection or virus production are likely to be effective if and only if initiated before the viral load peak (which appears 2–3 days after symptom onset), but therapies that promote cytotoxicity of infected cells are likely to have effects with less sensitivity to the timing of treatment initiation. Furthermore, combining a therapy that promotes cytotoxicity and one that blocks de novo infection or virus production synergistically reduces the AUC with early treatment. Our unique modeling approach provides insights into the pathogenesis of SARS-CoV-2 and may be useful for development of antiviral therapies.

59 BASIC BIOLOGICAL SCIENCES↗

MER Field Geologic Traverse in Gusev Crater, Mars: Initial Results From the Perspective of Spirit

This report casts the initial results of the traverse and science investigations by the Mars Exploration Rover (MER) Spirit at Gusev crater [1] in terms of data sets commonly used in field geologic investigations: Local mapping of geologic features, analyses of selected samples, and their location within the local map, and the regional context of the field traverse in terms of the larger geologic and physiographic region. These elements of the field method are represented in the MER characterization of the Gusev traverse by perspective-based geologic/morphologic maps, the placement of the results from Mossbauer, APXS, Microscopic Imager, Mini-TES and Pancam multispectral studies in context within this geologic/ morphologic map, and the placement of the overall traverse in the context of narrow-angle MOC (Mars Orbiter Camera) and descent images. A major campaign over a significance fraction of the mission will be the first robotic traverse of the ejecta from a Martian impact crater along an approximate radial from the crater center. The Mars Exploration Rovers have been conceptually described as 'robotic field geologists', that is, a suite of instruments with mobility that enables far-field traverses to multiple sites located within a regional map/image base at which in situ analyses may be done. Initial results from MER, where the field geologic method has been used throughout the initial course of the investigation, confirm that this field geologic model is applicable for remote planetary surface exploration. The field geologic method makes use of near-field geologic characteristics ('outcrops') to develop an understanding of the larger geologic context through continuous loop of rational steps focused on real-time hypothesis identification and testing. This poster equates 'outcrops' with the locations of in situ investigations and 'regional context' with the geology over distance of several kilometers. Using this fundamental field geologic method, we have identified the basic local geologic materials on the floor of Gusev at this site, their compositions and likely lithologies, origins, processes that have modified these materials, and their potential significance in the interpretation of the regional geology both spatially and temporally.

Crumpler, L.↗

MIMOS II on MER One Year of Mossbauer Spectroscopy on the Surface of Mars: From Jarosite at Meridiani Planum to Goethite at Gusev Crater

The miniaturized Mossbauer (MB) spectrometer MIMOS II [1] is part of the Athena payload of NASA s twin Mars Exploration Rovers "Spirit" (MER-A) and "Opportunity" (MER-B). It determines the Fe-bearing mineralogy of Martian soils and rocks at the Rovers respective landing sites, Gusev crater and Meridiani Planum. Both spectrometers performed successfully during first year of operation. Total integration time is about 49 days for MERA (79 samples) and 34 days for MER-B (85 samples). For curiosity it might be interesting to mention that the total odometry of the oscillating part of the MB drive exceeds 35 km for both rovers.

Klingelhoefer, G.↗

MER ARA pyroshock test results

This paper presents the shock test results achieved in the MER ARA/brush motor pyroshock qualification. The results of MER flight system pyrofiring tests in comparison with the ARA shock test requirements are discussed herein. Alternate test methods were developed in an effort to qualify the critical MER equipment for adequate performance in the actual flight pyroshock condition.

pyroshock qualification↗

The Effects of the Mars Exploration Rovers (MER) Work Schedule Regime on Locomotor Activity Circadian Rhythms, Sleep and Fatigue

This study assessed human adaptation to a Mars sol by evaluating sleep metrics obtained by actigraphy and subjective responses in 22 participants, and circadian rhythmicity in locomotor activity in 9 participants assigned to Mars Exploration Rover (MER) operational work schedules (24.65 hour days) at the Jet Propulsion Laboratory in 2004. During MER operations, increased work shift durations and reduced sleep durations and time in bed were associated with the appearance of pronounced 12-hr (circasemidian) rhythms with reduced activity levels. Sleep duration, workload, and circadian rhythm stability have important implications for adaptability and maintenance of operational performance not only of MER operations personnel but also in space crews exposed to a Mars sol of 24.65 hours during future Mars missions.

DeRoshia, Charles W.↗

Translating MAPGEN to ASPEN for MER

This software translates MAPGEN (Europa and APGEN) domains to ASPEN, and the resulting domain can be used to perform planning for the Mars Exploration Rover (MER). In other words, this is a conversion of two distinct planning languages (both declarative and procedural) to a third (declarative) planning language in order to solve the problem of faithful translation from mixed-domain representations into the ASPEN Modeling Language. The MAPGEN planning system is an example of a hybrid procedural/declarative system where the advantages of each are leveraged to produce an effective planner/scheduler for MER tactical planning. The adaptation of the planning system (ASPEN) was investigated, and, with some translation, much of the procedural knowledge encoding is amenable to declarative knowledge encoding. The approach was to compose translators from the core languages used for adapting MAGPEN, which consists of Europa and APGEN. Europa is a constraint- based planner/scheduler where domains are encoded using a declarative model. APGEN is also constraint-based, in that it tracks constraints on resources and states and other variables. Domains are encoded in both constraints and code snippets that execute according to a forward sweep through the plan. Europa and APGEN communicate to each other using proxy activities in APGEN that represent constraints and/or tokens in Europa. The composition of a translator from Europa to ASPEN was fairly straightforward, as ASPEN is also a declarative planning system, and the specific uses of Europa for the MER domain matched ASPEN s native encoding fairly closely. On the other hand, translating from APGEN to ASPEN was considerably more involved. On the surface, the types of activities and resources one encodes in APGEN appear to match oneto- one to the activities, state variables, and resources in ASPEN. But, when looking into the definitions of how resources are profiled and activities are expanded, one sees code snippets that access various information available during planning for the moment in time being planned to decide at the time what the appropriate profile or expansion is. APGEN is actually a forward (in time) sweeping discrete event simulator, where the model is composed of code snippets that are artfully interleaved by the engine to produce a plan/schedule. To solve this problem, representative code is simulated as a declarative series of task expansions. Predominantly, three types of procedural models were translated: loops, if statements, and code blocks. Loops and if statements were handled using controlled task expansion, and code blocks were handled using constraint networks that maintained the generation of results based on what the order of execution would be for a procedural representation. One advantage with respect to performance for MAPGEN is the use of APGEN s GUI. This GUI is written in C++ and Motif, and performs very well for large plans.

Rabideau, Gregg R.↗

Managing PV Power on Mars - MER Rovers

The MER Rovers have recently completed over 5 years of operation! This is a remarkable demonstration of the capabilities of PV power on the Martian surface. The extended mission required the development of an efficient process to predict the power available to the rovers on a day-to-day basis. The performance of the MER solar arrays is quite unlike that of any other Space array and perhaps more akin to Terrestrial PV operation, although even severe by that comparison. The impact of unpredictable factors, such as atmospheric conditions and dust accumulation (and removal) on the panels limits the accurate prediction of array power to short time spans. Based on the above, it is clear that long term power predictions are not sufficiently accurate to allow for detailed long term planning. Instead, the power assessment is essentially a daily activity, effectively resetting the boundary points for the overall predictive power model. A typical analysis begins with the importing of the telemetry from each rover's previous day's power subsystem activities. This includes the array power generated, battery state-of-charge, rover power loads, and rover orientation, all as functions of time. The predicted performance for that day is compared to the actual performance to identify the extent of any differences. The model is then corrected for these changes. Details of JPL's MER power analysis procedure are presented, including the description of steps needed to provide the final prediction for the mission planners. A dust cleaning event of the solar array is also highlighted to illustrate the impact of Martian weather on solar array performance

Mars dust↗

Automated Targeting for the MER Rovers

The Autonomous Exploration for Gathering Increased Science System (AEGIS) will soon provide automated targeting for remote sensing instruments on the Mars Exploration Rover (MER) mission, which currently which currently has two rovers exploring the surface of Mars. Currently, targets for rover remote-sensing instruments, especially narrow field-of-view instruments (such as the MER Mini- TES spectrometer or the 2011 Mars Science Laboratory (MSL) Mission ChemCam Spectrometer), must be selected manually based on imagery already on the ground with the operations team. AEGIS enables the rover flight software to analyze imagery onboard in order to autonomously select and sequence targeted remote-sensing observations in an opportunistic fashion. In this paper, we first provide some background information on the larger autonomous science framework in which AEGIS was developed. We then describe how AEGIS was specifically developed and tested on the JPL FIDO rover. Finally we discuss how AEGIS will be uploaded and used on the Mars Exploration Rover (MER) mission in early 2009.

rover autonomy↗

MER Opportunity dust-storm recovery operations and implications for future Mars surface missions

In June 2018, NASA’s Mars Exploration Rover Opportunity became engulfed in the most intense global dust storm observed in its 14-year mission and in Mars’ recorded history. Sapped of life-giving solar energy, Opportunity fell silent to ground operators on June 11, in what would be its final call home. Over the course of the next eight months, the MER team employed numerous recovery efforts and radiated over one thousand commands to wake the silent rover. Although unsuccessful, MER’s dust-storm recovery team changed the paradigm of dust-storm operations from Opportunity’s survival of a previous global dust storm in 2007. In this paper, the authors offer a glimpse into MER’s recovery efforts and lessons learned from Opportunity dust-storm operations for future solar-powered Mars surface missions. In the first section, the authors discuss the indicators of the approaching dust storm and the actions the team employed to reduce Opportunity’s power consumption and preserve available battery charge prior to loss of contact. The second section discusses the team’s recovery efforts until Opportunity’s declared End-of-Mission, the steps the team took to re-establish contact with Opportunity, the assumptions made during each step of the recovery process, and the commanding actions employed. Finally, the authors discuss the operational impacts of global dust storms on the safe and successful operation of solar-powered spacecraft on the Martian surface, and offer design recommendations for future solar-powered missions from the lessons learned during Opportunity’s 14-year mission and experience through two global dust storms.

Nelson, Robert W.↗

Omics Lethal Human Viruses Project Profiling of the Host Response to MERS-CoV Infection, Processed Experimental Dataset Catalog

Middle East Respiratory Syndrome coronavirus (MERS-CoV) is classified as a Category C priority pathogen (Coronaviridae) by the National Institute of Allergy and Infectious Diseases (NIAID), and is known to cause severe respiratory disease with high mortality rates in humans. Lethal host-pathogen invasion mechanisms and the cellular intricacies behind these fatal infections still remain unclear. The NIAID Modeling Host Responses to Understand Severe Human Virus Infections Research Program project (2013-2018) aimed to develop an improved comprehensive understanding of the host response to a suite of viruses causing lethal infections leveraging a systems biology approach. Herein, PNNL sub-projects provide a never before released comprehensive infectious disease collection of primary and secondary transformation multi-Omics data profiling a series of priority pathogen primary experimental studies for enhanced open-access to viral Omics datasets and project lifecycle metadata. Secondary host-pathogen viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Leveraging unique high-resolution Omics capabilities for proteomics (P), metabolomics (M), lipidomics (L), and transcriptomics (T) dataset downloads each have a direct relationship to a primary sample submission corresponding to a specific MERS-CoV [NCBITAXON:1335626] experimental infection study. Host sample types include human lung adenocarcinoma cells ["Calu-3", BTO:0002750], human bronchial epithelial cells ["Calu-3 clone 2B4"; BTO:0002022], primary human fibroblasts ["FB"; BTO:0000452], primary human airway epithelial cells ["HAE"; BTO:0005571], human microvascular endothelial cells ["HMVE"; BTO:0003123], and whole mouse lung [BTO:0000763] tissue collections.

59 BASIC BIOLOGICAL SCIENCES↗

MAPGEN : mixed initiative planning and scheduling for the Mars '03 MER mission

The Mars Exploration Rovers Mars '03 mission is one of NASA's most ambitious science missions to date. The rovers will be launched in the summer of 2003 with each rover carrying instruments to conduct remote and in-situ observation to elucidate the planet's past climate, water activity, and habitability. Science is the primary driver of MER and, as a consequence, making best use of the scientific instruments, within the available resources, is a crucial aspect of the mission. To address this critically, the MER project has selected MAPGEN (Mixed-Initiative Activity Plan GENerator) as an activity planning tool. MAPGEN combines two exiting systems, each with a strong heritage: APGEN the Activity Planning tool from the Jet Propulsion Laboratory and the Europs Planning/Scheduling system from NASA Ames Research Center. This paper discusses the issues arising from combining these tools in the context of this mission.

planning and scheduling↗

Two Years Onboard the MER Opportunity Rover

The Autonomous Exploration for Gathering Increased Science (AEGIS) system provides automated data collection for planetary rovers. AEGIS is currently being used onboard the Mars Exploration Rover (MER) mission's Opportunity to provide autonomous targeting of the MER Panoramic camera. Prior to AEGIS, targeted data was collected in a manual fashion where targets were manually identified in images transmitted to Earth and the rover had to remain in the same location for one to several communication cycles. AEGIS enables targeted data to be rapidly acquired with no delays for ground communication. Targets are selected by AEGIS through the use of onboard data analysis techniques that are guided by scientist-specified objectives. This paper provides an overview of the how AEGIS has been used on the Opportunity rover, focusing on usage that occurred during a 21 kilometer historic trek to the Mars Endeavour crater.

Mars Exploration Rover (MER)↗

Omics-Lethal Human Viruses, MERS-CoV Experiment MFB001

The purpose of this experiment was to evaluate the human host response to wild-type MERS-CoV (icMERS-CoV) virus infection. Sample data was obtained from primary human fibroblasts and processed for mRNA, miRNA, proteomics, metabolomics, and lipidomics expression analysis. econdary host-associated viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Leveraging unique high-resolution Omics capabilities for proteomics, metabolomics, lipidomics, and transcriptomics dataset downloads each have a direct relationship to a primary sample submission corresponding to a specific MERS-CoV virus infection.

59 BASIC BIOLOGICAL SCIENCES↗

Omics-Lethal Human Viruses, MERS-CoV Experiment MM001

The purpose of this experiment was to evaluate the host response to wild-type Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) virus infection. Sample data was obtained from primary mouse lung for mRNA, proteomics, lipidomics, and metabolomics expression analysis. Secondary host-associated viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Leveraging unique high-resolution Omics capabilities for proteomics, metabolomics, lipidomics, and transcriptomics dataset downloads each have a direct relationship to a primary sample submission corresponding to a specific MERS-CoV virus infection.

59 BASIC BIOLOGICAL SCIENCES↗

High-Resolution Topomapping of Mars: Life After MER Site Selection

In this abstract we describe our ongoing use of high-resolution images from the Mars Global Surveyor Mars Orbiter Camera Narrow-Angle subsystem (MGS MOC-NA) to derive quantitative topographic and slope data for the martian surface at 3 - 10-m resolution. Our efforts over the past several years focused on assessment of candidate landing sites for the Mars Exploration Rovers (MER) and culminated in the selection of sites in Gusev crater and Meridiani Planum as safe as well as scientifically compelling. As of this writing, MER-A (Spirit) has landed safely in Gusev and we are performing a limited amount of additional mapping near the landing point to support localization of the lander and rover operations planning. The primary focus of our work, however, has been extending our techniques to sample a variety of geologic terrains planetwide to support both a variety of geoscientific studies and planning and data analysis for missions such as Mars Express, Mars Reconnaissance Orbiter, and Phoenix.

Kirk, R. L.↗

The Ames MER Microscopic Imager Toolkit

The Mars Exploration Rovers, Spirit and Opportunity, have spent several successful months on Mars, returning gigabytes of images and spectral data to scientists on Earth. One of the instruments on the MER rovers, the Athena Microscopic Imager (MI), is a fixed focus, megapixel camera providing a plus or minus mm depth of field and a 3lx31mm field of view at a working distance of 63 mm from the lens to the object being imaged. In order to maximize the science return from this instrument, we developed the Ames MI Toolkit and supported its use during the primary mission. The MI Toolkit is a set of programs that operate on collections of MI images, with the goal of making the data more understandable to the scientists on the ground. Because of the limited depth of field of the camera, and the often highly variable topography of the terrain being imaged, MI images of a given rock are often taken as a stack, with the Instrument Deployment Device (IDD) moving along a computed normal vector, pausing every few millimeters for the MI to acquire an image. The MI Toolkit provides image registration and focal section merging, which combine these images to form a single, maximally in-focus image, while compensating for changes in lighting as well as parallax due to the motion of the camera. The MI Toolkit also provides a 3-D reconstruction of the surface being imaged using stereo and can embed 2-D MI images as texture maps into 3-D meshes produced by other imagers on board the rover to provide context. The 2-D images and 3-D meshes output from the Toolkit are easily viewed by scientists using other mission tools, such as Viz or the MI Browser. This paper describes the MI Toolkit in detail, as well as our experience using it with scientists at JPL during the primary MER mission.

Sargent, Randy↗