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Miller, Matthew J.

Publications and source records attributed to Miller, Matthew J..

17 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Structure-guided design of direct-acting antivirals that exploit the gem-dimethyl effect and potently inhibit 3CL proteases of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) and middle east respiratory syndrome coronavirus (MERS-CoV)

The high morbidity and mortality associated with SARS-CoV-2 infection, the etiological agent of COVID-19, has had a major impact on global public health. Significant progress has been made in the development of an array of vaccines and biologics, however, the emergence of SARS-CoV-2 variants and breakthrough infections are an ongoing major concern. Furthermore, there is an existing paucity of small-molecule host and virus-directed therapeutics and prophylactics that can be used to counter the spread of SARS-CoV-2, and any emerging and re-emerging coronaviruses. Here, we describe herein our efforts to address this urgent need by focusing on the structure-guided design of potent broad-spectrum inhibitors of SARS-CoV-2 3C-like protease (3CL pro or Main protease), an enzyme essential for viral replication. The inhibitors exploit the directional effects associated with the presence of a gem-dimethyl group that allow the inhibitors to optimally interact with the S4 subsite of the enzyme. Several compounds were found to potently inhibit SARS-CoV-2 and MERS-CoV 3CL proteases in biochemical and cell-based assays. Specifically, the EC50 values of aldehyde 1c and its corresponding bisulfite adduct 1d against SARS-CoV-2 were found to be 12 and 10 nM, respectively, and their CC50 values were >50 μM. Furthermore, deuteration of these compounds yielded compounds 2c/2d with EC50 values 11 and 12 nM, respectively. Replacement of the aldehyde warhead with a nitrile (CN) or an α-ketoamide warhead or its corresponding bisulfite adduct yielded compounds 1g, 1e and 1f with EC50 values 60, 50 and 70 nM, respectively. High-resolution cocrystal structures have identified the structural determinants associated with the binding of the inhibitors to the active site of the enzyme and, furthermore, have illuminated the mechanism of action of the inhibitors. Overall, the high Safety Index (SI) (SI=CC50/EC50) displayed by these compounds suggests that they are well-suited to conducting further preclinical studies.

3-Chymotrypsin-like protease (3CLpro)↗
NASA NTRS2019

Envisioning an Analog Work Domain Across Deep-Ocean Exploration and Human-Robot Spaceflight Exploration

What if one existing work domain could be leveraged to inform an instantiation of a second type of work domain? This is the question that informed a three year NASA-funded study, SUBSEA (Systematic Underwater Biogeochemical Science and Exploration Analog), on the use of ocean science and exploration via telepresence as an analog for future human-robot spaceflight. SUBSEA included two field programs performed in 2018 and 2019. Each was comprised of a multidisciplinary team of natural scientists studying deep-sea venting sites in tandem with a team of social scientists conducting work ethnography to understand the existing ocean exploration domain. This paper presents results from the 2018 field program which includes analyses that were required to generate specific “flight-like” conditions for the 2019 field program.

Miller, Matthew J.↗
NASA NTRS2017

Minerva: User-Centered Science Operations Software Capability for Future Human Exploration

In June of 2016, the Biologic Analog Science Associated with Lava Terrains (BASALT) research project conducted its first field deployment, which we call BASALT-1. BASALT-1 consisted of a science-driven field campaign in a volcanic field in Idaho as a simulated human mission to Mars. Scientists and mission operators were provided a suite of ground software tools that we refer to collectively as Minerva to carry out their work. Minerva provides capabilities for traverse planning and route optimization, timeline generation and display, procedure management, execution monitoring, data archiving, visualization, and search. This paper describes the Minerva architecture, constituent components, use cases, and some preliminary findings from the BASALT-1 campaign.

Deans, Matthew↗
NASA NTRS2017

Minerva: User-Centered Science Operations Software Capability for Future Human Exploration

In June of 2016, the Biologic Analog Science Associated with Lava Terrains (BASALT) research project conducted its first field deployment, which we call BASALT-1. BASALT-1 consisted of a science-driven field campaign in a volcanic field in Idaho as a simulated human mission to Mars. Scientists and mission operators were provided a suite of ground software tools that we refer to collectively as Minerva to carry out their work. Minerva provides capabilities for traverse planning and route optimization, timeline generation and display, procedure management, execution monitoring, data archiving, visualization, and search. This paper describes the Minerva architecture, constituent components, use cases, and some preliminary findings from the BASALT-1 campaign.

Deans, Matthew↗
NASA NTRS2017

Extravehicular Activity Operations Concepts Under Communication Latency and Bandwidth Constraints

The Biologic Analog Science Associated with Lava Terrains (BASALT) project is a multi-year program dedicated to iteratively develop, implement, and evaluate concepts of operations (ConOps) and supporting capabilities intended to enable and enhance human scientific exploration of Mars. This pa-per describes the planning, execution, and initial results from the first field deployment, referred to as BASALT-1, which consisted of a series of 10 simulated extravehicular activities (EVAs) on volcanic flows in Idaho's Craters of the Moon (COTM) National Monument. The ConOps and capabilities deployed and tested during BASALT-1 were based on previous NASA trade studies and analog testing. Our primary research question was whether those ConOps and capabilities work acceptably when performing real (non-simulated) biological and geological scientific exploration under 4 different Mars-to-Earth communication conditions: 5 and 15 min one-way light time (OWLT) communication latencies and low (0.512 Mb/s uplink, 1.54 Mb/s downlink) and high (5.0 Mb/s uplink, 10.0 Mb/s downlink) bandwidth conditions representing the lower and higher limits of technical communication capabilities currently proposed for future human exploration missions. The synthesized results of BASALT-1 with respect to the ConOps and capabilities assessment were derived from a variety of sources, including EVA task timing data, network analytic data, and subjective ratings and comments regarding the scientific and operational acceptability of the ConOp and the extent to which specific capabilities were enabling and enhancing, and are presented here. BASALT-1 established preliminary findings that baseline ConOp, software systems, and communication protocols were scientifically and operationally acceptable with minor improvements desired by the "Mars" extravehicular (EV) and intravehicular (IV) crewmembers, but unacceptable with improvements required by the "Earth" Mission Support Center. These data will provide a basis for guiding and prioritizing capability development for future BASALT deployments and, ultimately, future human exploration missions.

Beaton, Kara H.↗
DOE OSTI2016

The interaction of the Fermi bubbles with the Milky Way's hot gas halo

The Fermi bubbles are two lobes filled with non-thermal particles that emit gamma rays, extend ≈10 kpc vertically from the Galactic center, and formed from either nuclear star formation or accretion activity on Sgr A*. Simulations predict a range of shock strengths as the bubbles expand into the surrounding hot gas halo (T{sub halo}≈2×10{sup 6} K), but with significant uncertainties in the energetics, age, and thermal gas structure. The bubbles should contain thermal gas with temperatures between 10{sup 6} and 10{sup 8} K, with potential X-ray signatures. In this work, we constrain the bubbles’ thermal gas structure by modeling O vii and O viii emission line strengths from archival XMM-Newton and Suzaku data. Our emission model includes a hot thermal volume-filled bubble component cospatial with the gamma-ray region, and a shell of compressed material. We find that a bubble/shell model with n≈1×10{sup −3} cm{sup −3} and with log(T) ≈ 6.60–6.70 is consistent with the observed line intensities. In the framework of a continuous Galactic outflow, we infer a bubble expansion rate, age, and energy injection rate of 490{sub −77}{sup +230} km s{sup −1}, 4.3{sub −1.4}{sup +0.8} Myr, and 2.3{sub −0.9}{sup +5.1}×10{sup 42} erg s{sup −1}. These estimates are consistent with the bubbles forming from a Sgr A* accretion event rather than from nuclear star formation.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2016

THE ROTATION OF THE HOT GAS AROUND THE MILKY WAY

The hot gaseous halos of galaxies likely contain a large amount of mass and are an integral part of galaxy formation and evolution. The Milky Way has a 2×10{sup 6} K halo that is detected in emission and by absorption in the O vii resonance line against bright background active galactic nuclei (AGNs), and for which the best current model is an extended spherical distribution. Using XMM-Newton Reflection Grating Spectrometer data, we measure the Doppler shifts of the O vii absorption-line centroids toward an ensemble of AGNs. These Doppler shifts constrain the dynamics of the hot halo, ruling out a stationary halo at about 3σ and a co-rotating halo at 2σ, and leading to a best-fit rotational velocity of v{sub ϕ}=183±41 km s{sup −1} for an extended halo model. These results suggest that the hot gas rotates and that it contains an amount of angular momentum comparable to that in the stellar disk. We examined the possibility of a model with a kinematically distinct disk and spherical halo. To be consistent with the emission-line X-ray data, the disk must contribute less than 10% of the column density, implying that the Doppler shifts probe motion in the extended hot halo.

79 ASTRONOMY AND ASTROPHYSICS↗
NASA NTRS2016

Analog Testing of Operations Concepts for Mitigation of Communication Latency During Human Space Exploration

OBJECTIVES: NASA Extreme Environment Mission Operations (NEEMO) is an underwater spaceflight analog that allows a true mission‐like operational environment and uses buoyancy effects and added weight to simulate different gravity levels. Three missions were undertaken from 2014‐2015, NEEMO's 18‐20. All missions were performed at the Aquarius undersea research habitat. During each mission, the effects of varying operations concepts and tasks type and complexity on representative communication latencies associated with Mars missions were studied. METHODS: 12 subjects (4 per mission) were weighed out to simulate near‐zero or partial gravity extravehicular activity (EVA) and evaluated different operations concepts for integration and management of a simulated Earth‐based science backroom team (SBT) to provide input and direction during exploration activities. Exploration traverses were planned in advance based on precursor data collected. Subjects completed science‐related tasks including presampling surveys, geologic‐based sampling, and marine‐based sampling as a portion of their tasks on saturation dives up to 4 hours in duration that were to simulate extravehicular activity (EVA) on Mars or the moons of Mars. One‐way communication latencies, 5 and 10 minutes between space and mission control, were simulated throughout the missions. Objective data included task completion times, total EVA times, crew idle time, translation time, SBT assimilation time (defined as time available for SBT to discuss data/imagery after it has been collected, in addition to the time taken to watch imagery streaming over latency). Subjective data included acceptability, simulation quality, capability assessment ratings, and comments. RESULTS: Precursor data can be used effectively to plan and execute exploration traverse EVAs (plans included detailed location of science sites, high‐fidelity imagery of the sites, and directions to landmarks of interest within a site). Operations concepts that allow for presampling surveys enable efficient traverse execution and meaningful Mission Control Center (MCC) interaction across long communication latencies and can be done with minimal crew idle time. Imagery and information from the EVA crew that is transmitted real‐time to the intravehicular (IV) crewmember(s) can be used to verify that exploration traverse plans are being executed correctly. That same data can be effectively used by MCC (across comm latency) to provide further instructions to the crew from a SBT on sampling priorities, additional tasks, and changes to the plan. Text / data capabilities are preferred over voice capabilities between MCC and IV when executing exploration traverse plans over communication latency. Autonomous crew planning tools can be effective at modifying existing plans if the objectives and constraints are clearly defined.

Chappell, Steven P.↗
NASA NTRS2016

NEEMO 18-20: Analog Testing for Mitigation of Communication Latency During Human Space Exploration

NASA Extreme Environment Mission Operations (NEEMO) is an underwater spaceflight analog that allows a true mission-like operational environment and uses buoyancy effects and added weight to simulate different gravity levels. Three missions were undertaken from 2014-2015, NEEMO's 18-20. All missions were performed at the Aquarius undersea research habitat. During each mission, the effects of communication latencies on operations concepts, timelines, and tasks were studied. METHODS: Twelve subjects (4 per mission) were weighed out to simulate near-zero or partial gravity extravehicular activity (EVA) and evaluated different operations concepts for integration and management of a simulated Earth-based science team (ST) to provide input and direction during exploration activities. Exploration traverses were preplanned based on precursor data. Subjects completed science-related tasks including pre-sampling surveys, geologic-based sampling, and marine-based sampling as a portion of their tasks on saturation dives up to 4 hours in duration that were designed to simulate extravehicular activity (EVA) on Mars or the moons of Mars. One-way communication latencies, 5 and 10 minutes between space and mission control, were simulated throughout the missions. Objective data included task completion times, total EVA times, crew idle time, translation time, ST assimilation time (defined as time available for ST to discuss data/imagery after data acquisition). Subjective data included acceptability, simulation quality, capability assessment ratings, and comments. RESULTS: Precursor data can be used effectively to plan and execute exploration traverse EVAs (plans included detailed location of science sites, high-fidelity imagery of the sites, and directions to landmarks of interest within a site). Operations concepts that allow for pre-sampling surveys enable efficient traverse execution and meaningful Mission Control Center (MCC) interaction across communication latencies and can be done with minimal crew idle time. Imagery and contextual information from the EVA crew that is transmitted real-time to the intravehicular (IV) crewmember(s) can be used to verify that exploration traverse plans are being executed correctly. That same data can be effectively used by MCC (across comm latency) to provide meaningful feedback and instruction to the crew regarding sampling priorities, additional tasks, and changes to the EVA timeline. Text / data capabilities are preferred over voice capabilities between MCC and IV when executing exploration traverse plans over communication latency.

Chappell, Steven P.↗
NASA NTRS2016

PLRP-3: Operational Perspectives of Conducting Science-Driven Extravehicular Activity with Communications Latency

The Pavilion Lake Research Project (PLRP) is a unique platform where the combination of scientific research and human space exploration concepts can be tested in an underwater spaceflight analog environment. The 2015 PLRP field season was performed at Pavilion Lake, Canada, where science-driven exploration techniques focusing on microbialite characterization and acquisition were evaluated within the context of crew and robotic extravehicular activity (EVA) operations. The primary objectives of this analog study were to detail the capabilities, decision-making process, and operational concepts required to meet non-simulated scientific objectives during 5-minute one-way communication latency utilizing crew and robotic assets. Furthermore, this field study served as an opportunity build upon previous tests at PLRP, NASA Desert Research and Technology Studies (DRATS), and NASA Extreme Environment Mission Operations (NEEMO) to characterize the functional roles and responsibilities of the personnel involved in the distributed flight control team and identify operational constraints imposed by science-driven EVA operations. The relationship and interaction between ground and flight crew was found to be dependent on the specific scientific activities being addressed. Furthermore, the addition of a second intravehicular operator was found to be highly enabling when conducting science-driven EVAs. Future human spaceflight activities will need to cope with the added complexity of dynamic and rapid execution of scientific priorities both during and between EVA execution to ensure scientific objectives are achieved.

Miller, Matthew J.↗
DOE OSTI2016

The Milky Way’s hot gas kinematics: Signatures in current and future O vii absorption line observations

Detections of z ≈ 0 oxygen absorption and emission lines indicate the Milky Way hosts a hot (∼10{sup 6} K), low-density plasma extending ≳50 kpc into the Mily Way’s halo. Current X-ray telescopes cannot resolve the line profiles, but the variation of their strengths on the sky constrains the radial gas distribution. Interpreting the O vii Kα absorption line strengths has several complications, including optical depth and line of sight velocity effects. Here, we present model absorption line profiles accounting for both of these effects to show the lines can exhibit asymmetric structures and be broader than the intrinsic Doppler width. The line profiles encode the hot gas rotation curve, the net inflow or outflow of hot gas, and the hot gas angular momentum profile. We show how line of sight velocity effects impact the conversion between equivalent width and the column density, and provide modified curves of growth accounting for these effects. As an example, we analyze the LMC sight line pulsar dispersion measure and O vii equivalent width to show the average gas metallicity is ≳0.6Z{sub ⊙} and b ≳ 100 km s{sup −1}. Determining these properties offers valuable insights into the dynamical state of the Milky Way’s hot gas, and improves the line strength interpretation. We discuss future strategies to observe these effects with an instrument that has a spectral resolution of about 3000, a goal that is technically possible today.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2015

CONSTRAINING THE MILKY WAY'S HOT GAS HALO WITH O VII AND O VIII EMISSION LINES

The Milky Way hosts a hot (≈2 × 10{sup 6} K), diffuse, gaseous halo based on detections of z = 0 O VII and O VIII absorption lines in quasar spectra and emission lines in blank-sky spectra. Here we improve constraints on the structure of the hot gas halo by fitting a radial model to a much larger sample of O VII and O VIII emission line measurements from XMM-Newton/EPIC-MOS spectra compared to previous studies (≈650 sightlines). We assume a modified β-model for the halo density distribution and a constant-density Local Bubble from which we calculate emission to compare with the observations. We find an acceptable fit to the O VIII emission line observations with χ{sub red}{sup 2} (dof) = 1.08 (644) for best-fit parameters of n{sub o}r{sub c}{sup 3β}=1.35±0.24 cm{sup –3} kpc{sup 3β} and β = 0.50 ± 0.03 for the hot gas halo and negligible Local Bubble contribution. The O VII observations yield an unacceptable χ{sub red}{sup 2} (dof) = 4.69 (645) for similar best-fit parameters, which is likely due to temperature or density variations in the Local Bubble. The O VIII fitting results imply hot gas masses of M(<50 kpc) = 3.8{sub −0.3}{sup +0.3}×10{sup 9} M{sub ⊙} and M(<250 kpc) = 4.3{sub −0.8}{sup +0.9}×10{sup 10} M{sub ⊙}, accounting for ≲50% of the Milky Way's missing baryons. We also explore our results in the context of optical depth effects in the halo gas, the halo gas cooling properties, temperature and entropy gradients in the halo gas, and the gas metallicity distribution. The combination of absorption and emission line analyses implies a sub-solar gas metallicity that decreases with radius, but that also must be ≥0.3 Z {sub ☉} to be consistent with the pulsar dispersion measure toward the Large Magellanic Cloud.

79 ASTRONOMY AND ASTROPHYSICS↗
NASA NTRS2014

Information Flow Model of Human Extravehicular Activity Operations

Future human spaceflight missions will face the complex challenge of performing human extravehicular activity (EVA) beyond the low Earth orbit (LEO) environment. Astronauts will become increasingly isolated from Earth-based mission support and thus will rely heavily on their own decision-making capabilities and onboard tools to accomplish proposed EVA mission objectives. To better address time delay communication issues, EVA characters, e.g. flight controllers, astronauts, etc., and their respective work practices and roles need to be better characterized and understood. This paper presents the results of a study examining the EVA work domain and the personnel that operate within it. The goal is to characterize current and historical roles of ground support, intravehicular (IV) crew and EV crew, their communication patterns and information needs. This work provides a description of EVA operations and identifies issues to be used as a basis for future investigation.

Miller, Matthew J.↗
DOE OSTI2013

THE STRUCTURE OF THE MILKY WAY'S HOT GAS HALO

The Milky Way's million degree gaseous halo contains a considerable amount of mass that, depending on its structural properties, can be a significant mass component. In order to analyze the structure of the Galactic halo, we use XMM-Newton Reflection Grating Spectrometer archival data and measure O VII K{alpha} absorption-line strengths toward 26 active galactic nuclei, LMC X-3, and two Galactic sources (4U 1820-30 and X1735-444). We assume a {beta}-model as the underlying gas density profile and find best-fit parameters of n{sub circle} = 0.46{sup +0.74}{sub -0.35} cm{sup -3}, r{sub c} = 0.35{sup +0.29}{sub -0.27} kpc, and {beta} = 0.71{sup +0.13}{sub -0.14}. These parameters result in halo masses ranging between M(18 kpc) = 7.5{sub -4.6}{sup +}2{sup 2.0} x 10{sup 8} M{sub Sun} and M (200 kpc) = 3.8{sub -0.5}{sup +6.0} x 10{sup 10} M{sub Sun} assuming a gas metallicity of Z = 0.3 Z{sub Sun }, which are consistent with current theoretical and observational work. The maximum baryon fraction from our halo model of f{sub b} = 0.07{sup +0.03}{sub -0.01} is significantly smaller than the universal value of f{sub b} = 0.171, implying the mass contained in the Galactic halo accounts for 10%-50% of the missing baryons in the Milky Way. We also discuss our model in the context of several Milky Way observables, including ram pressure stripping in dwarf spheroidal galaxies, the observed X-ray emission measure in the 0.5-2 keV band, the Milky Way's star formation rate, spatial and thermal properties of cooler gas ({approx}10{sup 5} K), and the observed Fermi bubbles toward the Galactic center. Although the metallicity of the halo gas is a large uncertainty in our analysis, we place a lower limit on the halo gas between the Sun and the Large Magellanic Cloud (LMC). We find that Z {approx}> 0.2 Z{sub Sun} based on the pulsar dispersion measure toward the LMC.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2013

OUTFLOW VERSUS INFALL IN SPIRAL GALAXIES: METAL ABSORPTION IN THE HALO OF NGC 891

Gas accreting onto a galaxy will be of low metallicity while halo gas due to a galactic fountain will be of near-solar metallicity. We test these predictions by measuring the metal absorption line properties of halo gas 5 kpc above the plane of the edge-on galaxy NGC 891, using observations taken with HST/STIS toward a bright background quasar. Metal absorption lines of Fe II, Mg II, and Mg I in the halo of NGC 891 are clearly seen, and when combined with recent deep H I observations, we are able to place constraints on the metallicity of the halo gas for the first time. The H I line width defines the line broadening, from which we model opacity effects in these metal lines, assuming that the absorbing gas is continuously distributed in the halo. The gas-phase metallicities are [Fe/H] = -1.18 {+-} 0.07 and [Mg/H] = -0.23 + 0.36/ - 0.27 (statistical errors) and this difference is probably due to differential depletion onto grains. When corrected for such depletion using Galactic gas as a guide, both elements have approximately solar or even supersolar abundances. This suggests that the gas is from the galaxy disk, probably expelled into the halo by a galactic fountain, rather than from accretion of intergalactic gas, which would have a low metallicity. The abundances would be raised by significant amounts if the absorbing gas lies in a few clouds with thermal widths smaller than the rotational velocity of the halo. If this is the case, both the abundances and [Mg/Fe] would be supersolar.

79 ASTRONOMY AND ASTROPHYSICS↗