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Integrative Circuit-Host Modeling of a Genetic Switch in Varying Environments
Synthetic biology is advancing into a new phase where real-world applications are emphasized. There is hence an urgent need for mathematical modeling that can quantitatively describe the behaviors of genetic devices in natural, fluctuating environments. We utilize an integrative circuit-host modeling framework to examine the dynamics of a genetic switch and its host cell in varying environments. For both steady-state and transient cases, we find increasing nutrient reduces the bistability region of the phase space and eventually drives the switch from bistability to monostability. In response, cellular growth and proteome partitioning experience the same transition. Antibiotic perturbations cause the similar circuit and host responses as nutrient variations. However, one difference is the trend of growth rate, which augments with nutrient but declines with antibiotic levels. The framework provides a mechanistic scheme to account for both the dynamic and static characteristics of the circuit-host system upon environmental perturbations, underscoring the intimacy of gene circuits and their hosts and elucidating the complexity of circuit behaviors arising from environmental variations.
Visualization of the HIV-1 Env glycan shield across scales
The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the “glycan shield,” is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure–function analysis. Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels. We found that dynamics lead to an extensive network of interglycan interactions that drive the formation of higher-order structure within the glycan shield. This structure defines diffuse boundaries between buried and exposed protein surface and creates a mapping of potentially immunogenic sites on Env. Analysis of Env expressed in different cell lines revealed how cryo-EM can detect subtle changes in glycan occupancy, composition, and dynamics that impact glycan shield structure and epitope accessibility. Importantly, this identified unforeseen changes in the glycan shield of Env obtained from expression in the same cell line used for vaccine production. Finally, by capturing the enzymatic deglycosylation of Env in a time-resolved manner, we found that highly connected glycan clusters are resistant to digestion and help stabilize the prefusion trimer, suggesting the glycan shield may function beyond immune evasion.
Transport and stability in sustained high q min , high β N discharges on DIII-D
Abstract To address the needs for a fusion pilot plan design, DIII-D/EAST joint experiments on DIII-D have demonstrated high normalized beta β N ∼ 4.2, toroidal beta β T ∼ 3.3% with q min > 2, q 95 ⩽ 8 sustained for more than six energy confinement times in high poloidal beta regime. The excellent energy confinement quality ( H 98y2 ∼ 1.8) is achieved with an internal transport barrier at high line-averaged Greenwald density fraction f Gr > 0.9. The trapped gyro-Landau fluid (TGLF) modeling of the transport characteristics shows that the beam-driven rotation does not play an important role in the high confinement quality. The modeling also captures very well several transport features, giving us confidence in using integrated modeling to project these experimental results to future machines. The high-performance phase is terminated by fast-growing modes triggered near the n = 1 ideal-wall kink stability limit. New radio frequency (RF) capabilities for off-axis current drive could remove the residual ohmic current to achieve a fully non-inductive state, and improve the mode–wall coupling to increase the ideal-wall β N limit, enabling sustainment of the fully non-inductive high performance plasma in stationary conditions.
Dispersive optical systems for scalable Raman driving of hyperfine qubits
Hyperfine atomic states are among the most promising candidates for qubit encoding in quantum information processing. In atomic systems, hyperfine transitions are typically driven through a two-photon Raman process by a laser field which is amplitude modulated at the hyperfine qubit frequency. Here we introduce a method for generating amplitude modulation by phase modulating a laser and reflecting it from a highly dispersive optical element known as a chirped Bragg grating. This approach is passively stable, offers high efficiency, and is compatible with high-power laser sources, enabling large Rabi frequencies and improved quantum coherence. We benchmark this approach by globally driving an array of approximately 300 neutral 87 Rb atomic qubits trapped in optical tweezers and obtain Rabi frequencies of 2 MHz with photon-scattering error rates of less than 2×10 -4 per π pulse. This robust approach can be directly integrated with local addressing optics in both neutral atom and trapped ion systems to facilitate high-fidelity single-qubit operations for quantum information processing.
Shaping the Future of Self-Driving Autonomous Laboratories Workshop
The "Shaping the Future of Self-Driving Autonomous Laboratories" workshop, held in Denver on November 7-8, 2024, brought together leading experts from materials science and computing to address the growing need to revolutionize scientific research through AI-driven autonomous laboratories. The workshop identified critical challenges, including the integration of heterogeneous data, development of AI systems that understand fundamental physical principles, and comprehensive safety protocols. Key recommendations emerged around developing universal laboratory equipment interfaces, implementing automated metadata collection systems, and creating hybrid AI approaches that combine data-driven learning with scientific principles. The workshop emphasized maintaining human oversight while leveraging automation, transforming scientific education to prepare the next generation of researchers, and establishing a national consortium leveraging DOE facilities as anchors for broader collaboration with academia and industry. Participants stressed the urgency of addressing the growing disconnect between human decision-making timescales and modern instrumentation capabilities, highlighting the need for strategic automation while preserving essential human insight and oversight in the research process.
Micromechanics Analysis Code (MAC) User Guide: Version 1.0
The ability to accurately predict the thermomechanical deformation response of advanced composite materials continues to play an important role in the development of these strategic materials. Analytical models that predict the effective behavior of composites are used not only by engineers performing structural analysis of large-scale composite components but also by material scientists in developing new material systems. For an analytical model to fulfill these two distinct functions it must be based on a micromechanics approach which utilizes physically based deformation and life constitutive models and allows one to generate the average (macro) response of a composite material given the properties of the individual constituents and their geometric arrangement. Here the user guide for the recently developed, computationally efficient and comprehensive micromechanics analysis code, MAC, who's predictive capability rests entirely upon the fully analytical generalized method of cells, GMC, micromechanics model is described. MAC is a versatile form of research software that 'drives' the double or triple ply periodic micromechanics constitutive models based upon GMC. MAC enhances the basic capabilities of GMC by providing a modular framework wherein (1) various thermal, mechanical (stress or strain control), and thermomechanical load histories can be imposed; (2) different integration algorithms may be selected; (3) a variety of constituent constitutive models may be utilized and/or implemented; and (4) a variety of fiber architectures may be easily accessed through their corresponding representative volume elements.
Convective Weather Forecast Quality Metrics for Air Traffic Management Decision-Making
Since numerical weather prediction models are unable to accurately forecast the severity and the location of the storm cells several hours into the future when compared with observation data, there has been a growing interest in probabilistic description of convective weather. The classical approach for generating uncertainty bounds consists of integrating the state equations and covariance propagation equations forward in time. This step is readily recognized as the process update step of the Kalman Filter algorithm. The second well known method, known as the Monte Carlo method, consists of generating output samples by driving the forecast algorithm with input samples selected from distributions. The statistical properties of the distributions of the output samples are then used for defining the uncertainty bounds of the output variables. This method is computationally expensive for a complex model compared to the covariance propagation method. The main advantage of the Monte Carlo method is that a complex non-linear model can be easily handled. Recently, a few different methods for probabilistic forecasting have appeared in the literature. A method for computing probability of convection in a region using forecast data is described in Ref. 5. Probability at a grid location is computed as the fraction of grid points, within a box of specified dimensions around the grid location, with forecast convection precipitation exceeding a specified threshold. The main limitation of this method is that the results are dependent on the chosen dimensions of the box. The examples presented Ref. 5 show that this process is equivalent to low-pass filtering of the forecast data with a finite support spatial filter. References 6 and 7 describe the technique for computing percentage coverage within a 92 x 92 square-kilometer box and assigning the value to the center 4 x 4 square-kilometer box. This technique is same as that described in Ref. 5. Characterizing the forecast, following the process described in Refs. 5 through 7, in terms of percentage coverage or confidence level is notionally sound compared to characterizing in terms of probabilities because the probability of the forecast being correct can only be determined using actual observations. References 5 through 7 only use the forecast data and not the observations. The method for computing the probability of detection, false alarm ratio and several forecast quality metrics (Skill Scores) using both the forecast and observation data are given in Ref. 2. This paper extends the statistical verification method in Ref. 2 to determine co-occurrence probabilities. The method consists of computing the probability that a severe weather cell (grid location) is detected in the observation data in the neighborhood of the severe weather cell in the forecast data. Probabilities of occurrence at the grid location and in its neighborhood with higher severity, and with lower severity in the observation data compared to that in the forecast data are examined. The method proposed in Refs. 5 through 7 is used for computing the probability that a certain number of cells in the neighborhood of severe weather cells in the forecast data are seen as severe weather cells in the observation data. Finally, the probability of existence of gaps in the observation data in the neighborhood of severe weather cells in forecast data is computed. Gaps are defined as openings between severe weather cells through which an aircraft can safely fly to its intended destination. The rest of the paper is organized as follows. Section II summarizes the statistical verification method described in Ref. 2. The extension of this method for computing the co-occurrence probabilities in discussed in Section HI. Numerical examples using NCWF forecast data and NCWD observation data are presented in Section III to elucidate the characteristics of the co-occurrence probabilities. This section also discusses the procedure for computing throbabilities that the severity of convection in the observation data will be higher or lower in the neighborhood of grid locations compared to that indicated at the grid locations in the forecast data. The probability of coverage of neighborhood grid cells is also described via examples in this section. Section IV discusses the gap detection algorithm and presents a numerical example to illustrate the method. The locations of the detected gaps in the observation data are used along with the locations of convective weather cells in the forecast data to determine the probability of existence of gaps in the neighborhood of these cells. Finally, the paper is concluded in Section V.
A Tale of Two Chambers: Iterative Approaches and Lessons Learned from Life Support Systems Testing in Altitude Chambers
The drive for the journey to Mars is in a higher gear than ever before. We are developing new spacecraft and life support systems to take humans to the Red Planet. The journey that development hardware takes before its final incarnation in a fully integrated spacecraft can take years, as is the case for the Orion environmental control and life support system (ECLSS). Through the Pressure Integrated Suit Test (PIST) series, NASA personnel at Johnson Space Center have been characterizing the behavior of a closed loop ECLSS in the event of cabin depressurization. This kind of testing - one of the most hazardous activities performed at JSC - requires an iterative approach, increasing in complexity and hazards). The PIST series, conducted in the Crew and Thermal Systems Division (CTSD) 11-ft Chamber, started with unmanned test precursors before moving to a human-in-the-loop phase, and continues to evolve with the eventual goal of a qualification test for the final system that will be installed on Orion. Meanwhile, the Human Exploration Spacecraft Testbed for Integration and Advancement (HESTIA) program is an effort to research and develop technologies that will work in concert to support habitation on Mars. September 2015 marked the first unmanned HESTIA test, with the goal of characterizing how ECLSS technologies work together in a closed environment. HESTIA will culminate in crewed testing, but it can benefit from the lessons learned from another test that is farther ahead in its development and life cycle. Discussing PIST and HESTIA, this paper illustrates how we approach testing, the kind of information that facility teams need to ensure efficient collaborations and successful testing, and how we can apply what we learn to execute future tests.
Ecological Study of Lagoons Surrounding the John F. Kennedy Space Center, Brevard County, Florida : Theses and Project Reports - Volume 2
Many of the detailed studies done in connection with Ecological Study of the Lagoons surrounding the John F. Kennedy Space Port were performed as Master's Thesis investigations by various graduate students enrolled at F. I. T. during and subsequent to the report. The scope and purpose of what we came to call "the KSC Baseline Study" caught the imagination and interest of our student body. Many who were not financially or otherwise connected with the project found their inspiration in studies that were directly connected with project, and thus added materially to the totality of the knowledge gained. An example of one such study is the first article included in this Volume, A Master's Thesis study performed by Shen Phillip Chen, who chose the site for his investigation so that his results would correlate with and extend the results of others. In addition to the Master's Theses contained in this Volume, six other graduate studies must be acknowledged here as contributing to this Report, although they have not reached the stage of final publication. Ms. Sandra Fettes has completed a study of the amounts of five trace metals in mangrove leaves from plants at various locations around the Kennedy Space Center. Mr. Bernard Cohenour has isolated and identified a number of oil consuming bacteria endemic in the waters of the Indian Rivers. Mr. Charles Waterhouse has analyzed historic data of tidal gauges in the lagoonal area and correlated it with wind field records. Mr. Renkert Meyer has measured the vertical and horizontal currents of the lagoons and is attempting an interpretation of them in terms of the wind field as a driving force. Mr. Richard Campbell has measured the rate of nitrogen fixation in both the water columns and the sediments under them in the lagoons. Mr. Craig Weiderhold has measured thl3 annual variations in the populations of benthic invertebrates in the lagoons. An integral part of the F. I. T. curriculum is a requirement that each undergraduate student perform an independent study during his Senior year and submit his results in the form and format of a professional scientific report. While none of these senior Project Reports have been included in this Volume because of space limitations, many of them aided significantly in the overall study. Typical of these were: light and dark bottle studies of the blue-green algae respiration; writing and executing computer studies comparing the water chemistry data from various sites; detection and identification of nitrogen fixation bacteria in the Indian River; measurement of dissolved oils and greases in the river, photographically recording the benthic life-forms found in the river bottom; measuring the vertical structure of drift and slope currents in too lagoons; and measurement of water level variations along the long axis of a lagoon as a function of wind stress. These articles are published as a part of this Final Report in an effort to make available for the record as much of the basic data as possible. The few articles published on the Indian River have in general not contained much detailed data, so that comparisons of current status to conditions of the past are difficult or impossible. A major effort of both the Oceanographic and Ecological communities for the past decade has been the retrieval and storage of basic data in order to permit determinations of trends or changes in baseline conditions. It is believed that the information compiled here will be of great value in any future investigations.
Predicting Gate Conflicts at Charlotte Douglas International Airport Using NASA ATD-2 Fused Data Sources
NASA is conducting the Airspace Technology Demonstration-2 to evaluate an Integrated Arrival, Departure, and Surface (IADS) traffic management system. The IADS system is powered by real-time System Wide Information Management feeds which provide an accurate and high fidelity view of the lifecycle of a flight. This data can be leveraged to drive efficiencies in the National Airspace System. For non safety critical applications there is opportunity for third party service providers to offer this type of data-driven prediction service in near real-time. This paper investigates the gate conflict prediction problem as a concrete use case which could help drive efficiencies. We model gate conflicts as a regression problem and describe the iterative process of model building, model validation, and evaluation used to assess the efficacy of our approach. We quantify our predictive accuracy and identify paths for improvement. Through this iterative process we hope to evolve our models and methods to a near real-time prediction service.
Transient Resonances in EMRIs: A Scalar Toy Model
We present calculations of the scalar self-force for a scalar point-charge following different $r\theta$-resonant geodesics in Kerr spacetime. Using this scalar model, we present two methods for constructing the self-force for resonant sources using two different phase parameterizations of the point-particle motion. We relate these two methods via a simple shifting relation that holds for both the scalar and gravitational self-forces. We discuss how this shifting relation allows us to compare self-force results both at and away from resonances. Finally, we provide new evidence that conservative scalar perturbations can drive the leading-order evolution of the orbital dynamics during resonances (i.e., the orbit-averaged rate of change of the Carter constant depends on contributions from the conservative self-force). This evidence conflicts with a commonly assumed conjecture that these integrated conservative contributions should vanish during both resonant and non-resonant motion.
Spaceflight Ground Support Equipment Reliability & System Safety Data
Presented were Reliability Analysis, consisting primarily of Failure Modes and Effects Analysis (FMEA), and System Safety Analysis, consisting of Preliminary Hazards Analysis (PHA), performed to ensure that the CoNNeCT (Communications, Navigation, and Networking re- Configurable Testbed) Flight System was safely and reliably operated during its Assembly, Integration and Test (AI&T) phase. A tailored approach to the NASA Ground Support Equipment (GSE) standard, NASA-STD-5005C, involving the application of the appropriate Requirements, S&MA discipline expertise, and a Configuration Management system (to retain a record of the analysis and documentation) were presented. Presented were System Block Diagrams of selected GSE and the corresponding FMEA, as well as the PHAs. Also discussed are the specific examples of the FMEAs and PHAs being used during the AI&T phase to drive modifications to the GSE (via "redlining" of test procedures, and the placement of warning stickers to protect the flight hardware) before being interfaced to the Flight System. These modifications were necessary because failure modes and hazards were identified during the analysis that had not been properly mitigated. Strict Configuration Management was applied to changes (whether due to upgrades or expired calibrations) in the GSE by revisiting the FMEAs and PHAs to reflect the latest System Block Diagrams and Bill Of Material. The CoNNeCT flight system has been successfully assembled, integrated, tested, and shipped to the launch site without incident. This demonstrates that the steps taken to safeguard the flight system when it was interfaced to the various GSE were successful.
Equation of State Measurements on Iron Near the Melting Curve at Planetary Core Conditions by Shock and Ramp Compressions
The outer core of the Earth is composed primarily of liquid iron, and the inner core boundary is governed by the intersection of the melt line and the geotherm. While there are many studies on the thermodynamic equation of state for solid iron, the equation of state of liquid iron is relatively unexplored. In this work, we use dynamic compression to diagnose the high-pressure liquid equation of state of iron by utilizing the shock-ramp capability at Sandia National Laboratories’ Z-Machine. This technique enables measurements of material states off the Hugoniot by initially shocking samples and subsequently driving a further, shockless compression. Planetary studies benefit greatly from isentropic, off-Hugoniot experiments since they can cover pressure-temperature (P-T) conditions that are close to adiabatic profiles found in planetary interiors. We used this method to drive iron to P-T conditions similar to those of the Earth’s outer-inner core boundary, along an elevated-temperature isentrope in the liquid from 275 GPa to 400 GPa. We derive the equation of state using a hybrid backward integration – forward Lagrangian technique on particle velocity traces to determine the pressure-density history of the sample. Our results are in excellent agreement with SESAME 92141, a previously published equation of state table. With our data and previous experimental data on liquid iron we provide new information on the iron melting line and derive new parameters for a Vinet-based equation of state. The table and our parameterized equation of state are applied to provide an updated means of modeling the pressure, mass, and density of liquid iron cores in exoplanetary interiors.
Enhancing Active Distribution Systems Resilience by Fully Distributed Self-Healing Strategy
Distributed restoration can exploit smart grid technologies to enhance the resilience of active distribution networks toward a self-healing smart grid. However, the large number of decision variables, especially the binary ones for reconfiguration, bring challenges to developing scalable distributed distribution service restoration (DDSR) strategies. This paper proposes a fully distributed solution procedure based on the alternating direction method of multipliers (ADMM) for mixed-integer programming problems and applies to develop the DDSR framework. The method consists of relax-drive-polish phases, 1) relaxing binary variables, and applying the convex ADMM as a warm start; 2) driving the solutions toward Boolean values through a proximal operator; 3) fixing the obtained binding binary variables and solving the rest of the problem to polish results and achieve a high-quality suboptimal solution. Then, an autonomous clustering strategy and consensus ADMM are integrated with the proposed method to realize the fully distributed cluster-based framework of DDSR. This framework can first determine DER scheduling and switch status for reconfiguration to energize the out-of-service areas from local faults, and then provide the load restoration solution in a distributed manner for total blackouts in large-scale distribution networks. Furthermore, the effectiveness and scalability of the proposed DDSR framework are demonstrated through testing on the IEEE 123-node, IEEE 8500-node, and synthetic 100k-node test feeders.
A new method for hardware/software integration of strategic systems - Case study of the Space Shuttle
An advanced system integrated self-test has been developed to provide dynamic checkout of all critical subsystems and hardware/software interfaces of the Space Shuttle during pre-launch ground testing. The system modifies hardware sensor data to represent a real flight scenario. This modified data then drives the flight software. The system was sucessfully utilized for three phases of Space Shuttle testing, and will be expanded for use as a maintenance tool.
An intelligent multi-media human-computer dialogue system
Sophisticated computer systems are being developed to assist in the human decision-making process for very complex tasks performed under stressful conditions. The human-computer interface is a critical factor in these systems. The human-computer interface should be simple and natural to use, require a minimal learning period, assist the user in accomplishing his task(s) with a minimum of distraction, present output in a form that best conveys information to the user, and reduce cognitive load for the user. In pursuit of this ideal, the Intelligent Multi-Media Interfaces project is devoted to the development of interface technology that integrates speech, natural language text, graphics, and pointing gestures for human-computer dialogues. The objective of the project is to develop interface technology that uses the media/modalities intelligently in a flexible, context-sensitive, and highly integrated manner modelled after the manner in which humans converse in simultaneous coordinated multiple modalities. As part of the project, a knowledge-based interface system, called CUBRICON (CUBRC Intelligent CONversationalist) is being developed as a research prototype. The application domain being used to drive the research is that of military tactical air control.
Planned LMSS propagation experiment using ACTS: Preliminary antenna pointing results during mobile operations
An overview and a status description of the planned LMSS mobile K band experiment with ACTS is presented. As a precursor to the ACTS mobile measurements at 20.185 GHz, measurements at 19.77 GHz employing the Olympus satellite were originally planned. However, because of the demise of Olympus in June of 1991, the efforts described here are focused towards the ACTS measurements. In particular, we describe the design and testing results of a gyro controlled mobile-antenna pointing system. Preliminary pointing measurements during mobile operations indicate that the present system is suitable for measurements employing a 15 cm aperture (beamwidth at approximately 7 deg) receiving antenna operating with ACTS in the high gain transponder mode. This should enable measurements with pattern losses smaller than plus or minus 1 dB over more than 95 percent of the driving distance. Measurements with the present mount system employing a 60 cm aperture (beamwidth at approximately 1.7 deg) results in pattern losses smaller than plus or minus 3 dB for 70 percent of the driving distance. Acceptable propagation measurements may still be made with this system by employing developed software to flag out bad data points due to extreme pointing errors. The receiver system including associated computer control software has been designed and assembled. Plans are underway to integrate the antenna mount with the receiver on the University of Texas mobile receiving van and repeat the pointing tests on highways employing a recently designed radome system.