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This manual describes a modification of the Banning placement routing folding program. The modifications to this program have been made to implement it on a Sigma 5 computer. Flow charts of various levels, beginning with high level functional diagrams and working down to the level of detail deemed necessary to understand the operations of the various sections of the program are included. Along with the flow charts of each subroutine is a narrative description of its functional operation and definitions of its arrays and key variables, and a section to assist the programmer in dimensioning the program's arrays.
Project Managers often face challenging technical, schedule and budget issues. This presentation will explore how the Ares I-X Roll Control System Integrated Product Team (IPT) mitigated challenges such as concurrent engineering requirements and environments and evolving program processes, while successfully managing an aggressive project schedule and tight budget. IPT challenges also included communications and negotiations among inter- and intra-government agencies, including the US Air Force, NASA/MSFC Propulsion Engineering, LaRC, GRC, KSC, WSTF, and the Constellation Program. In order to successfully meet these challenges it was essential that the IPT define those items that most affected the schedule critical path, define early mitigation strategies to reduce technical, schedule, and budget risks, and maintain the end-product focus of an "unmanned test flight" context for the flight hardware. The makeup of the IPT and how it would function were also important considerations. The IPT consisted of NASA/MSFC (project management, engineering, and safety/quality) and contractors (Teledyne Brown Engineering and Pratt and Whitney Rocketdyne, who supplied heritage hardware experience). The early decision to have a small focused IPT working "badgelessly" across functional lines to eliminate functional stove-piping allowed for many more tasks to be done by fewer people. It also enhanced a sense of ownership of the products, while still being able to revert back to traditional roles in order to provide the required technical independence in design reviews and verification closures. This presentation will highlight several prominent issues and discuss how they were mitigated and the resulting Lessons Learned that might benefit other projects.
Abstract Only a handful of somatic alterations have been linked to endocrine therapy resistance in hormone-dependent breast cancer, potentially explaining ∼40% of relapses. If other mechanisms underlie the evolution of hormone-dependent breast cancer under adjuvant therapy is currently unknown. In this work, we employ functional genomics to dissect the contribution of cis-regulatory elements (CRE) to cancer evolution by focusing on 12 megabases of noncoding DNA, including clonal enhancers, gene promoters, and boundaries of topologically associating domains. Parallel epigenetic perturbation (CRISPRi) in vitro reveals context-dependent roles for many of these CREs, with a specific impact on dormancy entrance and endocrine therapy resistance. Profiling of CRE somatic alterations in a unique, longitudinal cohort of patients treated with endocrine therapies identifies a limited set of noncoding changes potentially involved in therapy resistance. Overall, our data uncover how endocrine therapies trigger the emergence of transient features which could ultimately be exploited to hinder the adaptive process. Significance: This study shows that cells adapting to endocrine therapies undergo changes in the usage or regulatory regions. Dormant cells are less vulnerable to regulatory perturbation but gain transient dependencies which can be exploited to decrease the formation of dormant persisters.
Functional expansion tallies (FETs) are a powerful tool for getting more information per history from Monte Carlo simulations, but in the past they have been constrained to orthogonal bases. Bezier curves, from computer aided design (CAD), could be well suited for FET due to their ability to assume many arbitrary shapes, but are non-orthogonal. Recent development has made non-orthongal FET possible. The convergence of B ´ezier curve FETs in both polynomial order and number of samples is explored. These bases are well suited for representing normal distributions, and opens the door to possible other CAD derived FET bases.
Long-term stay in weightlessness is accompanied by alterations in the activity of main physiological body systems including sensory-motor, skeletal-muscular disturbances and cardiovascular deconditioning. However, up to now, there are no data on the state and level of functional performance of cosmonauts/astronauts directly after flight, nor are there data to help define the dynamic recovery of functional characteristics and work efficiency which are greatly needed to provide the safety and planning of their activity once they reach space objects. The Russian and American scientists are currently engaged in a joint experiment known as the "Field Test" with the goal of studying the functional performance and the state of main physiological body systems directly after landing and their temporal recovery dynamics. The functional performance is identified during the test by temporal characteristics of the movements of spatial translation, the stability of the vertical stance for 3.5 min, and the kinematic characteristics of walking - non-complicated and complicated. The following characteristics are identified as physiological characteristics of the test: a) orthostatic tolerance during stand test, b) back muscle tone; c) vertical stability - by characteristics of the correction responses to unexpected perturbations of the vertical stance, and d) support reactions during the performance of the full battery of tests. To date, a pilot version of the "Field Test" has been conducted with participation from four Russian cosmonauts. The results of studies have shown that in 1 - 5 hours after landing the functional abilities of the cosmonauts are considerably reduced. All the test movements at this time are considerably slower than preflight and the more complicated the task is, the greater significant reduction in orthostatic tolerance: during the first test that occurs 1 - 5 hours after landing. two of four cosmonauts declined to continue the task after the orthostatic test (one of them did not wear the anti-G suit "Centaurus" during testing). Blood pressure during moving out of prone posture to vertical stance in one of the cosmonauts and of sitting to standing position in the other dropped to the precollapse level. The results of the studies have confirmed the feasibility, the usefulness and the safety of conducting tests as close as possible to the landing. The program of "Field Test" experiment will be continued and extended.
The objective of this paper is to present an estimate of the second law thermodynamic efficiency of the various units comprising an Environmental Control and Life Support System (ECLSS). The technique adopted here is based on an evaluation of the 'lost work' within each functional unit of the subsystem. Pertinent information for our analysis is obtained from a user interactive integrated model of an ECLSS. The model was developed using ASPEN. A potential benefit of this analysis is the identification of subsystems with high entropy generation as the most likely candidates for engineering improvements. This work has been motivated by the fact that the design objective for a long term mission should be the evaluation of existing ECLSS technologies not only the basis of the quantity of work needed for or obtained from each subsystem but also on the quality of work. In a previous study Brandhorst showed that the power consumption for partially closed and completely closed regenerable life support systems was estimated as 3.5 kw/individual and 10-12 kw/individual respectively. With the increasing cost and scarcity of energy resources, our attention is drawn to evaluate the existing ECLSS technologies on the basis of their energy efficiency. In general the first law efficiency of a system is usually greater than 50 percent. From literature, the second law efficiency is usually about 10 percent. The estimation of second law efficiency of the system indicates the percentage of energy degraded as irreversibilities within the process. This estimate offers more room for improvement in the design of equipment. From another perspective, our objective is to keep the total entropy production of a life support system as low as possible and still ensure a positive entropy gradient between the system and the surroundings. The reason for doing so is as the entropy production of the system increases, the entropy gradient between the system and the surroundings decreases, and the system will gradually approach equilibrium with the surroundings until it reaches the point where the entropy gradient is zero. At this point no work can be extracted from the system. This is called the 'dead state' of the system.
In the current work, multi-function beam control arrays have been fabricated and have successfully demonstrated amplitude control of transmitted beams in the W and D bands (75-170 GHz). While these arrays are designed to provide beam control under DC bias operation, new designs for high-speed electronic and optical control are under development. These arrays will fill a need for high-speed watt-level beam switches in pulsed reflectometer systems under development for magnetic fusion plasma diagnostics. A second experimental accomplishment of the current work is the demonstration in the 100-170 GHz (D band) frequency range of a new technique for the measurement of the transmission phase as well as amplitude. Transmission data can serve as a means to extract ('de-embed') the grid parameters; phase information provides more complete data to assist in this process. Additional functions of the array beam controller yet to be tested include electronically controlled steering and focusing of a reflected beam. These have application in the areas of millimeter-wave electronic scanning radar and reflectometry, respectively.
Grubbs 3rd-generation (G3) pre-catalyst-initiated ring-opening metathesis polymerization (ROMP) remains an indispensable tool in the polymer chemist's toolbox. Tricyclononenes (TCN) and tricyclononadienes (TCND) represent under-explored classes of monomers for ROMP that have the potential to both advance fundamental knowledge (e.g., structure-polymerization kinetics relationships) and serve as practical tools for the polymer chemist (e.g., post-polymerization functionalization). In this work, a library of TCN and TCND imides, monoesters, and diesters, along with their exo-norbornene counterparts, were synthesized to compare their behaviors in G3-initiated ROMP. Real-time 1 H NMR was used to study their polymerization kinetics; propagation rates ( k p ) were extracted for each monomer. To understand the relationships between monomer structure and ROMP propagation rates, density functional theory methods were used to calculate a variety of electronic and steric parameters for each monomer. While electronic parameters (e.g., HOMO energy levels) correlated positively with the measured k p values, steric parameters generally gave improved correlations, which indicates that monomer size and shape are better predictors for k p than electronic parameters for this data set. Furthermore, the TCND diester—which contains an electron-deficient cyclobutene that is resistant to ROMP—and its polymer p(TCND) are shown to be highly reactive toward DBU-catalyzed conjugate addition reactions with thiols, providing a protecting- and activating-group free strategy for post-polymerization modification.
The main protease enzyme (Mpro) of coronaviruses cleaves the viral polyprotein into functional units essential for virus replication. Prior work has demonstrated that Mpro functions as a homodimer. However, studies on the mechanism of dimerization have been challenging because the purified protease is mostly dimeric, dimerization-defective mutants lack proteolytic activity, and robust cell-based assays have yet to be reported. To enable work on Mpro dimerization, we have developed a quantitative luciferase-based SARS-CoV-2 (SARS2) Mpro biosensor that accurately reports protein dimerization in living cells and, upon purification, also in vitro. Co-transfection of cells with a construct expressing Mpro fused to the 18 kDa LargeBiT of luciferase (LgBiT) and a second construct with Mpro fused to the 1 kDa SmallBiT of luciferase (SmBiT) results in a reconstitution of luciferase activity in a dose-dependent manner that requires conserved residues within the dimerization interface. Proteolytic activity is dispensable for dimerization and, uniquely, a C145A catalytically inactive mutant exhibits enhanced dimerization signal likely due to lower cytotoxicity. Mpro enzymes from multiple different coronaviruses also dimerize in this system, indicating mechanistic conservation. Interestingly, this dimerization biosensor also provides a quantitative read-out of inhibitor-facilitated dimerization. Covalent SARS2 Mpro inhibitors such as nirmatrelvir cause a 3- to 5-fold increase in luciferase activity. Together with corroborating structural, biophysical, and molecular dynamics experiments, our studies support a model in which covalent Mpro inhibitors such as nirmatrelvir simultaneously block catalytic activity and induce allosteric stabilization of the dimeric complex.
The Environmental Controls and Life Support Systems (ECLSS) branch at Kennedy Space Center (KSC) is currently undergoing preparations for ground testing of the Orion Multi-Purpose Crew Vehicle (MPCV) to prepare its subsystems for EM-1 (Exploration Mission-1). EM-1, Orions second unmanned flight, is a three-week long lunar mission during which the vehicle will complete a 6-day retrograde lunar orbit before returning to Earth. This paper focuses on the work done during the authors 16-week internship with the Mechanical Engineering Branch of KSCs Engineering Directorate. The authors project involved assisting with the preparations for testing the Orion MPCVs ammonia boiler system. The purpose of the ammonia boiler system is to keep the spacecraft sufficiently cool during the reentry portion of its mission, from service module (SM) separation to post-landing. This system is critical for keeping both the spacecraft (avionics and electronics) and crew alive during reentry, thus a successful test of the system is essential to the success of EM-1. XXXX The author was able to draft a detailed outline of the procedure for the ammonia system functional test. More work will need to be done on the vehicle power-up and power-down portions of the procedure, but the ammonia system testing portion of the procedure is thorough and includes vehicle test configurations, vehicle commands, and GSE. The author was able to compile a substantial list of questions regarding the ammonia system functional test with the help of her mentors. A significant number of these questions were answered in the teleconferences with Lockheed Martin.
Some forms of nanotechnology appear to have enormous potential to improve aerospace and computer systems; computational nanotechnology, the design and simulation of programmable molecular machines, is crucial to progress. NASA Ames Research Center has begun a computational nanotechnology program including in-house work, external research grants, and grants of supercomputer time. Four goals have been established: (1) Simulate a hypothetical programmable molecular machine replicating itself and building other products. (2) Develop molecular manufacturing CAD (computer aided design) software and use it to design molecular manufacturing systems and products of aerospace interest, including computer components. (3) Characterize nanotechnologically accessible materials of aerospace interest. Such materials may have excellent strength and thermal properties. (4) Collaborate with experimentalists. Current in-house activities include: (1) Development of NanoDesign, software to design and simulate a nanotechnology based on functionalized fullerenes. Early work focuses on gears. (2) A design for high density atomically precise memory. (3) Design of nanotechnology systems based on biology. (4) Characterization of diamonoid mechanosynthetic pathways. (5) Studies of the laplacian of the electronic charge density to understand molecular structure and reactivity. (6) Studies of entropic effects during self-assembly. Characterization of properties of matter for clusters up to sizes exhibiting bulk properties. In addition, the NAS (NASA Advanced Supercomputing) supercomputer division sponsored a workshop on computational molecular nanotechnology on March 4-5, 1996 held at NASA Ames Research Center. Finally, collaborations with Bill Goddard at CalTech, Ralph Merkle at Xerox Parc, Don Brenner at NCSU (North Carolina State University), Tom McKendree at Hughes, and Todd Wipke at UCSC are underway.
Variational Quantum Algorithms (VQAs) and Quantum Machine Learning (QML) models train a parametrized quantum circuit to solve a given learning task. The success of these algorithms greatly hinges on appropriately choosing an ansatz for the quantum circuit. Perhaps one of the most famous ansatzes is the one-dimensional layered Hardware Efficient Ansatz (HEA), which seeks to minimize the effect of hardware noise by using native gates and connectives. The use of this HEA has generated a certain ambivalence arising from the fact that while it suffers from barren plateaus at long depths, it can also avoid them at shallow ones. In this work, we attempt to determine whether one should, or should not, use a HEA. We rigorously identify scenarios where shallow HEAs should likely be avoided (e.g., VQA or QML tasks with data satisfying a volume law of entanglement). More importantly, we identify a Goldilocks scenario where shallow HEAs could achieve a quantum speedup: QML tasks with data satisfying an area law of entanglement. We provide examples for such scenario (such as Gaussian diagonal ensemble random Hamiltonian discrimination), and we show that in these cases a shallow HEA is always trainable and that there exists an anti-concentration of loss function values. Our work highlights the crucial role that input states play in the trainability of a parametrized quantum circuit, a phenomenon that is verified in our numerics.
Machine learning (ML) is a powerful tool for functional material design. In this work, we combine first-principles density function theory with ML to develop perovskite database and design O<sub>2</sub> sensors for harsh environmental applications.
Inflatable structures technology utilizes high-strength fabric materials and internal pressure to create a stiffened pressure vessel that can replace traditional metallic primary structure in a habitable spacecraft. The flexibility of fabric structures allows them to be compactly stowed for launch and expanded in space, providing significant launch volume savings. The unique construction and design flexibility of these structures can be customized for a variety of uses in space including landing bags, decelerators, long duration in-space and planetary surface habitats, and even airlocks. An airlock is often a required component of a crewed spacecraft to allow for maintenance and human exploration outside of the vehicle. Airlock designs in use today rely on complex hatches and seals connected by metallic walls. Recent developments towards the design of an inflatable airlock structure show feasibility and a significant launch volume savings over a traditional metallic design. This paper will provide a high-level summary of these projects and the current state-of-the-art in inflatable airlock development with additional references and detail about previous and on-going research, providing guidance for the design of a softgoods airlock system. The use of inflatables in space has been in development since the 1960’s for both habitats and airlocks. The first ever EVA was conducted by the USSR in 1965 using an inflatable airlock known as the Volga. This airlock was attached to the Voskhod 2 spacecraft and turned the vehicle into a dual chamber airlock. The airlock was successfully deployed, used and jettisoned after Alexey Leonov’s historic spacewalk. Additional work on human-rated inflatable structures was not continued until the late 1990’s when NASA-JSC led an effort to demonstrate these structures as feasible long-term pressurized elements with the TransHab project. The technology developed and pioneered during this project led to multiple patents and proven feasibility that inflatables could be used for large habitable structures. Following TransHab, Bigelow Aerospace continued the development of inflatable structures with technical support from NASA. This partnership eventually led to the successful flight certification, launch, attachment and deployment of the Bigelow Expandable Activities Module (BEAM) on the ISS in 2016. Inflatable and expandable airlock structures have undergone various detailed feasibility studies and testing for over 15 years, most notably with the Advanced Inflatable Airlock (AIA), Dual-Chamber Hybrid Inflatable Suitlock (DCIS), Minimalistic Advanced Soft Hatch (MASH), and Lightweight External Inflatable Airlock (LEIA). During this time, full-scale articles have been built and pressure-tested, and mock-ups and demonstrators have been constructed and evaluated. During the 2001-2003 timeframe, the AIA concept was matured through requirements development, conceptual design, subscale and full-scale engineering breadboards subjecting various test articles to deployment and pressure testing up to four times operating pressure. These tests proved the feasibility of successful deployment and structural integrity of an inflatable crewlock. Additional testing was performed in the ensuing years, as funding permitted, to further refine additional structural and deployment concepts and to understand the EVA crewmember interfaces, hatches and EVA support equipment interfaces that would be required for a fully functioning airlock. This work resulted in a refinement of the structural requirements and an accounting of the systems needed in an inflatable airlock. In 2014, the MASH project developed an ultra-lightweight airlock concept with a fabric hatch that utilized a unique pressure vessel shape to minimize structural loads around a linear seal. The concept uses an automated zipper-like seal that allows for crew egress/ingress. Most of the development work on the project thus far has focused on the design, analysis and testing of the primary structure and the zipper-like seal system is in the preliminary stages of development with a successful proof-of-concept test. As part of the 2017 LEIA effort, studies were conducted on EVA crewmember interfaces on the inside of an inflatable airlock. These efforts included the design of an internal secondary structure and placement of handholds and foot restraints to enable hatch opening, closing and translation through the airlock. Structural design, analysis and testing was completed on several secondary structure candidates. Crew interface testing was also completed using an inflatable crewlock mockup and the JSC Active Response Gravity Offload System (ARGOS) to simulate the movement of an EVA crewmember through an inflatable crewlock in microgravity. The results of these tests helped demonstrate the feasibility of utilizing an inflatable structure as an airlock and informed the required volume, hatch size, and configuration and location of translation aids for crewmembers in a microgravity crewlock. The ISS Quest airlock uses a dual-chamber design with isolated compartments known as the equipment-lock and the crewlock. The equipment-lock houses the Servicing, Performance and Checkout Equipment (SPCE) items (suit batteries, consumables, etc.) while the crewlock has limited internal hardware and is the nominally depressurized compartment during US EVAs. While inflatable dual chamber airlocks have been studied, the current state of the art emphasizes an inflatable crewlock-type structure attached to a rigid equipment-lock type or habitat structure. Since a large portion of the hardware in the equipment-lock are rigid components and connectors that are installed on the ground - and an inflatable structure does not achieve full structural capabilities until pressurized in space - a depressurized fabric structure cannot provide the capabilities of a full equipment-lock. The use of an inflatable as a crewlock, however, provides all the required capabilities for EVA operations in a small launch package that offers significant volume savings over a metallic crewlock. The functions of a traditional equipment lock, including the SPCE, could be provided by a spacecraft’s habitat module or node and not necessarily in a separate equipment lock. An inflatable crewlock would be attached to the vehicle and launched in a packed and compressed state, saving volume under the launch shroud and mass for the overall airlock element compared to a rigid crewlock. Work is currently underway to continue development of an inflatable airlock with a variety of focus areas including the consideration of crew-induced loads and interfaces, the design and development of an internal sub-structure to provide translation aids and restraints, the thermal considerations of a fabric shell depressurized during an EVA, the micrometeorite environment in deep space, and the packaging and deployment of an inflatable airlock.
The PSEC5 ASIC is a high-speed waveform sampling chip designed for ultra-fast timing detectors, offering up to 40 GSPS sampling with 10-bit resolution. This makes it well-suited for applications requiring fine time resolution, such as MCPs and LGADs. This work focuses on the physical testing and validation of the chip s internal clocking and SPI-controlled registers. Testing began with inspection of schematics and the prototype to identify and resolve design issues. Then, custom firmware was developed for an Arduino controller to interface with the chip via SPI, enabling read and write access to key control registers. Results confirm that the VCO operates between ~3.2 4.0 GHz and remains stable under non-VCOVDD fluctuations. The Division Ratio register enables frequency division by known factors (256, 128, 64, etc.), indicating a pre-division frequency of 3.2 GHz when the digital band is unmodified. While most registers responded correctly, some issues were observed, including unexpected current draw and unstable discriminator behavior. Overall, the chip shows promising functionality, but further work is needed to understand the state of the read only registers and address the existing issues. Continued testing and firmware development will be critical to ensuring reliable integration into detector systems.
Theoretical descriptions of the non-equilibrium dynamics of quantum many-body systems essentially employ either (i) explicit treatments, relying on the truncation of the expansion of the many-body wave function, (ii) compressed representations of the many-body wave function, or (iii) evolution of an effective (downfolded) representation through Green's functions. In this work, we select representative cases of each of the methods and address how these complementary approaches capture the dynamics driven by intense field perturbations to non-equilibrium states. Under strong driving, the systems are characterized by strong entanglement of the single-particle density matrix and natural populations approaching those of a strongly interacting equilibrium system. We generate a representative set of results that are numerically exact and form a basis for a critical comparison of the distinct families of methods. We demonstrate that the compressed formulation based on similarity-transformed Hamiltonians (coupled-cluster approach) is practically exact in weak fields and, hence, weakly or moderately correlated systems. Coupled cluster, however, struggles for strong driving fields, under which the system exhibits strongly correlated behavior, as measured by the von Neumann entropy of the single-particle density matrix. The dynamics predicted by Green's functions in the (widely popular) G W approximation are less accurate, but improve significantly upon the mean-field results in the strongly driven regime. Published by the American Physical Society 2025
The Kennedy Space Center (KSC) has developed its own Command and Control System for the launch of the Space Launch System (SLS) and Orion capsule. The Command and Control System (CCS) is used by console engineers for the launch and system checkout of aerospace vehicles. The CCS allows console engineers to read data from the flight hardware on the launch pad and from the ground control systems and allows console engineers to issue commands, like opening a valve, to the flight hardware and ground control systems. The CCS needs to interact with thousands of devices and hardware controllers for the spacecraft and ground systems, receive data from these devices, distribute the data to console engineers in real-time, and allow console engineers to issue commands to manipulate hardware on the launch pad. The system needs to be robust, fault tolerant, responsive, and fast. In order to keep up with the pace of development of the CCS, a Test Automation System (TAS) is needed to validate the integrity of the system as a whole along with its individual components. Automated tests allow for faster development time, since tests can be ran through a Continuous Integration system and allow developers to check their code faster. Currently, the different modules, classes, and functions that make up the CCS are tested at the unit level, and the system level, with all the modules working together. My project was to implement a system for the data protocol layer of the Command Control System to be tested as a complete functional unit, with all of its classes and functions working together, but independent of the other modules of the CCS.