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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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11 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS1994

Re-engineering Nascom's network management architecture

The development of Nascom systems for ground communications began in 1958 with Project Vanguard. The low-speed systems (rates less than 9.6 Kbs) were developed following existing standards; but, there were no comparable standards for high-speed systems. As a result, these systems were developed using custom protocols and custom hardware. Technology has made enormous strides since the ground support systems were implemented. Standards for computer equipment, software, and high-speed communications exist and the performance of current workstations exceeds that of the mainframes used in the development of the ground systems. Nascom is in the process of upgrading its ground support systems and providing additional services. The Message Switching System (MSS), Communications Address Processor (CAP), and Multiplexer/Demultiplexer (MDM) Automated Control System (MACS) are all examples of Nascom systems developed using standards such as, X-windows, Motif, and Simple Network Management Protocol (SNMP). Also, the Earth Observing System (EOS) Communications (Ecom) project is stressing standards as an integral part of its network. The move towards standards has produced a reduction in development, maintenance, and interoperability costs, while providing operational quality improvement. The Facility and Resource Manager (FARM) project has been established to integrate the Nascom networks and systems into a common network management architecture. The maximization of standards and implementation of computer automation in the architecture will lead to continued cost reductions and increased operational efficiency. The first step has been to derive overall Nascom requirements and identify the functionality common to all the current management systems. The identification of these common functions will enable the reuse of processes in the management architecture and promote increased use of automation throughout the Nascom network. The MSS, CAP, MACS, and Ecom projects have indicated the potential value of commercial-off-the-shelf (COTS) and standards through reduced cost and high quality. The FARM will allow the application of the lessons learned from these projects to all future Nascom systems.

Drake, Brian C.↗
NASA NTRS1994

Automated Instrumentation, Monitoring and Visualization of PVM Programs Using AIMS

We present views and analysis of the execution of several PVM (Parallel Virtual Machine) codes for Computational Fluid Dynamics on a networks of Sparcstations, including: (1) NAS Parallel Benchmarks CG and MG; (2) a multi-partitioning algorithm for NAS Parallel Benchmark SP; and (3) an overset grid flowsolver. These views and analysis were obtained using our Automated Instrumentation and Monitoring System (AIMS) version 3.0, a toolkit for debugging the performance of PVM programs. We will describe the architecture, operation and application of AIMS. The AIMS toolkit contains: (1) Xinstrument, which can automatically instrument various computational and communication constructs in message-passing parallel programs; (2) Monitor, a library of runtime trace-collection routines; (3) VK (Visual Kernel), an execution-animation tool with source-code clickback; and (4) Tally, a tool for statistical analysis of execution profiles. Currently, Xinstrument can handle C and Fortran 77 programs using PVM 3.2.x; Monitor has been implemented and tested on Sun 4 systems running SunOS 4.1.2; and VK uses XIIR5 and Motif 1.2. Data and views obtained using AIMS clearly illustrate several characteristic features of executing parallel programs on networked workstations: (1) the impact of long message latencies; (2) the impact of multiprogramming overheads and associated load imbalance; (3) cache and virtual-memory effects; and (4) significant skews between workstation clocks. Interestingly, AIMS can compensate for constant skew (zero drift) by calibrating the skew between a parent and its spawned children. In addition, AIMS' skew-compensation algorithm can adjust timestamps in a way that eliminates physically impossible communications (e.g., messages going backwards in time). Our current efforts are directed toward creating new views to explain the observed performance of PVM programs. Some of the features planned for the near future include: (1) ConfigView, showing the physical topology of the virtual machine, inferred using specially formatted IP (Internet Protocol) packets: and (2) LoadView, synchronous animation of PVM-program execution and resource-utilization patterns.

Mehra, Pankaj↗
NASA NTRS1994

Automated Instrumentation, Monitoring and Visualization of PVM Programs Using AIMS

We present views and analysis of the execution of several PVM codes for Computational Fluid Dynamics on a network of Sparcstations, including (a) NAS Parallel benchmarks CG and MG (White, Alund and Sunderam 1993); (b) a multi-partitioning algorithm for NAS Parallel Benchmark SP (Wijngaart 1993); and (c) an overset grid flowsolver (Smith 1993). These views and analysis were obtained using our Automated Instrumentation and Monitoring System (AIMS) version 3.0, a toolkit for debugging the performance of PVM programs. We will describe the architecture, operation and application of AIMS. The AIMS toolkit contains (a) Xinstrument, which can automatically instrument various computational and communication constructs in message-passing parallel programs; (b) Monitor, a library of run-time trace-collection routines; (c) VK (Visual Kernel), an execution-animation tool with source-code clickback; and (d) Tally, a tool for statistical analysis of execution profiles. Currently, Xinstrument can handle C and Fortran77 programs using PVM 3.2.x; Monitor has been implemented and tested on Sun 4 systems running SunOS 4.1.2; and VK uses X11R5 and Motif 1.2. Data and views obtained using AIMS clearly illustrate several characteristic features of executing parallel programs on networked workstations: (a) the impact of long message latencies; (b) the impact of multiprogramming overheads and associated load imbalance; (c) cache and virtual-memory effects; and (4significant skews between workstation clocks. Interestingly, AIMS can compensate for constant skew (zero drift) by calibrating the skew between a parent and its spawned children. In addition, AIMS' skew-compensation algorithm can adjust timestamps in a way that eliminates physically impossible communications (e.g., messages going backwards in time). Our current efforts are directed toward creating new views to explain the observed performance of PVM programs. Some of the features planned for the near future include: (a) ConfigView, showing the physical topology of the virtual machine, inferred using specially formatted IP (Internet Protocol) packets; and (b) LoadView, synchronous animation of PVM-program execution and resource-utilization patterns.

Mehra, Pankaj↗
NASA NTRS2004

The Conservation of Structure and Mechanism of Catalytic Action in a Family of Thiamin Pyrophosphate (TPP)-dependent Enzymes

Thiamin pyrophosphate (TPP)-dependent enzymes are a divergent family of TPP and metal ion binding proteins that perform a wide range of functions with the common decarboxylation steps of a -(O=)C-C(OH)- fragment of alpha-ketoacids and alpha- hydroxyaldehydes. To determine how structure and catalytic action are conserved in the context of large sequence differences existing within this family of enzymes, we have carried out an analysis of TPP-dependent enzymes of known structures. The common structure of TPP-dependent enzymes is formed at the interface of four alpha/beta domains from at least two subunits, which provide for two metal and TPP-binding sites. Residues around these catalytic sites are conserved for functional purpose, while those further away from TPP are conserved for structural reasons. Together they provide a network of contacts required for flip-flop catalytic action within TPP-dependent enzymes. Thus our analysis defines a TPP-action motif that is proposed for annotating TPP-dependent enzymes for advancing functional proteomics.

Dominiak, P.↗
NASA NTRS2013

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.↗
NASA NTRS2004

Structural Basis for the Catalytic Activity of Human SER/THR Protein Phosphatase-5

Serinekhreonine protein phosphatase-5 (PP5) affects many signaling networks that regulate cell growth. Here we report the 1.6 Angstrom resolution crystal structure of PP5 catalytic domain with metal and phosphate ions in the active site. The structure reveals a mechanism for PPS-mediated catalysis that requires the precise positioning of two metal ions within a conserved Asp(sup 271)-M(sub 1),-M(sub 2)-His(sup 427)-W(sup 2)-His(sup 304)-Asp(sup 274) catalytic motif, and provides a structural basis for the exceptional catalytic proficiency of protein phosphatases placing them among the most powerful catalysts. Resolution of the entire C-terminus revealed a novel subdomain, and the structure of PP5 should aid development of specific inhibitors.

Swingle, M. R.↗
NASA NTRS2004

Structural Basis for the Catalytic Activity of Human Serine/Threonine Protein Phosphatase-5

Serinehhreonine protein phosphatase-5 (PP5) affects many signaling networks that regulate cell growth and cellular responses to stress. Here we report the crystal structure of the PP5 catalytic domain (PP5c) at a resolution of 1.6 A. From this structure we resolved the mechanism for PP5-mediated hydrolysis of phosphoprotein substrates, which requires the precise positioning of two metal ions within a con served Aspn-271-M(sub 1):M(sub 2)-W(sup 1)-His-427-His-304-Asp-274 catalytic motif. The structure of PPSc provides a structural basis for explaining the exceptional catalytic proficiency of protein phosphatases, which are among the most powerful known catalysts. Resolution of the entire C-terminus revealed a novel subdomain, and the structure of the PP5c should also aid development of type-specific inhibitors.

Swingle, M. R.↗
NASA NTRS2021

Predicting the Functional State of Protein Kinases Using Interpretable Graph Neural Networks

Kinases are a family of proteins that function as molecular switches, regulating several essential cellular activities such as cell proliferation. Dysfunctional kinases are implicated in several types of cancers and hence they are actively pursued as drug targets. Given the vast number of complex kinase structures that are available in the protein data bank (PDB), there is a necessity to develop methodologies that can identify structurally important moieties of the kinases in an automated fashion, for such techniques can be instrumental in identifying novel drug targets. In this work, we develop a graph neural network (GNN) based deep learning framework for classifying the functionally active and inactive states of a large set of eukaryotic protein kinases, making use of their 3D structure from the PDB. We show that GNN based machine learning models can classify protein states with an accuracy greater than 97%. We further use the GNN models to automatically identify regions of the kinases that are important for its function. For this purpose, Gradient-weighted Class Activation Mapping (Grad-CAM) was implemented on the protein graphs. Remarkably, Grad-CAM consistently identifies the highly conserved DFG motif as the most important part of the protein across the entire kinome, without any prior input. Other regions of the hydrophobic core such as the HRD motif were also identified by the interpretable GNN framework, consistent with the literature. We discuss the significance of each of these regions in detail.

Ashwin Ravichandran↗
NASA NTRS2009

Emergence of Complexity in Protein Functions and Metabolic Networks

In modern organisms proteins perform a majority of cellular functions, such as chemical catalysis, energy transduction and transport of material across cell walls. Although great strides have been made towards understanding protein evolution, a meaningful extrapolation from contemporary proteins to their earliest ancestors is virtually impossible. In an alternative approach, the origin of water-soluble proteins was probed through the synthesis of very large libraries of random amino acid sequences and subsequently subjecting them to in vitro evolution. In combination with computer modeling and simulations, these experiments allow us to address a number of fundamental questions about the origins of proteins. Can functionality emerge from random sequences of proteins? How did the initial repertoire of functional proteins diversify to facilitate new functions? Did this diversification proceed primarily through drawing novel functionalities from random sequences or through evolution of already existing proto-enzymes? Did protein evolution start from a pool of proteins defined by a frozen accident and other collections of proteins could start a different evolutionary pathway? Although we do not have definitive answers to these questions, important clues have been uncovered. Considerable progress has been also achieved in understanding the origins of membrane proteins. We will address this issue in the example of ion channels - proteins that mediate transport of ions across cell walls. Remarkably, despite overall complexity of these proteins in contemporary cells, their structural motifs are quite simple, with -helices being most common. By combining results of experimental and computer simulation studies on synthetic models and simple, natural channels, I will show that, even though architectures of membrane proteins are not nearly as diverse as those of water-soluble proteins, they are sufficiently flexible to adapt readily to the functional demands arising during evolution.

Pohorille, Andzej↗
NASA NTRS2004

Structural Basis for the Catalytic Activity of Human Serine/Threonine Protein Phosphatase type 5 (PP5)

Serine/threonine protein phosphatase-5 (PP5) is a member of the PPP-gene family of protein phosphatases that is widely expressed in mammalian tissues and is highly conserved among eukaryotes. PP5 associates with several proteins that affect signal transduction networks, including the glucocorticoid receptor (GR)-heat shock protein-90 (Hsp90)-heterocomplex, the CDC16 and CDC27 subunits of the anaphase-promoting complex, elF2alpha kinase, the A subunit of PP2A, the G12-alpha / G13-alpha subunits of heterotrimeric G proteins and DNA-PK. The catalytic domain of PP5 (PP5c) shares 35-45% sequence identity with the catalytic domains of other PPP-phosphatases, including protein phosphatase-1 (PP1), -2A (PP2A), -2B / calcineurin (PP2B), -4 (PP4), -6 (PP6), and -7 (PP7). Like PP1, PP2A and PP4, PP5 is also sensitive to inhibition by okadaic acid, microcystin, cantharidin, tautomycin, and calyculin A. Here we report the crystal structure of the PP5 catalytic domain (PP5c) at a resolution of 1.6 angstroms. From this structure we propose a mechanism for PP5-mediated hydrolysis of phosphoprotein substrates, which requires the precise positioning of two metal ions within a conserved Asp(sup 271)-M(sub 1):M(sub 2)-W(sup 1)-His(sup 304)-Asp(sup 274) catalytic motif. The structure of PP5c provides a possible structural basis for explaining the exceptional catalytic proficiency of protein phosphatases, which are among the most powerful known catalysts. Resolution of the entire C-terminus revealed a novel subdomain, and the structure of the PP5c should also aid development of type-specific inhibitors.

Swingle, Mark R.↗
NASA NTRS2017

Exploring Connectivity in Sequence Space of Functional RNA

Emergence of replicable genetic molecules was one of the marking points in the origin of life, evolution of which can be conceptualized as a walk through the space of all possible sequences. A theoretical concept of fitness landscape helps to understand evolutionary processes through assigning a value of fitness to each genotype. Then, evolution of a phenotype is viewed as a series of consecutive, single-point mutations. Natural selection biases evolution toward peaks of high fitness and away from valleys of low fitness. whereas neutral drift occurs in the sequence space without direction as mutations are introduced at random. Large networks of neutral or near-neutral mutations on a fitness landscape, especially for sufficiently long genomes, are possible or even inevitable. Their detection in experiments, however, has been elusive. Although a few near-neutral evolutionary pathways have been found, recent experimental evidence indicates landscapes consist of largely isolated islands. The generality of these results, however, is not clear, as the genome length or the fraction of functional molecules in the genotypic space might have been insufficient for the emergence of large, neutral networks. Thorough investigation on the structure of the fitness landscape is essential to understand the mechanisms of evolution of early genomes. RNA molecules are commonly assumed to play the pivotal role in the origin of genetic systems. They are widely believed to be early, if not the earliest, genetic and catalytic molecules, with abundant biochemical activities as aptamers and ribozymes, i.e. RNA molecules capable, respectively, to bind small molecules or catalyze chemical reactions. Here, we present results of our recent studies on the structure of the sequence space of RNA ligase ribozymes selected through in vitro evolution. Several hundred thousands of sequences active to a different degree were obtained by way of deep sequencing. Analysis of these sequences revealed several large clusters defined such that every sequence in a cluster can be reached from any other sequence in the same cluster through a series of single point mutations. Sequences in a single cluster appear to adopt more than one secondary structure. The mechanism of refolding within a single cluster was examined. To shed light on possible evolutionary paths in the space of ribozymes, the connectivity between clusters was investigated. The effect of length of RNA molecules on the structure of the fitness landscape and possible evolutionary paths was examined by way of comparing functional sequences of 20 and 80 nucleobases in length. It was found that sequences of different lengths shared secondary structure motifs that were presumed responsible for catalytic activity, with increasing complexity and global structural rearrangements emerging in longer molecules.

Wei, Chenyu↗