Search NASA⌕ Search

SEARCH · Search NASA

Results for “combinatorial data”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

36 records · Page 2
All sourcesNASA NTRSDOE OSTI
NASA NTRS2008

Tool Support for Parametric Analysis of Large Software Simulation Systems

The analysis of large and complex parameterized software systems, e.g., systems simulation in aerospace, is very complicated and time-consuming due to the large parameter space, and the complex, highly coupled nonlinear nature of the different system components. Thus, such systems are generally validated only in regions local to anticipated operating points rather than through characterization of the entire feasible operational envelope of the system. We have addressed the factors deterring such an analysis with a tool to support envelope assessment: we utilize a combination of advanced Monte Carlo generation with n-factor combinatorial parameter variations to limit the number of cases, but still explore important interactions in the parameter space in a systematic fashion. Additional test-cases, automatically generated from models (e.g., UML, Simulink, Stateflow) improve the coverage. The distributed test runs of the software system produce vast amounts of data, making manual analysis impossible. Our tool automatically analyzes the generated data through a combination of unsupervised Bayesian clustering techniques (AutoBayes) and supervised learning of critical parameter ranges using the treatment learner TAR3. The tool has been developed around the Trick simulation environment, which is widely used within NASA. We will present this tool with a GN&C (Guidance, Navigation and Control) simulation of a small satellite system.

Schumann, Johann↗
NASA NTRS1998

Optical Sensor/Actuator Locations for Active Structural Acoustic Control

Researchers at NASA Langley Research Center have extensive experience using active structural acoustic control (ASAC) for aircraft interior noise reduction. One aspect of ASAC involves the selection of optimum locations for microphone sensors and force actuators. This paper explains the importance of sensor/actuator selection, reviews optimization techniques, and summarizes experimental and numerical results. Three combinatorial optimization problems are described. Two involve the determination of the number and position of piezoelectric actuators, and the other involves the determination of the number and location of the sensors. For each case, a solution method is suggested, and typical results are examined. The first case, a simplified problem with simulated data, is used to illustrate the method. The second and third cases are more representative of the potential of the method and use measured data. The three case studies and laboratory test results establish the usefulness of the numerical methods.

Piezoelectric actuators↗
NASA NTRS2005

Review of high-throughput techniques for detecting solid phase Transformation from material libraries produced by combinatorial methods

High-throughput measurement techniques are reviewed for solid phase transformation from materials produced by combinatorial methods, which are highly efficient concepts to fabricate large variety of material libraries with different compositional gradients on a single wafer. Combinatorial methods hold high potential for reducing the time and costs associated with the development of new materials, as compared to time-consuming and labor-intensive conventional methods that test large batches of material, one- composition at a time. These high-throughput techniques can be automated to rapidly capture and analyze data, using the entire material library on a single wafer, thereby accelerating the pace of materials discovery and knowledge generation for solid phase transformations. The review covers experimental techniques that are applicable to inorganic materials such as shape memory alloys, graded materials, metal hydrides, ferric materials, semiconductors and industrial alloys.

Lee, Jonathan A.↗
NASA NTRS1990

Dissolving variables in connectionist combinatory logic

A connectionist system which can represent and execute combinator expressions to elegantly solve the variable binding problem in connectionist networks is presented. This system is a graph reduction machine utilizing graph representations and traversal mechanisms similar to ones described in the BoltzCONS system of Touretzky (1986). It is shown that, as combinators eliminate variables by introducing special functions, these functions can be connectionistically implemented without reintroducing variable binding. This approach 'dissolves' an important part of the variable binding problem, in that a connectionist system still has to manipulate complex data structures, but those structures and their manipulations are rendered more uniform.

Barnden, John↗
NASA NTRS2017

Knowledge Base for Distributed Spacecraft Mission Design Using the Trade-Space Analysis Tool for Constellations (TAT-C)

Opportunities for multi-point measurements, greater revisit frequency, failure robustness, and improved cost effectiveness motivate consideration of Distributed Spacecraft Missions (DSMs) for future Earth science missions. However, careful analysis is required to assess the distributed sensing capabilities of a constellation compared to more mature monolithic spacecraft while also considering other important dimensions such as cost and risk. The large combinatorial DSM design space limits existing mission analysis tools and exploration methods which emphasize monolithic design variables. The Trade-space Analysis Tool for Constellations (TAT-C) under development at Goddard seeks to enumerate and evaluate alternative mission architectures to minimize cost and maximize scientific return for pre-defined goals during pre-phase A analysis.Similar to other model-centric engineering efforts, efficient data management is a significant challenge for DSM mission analysis. In TAT-C, a Knowledge Base (KB) is envisioned as a cumulative central repository of information and meta-information about DSMs. Initial KB concepts store related data for reuse within or across mission analyses; however, over time, the KB is envisioned to be an important layer to coordinate actions of both human analysts and automated design agents to search a large design space for desirable mission alternatives. Preliminary KB research builds on a modern web technology stack to provide the following functionality: 1) storage of trade-space search requests which set requirements and constraints for DSM concepts, 2) storage of analysis results which quantify performance metrics for evaluated DSM concepts, 3) a RESTful application programming interface (API) for scripted access to data from TAT-C modules, 4) web-based graphical user interface (GUI) for manual access to underlying data, and 5) access control and management restrictions relevant to data protection and security. These efforts have culminated in a prototype KB used by the research team during TAT-C development to assess opportunities for future work.

Pattern Recognition↗
NASA NTRS1987

Optimization of the computational load of a hypercube supercomputer onboard a mobile robot

A combinatorial optimization methodology is developed, which enables the efficient use of hypercube multiprocessors onboard mobile intelligent robots dedicated to time-critical missions. The methodology is implemented in terms of large-scale concurrent algorithms based either on fast simulated annealing, or on nonlinear asynchronous neural networks. In particular, analytic expressions are given for the effect of single-neuron perturbations on the systems' configuration energy. Compact neuromorphic data structures are used to model effects such as precedence constraints, processor idling times, and task-schedule overlaps. Results for a typical robot-dynamics benchmark are presented.

Barhen, Jacob↗
NASA NTRS2013

The Evolution of Software and Its Impact on Complex System Design in Robotic Spacecraft Embedded Systems

The growth in computer hardware performance, coupled with reduced energy requirements, has led to a rapid expansion of the resources available to software systems, driving them towards greater logical abstraction, flexibility, and complexity. This shift in focus from compacting functionality into a limited field towards developing layered, multi-state architectures in a grand field has both driven and been driven by the history of embedded processor design in the robotic spacecraft industry.The combinatorial growth of interprocess conditions is accompanied by benefits (concurrent development, situational autonomy, and evolution of goals) and drawbacks (late integration, non-deterministic interactions, and multifaceted anomalies) in achieving mission success, as illustrated by the case of the Mars Reconnaissance Orbiter. Approaches to optimizing the benefits while mitigating the drawbacks have taken the form of the formalization of requirements, modular design practices, extensive system simulation, and spacecraft data trend analysis. The growth of hardware capability and software complexity can be expected to continue, with future directions including stackable commodity subsystems, computer-generated algorithms, runtime reconfigurable processors, and greater autonomy.

software↗
NASA NTRS2010

Fast Solution in Sparse LDA for Binary Classification

An algorithm that performs sparse linear discriminant analysis (Sparse-LDA) finds near-optimal solutions in far less time than the prior art when specialized to binary classification (of 2 classes). Sparse-LDA is a type of feature- or variable- selection problem with numerous applications in statistics, machine learning, computer vision, computational finance, operations research, and bio-informatics. Because of its combinatorial nature, feature- or variable-selection problems are NP-hard or computationally intractable in cases involving more than 30 variables or features. Therefore, one typically seeks approximate solutions by means of greedy search algorithms. The prior Sparse-LDA algorithm was a greedy algorithm that considered the best variable or feature to add/ delete to/ from its subsets in order to maximally discriminate between multiple classes of data. The present algorithm is designed for the special but prevalent case of 2-class or binary classification (e.g. 1 vs. 0, functioning vs. malfunctioning, or change versus no change). The present algorithm provides near-optimal solutions on large real-world datasets having hundreds or even thousands of variables or features (e.g. selecting the fewest wavelength bands in a hyperspectral sensor to do terrain classification) and does so in typical computation times of minutes as compared to days or weeks as taken by the prior art. Sparse LDA requires solving generalized eigenvalue problems for a large number of variable subsets (represented by the submatrices of the input within-class and between-class covariance matrices). In the general (fullrank) case, the amount of computation scales at least cubically with the number of variables and thus the size of the problems that can be solved is limited accordingly. However, in binary classification, the principal eigenvalues can be found using a special analytic formula, without resorting to costly iterative techniques. The present algorithm exploits this analytic form along with the inherent sequential nature of greedy search itself. Together this enables the use of highly-efficient partitioned-matrix-inverse techniques that result in large speedups of computation in both the forward-selection and backward-elimination stages of greedy algorithms in general.

Moghaddam, Baback↗
NASA NTRS1993

Modulation and coding for throughput-efficient optical free-space links

Optical direct-detection systems are currently being considered for some high-speed inter-satellite links, where data-rates of a few hundred megabits per second are evisioned under power and pulsewidth constraints. In this paper we investigate the capacity, cutoff-rate and error-probability performance of uncoded and trellis-coded systems for various modulation schemes and under various throughput and power constraints. Modulation schemes considered are on-off keying (OOK), pulse-position modulation (PPM), overlapping PPM (OPPM) and multi-pulse (combinatorial) PPM (MPPM).

Georghiades, Costas N.↗
NASA NTRS2004

Rapid Chemometric Filtering of Spectral Data

A method of rapid, programmable filtering of spectral transmittance, reflectance, or fluorescence data to measure the concentrations of chemical species has been proposed. By programmable is meant that a variety of spectral analyses can readily be performed and modified in software, firmware, and/or electronic hardware, without need to change optical filters or other optical hardware of the associated spectrometers. The method is intended to enable real-time identification of single or multiple target chemical species in applications that involve high-throughput screening of multiple samples. Examples of such applications include (but are not limited to) combinatorial chemistry, flow cytometry, bead assays, testing drugs, remote sensing, and identification of targets. The basic concept of the proposed method is to perform real-time crosscorrelations of a measured spectrum with one or more analytical function(s) of wavelength that could be, for example, the known spectra of target species. Assuming that measured spectral intensities are proportional to concentrations of target species plus background spectral intensities, then after subtraction of background levels, it should be possible to determine target species concentrations from cross-correlation values. Of course, the problem of determining the concentrations is more complex when spectra of different species overlap, but the problem can be solved by use of multiple analytical functions in combination with computational techniques that have been developed previously for analyses of this type. The method is applicable to the design and operation of a spectrometer in which spectrally dispersed light is measured by means of an active-pixel sensor (APS) array. The row or column dimension of such an array is generally chosen to be aligned along the spectral-dispersion dimension, so that each pixel intercepts light in a narrow spectral band centered on a wavelength that is a known function of the pixel position. The proposed method admits of two hardware implementations for computing cross-correlations in real time.

Beaman, Gregory↗
NASA NTRS1998

RH1020 Single Event Clock Upset Summary Report

This report summarizes the testing and analysis of "single event clock upset' in the RH1020. Also included are SEU-rate predictions and design recommendations for risk analysis and reduction. The subject of "upsets" in the RH1020 is best understood by using a model consisting of a global clock buffer and a D-type flip-flop as the basic memory unit. The RH1020 is built on the ACT 1 family architecture. As such, it has one low-skew global clock buffer with a TTL-level input threshold that is accessed via a single dedicated pin. The clock signal is driven to full CMOS levels, buffered, and sent to individual row buffers with one buffer per channel. For low-skew performance, the outputs of all of the RH1020 row buffers are shorted together via metal lines, as is done in the A1020B. All storage in the RH1020 consists of routed flip-flops, constructed with multiplexors and feedback through the routing segments. A simple latch can be constructed from a single (combinatorial or C) module; an edge-triggered flip-flop is constructed using two concatenated latches. There is no storage in the I/O modules. The front end of the clock buffering circuitry, at a common point relative to the row buffer, is a sub-circuit that was determined to be the most susceptible to heavy ions. This is due, in part, to its smaller transistors compared to the rest of the circuitry. This conclusion is also supported by SPICE simulations and an analysis of the heavy ion data, described in this report. The edge triggered D flip-flop has two single-event-upset modes. Mode one, called C-module upset, is caused by a heavy ion striking the C-module's sensitive area on the silicon and produces a soft single bit error at the output of the flip-flop. Mode two, called clock upset, is caused by a heavy ion strike on the clock buffer, generating a runt pulse interpreted as a false clock signal and consequently producing errors at the flip-flop outputs. C-module upset sensitivity in the RH1020 is essentially the same as that of its ACT 1 siblings (A1020, A1020A and A1020B), which were well tested, analyzed, and documented in the literature.

Katz, Richard B.↗
NASA NTRS1984

A high-speed digital signal processor for atmospheric radar, part 7.3A

The Model SP-320 device is a monolithic realization of a complex general purpose signal processor, incorporating such features as a 32-bit ALU, a 16-bit x 16-bit combinatorial multiplier, and a 16-bit barrel shifter. The SP-320 is designed to operate as a slave processor to a host general purpose computer in applications such as coherent integration of a radar return signal in multiple ranges, or dedicated FFT processing. Presently available is an I/O module conforming to the Intel Multichannel interface standard; other I/O modules will be designed to meet specific user requirements. The main processor board includes input and output FIFO (First In First Out) memories, both with depths of 4096 W, to permit asynchronous operation between the source of data and the host computer. This design permits burst data rates in excess of 5 MW/s.

Brosnahan, J. W.↗
NASA NTRS2017

A Dose of Reality: Radiation Analysis for Realistic Human Spacecraft

INTRODUCTION As with most computational analyses, a tradeoff exists between problem complexity, resource availability and response accuracy when modeling radiation transport from the source to a detector. The largest amount of analyst time for setting up an analysis is often spent ensuring that any simplifications made have minimal impact on the results. The vehicle shield geometry of interest is typically simplified from the original CAD design in order to reduce computation time, but this simplification requires the analyst to "re-draw" the geometry with a limited set of volumes in order to accommodate a specific radiation transport software package. The resulting low-fidelity geometry model cannot be shared with or compared to other radiation transport software packages, and the process can be error prone with increased model complexity. The work presented here demonstrates the use of the DAGMC (Direct Accelerated Geometry for Monte Carlo) Toolkit from the University of Wisconsin, to model the impacts of several space radiation sources on a CAD drawing of the US Lab module. METHODS The DAGMC toolkit workflow begins with the export of an existing CAD geometry from the native CAD to the ACIS format. The ACIS format file is then cleaned using SpaceClaim to remove small holes and component overlaps. Metadata is then assigned to the cleaned geometry file using CUBIT/Trelis from csimsoft (Registered Trademark). The DAGMC plugin script removes duplicate shared surfaces, facets the geometry to a specified tolerance, and ensures that the faceted geometry is water tight. This step also writes the material and scoring information to a standard input file format that the analyst can alter as desired prior to running the radiation transport program. The scoring results can be transformed, via python script, into a 3D format that is viewable in a standard graphics program. RESULTS The CAD model of the US Lab module of the International Space Station, inclusive of all the racks and components, was simplified to remove holes and volume overlaps. Problematic features within the drawing were also removed or repaired to prevent runtime issues. The cleaned drawing was then run through the DAGMC workflow to prepare for analysis. Pilot tests modeling transport of 1GeV proton and 800MeV/A oxygen sources show that reasonable results are converged upon in an acceptable amount of overall computation time from drawing preparation to data analysis. The FLUKA radiation transport code will next be used to model both a GCR and a trapped radiation source. These results will then be compared with measurements that have been made by the radiation instrumentation deployed inside the US Lab module. DISCUSSION Early analyses have indicated that the DAGMC workflow is a promising toolkit for running vehicle geometries of interest to NASA through multiple radiation transport codes. In addition, recent work has shown that a realistic human phantom, provided via a subcontract with the University of Florida, can be placed inside any vehicle geometry for a combinatorial analysis. This added functionality gives the user the ability to score various parameters at the organ level, and the results can then be used as input for cancer risk models.

Barzilla, J. E.↗
NASA NTRS2005

A Method for Aircraft Concept Selection Using Multicriteria Interactive Genetic Algorithms

The problem of aircraft concept selection has become increasingly difficult in recent years as a result of a change from performance as the primary evaluation criteria of aircraft concepts to the current situation in which environmental effects, economics, and aesthetics must also be evaluated and considered in the earliest stages of the decision-making process. This has prompted a shift from design using historical data regression techniques for metric prediction to the use of physics-based analysis tools that are capable of analyzing designs outside of the historical database. The use of optimization methods with these physics-based tools, however, has proven difficult because of the tendency of optimizers to exploit assumptions present in the models and drive the design towards a solution which, while promising to the computer, may be infeasible due to factors not considered by the computer codes. In addition to this difficulty, the number of discrete options available at this stage may be unmanageable due to the combinatorial nature of the concept selection problem, leading the analyst to arbitrarily choose a sub-optimum baseline vehicle. These concept decisions such as the type of control surface scheme to use, though extremely important, are frequently made without sufficient understanding of their impact on the important system metrics because of a lack of computational resources or analysis tools. This paper describes a hybrid subjective/quantitative optimization method and its application to the concept selection of a Small Supersonic Transport. The method uses Genetic Algorithms to operate on a population of designs and promote improvement by varying more than sixty parameters governing the vehicle geometry, mission, and requirements. In addition to using computer codes for evaluation of quantitative criteria such as gross weight, expert input is also considered to account for criteria such as aeroelasticity or manufacturability which may be impossible or too computationally expensive to consider explicitly in the analysis. Results indicate that concepts resulting from the use of this method represent designs which are promising to both the computer and the analyst, and that a mapping between concepts and requirements that would not otherwise be apparent is revealed.

Buonanno, Michael↗
NASA NTRS2006

NASA Tech Briefs, October 2006

Topics covered include: Protein Sensors Based on Optical Ring Resonators; Phase Sensor for Aligning a Segmented Telescope Mirror; Control Software for Advanced Video Guidance Sensor; Generating Control Commands From Gestures Sensed by EMG; Multiple-Flat-Panel System Displays Multidimensional Data; 3D X-Ray Luggage-Screening System; Probe Station and Near-Field Scanner for Testing Antennas; Photodetector Arrays for Multicolor Visible/Infrared Imaging; Semiconductor Bolometers Give Background-Limited Performance; Multichannel X-Band Dielectric-Resonator Oscillator; Automatic Alignment of Displacement-Measuring Interferometer; Earth Observing System Data Gateway; Power User Interface; Mercury Shopping Cart Interface; Cassini Archive Tracking System; Architecture Adaptive Computing Environment; Computing Fault Displacements from Surface Deformations; Oxygen-Permeable, Hydrophobic Membranes of Silanized alpha-Al2O3; SiC Composite Turbine Vanes; Retaining Device for the Interior Structure of a Spacecraft Payload; Tool for Torquing Circular Electrical-Connector Collars; System for Continuous Deaeration of Hydraulic Oil; Solar-Powered Cooler and Heater for an Automobile Interior; Improved Oxygen-Beam Texturing of Glucose-Monitoring Optics; Tool for Two Types of Friction Stir Welding; Stationary Apparatus Would Apply Forces of Walking to Feet; Instrument Would Detect and Collect Biological Aerosols; Boundary Condition for Modeling Semiconductor Nanostructures; Miniature Distillation Column for Producing LOX From Air; Even Illumination from Fiber-Optic-Coupled Laser Diodes; Optically Driven Deformable Mirrors; Algorithm for Automated Detection of Edges of Clouds; Exploiting Quantum Resonance to Solve Combinatorial Problems; Hybrid Terrain Database; On Release of Microbe-Laden Particles from Mars Landers; A Concept for Run-Time Support of the Chapel Language; Thermoelectric Inhomogeneities in (Ag(sub 1-y)SbTe2)(sub x)(PbTe)(sub 1-x); and Spacecraft Escape Capsule.

Source record↗
NASA NTRS2002

Overall Traveling-Wave-Tube Efficiency Improved By Optimized Multistage Depressed Collector Design

Depressed Collector Design The microwave traveling wave tube (TWT) is used widely for space communications and high-power airborne transmitting sources. One of the most important features in designing a TWT is overall efficiency. Yet, overall TWT efficiency is strongly dependent on the efficiency of the electron beam collector, particularly for high values of collector efficiency. For these reasons, the NASA Glenn Research Center developed an optimization algorithm based on simulated annealing to quickly design highly efficient multistage depressed collectors (MDC's). Simulated annealing is a strategy for solving highly nonlinear combinatorial optimization problems. Its major advantage over other methods is its ability to avoid becoming trapped in local minima. Simulated annealing is based on an analogy to statistical thermodynamics, specifically the physical process of annealing: heating a material to a temperature that permits many atomic rearrangements and then cooling it carefully and slowly, until it freezes into a strong, minimum-energy crystalline structure. This minimum energy crystal corresponds to the optimal solution of a mathematical optimization problem. The TWT used as a baseline for optimization was the 32-GHz, 10-W, helical TWT developed for the Cassini mission to Saturn. The method of collector analysis and design used was a 2-1/2-dimensional computational procedure that employs two types of codes, a large signal analysis code and an electron trajectory code. The large signal analysis code produces the spatial, energetic, and temporal distributions of the spent beam entering the MDC. An electron trajectory code uses the resultant data to perform the actual collector analysis. The MDC was optimized for maximum MDC efficiency and minimum final kinetic energy of all collected electrons (to reduce heat transfer). The preceding figure shows the geometric and electrical configuration of an optimized collector with an efficiency of 93.8 percent. The results show the improvement in collector efficiency from 89.7 to 93.8 percent, resulting in an increase of three overall efficiency points. In addition, the time to design a highly efficient MDC was reduced from a month to a few days. All work was done in-house at Glenn for the High Rate Data Delivery Program. Future plans include optimizing the MDC and TWT interaction circuit in tandem to further improve overall TWT efficiency.

Vaden, Karl R.↗
NASA NTRS2020

Disruptive Technologies and Their Putative Impacts Upon Society and Aerospace- Entering The Virtual Age

Developments in technology over the recent decades have been extraordinary. They include the IT, bio, nano, and now quantum and energetics technology arenas and their many combinatorial interactions and impacts. In the main, these are at the frontiers of the small and in a combinational, synergistic feeding frenzy with each other. They fall under the broad category of Disruptive Technologies and have greatly altered society. The outlook for the runout of these and other technology developments augers mid-term to later alterations in components of the human existence theorem, including the requirement to work for our living and our physiological makeup and longevity (Ref 1). The IT revolution began in the 1950s with the development of solid-state electronics. The biologics revolution began later in the 1960s and 1970s with DNA and genomics, and the nano revolution in the 1990s with self-forming nano systems and carbon nanotubes. Quantum technology is now developing rapidly, aided by enabling nano systems, and the energetics revolution is providing ever more efficient and less expensive renewable energy sources. The IT revolution has produced improvements of an astounding eleven orders of magnitude in computing speed since the late 1950s. As we shift from silicon to biological, optical, nano, molecular, and atomic computing, improvements of some 4 orders of magnitude are evidently possible from either optical or DNA computing [Refs 2and 3], then there are combinatorials. Then there is quantum computing, under development worldwide for an increasing number of applications and proffering phenomenal capabilities. The current fastest computers are considerably beyond human brain speed. Machine intelligence is developing well after decades of inadequate machine capability, now no longer the case, and a detour into expert systems. Researchers in machine intelligence are now pursuing deep learning approaches using neural nets, which are proving to be extremely useful. Some believe the frontier of potential human-level machine intelligence may be found in biomimetics and brain-emulation approaches. There is even a possibility of “emergence”—i.e., when the machine intelligence is complex enough that it “wakes up,” as when human intelligence emerged via evolution during the million-plus years of the hunter-gatherer epoch [ Ref 4]. In fact, some posit that human intelligence can be improved upon and is only a cul-de-sac of what is conceivable. The IT revolution has produced massive changes in human society and economics—from the Internet, enabling the rapid expansion of knowledgeability (and even what is knowable), to an increasingly pervasive trend of “tele-everything.” The extraordinary compilation, storage, and availability of truly massive amounts of information could, when combined with AI and under the mantra of “big data,” greatly improve many of our technical and commercial processes and their content including elucidating new heuristic governing laws.

Dennis M. Bushnell↗
NASA NTRS2000

Constructing high complexity synthetic libraries of long ORFs using in vitro selection

We present a method that can significantly increase the complexity of protein libraries used for in vitro or in vivo protein selection experiments. Protein libraries are often encoded by chemically synthesized DNA, in which part of the open reading frame is randomized. There are, however, major obstacles associated with the chemical synthesis of long open reading frames, especially those containing random segments. Insertions and deletions that occur during chemical synthesis cause frameshifts, and stop codons in the random region will cause premature termination. These problems can together greatly reduce the number of full-length synthetic genes in the library. We describe a strategy in which smaller segments of the synthetic open reading frame are selected in vitro using mRNA display for the absence of frameshifts and stop codons. These smaller segments are then ligated together to form combinatorial libraries of long uninterrupted open reading frames. This process can increase the number of full-length open reading frames in libraries by up to two orders of magnitude, resulting in protein libraries with complexities of greater than 10(13). We have used this methodology to generate three types of displayed protein library: a completely random sequence library, a library of concatemerized oligopeptide cassettes with a propensity for forming amphipathic alpha-helical or beta-strand structures, and a library based on one of the most common enzymatic scaffolds, the alpha/beta (TIM) barrel. Copyright 2000 Academic Press.

Non-NASA Center↗