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At least 307 records · Page 17
All sourcesNASA NTRSDOE OSTI
NASA NTRS2017

Behavioral, Brain Imaging and Genomic Measures to Predict Functional Outcomes Post-Bed Rest and Space Flight

Astronauts experience sensorimotor disturbances during their initial exposure to microgravity and during the re-adaptation phase following a return to an Earth-gravitational environment. These alterations may disrupt crewmembers' ability to perform mission critical functional tasks requiring ambulation, manual control and gaze stability. Interestingly, astronauts who return from spaceflight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts are affected will improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. For such an approach to succeed, we must develop predictive measures of sensorimotor adaptability that will allow us to foresee, before actual spaceflight, which crewmembers are likely to experience greater challenges to their adaptive capacities. The goals of this project are to identify and characterize this set of predictive measures. Our approach includes: 1) behavioral tests to assess sensory bias and adaptability quantified using both strategic and plastic-adaptive responses; 2) imaging to determine individual brain morphological and functional features, using structural magnetic resonance imaging (MRI), diffusion tensor imaging, resting state functional connectivity MRI, and sensorimotor adaptation task-related functional brain activation; and 3) assessment of genetic polymorphisms in the catechol-O-methyl transferase, dopamine receptor D2, and brain-derived neurotrophic factor genes and genetic polymorphisms of alpha2-adrenergic receptors that play a role in the neural pathways underlying sensorimotor adaptation. We anticipate that these predictive measures will be significantly correlated with individual differences in sensorimotor adaptability after long-duration spaceflight and exposure to an analog bed rest environment. We will be conducting a retrospective study, leveraging data already collected from relevant ongoing or completed bed rest and spaceflight studies. This data will be combined with predictor metrics that will be collected prospectively (as described for behavioral, brain imaging and genomic measures) from these returning subjects to build models for predicting post spaceflight and bed rest adaptive capability. In this presentation we will discuss the optimized set of tests for predictive metrics to be used for evaluating post mission adaptive capability as manifested in their outcome measures. Comparisons of model performance will allow us to better design and implement sensorimotor adaptability training countermeasures against decrements in post-mission adaptive capability that are customized for each crewmember's sensory biases, adaptive ability, brain structure, brain function, and genetic predispositions. The ability to customize adaptability training will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to mitigate the deleterious effects of spaceflight.

Mulavara, A. P.↗
NASA NTRS2016

Behavioral, Brain Imaging and Genomic Measures to Predict Functional Outcomes Post - Bed Rest and Spaceflight

Astronauts experience sensorimotor disturbances during their initial exposure to microgravity and during the re-adaptation phase following a return to an Earth-gravitational environment. These alterations may disrupt crewmembers' ability to perform mission critical functional tasks requiring ambulation, manual control and gaze stability. Interestingly, astronauts who return from spaceflight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts would be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. For such an approach to succeed, we must develop predictive measures of sensorimotor adaptability that will allow us to foresee, before actual spaceflight, which crewmembers are likely to experience the greatest challenges to their adaptive capacities. The goals of this project are to identify and characterize this set of predictive measures. Our approach includes: 1) behavioral tests to assess sensory bias and adaptability quantified using both strategic and plastic-adaptive responses; 2) imaging to determine individual brain morphological and functional features, using structural magnetic resonance imaging (MRI), diffusion tensor imaging, resting state functional connectivity MRI, and sensorimotor adaptation task-related functional brain activation; and 3) assessment of genotypic markers of genetic polymorphisms in the catechol-O-methyl transferase, dopamine receptor D2, and brain-derived neurotrophic factor genes and genetic polymorphisms of alpha2-adrenergic receptors that play a role in the neural pathways underlying sensorimotor adaptation. We anticipate that these predictive measures will be significantly correlated with individual differences in sensorimotor adaptability after long-duration spaceflight and exposure to an analog bed rest environment. We will be conducting a retrospective study, leveraging data already collected from relevant ongoing or completed bed rest and spaceflight studies. These data will be combined with predictor metrics that will be collected prospectively (as described for behavioral, brain imaging and genomic measures) from these returning subjects to build models for predicting post-mission (bed rest - non-astronauts or space flight - astronauts) adaptive capability as manifested in their outcome measures. To date we have completed a study on 15 normal subjects with all of the above measures. In this presentation we will discuss the optimized set of tests for predictive metrics to be used for evaluating post mission adaptive capability as manifested in their outcome measures. Comparisons of model performance will allow us to better design and implement sensorimotor adaptability training countermeasures against decrements in post-mission adaptive capability that are customized for each crewmember's sensory biases, adaptive capacity, brain structure and functional capacities, and genetic predispositions. The ability to customize adaptability training will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes.

Mulavara, A. P.↗
NASA NTRS2004

Optimum Actuator Selection with a Genetic Algorithm for Aircraft Control

The placement of actuators on a wing determines the control effectiveness of the airplane. One approach to placement maximizes the moments about the pitch, roll, and yaw axes, while minimizing the coupling. For example, the desired actuators produce a pure roll moment without at the same time causing much pitch or yaw. For a typical wing, there is a large set of candidate locations for placing actuators, resulting in a substantially larger number of combinations to examine in order to find an optimum placement satisfying the mission requirements and mission constraints. A genetic algorithm has been developed for finding the best placement for four actuators to produce an uncoupled pitch moment. The genetic algorithm has been extended to find the minimum number of actuators required to provide uncoupled pitch, roll, and yaw control. A simplified, untapered, unswept wing is the model for each application.

Rogers, James L.↗
NASA NTRS1994

(abstract) Modeling Protein Families and Human Genes: Hidden Markov Models and a Little Beyond

We will first give a brief overview of Hidden Markov Models (HMMs) and their use in Computational Molecular Biology. In particular, we will describe a detailed application of HMMs to the G-Protein-Coupled-Receptor Superfamily. We will also describe a number of analytical results on HMMs that can be used in discrimination tests and database mining. We will then discuss the limitations of HMMs and some new directions of research. We will conclude with some recent results on the application of HMMs to human gene modeling and parsing.

Hidden Markov Models HMMs proteins computational m↗
NASA NTRS2024

Metabolic Stress in Space: ROS-Induced Mutations in Mice Hint at A New Path to Cancer

Long-duration spaceflight beyond Earth's magnetosphere poses serious health risks, including muscle atrophy, bone loss, liver and kidney damage, and the Spaceflight-Associated Neuro-ocular Syndrome (SANS). RNA-seq of mice aboard the International Space Station (ISS) for 37 days revealed extraordinary hypermutation in tissue-specific genes, with guanine base conversion predominating, potentially contributing to spaceflight-associated health risks. Our results suggest that the genome-wide accelerated mutation that we measured, seemingly independent of radiation dose, was induced by oxidative damage from higher atmospheric carbon dioxide (CO 2 ) levels and increased reactive oxygen species (ROS) on the ISS. This accelerated mutation, faster via RNA transcription than replication and more numerous than by radiation alone, unveils novel hotspots in the mammalian proteome. Notably, these hotspots correlate with commonly mutated genes across various human cancers, highlighting the ISS as a crucial platform for studying accelerated mutation, genome instability, and the induction of disease-causing mutations in model organisms. Our results suggest that metabolic processes can contribute to somatic mutation, and thus may play a role in the development of cancer. A metabolic link to genetic instability potentially has far-reaching implications for various diseases, with implications for human health on Earth and in space.

mice↗
NASA NTRS2004

Chondrites and the Protoplanetary Disk, Part 2

Contents include the following: On the Dynamical Evolution of a Nebula and Its Effect on Dust Coagulation and the Formation of Centimeter-sized Particles. The Mineralogy and Grain Properties of the Disk Surfaces in Three Herbig Ae/Be Stars. Astrophysical Observations of Disk Evolution Around Solar Mass Stars. The Systematic Petrology of Chondrites: A Consistent Approach to Assist Classification and Interpretation. Understanding Our Origins: Formation of Sun-like Stars in H II Region Environments. Chondrule Crystallization Experiments. Formation of SiO2-rich Chondrules by Fractional Condensation. Refractory Forsterites from Murchison (CM2) and Yamato 81020 (CO3.0) Chondrites: Cathodoluminescence, Chemical Compositions and Oxygen Isotopes. Apparent I-Xe Cooling Rates of Chondrules Compared with Silicates from the Colomera Iron Meteorite. Chondrule Formation in Planetesimal Bow Shocks: Physical Processes in the Near Vicinity of the Planetesimal. Genetic Relationships Between Chondrules, Rims and Matrix. Chondrite Fractionation was Cosmochemical; Chondrule Fractionation was Geochemical. Chondrule Formation and Accretion of Chondrite Parent Bodies: Environmental Constraints. Amoeboid Olivine Aggregates from the Semarkona LL3.0 Chondrite. The Evolution of Solids in Proto-Planetary Disks. New Nickel Vapor Pressure Measurements: Possible Implications for Nebular Condensates. Chemical, Mineralogical and Isotopic Properties of Chondrules: Clues to Their Origin. Maximal Size of Chondrules in Shock-Wave Heating Model: Stripping of Liquid Surface in Hypersonic Rarefied Gas Flow. The Nature and Origin of Interplanetary Dust: High Temperature Components. Refractory Relic Components in Chondrules from Ordinary Chondrites. Constraints on the Origin of Chondrules and CAIs from Short-lived and Long-lived Radionuclides. The Genetic Relationship Between Refractory Inclusions and Chondrules. Contemporaneous Chondrule Formation Between Ordinary and Carbonaceous Chondrites. Chondrules and Isolated Grains in the Fountain Hills Bencubbinite. Implications of Chondrule Formation in a Gas of Solar Composition. Implications of Meteoritic Cl-36 Abundance for the Origin of Short-lived Radionuclides in the Early Solar System. Size Sorting and the Chondrule Size Spectrum. Comparative Study of Refractory Inclusions from Different Groups of Chondrites. In Situ Investigation of Mg Isotope Distributions in an Allende CAI by Combined LA-ICPMS and SIMS Analyses Photochemical Speciation of Oxygen Isotopes in the Solar Nebula.

Source record↗
NASA NTRS1990

Evolution of land mammal diversity in North America during the Cenozoic

The North American continental patterns of generic richness, extinction, and origination have been reexamined and analyzed in the context of alpha and beta species diversity. The major models of diversity are discussed as well as primary concepts and theories based on studies of living organisms. The adequacy of the fossil record is considered and patterns of genetic richness and species level diversity are outlined. Major shifts in mammalian community structures are reviewed and hypotheses are presented on diversity origin, regulation, and maintenance for the North American record. Results demonstrate a complex relationship between continental alpha and beta diversity characterized by marked changes through time and differences in patterns at each level. It is clear that both biotic and abiotic factors have strongly influenced the evolution of North American species diversity and that major restructuring occurred in Cenozoic mammalian communities.

Stucky, Richard K.↗
NASA NTRS2011

A Miniaturized Video System for Monitoring Drosophila Behavior

Long-term spaceflight may induce a variety of harmful effects in astronauts, resulting in altered motor and cognitive behavior. The stresses experienced by humans in space - most significantly weightlessness (microgravity) and cosmic radiation - are difficult to accurately simulate on Earth. In fact, prolonged and concomitant exposure to microgravity and cosmic radiation can only be studied in space. Behavioral studies in space have focused on model organisms, including Drosophila melanogaster. Drosophila is often used due to its short life span and generational cycle, small size, and ease of maintenance. Additionally, the well-characterized genetics of Drosophila behavior on Earth can be applied to the analysis of results from spaceflights, provided that the behavior in space is accurately recorded. In 2001, the BioExplorer project introduced a low-cost option for researchers: the small satellite. While this approach enabled multiple inexpensive launches of biological experiments, it also imposed stringent restrictions on the monitoring systems in terms of size, mass, data bandwidth, and power consumption. Suggested parameters for size are on the order of 100 mm3 and 1 kg mass for the entire payload. For Drosophila behavioral studies, these engineering requirements are not met by commercially available systems. One system that does meet many requirements for behavioral studies in space is the actimeter. Actimeters use infrared light gates to track the number of times a fly crosses a boundary within a small container (3x3x40 mm). Unfortunately, the apparatus needed to monitor several flies at once would be larger than the capacity of the small satellite. A system is presented, which expands on the actimeter approach to achieve a highly compact, low-power, ultra-low bandwidth solution for simultaneous monitoring of the behavior of multiple flies in space. This also provides a simple, inexpensive alternative to the current systems for monitoring Drosophila populations in terrestrial experiments, and could be especially useful in field experiments in remote locations. Two practical limitations of the system should be noted: first, only walking flies can be observed - not flying - and second, although it enables population studies, tracking individual flies within the population is not currently possible. The system used video recording and an analog circuit to extract the average light changes as a function of time. Flies were held in a 5-cm diameter Petri dish and illuminated from below by a uniform light source. A miniature, monochrome CMOS (complementary metal-oxide semiconductor) video camera imaged the flies. This camera had automatic gain control, and this did not affect system performance. The camera was positioned 5-7 cm above the Petri dish such that the imaging area was 2.25 sq cm. With this basic setup, still images and continuous video of 15 flies at one time were obtained. To reduce the required data bandwidth by several orders of magnitude, a band-pass filter (0.3-10 Hz) circuit compressed the video signal and extracted changes in image luminance over time. The raw activity signal output of this circuit was recorded on a computer and digitally processed to extract the fly movement "events" from the waveform. These events corresponded to flies entering and leaving the image and were used for extracting activity parameters such as inter-event duration. The efficacy of the system in quantifying locomotor activity was evaluated by varying environmental temperature, then measuring the activity level of the flies.

Bhattacharya, Sharmila↗
NASA NTRS2005

Range Process Simulation Tool

Range Process Simulation Tool (RPST) is a computer program that assists managers in rapidly predicting and quantitatively assessing the operational effects of proposed technological additions to, and/or upgrades of, complex facilities and engineering systems such as the Eastern Test Range. Originally designed for application to space transportation systems, RPST is also suitable for assessing effects of proposed changes in industrial facilities and large organizations. RPST follows a model-based approach that includes finite-capacity schedule analysis and discrete-event process simulation. A component-based, scalable, open architecture makes RPST easily and rapidly tailorable for diverse applications. Specific RPST functions include: (1) definition of analysis objectives and performance metrics; (2) selection of process templates from a processtemplate library; (3) configuration of process models for detailed simulation and schedule analysis; (4) design of operations- analysis experiments; (5) schedule and simulation-based process analysis; and (6) optimization of performance by use of genetic algorithms and simulated annealing. The main benefits afforded by RPST are provision of information that can be used to reduce costs of operation and maintenance, and the capability for affordable, accurate, and reliable prediction and exploration of the consequences of many alternative proposed decisions.

Phillips, Dave↗
NASA NTRS2004

Strategy Developed for Selecting Optimal Sensors for Monitoring Engine Health

Sensor indications during rocket engine operation are the primary means of assessing engine performance and health. Effective selection and location of sensors in the operating engine environment enables accurate real-time condition monitoring and rapid engine controller response to mitigate critical fault conditions. These capabilities are crucial to ensure crew safety and mission success. Effective sensor selection also facilitates postflight condition assessment, which contributes to efficient engine maintenance and reduced operating costs. Under the Next Generation Launch Technology program, the NASA Glenn Research Center, in partnership with Rocketdyne Propulsion and Power, has developed a model-based procedure for systematically selecting an optimal sensor suite for assessing rocket engine system health. This optimization process is termed the systematic sensor selection strategy. Engine health management (EHM) systems generally employ multiple diagnostic procedures including data validation, anomaly detection, fault-isolation, and information fusion. The effectiveness of each diagnostic component is affected by the quality, availability, and compatibility of sensor data. Therefore systematic sensor selection is an enabling technology for EHM. Information in three categories is required by the systematic sensor selection strategy. The first category consists of targeted engine fault information; including the description and estimated risk-reduction factor for each identified fault. Risk-reduction factors are used to define and rank the potential merit of timely fault diagnoses. The second category is composed of candidate sensor information; including type, location, and estimated variance in normal operation. The final category includes the definition of fault scenarios characteristic of each targeted engine fault. These scenarios are defined in terms of engine model hardware parameters. Values of these parameters define engine simulations that generate expected sensor values for targeted fault scenarios. Taken together, this information provides an efficient condensation of the engineering experience and engine flow physics needed for sensor selection. The systematic sensor selection strategy is composed of three primary algorithms. The core of the selection process is a genetic algorithm that iteratively improves a defined quality measure of selected sensor suites. A merit algorithm is employed to compute the quality measure for each test sensor suite presented by the selection process. The quality measure is based on the fidelity of fault detection and the level of fault source discrimination provided by the test sensor suite. An inverse engine model, whose function is to derive hardware performance parameters from sensor data, is an integral part of the merit algorithm. The final component is a statistical evaluation algorithm that characterizes the impact of interference effects, such as control-induced sensor variation and sensor noise, on the probability of fault detection and isolation for optimal and near-optimal sensor suites.

Source record↗
NASA NTRSDate not supplied

Voxel Based Three-Dimensional Topology Optimization of Heat Exchanger Fins

Increasing interest in novel aircraft propulsion systems and potential for unwanted heat generation, or capture and reuse of waste heat, may require increasingly lightweight and high performing heat exchangers. Advances in manufacturing technologies have shown potential to create complex designs, but design tools need more flexibility. This study utilizes genetic algorithm-driven topology optimization to develop high performance heat exchanger fins for critical applications such as aerospace. The solid domain is generated using voxel representation where a voxel value of 1 indicates the solid domain and a voxel value of 0 refers to the fluid domain. The use of voxel representation somewhat matches the digitization of a model that is required to fabricate using additive manufacturing, and also allows for a highly unconstrained geometry. To test the topology optimization approach, a three-dimensional(3D)baseline offset strip fin geometry in steady laminar flow(Reynolds number = 215)with conjugate heat transfer(simultaneous solution of solid and fluid temperature fields)is optimized. New designs are generated using the genetic algorithm (GA) and sent to evaluation by the CFD software OpenFOAM; then the GA sorts and selects the reproduction pool for the following generation. This process is repeated for 60 generations. The study also investigates the effect off in material on the performance of the GA and the resulting designs. The results show that the optimal designs have overall performance improvement of 18% relative to the baseline. Additionally, a fin constructed of a lower conductivity material (such as an Inconel super alloy that might be necessary for waste heat recovery applications)results in lower overall performance improvement (11%)and optimal designs with higher pressure drop relative to their baseline, and relative to optimal designs produced using higher conductivity materials.

3D Optimization↗
NASA NTRS1986

Studies on precellular evolution - The encapsulation of polyribonucleotides by liposomes

Liposomes have been suggested as possible models of precellular systems formed in the early Archean earth from lipids of nonenzymatic origin. Since it is generally accepted that RNA molecules preceded double-stranded DNA molecules as genetic material, the encapsulation of polyribonucleotides within liposomes (made from dipalmitoyl phosphatidylcholine and from egg yolk phosphatidylcholine) was studied. Quantitative determinations show that approximately 50 percent of the available lipids form liposomes, and that up to 5 percent of the polyribonucleotides can be entrapped by them. Also studied was the encapsulation of polyribonucleotides in the presence of urea and cyanamide and of Zn(2+) and Pb(2+).

Baeza, I.↗
NASA NTRS2005

Development and Function of the Mouse Vestibular System in the Absence of Gravity Perception

The hypothesis that was tested in this research was that the absence of gravity perception, such as would occur in space, would affect the development and function of the vestibular and central nervous systems. Further, we postulated that these effects would be more significant at specific stages of post-natal development of the animal. We also proposed the use of molecular genetic approaches that would provide important information as to the hierarchy of gene function during the development and subsequent function of the vestibular system. The tilted (tlt) mutant mouse has been characterized as lacking the ability to provide sensory input to the gravity receptors. The tlt/tlt mutant mice were a particularly attractive model for the study of vestibular function since the primary defect was limited to the receptor part of the vestibular system, and there were no detectable abnormal phenotypes in other organ systems. The goal of the proposed studies was to assess immediate and delayed effects of the lack of gravity perception on the vestibular system. Particular attention was paid to characterizing primarily affected periods of vestibular morphogenesis, and to identifying downstream genetic pathways that are altered in the CNS of the tlt/tlt mutant mouse. The specific aims were: (1) to characterize the postnatal morphogenesis of the CNS in the tlt mutant mouse, using detailed morphometric analysis of isolated vestibular ganglia and brain tissue at different stages of postnatal development and assessment of apoptotic cell death; (2) to examine the expression of selected genes implicated by mutational analysis to be important in vestibular development or function by in situ hybridization or immunohistochemistry in the mutant mice; and (3) to identify other genes involved in vestibular development and function, using differential cloning strategies to isolate genes whose expression is changed in the mutant versus normal vestibular system.

Wolgemuth, Debra J.↗
NASA NTRS1984

First known EL5 chondrite - Evidence for dual genetic sequence for enstatite chondrites

The compositionally distinct EH and EL groups together with four (3-6) petrologic types which constitute the enstatite chondrites represent increasing degrees of metamorphic alteration. Although bulk composition variations preclude a simple conversion of EH4 into EL6 material, complex models which involve simultaneous bulk composition and petrologic type variations may be implied by other classification schemes in common use. Attention is presently given to the discovery of the first EL5 chondrite, which breaks the EH3,4-EH5-EL6 sequence and indicates that the enstatite chondrites constitute the two discrete, isochemical metamorphic sequences EH3-5 and EL5-6.

Sears, D. W. G.↗
NASA NTRS1972

Algebraic, geometric, and stochastic aspects of genetic operators

Genetic algorithms for function optimization employ genetic operators patterned after those observed in search strategies employed in natural adaptation. Two of these operators, crossover and inversion, are interpreted in terms of their algebraic and geometric properties. Stochastic models of the operators are developed which are employed in Monte Carlo simulations of their behavior.

Foo, N. Y.↗
NASA NTRS1978

Ames interactive molecular model building system - A 3-D computer modelling system applied to the study of the origin of life

The investigation of specific interactions among biological molecules must take into consideration the stereochemistry of the structures. Thus, models of the molecules are essential for describing the spatial organization of potentially interacting groups, and estimations of conformation are required for a description of spatial organization. Both the function of visualizing molecules, and that of estimating conformation through calculations of energy, are part of the molecular modeling system described in the present paper. The potential uses of the system in investigating some aspects of the origin of life rest on the assumption that translation of conformation from genetic elements to catalytic elements would have been required for the development of the first replicating systems subject to the process of biological evolution.

Coeckelenbergh, Y.↗
NASA NTRS2014

Artificial Intelligence Based Control Power Optimization on Tailless Aircraft

Traditional methods of control allocation optimization have shown difficulties in exploiting the full potential of controlling large arrays of control devices on innovative air vehicles. Artificial neutral networks are inspired by biological nervous systems and neurocomputing has successfully been applied to a variety of complex optimization problems. This project investigates the potential of applying neurocomputing to the control allocation optimization problem of Hybrid Wing Body (HWB) aircraft concepts to minimize control power, hinge moments, and actuator forces, while keeping system weights within acceptable limits. The main objective of this project is to develop a proof-of-concept process suitable to demonstrate the potential of using neurocomputing for optimizing actuation power for aircraft featuring multiple independently actuated control surfaces. A Nastran aeroservoelastic finite element model is used to generate a learning database of hinge moment and actuation power characteristics for an array of flight conditions and control surface deflections. An artificial neural network incorporating a genetic algorithm then uses this training data to perform control allocation optimization for the investigated aircraft configuration. The phase I project showed that optimization results for the sum of required hinge moments are improved by more than 12% over the best Nastran solution by using the neural network optimization process.

Gern, Frank↗
NASA NTRS2002

A provisional regulatory gene network for specification of endomesoderm in the sea urchin embryo

We present the current form of a provisional DNA sequence-based regulatory gene network that explains in outline how endomesodermal specification in the sea urchin embryo is controlled. The model of the network is in a continuous process of revision and growth as new genes are added and new experimental results become available; see http://www.its.caltech.edu/~mirsky/endomeso.htm (End-mes Gene Network Update) for the latest version. The network contains over 40 genes at present, many newly uncovered in the course of this work, and most encoding DNA-binding transcriptional regulatory factors. The architecture of the network was approached initially by construction of a logic model that integrated the extensive experimental evidence now available on endomesoderm specification. The internal linkages between genes in the network have been determined functionally, by measurement of the effects of regulatory perturbations on the expression of all relevant genes in the network. Five kinds of perturbation have been applied: (1) use of morpholino antisense oligonucleotides targeted to many of the key regulatory genes in the network; (2) transformation of other regulatory factors into dominant repressors by construction of Engrailed repressor domain fusions; (3) ectopic expression of given regulatory factors, from genetic expression constructs and from injected mRNAs; (4) blockade of the beta-catenin/Tcf pathway by introduction of mRNA encoding the intracellular domain of cadherin; and (5) blockade of the Notch signaling pathway by introduction of mRNA encoding the extracellular domain of the Notch receptor. The network model predicts the cis-regulatory inputs that link each gene into the network. Therefore, its architecture is testable by cis-regulatory analysis. Strongylocentrotus purpuratus and Lytechinus variegatus genomic BAC recombinants that include a large number of the genes in the network have been sequenced and annotated. Tests of the cis-regulatory predictions of the model are greatly facilitated by interspecific computational sequence comparison, which affords a rapid identification of likely cis-regulatory elements in advance of experimental analysis. The network specifies genomically encoded regulatory processes between early cleavage and gastrula stages. These control the specification of the micromere lineage and of the initial veg(2) endomesodermal domain; the blastula-stage separation of the central veg(2) mesodermal domain (i.e., the secondary mesenchyme progenitor field) from the peripheral veg(2) endodermal domain; the stabilization of specification state within these domains; and activation of some downstream differentiation genes. Each of the temporal-spatial phases of specification is represented in a subelement of the network model, that treats regulatory events within the relevant embryonic nuclei at particular stages. (c) 2002 Elsevier Science (USA).

Non-NASA Center↗