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DOE OSTI2021

Diverse ATPase Proteins in Mobilomes Constitute a Large Potential Sink for Prokaryotic Host ATP

Prokaryote mobilome genomes rely on host machineries for survival and replication. Given that mobile genetic elements (MGEs) derive their energy from host cells, we investigated the diversity of ATP-utilizing proteins in MGE genomes to determine whether they might be associated with proteins that could suppress related host proteins that consume energy. A comprehensive search of 353 huge phage genomes revealed that up to 9% of the proteins have ATPase domains. For example, ATPase proteins constitute ~3% of the genomes of Lak phages with ~550 kbp genomes that occur in the microbiomes of humans and other animals. Statistical analysis shows the number of ATPase proteins increases linearly with genome length, consistent with a large sink for host ATP during replication of megaphages. Using metagenomic data from diverse environments, we found 505 mobilome proteins with ATPase domains fused to diverse functional domains. Among these composite ATPase proteins, 61.6% have known functional domains that could contribute to host energy diversion during the mobilome infection cycle. As many have domains that are known to interact with nucleic acids and proteins, we infer that numerous ATPase proteins are used during replication and for protection from host immune systems. We found a set of uncharacterized ATPase proteins with nuclease and protease activities, displaying unique domain architectures that are energy intensive based on the presence of multiple ATPase domains. In many cases, these composite ATPase proteins genomically co-localize with small proteins in genomic contexts that are reminiscent of toxin-antitoxin systems and phage helicase-antibacterial helicase systems. Small proteins that function as inhibitors may be a common strategy for control of cellular processes, thus could inspire future biochemical experiments for the development of new nucleic acid and protein manipulation tools, with diverse biotechnological applications.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS1983

Large numbers hypothesis. II - Electromagnetic radiation

This paper develops the theory of electromagnetic radiation in the units covariant formalism incorporating Dirac's large numbers hypothesis (LNH). A direct field-to-particle technique is used to obtain the photon propagation equation which explicitly involves the photon replication rate. This replication rate is fixed uniquely by requiring that the form of a free-photon distribution function be preserved, as required by the 2.7 K cosmic radiation. One finds that with this particular photon replication rate the units covariant formalism developed in Paper I actually predicts that the ratio of photon number to proton number in the universe varies as t to the 1/4, precisely in accord with LNH. The cosmological red-shift law is also derived and it is shown to differ considerably from the standard form of (nu)(R) - const.

Adams, P. J.↗

NASA NTRS1986

Cooperation of catalysts and templates

In order to understand how self-reproducing molecules could have originated on the primitive Earth or extraterrestrial bodies, it would be useful to find laboratory models of simple molecules which are able to carry out processes of catalysis and templating. Furthermore, it may be anticipated that systems in which several components are acting cooperatively to catalyze each other's synthesis will have different behavior with respect to natural selection than those of purely replicating systems. As the major focus of this work, laboratory models are devised to study the influence of short peptide catalysts on template reactions which produce oligonucleotides or additional peptides. Such catalysts could have been the earliest protoenzymes of selective advantage produced by replicating oligonucleotides. Since this is a complex problem, simpler systems are also studied which embody only one aspect at a time, such as peptide formation with and without a template, peptide catalysis of nontemplated peptide synthesis, and model reactions for replication of the type pioneered by Orgel.

White, D. H.↗

NASA NTRS1990

Formal design and verification of a reliable computing platform for real-time control. Phase 1: Results

A high-level design is presented for a reliable computing platform for real-time control applications. Design tradeoffs and analyses related to the development of the fault-tolerant computing platform are discussed. The architecture is formalized and shown to satisfy a key correctness property. The reliable computing platform uses replicated processors and majority voting to achieve fault tolerance. Under the assumption of a majority of processors working in each frame, it is shown that the replicated system computes the same results as a single processor system not subject to failures. Sufficient conditions are obtained to establish that the replicated system recovers from transient faults within a bounded amount of time. Three different voting schemes are examined and proved to satisfy the bounded recovery time conditions.

Divito, Ben L.↗

NASA NTRS1990

Surrogate oracles, generalized dependency and simpler models

Software reliability models require the sequence of interfailure times from the debugging process as input. It was previously illustrated that using data from replicated debugging could greatly improve reliability predictions. However, inexpensive replication of the debugging process requires the existence of a cheap, fast error detector. Laboratory experiments can be designed around a gold version which is used as an oracle or around an n-version error detector. Unfortunately, software developers can not be expected to have an oracle or to bear the expense of n-versions. A generic technique is being investigated for approximating replicated data by using the partially debugged software as a difference detector. It is believed that the failure rate of each fault has significant dependence on the presence or absence of other faults. Thus, in order to discuss a failure rate for a known fault, the presence or absence of each of the other known faults needs to be specified. Also, in simpler models which use shorter input sequences without sacrificing accuracy are of interest. In fact, a possible gain in performance is conjectured. To investigate these propositions, NASA computers running LIC (RTI) versions are used to generate data. This data will be used to label the debugging graph associated with each version. These labeled graphs will be used to test the utility of a surrogate oracle, to analyze the dependent nature of fault failure rates and to explore the feasibility of reliability models which use the data of only the most recent failures.

Wilson, Larry↗

NASA NTRS1991

Measuring the effects of distributed database models on transaction availability measures

Data distribution, data replication, and system reliability are key factors in determining the availability measures for transactions in distributed database systems. In order to simplify the evaluation of these measures, database designers and researchers tend to make unrealistic assumptions about these factors. Here, the effect of such assumptions on the computational complexity and accuracy of such evaluations is investigated. A database system is represented with five parameters related to the above factors. Probabilistic analysis is employed to evaluate the availability of read-one and read-write transactions. Both the read-one/write-all and the majority-read/majority-write replication control policies are considered. It is concluded that transaction availability is more sensitive to variations in degrees of replication, less sensitive to data distribution, and insensitive to reliability variations in a heterogeneous system. The computational complexity of the evaluations is found to be mainly determined by the chosen distributed database model, while the accuracy of the results are not so much dependent on the models.

Mukkamala, Ravi↗

NASA NTRS1991

Response of vegetation indices to changes in three measures of leaf water stress

The responses of vegetation indices to changes in water stress were evaluated in two separate laboratory experiments. In one experiment the normalized difference vegetation index (NDVI), the near-IR to red ratio (near-IR/red), the Infrared Index (II), and the Moisture Stress Index (MSI) were more highly correlated to leaf water potential in lodgepole pine branches than were the Leaf Water Content Index (LWCI), the mid-IR ratio (Mid-IR), or any of the single Thematic Mapper (TM) bands. In the other experiment, these six indices and the TM Tasseled Cap brightness, greenness, and wetness indices responded to changes in leaf relative water content (RWC) differently than they responded to changes in leaf water content (WC) of three plant species, and the responses were dependent on how experimental replicates were pooled. With no pooling, the LWCI was the most highly correlated index to both RWC and WC among replications, followed by the II, MSI, and wetness. Only the LWCI was highly correlated to RWC and WC when replications were pooled within species. With among species pooling the LWCI was the only index highly correlated with RWC, while the II, MSI, Mid-IR, and wetness were most highly correlated with WC.

Cohen, Warren B.↗

NASA NTRS1992

Results of Labscale Hybrid Rocket Motor investigation

This work was performed to establish a labscale hybrid rocket motor test and evaluation capability at NASA Marshall Space Flight Center. The scope included activation of a Labscale Hybrid Motor, determination of baseline burning rates for PMMA fuel, and replication of pressure oscillations for HTPB fuel. The 0.820-in.-diam port, 10-in.-long fuel grains were burned for two seconds with gaseous oxygen. PMMA fuels were tested at oxygen fluxes from 0.047 lbm/sec sq in. to 0.378 lbm/sec sq in., and the HTPB fuel was evaluated at 0.378 lbm/sec sq in. The results showed that the labscale hybrid motor replicated previously reported PMMA fuel regression rates. The results also replicated low-frequency (less than 100 Hz) pressure oscillations that have been observed for HTPB fuels. These results establish the Labscale Hybrid Motor facility at MSFC.

Greiner, B.↗

NASA NTRS1994

Surface roughness measurements

The Optics Division is currently in the research phase of producing grazing-incidence mirrors to be used in x-ray detector applications. The traditional method of construction involves labor-intensive glass grinding. This also culminates in a relatively heavy mirror. For lower resolution applications, the mirrors may be of a replicated design which involves milling a mandrel as a negative of the final shape and electroplating the cylindrical mirror onto it. The mirror is then separated from the mandrel by cooling. The mandrel will shrink more than the 'shell' (mirror) allowing it to be pulled from the mandrel. Ulmer (2) describes this technique and its variations in more detail. To date, several mirrors have been tested at MSFC by the Optical Fabrication Branch by focusing x-ray energy onto a detector with limited success. Little is known about the surface roughness of the actual mirror. Hence, the attempt to gather data on these surfaces. The test involves profiling the surface of a sample, replicating the surface as described above, and then profiling the replicated surface.

Howard, Thomas G.↗

NASA NTRS1994

Role of small ice crystals in radiative properties of cirrus: A case study, FIRE II, November 22, 1991

Aircraft observations of cirrus cloud were made near Coffeyville, Kansas, during November 1991 as part of the First ISCCP Regional Experiment II (FIRE II) project. Cloud ice particle spectra measurements were made using both a particle measuring system (PMS) 2DC probe and an ice particle replicator. Particles larger than 200 micrometers were column rosettes. The replicator shows the presence of large numbers of ice crystals smaller than 66 micrometers (two PMS size bins) that are not recorded by the PMS 2DC probe. Calculations based on the replicator data of the geometrical blocked area and absorption cross section of the cloud per unit volume show that small particles can contribute significantly to and sometimes dominate both the solar extinction and the infrared emission. Intercomparison is made of the ice particle size, area, and mass distributions determined by these different instruments. Power law relationships for area occluded by a crystal as a function of crystal maximum dimension were computed from the PMS 2DC data. The wavelength-dependent infrared absorption cross section per volume was computed using a simple model based on anomalous diffraction and area and mass dimensional relationships for the ice crystals.

Arnott, W. Patrick↗

NASA NTRS1993

The limits of template-directed synthesis with nucleoside-5'-phosphoro(2-methyl)imidazolides

In earler work we have shown that C-rich templates containing isolated A, T or G residues and short oligo(G) sequences can be copied effectively using nucleoside-5'-phosphoro(2-methyl)imidazolides as substrates. We now show that isolated A or T residues within an oligo(G) sequence are a complete block to copying and that an isolated C residue is copied inefficiently. Replication is possible only if there are two complementary oligonucleotides each of which acts as a template to facilitate the synthesis of the other. We emphasize the severity of the problems that need to be overcome to make possible non-enzymatic replication in homogeneous aqueous solution. We conclude that an efficient catalyst was involved in the origin of polynucleotide replication.

Hill, Aubrey R.↗

NASA NTRS1995

Part A: Cirrus ice crystal nucleation and growth. Part B: Automated analysis of aircraft ice particle data

Specific measurement of cirrus crystals by aircraft and temperature modified CN are used to specify measurements necessary to provide a basis for a conceptual model of cirrus particle formation. Key to this is the ability to measure the complete spectrum of particles at cirrus levels. The most difficult regions for such measurement is from a few to 100 microns, and uses a replicator. The details of the system to automate replicator data analysis are given, together with an example case study of the system provided from a cirrus cloud in FIRE 2, with particles detectable by replicator and FSSP, but not 2DC.

Arnott, William P.↗

NASA NTRS1994

Management of fluorescent lamps in controlled environment chambers

Management of fluorescent lights is recommended to (1) maintain uniformity of light intensity over time and (2) permit reproducibility of lighting conditions during experimental replications. At the McGill Phytotron, the lighting intensity can be controlled to desired level because any individual pair of the 40 lamps in each chamber can be set to be 'on' at any particular time. A lamp canopy service history is maintained for each experiment permitting accurate replication of lighting conditions for subsequent replicate trials.

Romer, Mark↗

NASA NTRS1993

The Limits of Template-Directed Synthesis with Nucleoside-5'-Phosphoro(2-Methyl) Imidazolides

In earlier work we have shown that C-rich templates containing isolated A, T or G residues and short oligo(G) sequences can be copied effectively using nucleoside-5'-phosphoro(2-methyl)imidazolides as substrates. We now show that isolated A or T residues within an oligo(G) sequence are a complete block to copying and that an isolated C residue is copied inefficiently. Replication is possible only if there are two complementary oligonucleotides each of which acts as a template to facilitate the synthesis of the other. We emphasize the severity of the problems that need to be overcome to make possible non-enzymatic replication in homogeneous aqueous solution. We conclude that an efficient catalyst was involved in the origin of polynucleotide replication.

Hill, Aubrey R., Jr.↗

NASA NTRS1999

Using Experiments to Build a Body of Knowledge

Experimentation in software engineering is important but difficult. One reason it is so difficult is that there are a large number of context variables, and so creating a cohesive understanding of experimental results requires a mechanism for motivating studies and integrating results. This paper argues for the necessity of a framework for organizing sets of related studies. With such a framework, experiments can be viewed as part of common families of studies, rather than being isolated events. Common families of studies can contribute to important and relevant hypotheses that may not be suggested by individual experiments. A framework also facilitates building knowledge in an incremental manner through the replication of experiments within families of studies. Building knowledge in this way requires a community of researchers that can replicate studies, vary context variables, and build abstract models that represent the common observations about the discipline. This paper also presents guidelines for lab packages, meant to encourage and support replications, that encapsulate materials, methods, and experiences concerning software engineering experiments.

Basili, Victor↗

NASA NTRS1991

Attempted nonenzymatic template-directed oligomerizations on a polyadenylic acid template: implications for the nature of the first genetic material

Previous attempts to produce nonenzymatic template-directed oligomerizations of activated pyrimidines on polypurine templates have been unsuccessful. The only efficient reactions are those where the template is composed primarily of pyrimidines, especially cytosine. Because molecular evolution requires that a synthesized daughter polynucleotide be capable of acting as a template for the synthesis of the original polynucleotide, the one-way replication achieved thus far is inadequate to initiate an evolving system. Several uracil analogs were used in this investigation in order to search for possible replacements for uracil. The monomers used in this investigation were the imidazolides of UMP, xanthosine 5'-monophosphate, the bis-monophosphates of the acyclic nucleosides of uracil, and 2,4-quinazolinedione. The concentrations of various salts, buffers, pH, and temperature were among the different variables investigated in attempts to find conditions that would permit template-directed oligomerizations. Although the different monomers in this study demonstrated varying abilities to form very short oligomers, we were unable to detect any enhancement of this oligomerization that could be attributed to the poly(A) template. Although special conditions might be found that would allow purine-rich templates to work, these reactions cannot be considered robust. The results of our experiments suggest that pyrimidines were not part of the original replicating system on the primitive Earth. It has already been shown that ribose is an unlikely component of the first replicating systems, and we now suggest that phosphate was absent as well. This is due to the low solubility of phosphate in the present ocean (3 x 10(-6) M), as well as the difficulty of prebiotic activation of phosphates.

Non-NASA Center↗

NASA NTRS1991

High Level Design Proof of a Reliable Computing Platform

An architecture for fault-tolerant computing is formalized and shown to satisfy a key correctness property. The reliable computing platform uses replicated processors and majority voting to achieve fault tolerance. Under the assumption of a majority of processors working in each frame, we show that the replicated system computes the same results as a single processor system not subject to failures. Sufficient conditions are obtained to establish that the replicated system recovers from transient faults within a bounded amount of time. Three different voting schemes are examined and proved to satisfy the bounded recovery time conditions.

DiVito, Ben L.↗

NASA NTRS1999

Cell and molecular biology of simian virus 40: implications for human infections and disease

Simian virus 40 (SV40), a polyomavirus of rhesus macaque origin, was discovered in 1960 as a contaminant of polio vaccines that were distributed to millions of people from 1955 through early 1963. SV40 is a potent DNA tumor virus that induces tumors in rodents and transforms many types of cells in culture, including those of human origin. This virus has been a favored laboratory model for mechanistic studies of molecular processes in eukaryotic cells and of cellular transformation. The viral replication protein, named large T antigen (T-ag), is also the viral oncoprotein. There is a single serotype of SV40, but multiple strains of virus exist that are distinguishable by nucleotide differences in the regulatory region of the viral genome and in the part of the T-ag gene that encodes the protein's carboxyl terminus. Natural infections in monkeys by SV40 are usually benign but may become pathogenic in immunocompromised animals, and multiple tissues can be infected. SV40 can replicate in certain types of simian and human cells. SV40-neutralizing antibodies have been detected in individuals not exposed to contaminated polio vaccines. SV40 DNA has been identified in some normal human tissues, and there are accumulating reports of detection of SV40 DNA and/or T-ag in a variety of human tumors. This review presents aspects of replication and cell transformation by SV40 and considers their implications for human infections and disease pathogenesis by the virus. Critical assessment of virologic and epidemiologic data suggests a probable causative role for SV40 in certain human cancers, but additional studies are necessary to prove etiology.

Review↗