Design for validation: An approach to systems validation

Every complex system built is validated in some manner. Computer validation begins with review of the system design. As systems became too complicated for one person to review, validation began to rely on the application of adhoc methods by many individuals. As the cost of the changes mounted and the expense of failure increased, more organized procedures became essential. Attempts at devising and carrying out those procedures showed that validation is indeed a difficult technical problem. The successful transformation of the validation process into a systematic series of formally sound, integrated steps is necessary if the liability inherent in the future digita-system-based avionic and space systems is to be minimized. A suggested framework and timetable for the transformtion are presented. Basic working definitions of two pivotal ideas (validation and system life-cyle) are provided and show how the two concepts interact. Many examples are given of past and present validation activities by NASA and others. A conceptual framework is presented for the validation process. Finally, important areas are listed for ongoing development of the validation process at NASA Langley Research Center

In Vitro Model of Essential Fatty Acid Deficiency

The polyunsaturated fatty acids linoleic acid (18:2, n-6) and arachidonic acid (20:4, n-6) are essential for normal skin function and structure, both as eicosanoid precursors and as components of lipids forming cell membranes. Adult human keratinocytes grow optimally in serum-free medium (MCDB 153) that contains no fatty acids. These keratinocytes expand rapidly and produce normal epidermis upon in vivo grafting. Analysis of lipid extracts of epidermis and of cultured keratinocytes was done to determine the fatty acid composition of cells grown in essential fatty acid (EFA) – deficient medium. Gas chromatography and high-performance liquid chromatography analyses were done of the fatty acids in the entire cell and in a thin-layer chromatography separated fraction containing those lipids that form cellular membranes. Comparison of snap-frozen epidermis and epidermal basal cell suspensions to passage 1 to 4 cultures shows that the cells are in an extreme essential fatty acid-deficient state by the first passage. The amount of the saturated fatty adds 16:0, 18:0, and 14:0 is unchanged by culture. The polyunsaturated fatty acids are found to be significantly decreased, the cells balancing their lack with a significant increase in the relative abundance of the monounsaturated fatty acids, 18:1 and 16:1. Greater than 85–90% of the fatty acids was found in lipids associated with membranes and no unusual fatty acids were detected. Because the serum-free medium is fatty acid free and the cells cannot synthesize essential fatty acids, the rapid division of the cells results in the predominance of an extreme EFA-deficient cell type. The essential fatty acid – deficient keratinocyte is an excellent adult, normal epidermal cell model that can be used to study EFA deficiency and the effect of the eicosanoid and fatty acids on cell function and structure

The Kepler Follow-up Observation Program

The Kepler Mission was launched on March 6, 2009 to perform a photometric survey of more than 100,000 dwarf stars to search for terrestrial-size planets with the transit technique. Follow-up observations of planetary candidates identified by detection of transit-like events are needed both for identification of astrophysical phenomena that mimic planetary transits and for characterization of the true planets and planetary systems found by Kepler. We have developed techniques and protocols for detection of false planetary transits and are currently conducting observations on 177 Kepler targets that have been selected for follow-up. A preliminary estimate indicates that between 24% and 62% of planetary candidates selected for follow-up will turn out to be true planets.Comment: 12 pages, submitted to the Astrophysical Journal Letter

Overly honest data repository development

After a year of development, the library at the University of Illinois at Urbana-Champaign has launched a repository, called the Illinois Data Bank (https://databank.illinois.edu/), to provide Illinois researchers with a free, self-serve publishing platform that centralizes, preserves, and provides persistent and reliable access to Illinois research data. This article presents a holistic view of development by discussing our overarching technical, policy, and interface strategies. By openly presenting our design decisions, the rationales behind those decisions, and associated challenges this paper aims to contribute to the library community’s work to develop repository services that meet growing data preservation and sharing needs.Ope

Quarter field resonance and integer-spin/half-spin interaction in the EPR of Thermus thermophilus ferrodoxin. Possible new fingerprints for three iron clusters

We describe two new characteristics of the EPR of the seven-iron containing ferrodoxin from Thermus thermophilus. First, the reduced state of the 3Fe center, which has traditionally been considered to be EPR-silent, has been found to exhibit [Delta]m = 4 transition, which is unique for Fe-S centers. This signal is similar to that of high-spin Fe2+-EDTA and supports the suggestion that the ground electronic state of the 3Fe cluster is S = 2. Second, we have recorded the EPR spectrum of the fully reduced protein at 9 and 15 GHz and found that changes occur in the signal which are consistent with a weak electronic spin-spin interaction between the [4Fe-4S]+ (S = 1/2) and the reduced 3Fe center. A theoretical explanation is given for the observation of interaction signals with constant effective g values.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25700/1/0000254.pd

Quantitative numerical analysis of g strain in the EPR of distributed systems and its importance for multicenter metalloproteins

A method for simulation of inhomogeneously broadened EPR of metallo-proteins based on recent theoretical advances is surveyed critically in terms of efficiency and accuracy. From the quality of the experimental spectrum, minimal boundary conditions are established for the spatial integration over the g-strained polycrystal. Computational efficiency is achieved by generating the spectrum as an absorption in g space, reducing the number of molecular orientations computed by filtering mosaic artifacts from the Fourier-transformed spectrum, and generating the lineshape due to g strain from a tabulated distribution function. These techniques provide a reduction in computation time by some two orders of magnitude and make the data analysis of EPR of metalloproteins by minimization practical. The resulting simulation program is superior to current approaches in that it does not introduce artifactual multiplicities, and it is expected to require a smaller number of fitting parameters for the quantitative analysis of most cases. To illustrate its potential, the method is applied to EPR data from the iron-sulfur centers in NADH:Q oxidoreductase and in QH2:ferricytochrome c oxidoreductase, clarifying existing controversies on the stoichiometries of these centers.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25873/1/0000436.pd

A statistical theory for powder EPR in distributed systems

A statistical interpretation is presented for "g strain," the dominant broadening in the EPR spectra of metallo-proteins. The direct cause of g strain is described by a three-dimensional tensor p, whose principal elements are random variables. The p and g tensors are not necessarily colinear. The observed EPR linewidth results from a distribution in the effective g value as a function of (a) the joint distribution function of the elements of the p tensor and (b) the spatial relationship between the two principal axis systems involved. The theory is reformulated in terms of matrices that facilitate a direct comparison with earlier work. Two previous theories of g strain represent different subsets of the general theory, namely, the case of zero rotation between axis systems and the case with nonzero rotation and full correlation between elements of the p tensor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25870/1/0000433.pd

Kepler-16: A Transiting Circumbinary Planet

We report the detection of a planet whose orbit surrounds a pair of low-mass stars. Data from the Kepler spacecraft reveal transits of the planet across both stars, in addition to the mutual eclipses of the stars, giving precise constraints on the absolute dimensions of all three bodies. The planet is comparable to Saturn in mass and size, and is on a nearly circular 229-day orbit around its two parent stars. The eclipsing stars are 20% and 69% as massive as the sun, and have an eccentric 41-day orbit. The motions of all three bodies are confined to within 0.5 degree of a single plane, suggesting that the planet formed within a circumbinary disk.Comment: Science, in press; for supplemental material see http://www.sciencemag.org/content/suppl/2011/09/14/333.6049.1602.DC1/1210923.Doyle.SOM.pd