The predictive information obtained by testing multiple software versions

Multiversion programming is a redundancy approach to developing highly reliable software. In applications of this method, two or more versions of a program are developed independently by different programmers and the versions are combined to form a redundant system. One variation of this approach consists of developing a set of n program versions and testing the versions to predict the failure probability of a particular program or a system formed from a subset of the programs. The precision that might be obtained, and also the effect of programmer variability if predictions are made over repetitions of the process of generating different program versions, are examined

Estimation in a discrete tail rate family of recapture sampling models

In the context of recapture sampling design for debugging experiments the problem of estimating the error or hitting rate of the faults remaining in a system is considered. Moment estimators are derived for a family of models in which the rate parameters are assumed proportional to the tail probabilities of a discrete distribution on the positive integers. The estimators are shown to be asymptotically normal and fully efficient. Their fixed sample properties are compared, through simulation, with those of the conditional maximum likelihood estimators

Genetics Analysis Workshop 16 Problem 2: tTe Framingham Heart Study Data

Genetic Analysis Workshop 16 (GAW16) Problem 2 presented data from the Framingham Heart Study (FHS), an observational, prospective study of risk factors for cardiovascular disease begun in 1948. Data have been collected in three generations of family participants in the study and the data presented for GAW16 included phenotype data from all three generations, with four examinations of data collected repeatedly for the first two generations. The trait data consisted of information on blood pressure, hypertension treatment, lipid levels, diabetes and blood glucose, smoking, alcohol consumed, weight, and coronary heart disease incidence. Additionally, genotype data obtained through a genome-wide scan (FHS SHARe) of 550,000 single-nucleotide polymorphisms from Affymetrix chips were included with the GAW16 data. The genotype data were also used for GAW16 Problem 3, where simulated phenotypes were generated using the actual FHS genotypes. These data served to provide investigators with a rich resource to study the behavior of genome-wide scans with longitudinally collected family data and to develop and apply new procedures.National Heart, Lung and Blood Institute (2 N01-HC-25195-06); National Institutes of Health (National Institute of General Medical Sciences R01 GM031575

New methods and results for quantification of lightning-aircraft electrodynamics

The NASA F-106 collected data on the rates of change of electromagnetic parameters on the aircraft surface during over 700 direct lightning strikes while penetrating thunderstorms at altitudes from 15,000 t0 40,000 ft (4,570 to 12,190 m). These in situ measurements provided the basis for the first statistical quantification of the lightning electromagnetic threat to aircraft appropriate for determining indirect lightning effects on aircraft. These data are used to update previous lightning criteria and standards developed over the years from ground-based measurements. The proposed standards will be the first which reflect actual aircraft responses measured at flight altitudes. Nonparametric maximum likelihood estimates of the distribution of the peak electromagnetic rates of change for consideration in the new standards are obtained based on peak recorder data for multiple-strike flights. The linear and nonlinear modeling techniques developed provide means to interpret and understand the direct-strike electromagnetic data acquired on the F-106. The reasonable results obtained with the models, compared with measured responses, provide increased confidence that the models may be credibly applied to other aircraft

Structural and functional analysis of critical amino acids in TMVI of the NHE1 isoform of the Na+/H+ exchanger

AbstractThe mammalian Na+/H+ exchanger isoform 1 (NHE1) resides on the plasma membrane and exchanges one intracellular H+ for one extracellular Na+. It maintains intracellular pH and regulates cell volume, and cell functions including growth and cell differentiation. Previous structural and functional studies on TMVI revealed several amino acids that are potentially pore lining. We examined these and other critical residues by site-directed mutagenesis substituting Asn227→Ala, Asp, Arg; Ile233→Ala; Leu243→Ala; Glu247→Asp, Gln; Glu248→Asp, Gln. Mutant NHE1 proteins were characterized in AP-1 cells, which do not express endogenous NHE1. All the TMVI critical amino acids were highly sensitive to substitution and changes often lead to a dysfunctional protein. Mutations of Asn227→Ala, Asp, Arg; Ile233→Ala; Leu243→Ala; Glu247→Asp; Glu248→Gln yielded significant reduction in NHE1 activity. Mutants of Asn227 demonstrated defects in protein expression, targeting and activity. Substituting Asn227→Arg and Ile233→Ala decreased the surface localization and expression of NHE1 respectively. The pore lining amino acids Ile233 and Leu243 were both essential for activity. Glu247 was not essential, but the size of the residue at this location was important while the charge on residue Glu248 was more critical to NHE1 function. Limited trypsin digestion on Leu243→Ala and Glu248→Gln revealed that they had increased susceptibility to proteolytic attack, indicating an alteration in protein conformation. Modeling of TMVI with TMXI suggests that these TM segments form part of the critical fold of NHE1 with Ile233 and Leu465 of TMXI forming a critical part of the extracellular facing ion conductance pathway

Karst of Western Cuba: Observations, Geomorphology, and Diagenesis

In Cuba, we observed many karst features in a variety of hydrogeologic settings. These hy-drogeologic settings occur in close proximity only because of the complex tectonic history of the is-land. We observed caves within rocks ranging from Pleistocene to Jurassic, and representing a range of diagenetic ages from eogenetic to teloge-netic. Our observations are from the western one-third of the island of Cuba; however, we believe they are representative of hydrogeologic settings found throughout the island

A broadly applicable method to characterize large DNA viruses and adenoviruses based on the DNA polymerase gene

BACKGROUND: Many viral pathogens are poorly characterized, are difficult to culture or reagents are lacking for confirmatory diagnoses. We have developed and tested a robust assay for detecting and characterizing large DNA viruses and adenoviruses. The assay is based on the use of degenerate PCR to target a gene common to these viruses, the DNA polymerase, and sequencing the products. RESULTS: We evaluated our method by applying it to fowl adenovirus isolates, catfish herpesvirus isolates, and largemouth bass ranavirus (iridovirus) from cell culture and lymphocystis disease virus (iridovirus) and avian poxvirus from tissue. All viruses with the exception of avian poxvirus produced the expected product. After optimization of extraction procedures, and after designing and applying an additional primer we were able to produce polymerase gene product from the avian poxvirus genome. The sequence data that we obtained demonstrated the simplicity and potential of the method for routine use in characterizing large DNA viruses. The adenovirus samples were demonstrated to represent 2 types of fowl adenovirus, fowl adenovirus 1 and an uncharacterized avian adenovirus most similar to fowl adenovirus 9. The herpesvirus isolate from blue catfish was shown to be similar to channel catfish virus (Ictalurid herpesvirus 1). The case isolate of largemouth bass ranavirus was shown to exactly match the type specimen and both were similar to tiger frog virus and frog virus 3. The lymphocystis disease virus isolate from largemouth bass was shown to be related but distinct from the two previously characterized lymphocystis disease virus isolates suggesting that it may represent a distinct lymphocystis disease virus species. CONCLUSION: The method developed is rapid and broadly applicable to cell culture isolates and infected tissues. Targeting a specific gene for in the large DNA viruses and adenoviruses provide a common reference for grouping the newly identified viruses according to relatedness to sequences of reference viruses and the submission of the sequence data to GenBank will build the database to make the BLAST analysis a valuable resource readily accessible by most diagnostic laboratories. We demonstrated the utility of this assay on viruses that infect fish and birds. These hosts are phylogenetically distant from mammals yet, sequence data suggests that the assay would work equally as well on mammalian counterparts of these groups of viruses. Furthermore, we demonstrated that obtaining genetic information on routine diagnostic samples has great potential for revealing new virus strains and suggesting the presence of new species

An experimental evaluation of software redundancy as a strategy for improving reliability

The strategy of using multiple versions of independently developed software as a means to tolerate residual software design faults is suggested by the success of hardware redundancy for tolerating hardware failures. Although, as generally accepted, the independence of hardware failures resulting from physical wearout can lead to substantial increases in reliability for redundant hardware structures, a similar conclusion is not immediate for software. The degree to which design faults are manifested as independent failures determines the effectiveness of redundancy as a method for improving software reliability. Interest in multi-version software centers on whether it provides an adequate measure of increased reliability to warrant its use in critical applications. The effectiveness of multi-version software is studied by comparing estimates of the failure probabilities of these systems with the failure probabilities of single versions. The estimates are obtained under a model of dependent failures and compared with estimates obtained when failures are assumed to be independent. The experimental results are based on twenty versions of an aerospace application developed and certified by sixty programmers from four universities. Descriptions of the application, development and certification processes, and operational evaluation are given together with an analysis of the twenty versions

Review Article: Molecular Beam Epitaxy of Lattice-Matched InAlAs and InGaAs Layers on InP (111)A, (111)B, and (110)

For more than 50 years, research into III–V compound semiconductors has focused almost exclusively on materials grown on (001)-oriented substrates. In part, this is due to the relative ease with which III–Vs can be grown on (001) surfaces. However, in recent years, a number of key technologies have emerged that could be realized, or vastly improved, by the ability to also grow high-quality III–Vs on (111)- or (110)-oriented substrates These applications include: next-generation field-effect transistors, novel quantum dots, entangled photon emitters, spintronics, topological insulators, and transition metal dichalcogenides. The first purpose of this paper is to present a comprehensive review of the literature concerning growth by molecular beam epitaxy (MBE) of III–Vs on (111) and (110) substrates. The second is to describe our recent experimental findings on the growth, morphology, electrical, and optical properties of layers grown on non-(001) InP wafers. Taking InP(111)A, InP(111)B, and InP(110) substrates in turn, the authors systematically discuss growth of both In0.52Al0.48As and In0.53Ga0.47As on these surfaces. For each material system, the authors identify the main challenges for growth, and the key growth parameter–property relationships, trends, and interdependencies. The authors conclude with a section summarizing the MBE conditions needed to optimize the structural, optical and electrical properties of GaAs, InAlAs and InGaAs grown with (111) and (110) orientations. In most cases, the MBE growth parameters the authors recommend will enable the reader to grow high-quality material on these increasingly important non-(001) surfaces, paving the way for exciting technological advances

Conserved Motifs and Prediction of Regulatory Modules in Caenorhabditis elegans

Transcriptional regulation, a primary mechanism for controlling the development of multicellular organisms, is carried out by transcription factors (TFs) that recognize and bind to their cognate binding sites. In Caenorhabditis elegans, our knowledge of which genes are regulated by which TFs, through binding to specific sites, is still very limited. To expand our knowledge about the C. elegans regulatory network, we performed a comprehensive analysis of the C. elegans, Caenorhabditis briggsae, and Caenorhabditis remanei genomes to identify regulatory elements that are conserved in all genomes. Our analysis identified 4959 elements that are significantly conserved across the genomes and that each occur multiple times within each genome, both hallmarks of functional regulatory sites. Our motifs show significant matches to known core promoter elements, TF binding sites, splice sites, and poly-A signals as well as many putative regulatory sites. Many of the motifs are significantly correlated with various types of experimental data, including gene expression patterns, tissue-specific expression patterns, and binding site location analysis as well as enrichment in specific functional classes of genes. Many can also be significantly associated with specific TFs. Combinations of motif occurrences allow us to predict the location of cis-regulatory modules and we show that many of them significantly overlap experimentally determined enhancers. We provide access to the predicted binding sites, their associated motifs, and the predicted cis-regulatory modules across the whole genome through a web-accessible database and as tracks for genome browsers