Steps to an advanced Ada programming environment

Conceptual simplicity, tight coupling of tools, and effective support of host-target software development will characterize advanced Ada programming support environments. Several important principles have been demonstrated in the Arcturus system, including template-assisted Ada editing, command completion using Ada as a command language, and combining the advantages of interpretation and compliation. Other principles, relating to analysis, testing, and debugging of concurrent Ada programs, have appeared in other contexts. This paper discusses several of these topics, considers how they can be integrated, and argues for their inclusion in an environment appropriate for software development in the late 1980's

Inferring HIV escape rates from multi-locus genotype data

Cytotoxic T-lymphocytes (CTLs) recognize viral protein fragments displayed by major histocompatibility complex (MHC) molecules on the surface of virally infected cells and generate an anti-viral response that can kill the infected cells. Virus variants whose protein fragments are not efficiently presented on infected cells or whose fragments are presented but not recognized by CTLs therefore have a competitive advantage and spread rapidly through the population. We present a method that allows a more robust estimation of these escape rates from serially sampled sequence data. The proposed method accounts for competition between multiple escapes by explicitly modeling the accumulation of escape mutations and the stochastic effects of rare multiple mutants. Applying our method to serially sampled HIV sequence data, we estimate rates of HIV escape that are substantially larger than those previously reported. The method can be extended to complex escapes that require compensatory mutations. We expect our method to be applicable in other contexts such as cancer evolution where time series data is also available

Coalescence, genetic diversity in sexual populations under selection

In sexual populations, selection operates neither on the whole genome, which is repeatedly taken apart and reassembled by recombination, nor on individual alleles that are tightly linked to the chromosomal neighborhood. The resulting interference between linked alleles reduces the efficiency of selection and distorts patterns of genetic diversity. Inference of evolutionary history from diversity shaped by linked selection requires an understanding of these patterns. Here, we present a simple but powerful scaling analysis identifying the unit of selection as the genomic "linkage block" with a characteristic length determined in a self-consistent manner by the condition that the rate of recombination within the block is comparable to the fitness differences between different alleles of the block. We find that an asexual model with the strength of selection tuned to that of the linkage block provides an excellent description of genetic diversity and the site frequency spectra when compared to computer simulations. This linkage block approximation is accurate for the entire spectrum of strength of selection and is particularly powerful in scenarios with many weakly selected loci. The latter limit allows us to characterize coalescence, genetic diversity, and the speed of adaptation in the infinitesimal model of quantitative genetics

Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain

Background: IPS-1/MAVS/VISA/Cardif is an adaptor protein that plays a crucial role in the induction of interferons in response to viral infection. In the initial stage of the intracellular antiviral response two RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-association gene 5 (MDA5), are independently able to bind viral RNA in the cytoplasm. The 62 kDa protein IPS-1/MAVS/VISA/Cardif contains an N-terminal caspase activation and recruitment (CARD) domain that associates with the CARD regions of RIG-I and MDA5, ultimately leading to the induction of type I interferons. As a first step towards understanding the molecular basis of this important adaptor protein we have undertaken structural studies of the IPS-1 MAVS/VISA/Cardif CARD region. Results: The crystal structure of human IPS-1/MAVS/VISA/Cardif CARD has been determined to 2.1 angstrom resolution. The protein was expressed and crystallized as a maltose-binding protein (MBP) fusion protein. The MBP and IPS-1 components each form a distinct domain within the structure. IPS-1/MAVS/VISA/Cardif CARD adopts a characteristic six-helix bundle with a Greek-key topology and, in common with a number of other known CARD structures, contains two major polar surfaces on opposite sides of the molecule. One face has a surface-exposed, disordered tryptophan residue that may explain the poor solubility of untagged expression constructs. Conclusion: The IPS-1/MAVS/VISA/Cardif CARD domain adopts the classic CARD fold with an asymmetric surface charge distribution that is typical of CARD domains involved in homotypic protein-protein interactions. The location of the two polar areas on IPS-1/MAVS/VISA/Cardif CARD suggest possible types of associations that this domain makes with the two CARD domains of MDA5 or RIG-I. The N-terminal CARD domains of RIG-I and MDA5 share greatest sequence similarity with IPS-1/MAVS/VISA/Cardif CARD and this has allowed modelling of their structures. These models show a very different charge profile for the equivalent surfaces compared to IPS-1/MAVS/VISA/Cardif CARD.Publisher PDFPeer reviewe

The dose-response relationship between training load and aerobic fitness in academy rugby union players

© 2018 Human Kinetics, Inc. Purpose: To identify the dose-response relationship between measures of training load (TL) and changes in aerobic fitness in academy rugby union players. Method: Training data from 10 academy rugby union players were collected during a 6-wk in-season period. Participants completed a lactate-threshold test that was used to assess VO 2 max, velocity at VO 2 max, velocity at 2 mmol/L (lactate threshold), and velocity at 4 mmol/L (onset of lactate accumulation; vOBLA) as measures of aerobic fitness. Internal-TL measures calculated were Banister training impulse (bTRIMP), Edwards TRIMP, Lucia TRIMP, individualized TRIMP (iTRIMP), and session RPE (sRPE). External-TL measures calculated were total distance, PlayerLoad™, high-speed distance > 15 km/h, very-high-speed distance > 18 km/h, and individualized high-speed distance based on each player’s vOBLA. Results: A second-order-regression (quadratic) analysis found that bTRIMP (R 2 = .78, P = .005) explained 78% of the variance and iTRIMP (R 2 = .55, P = .063) explained 55% of the variance in changes in VO 2 max. All other HR-based internal-TL measures and sRPE explained less than 40% of variance with fitness changes. External TL explained less than 42% of variance with fitness changes. Conclusions: In rugby players, bTRIMP and iTRIMP display a curvilinear dose-response relationship with changes in maximal aerobic fitness

Assessment of North Dakota's State and Local Tax Burden with Statistical Appendix

Public Economics,

POTENTIAL IMPACTS OF GM WHEAT ON UNITED STATES AND NORTHERN PLAINS WHEAT TRADE

The potential introduction of genetically modified (GM) wheat has both supporters and opponents waging battle in the popular press and scholarly research. Supporters highlight the benefits to producers, while the opponents highlight the unknown safety factors for consumers. The topic is very important to the United States, as a large portion of the wheat production is exported overseas. Consumer groups in some countries are resisting GM wheat. This study utilizes a spatial equilibrium model to evaluate the trade impacts associated with GM wheat introduction along with several assumed post-GM adoption scenarios. Wheat is converted into protein equivalents to allow for substitution between wheat classes. The importance of the U.S. handling/transportation system is highlighted in the ability of the system to develop an affordable and effective segregation system for GM wheat. Producers who do not produce GM wheat would face externalities associated with GM wheat contamination of non-GM wheat.genetically modified wheat, spatial equilibrium model, trade flows, protein equivalents, externalities, Crop Production/Industries, International Relations/Trade,

A token found at Lyme Regis, Dorset, England, apparently associated with Mary Anning (1799–1847), fossil collector

A lettered metal disc bearing the date 1810 and found on the beach at Lyme Regis appears, but cannot conclusively be proven, to be a childhood possession of the young Mary Anning (1799–1847), later the famous fossil collector whose name and age it bears. An alternative, but problematical, possibility is that it is a retrospective commemorative token produced for sale to tourists in later years

Regression-based seasonal unit root tests

The contribution of this paper is three-fold. Firstly, a characterisation theorem of the sub-hypotheses comprising the seasonal unit root hypothesis is presented which provides a precise formulation of the alternative hypotheses against which regression-based seasonal unit root tests test. Secondly, it proposes regressionbased tests for the seasonal unit root hypothesis which allow a general seasonal aspect for the data and are similar both exactly and asymptotically with respect to initial values and seasonal drift parameters. Thirdly, limiting distribution theory is given for these statistics where, in contrast to previous papers in the literature, in doing so it is not assumed that unit roots hold at all of the zero and seasonal frequencies. This is shown to alter the large sample null distribution theory for regression t-statistics for unit roots at the complex frequencies, but interestingly to not affect the limiting null distributions of the regression t-statistics for unit roots at the zero and Nyquist frequencies and regression Fstatistics for unit roots at the complex frequencies. Our results therefore have important implications for how tests of the seasonal unit root hypothesis should be conducted in practice. Associated simulation evidence on the size and power properties of the statistics presented in this paper is given which is consonant with the predictions from the large sample theory.Seasonal unit root tests; seasonal drifts; characterisation theorem