From diversity to convergence : British computer networks and the Internet, 1970-1995

The Internet's success in the 21st century has encouraged analysts to investigate the origin of this network. Much of this literature adopts a teleological approach. Works often begin by discussing the invention of packet switching, describe the design and development of the ARPANET, and then examine how this network evolved into the Internet. Although the ARPANET was a seminal computer network, these accounts usually only briefly consider the many other diverse networks that existed. In addition, apart from momentary asides to alternative internetworking solutions, such as the Open Systems Interconnection (OSI) seven-layer reference model, this literature concentrates exclusively on the ARPANET, the Internet, and the World Wide Web. While focusing on these subjects is important and therefore justified, it can leave the reader with the impression that the world of networking started with the ARPANET and ended with the Internet. This thesis is an attempt to help correct this misconception. This thesis analyses the evolution of British computer networks and the Internet between the years 1970 and 1995. After an introduction in Chapter 1, the thesis analyses several networks. In Chapters 2 and 3, the focus is on academic networks, especially JANET and SuperJANET. Attention moves to videotex networks in Chapter 4, specifically Prestel, and in Chapter 5, the dissertation examines electronic mail networks such as Telecom Gold and Cable & Wireless Easylink. Chapter 6 considers online services, including CompuServe, American Online, and the Microsoft Network, and the thesis ends with a conclusion in Chapter 7. All of the networks discussed used protocols that were incompatible with each other which limited the utility of the networks for their users. Although it was possible that OSI or another solution could have solved this problem, the Internet's protocols achieved this objective. This thesis shows how the networks converged around TCP/IP

High-Density SNP Genotypes for Predicting Genetic Merit of Beef Cattle

Current selection strategies result in annual rates of genetic improvement less than one-quarter of the progress that is theoretically possible if merit could be accurately predicted by breeding age. Tens of thousands of single gene markers (called SNPs), spread throughout the genome, enable the ancestral inheritance of small chromosome fragments to be tracked. Genetic merit of new, perhaps unrelated cattle can be predicted by summing up the values of all the fragments they have inherited. Such predictions at young ages will facilitate faster rates of genetic gain, especially for traits that are difficult to measure

Surprisingly low limits of selection in plant domestication

Current debate concerns the pace at which domesticated plants emerged from cultivated wild populations and how many genes were involved. Using an individual-based model, based on the assumptions of Haldane and Maynard Smith, respectively, we estimate that a surprisingly low number of 50–100 loci are the most that could be under selection in a cultivation regime at the selection strengths observed in the archaeological record. This finding is robust to attempts to rescue populations from extinction through selection from high standing genetic variation, gene flow, and the Maynard Smith-based model of threshold selection. Selective sweeps come at a cost, reducing the capacity of plants to adapt to new environments, which may contribute to the explanation of why selective sweeps have not been detected more frequently and why expansion of the agrarian package during the Neolithic was so frequently associated with collapse

Single Ion Free Energy Calculation in ASIC1: The Importance of the HG loop

Acid Sensing Ion Channels (ASICs) are one of the most studied channels of the Epithelial Sodium Channel/Degenerin (ENaC/DEG) superfamily. They are responsible for excitatory responses following acidification of the extracellular medium and are involved in several important physiological roles. The ASIC1 subunit can form a functional homotrimeric channel and its structure is currently the most characterised of the whole ENaC/DEG family. Here we computed the free energy profiles for single ion permeation in two different structures of ASIC1 using both Na+ and Cl- as permeating ions. The first structure is the open structure of the channel from the PDB entry 4NTW, and the second structure is the closed structure with the re-entrant loop which contains the highly conserved `HG' motif form PDB entry 6VTK. Both structures show cation selective free energy profiles, however the profiles of the permeating Na+ differ significantly between the two structures. Indeed, whereas there is only a small energetically favorable (-0.5 kcal mol-1) location for Na+ in the open channel (4NTW) near the end of the pore, we observed a clear ion binding site (-7.8 kcal mol-1) located in between the `GAS' belt and the `HG' loop for the channel containing the re-entrant loop (6VTK). Knowing that the `GAS' motif was determined as the selectivity filter, our results support previous observations while addressing the importance of the `HG' motif for the interactions between the pore and the permeating cations

Whole genome analysis of infectious bovine keratoconjunctivitis in Angus cattle using Bayesian threshold models

Infectious bovine keratoconjunctivitis (IBK), also known as pinkeye, is characterized by damage to the cornea and is an economically important, lowly heritable, categorical disease trait in beef cattle. Scores of eye damage were collected at weaning on 858 Angus cattle. SNP genotypes for each animal were obtained from BovineSNP50 Infinium-beadchips. Simultaneous associations of all SNP with IBK phenotype were determined using Bayes-C that treats SNP effects as random with equal variance for an assumed fraction (π=0.999) of SNP having no effect on IBK scores. Bayes-C threshold models were used to estimate SNP effects by classifying IBK into two, three or nine ordered categories. Magnitudes of genetic variances estimated in localized regions across the genome indicated that SNP within the most informative regions accounted for much of the genetic variance of IBK and pointed out some degree of association to IBK. There are many candidate genes in these regions which could include a gene or group of genes associated with bacterial disease in cattle

Quantitative Trait Locus on Sus scrofa Chromosome 4 Associated with Host Response to Experimental Infection with Porcine Reproductive and Respiratory Syndrome Virus

The objective of this study was to conduct a genomewide association study to discover the genetic basis of host response to PRRS virus using data from the PRRS Host Genetics Consortium NPB and PRRS-CAP project. Approximately 1,600 commercial crossbred piglets were experimentally infected with the Porcine Reproductive and Respiratory Syndrome (PRRS) virus. Blood samples and body weights were collected up to 42 days post infection (dpi). Experimental pigs and their parents were genotyped with Illumina’s Porcine 60k BeadChip. Phenotypes analyzed were viral load (VL = area under the curve for log-transformed qRT-PCR based serum virus from 0-21 dpi) and weight gain from 0-42 dpi (WG). Heritabilities estimated using pedigree information were moderate at 0.41 for VL and 0.29 for WG. A 1 Mb region on Sus scrofa chromosome (SSC) 4 was found to be associated with VL and WG and explained a substantial amount of genetic variation. The frequency of the favorable allele for the most significant single nucleotide polymorphism (SNP) was 0.15. These results show that there is a host genetic component to PRRS virus infection and that there is room for genetic improvement

Deriving Gene Networks from SNP Associated with Triacylglycerol and Phospholipid Fatty Acid Fractions from Ribeyes of Angus Cattle

The fatty acid profile of beef is a complex trait that can benefit from gene-interaction network analysis to understand relationships among loci that contribute to phenotypic variation. Phenotypic measures of fatty acid profile from triacylglycerol and phospholipid fractions of longissimus muscle, pedigree information, and Illumina 54 k bovine SNP genotypes were utilized to derive an annotated gene network associated with fatty acid composition in 1,833 Angus beef cattle. The Bayes-B statistical model was utilized to perform a genome wide association study to estimate associations between 54 k SNP genotypes and 39 individual fatty acid phenotypes within each fraction. Posterior means of the effects were estimated for each of the 54 k SNP and for the collective effects of all the SNP in every 1-Mb genomic window in terms of the proportion of genetic variance explained by the window. Windows that explained the largest proportions of genetic variance for individual lipids were found in the triacylglycerol fraction. There was almost no overlap in the genomic regions explaining variance between the triacylglycerol and phospholipid fractions. Partial correlations were used to identify correlated regions of the genome for the set of largest 1 Mb windows that explained up to 35% genetic variation in either fatty acid fraction. SNP were allocated to windows based on the bovine UMD3.1 assembly. Gene network clusters were generated utilizing a partial correlation and information theory algorithm. Results were used in conjunction with network scoring and visualization software to analyze correlated SNP across 39 fatty acid phenotypes to identify SNP of significance. Significant pathways implicated in fatty acid metabolism through GO term enrichment analysis included homeostasis of number of cells, homeostatic process, coenzyme/cofactor activity, and immunoglobulin. These results suggest different metabolic pathways regulate the development of different types of lipids found in bovine muscle tissues. Network analysis using partial correlations and annotation of significant SNPs can yield information about the genetic architecture of complex traits