1. Introduction Designing PCR and sequencing primers are essential activities for molecular biologists around the world. This chapter assumes acquaintance with the principles and practice of PCR, as outlined in, for example, refs. 1–4. Primer3 is a computer program that suggests PCR primers for a variety of applications, for example to create STSs (sequence tagged sites) for radiation hybrid mapping (5), or to amplify sequences for single nucleotide polymor-phism discovery (6). Primer3 can also select single primers for sequencing reactions and can design oligonucleotide hybridization probes. In selecting oligos for primers or hybridization probes, Primer3 can consider many factors. These include oligo melting temperature, length, GC content , 3′ stability, estimated secondary structure, the likelihood of annealing to or amplifying undesirable sequences (for example interspersed repeats), the likelihood of primer–dimer formation between two copies of the same primer, and the accuracy of the source sequence. In the design of primer pairs Primer3 can consider product size and melting temperature, the likelihood of primer– dimer formation between the two primers in the pair, the difference between primer melting temperatures, and primer location relative to particular regions of interest or to be avoided.

/pdf/primer3-on-the-www-for-general-users-and-for-biologist-pgzaqxkztz.pdf

Primer3 on the WWW for general users and for biologist programmers.

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

http://science.sciencemag.org/content/sci/291/5507/1304.full.pdf

The sequence of the human genome.

The goal of the International HapMap Project is to determine the common patterns of DNA sequence variation in the human genome and to make this information freely available in the public domain. An international consortium is developing a map of these patterns across the genome by determining the genotypes of one million or more sequence variants, their frequencies and the degree of association between them, in DNA samples from populations with ancestry from parts of Africa, Asia and Europe. The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance our ability to choose targets for therapeutic intervention.

The International HapMap Project

Preface, Notations 1.Introduction to Time-Delay Systems I.Frequency-Domain Approach 2.Systems with Commensurate Delays 3.Systems withIncommensurate Delays 4.Robust Stability Analysis II.Time Domain Approach 5.Systems with Single Delay 6.Robust Stability Analysis 7.Systems with Multiple and Distributed Delays III.Input-Output Approach 8.Input-output stability A.Matrix Facts B.LMI and Quadratic Integral Inequalities Bibliography Index

/pdf/stability-of-time-delay-systems-5d2qjgdknf.pdf

Stability of Time-Delay Systems

1. Introduction. 2. Linear Algebra. 3. Linear Systems. 4. H2 and Ha Spaces. 5. Internal Stability. 6. Performance Specifications and Limitations. 7. Balanced Model Reduction. 8. Uncertainty and Robustness. 9. Linear Fractional Transformation. 10. m and m- Synthesis. 11. Controller Parameterization. 12. Algebraic Riccati Equations. 13. H2 Optimal Control. 14. Ha Control. 15. Controller Reduction. 16. Ha Loop Shaping. 17. Gap Metric and ...u- Gap Metric. 18. Miscellaneous Topics. Bibliography. Index.

/pdf/essentials-of-robust-control-3kaks6yk3h.pdf

Essentials of Robust Control

We examine the dynamic and geometric phases of the electron in quantum mechanics using the space-time algebra formalism. In doing so we are able to relate the \beta parameter in Hestens' theory to these phases. We also comment on some of Hestenes' previous work regarding the phases.

Dynamic and Geometric Phase Formulas and the \beta Parameter in the Hestenes-Dirac Theory

This paper outlines the start of an exploratory study of the active control of wind-induced structural response in tall buildings. The approach combines computer simulations, based on mathematical models, with wind-tunnel experiments on a physical model. To this end we have constructed an experimental platform to investigate the closed-loop performance of different active control strategies for suppression of wind induced vibration. A first study utilizing this platform in conjunction with a simple structural model is described, and the initial results are very encouraging.

Experimental investigation of active control of wind-induced vibration in tall structures

We present a design approach for robust controller synthesis using a μ-synthesis procedure, which returns a controller in an observor/state-feedback form with physically meaningful states. We are also able to (approximately) retain this physical meaning when using balanced truncation to (significantly) reduce the controller order, as is often necessary in practice. The advantages of this physics-based approach are illustrated by a detailed outline of the controller design for Woodward Governor's GS16 Turbine Gas Metering Valve.

Servocontrol of the GS16 Turbine Gas Metering Valve by Physics-Based Robust Controller Synthesis

This paper describes a project to initiate a new undergraduate teaching laboratory in the Systems and Controls area at Colorado State University, USA. An important design goal was to provide an interdisciplinary facility, serving all the Departments of the College of Engineering. Another key design requirement for the facility was to provide the students with a real-world experience of industry standard problems and tools. A strong industry-academia partnership was invaluable in this regard.

An integrated engineering systems and controls laboratory

People and technology are at the centre of our climate crisis. Technological advances have contributed to the accumulation of GHG. On the other side of the coin, technological advances such as renewable energy hold promise for ameliorating our environmental woes. Similarly, rapid population growth has the potential to exacerbate our environmental problems, whilst behaviour change holds the key to conserving our natural resources. This is the sustainability paradox: the problem is also the solution.

Peter M. Young

Papers

Dynamic and Geometric Phase Formulas and the \beta Parameter in the Hestenes-Dirac Theory

Experimental investigation of active control of wind-induced vibration in tall structures

Servocontrol of the GS16 Turbine Gas Metering Valve by Physics-Based Robust Controller Synthesis

An integrated engineering systems and controls laboratory

The Problem Is Also the Solution: The Sustainability Paradox