Evaluation of waiting periods prior to laser refractive surgery after discontinuing wear of rigid and soft contact lenses

PURPOSE: This study evaluated how contact lens induced corneal warpage stabilizes upon discontinuation of lens wear and further evaluated whether the waiting periods for laser refractive surgery now in use can be safely shortened. METHODS: Using corneal topography, both retrospective and prospective analyses were conducted for 16 soft lens eyes and 8 rigid lens eyes. Corneal maps were taken prior to discontinuation of lens wear, serial maps taken during the waiting period (if an RGP wearer), and again on the date of surgery. Using the Humphrey PathFinder Analysis software, comparisons were made of the CIM, Shape Factor, and TKM to evaluate the changes over time. RESULTS: There is very little corneal reshaping once soft lens wear is discontinued. However, statistically significant changes in SF (Shape Factor) and TKM (Mean Toric Keratometry) before and after the waiting period were found for subjects wearing RGP (rigid gas permeable) lenses. CONCLUSION: Careful topographic analysis should allow many long-term RGP wearers without signs of corneal warpage to forego the long waiting period dictated by current standards in refractive surgery. Short waiting periods for soft lens wearers may be a prudent precaution, but is not a necessity

OFDM: From the Idea to Implementation

OFDM (orthogonal frequency-division multiplexing) is one of the key digital communication technologies of the current decade. The first part of this paper presents the fundamentals of OFDM and its benefits in the presence of multipath propagation in a tutorial-like fashion. The second part details on some of the most important aspects of OFDM transceiver implementation: concept of receiver channel filtering and A/D conversion, radio impairment compensation (I/Q mismatch), and OFDM demodulator (FFT) design

Evolutionary conservation and selection of human disease gene orthologs in the rat and mouse genomes

BACKGROUND: Model organisms have contributed substantially to our understanding of the etiology of human disease as well as having assisted with the development of new treatment modalities. The availability of the human, mouse and, most recently, the rat genome sequences now permit the comprehensive investigation of the rodent orthologs of genes associated with human disease. Here, we investigate whether human disease genes differ significantly from their rodent orthologs with respect to their overall levels of conservation and their rates of evolutionary change. RESULTS: Human disease genes are unevenly distributed among human chromosomes and are highly represented (99.5%) among human-rodent ortholog sets. Differences are revealed in evolutionary conservation and selection between different categories of human disease genes. Although selection appears not to have greatly discriminated between disease and non-disease genes, synonymous substitution rates are significantly higher for disease genes. In neurological and malformation syndrome disease systems, associated genes have evolved slowly whereas genes of the immune, hematological and pulmonary disease systems have changed more rapidly. Amino-acid substitutions associated with human inherited disease occur at sites that are more highly conserved than the average; nevertheless, 15 substituting amino acids associated with human disease were identified as wild-type amino acids in the rat. Rodent orthologs of human trinucleotide repeat-expansion disease genes were found to contain substantially fewer of such repeats. Six human genes that share the same characteristics as triplet repeat-expansion disease-associated genes were identified; although four of these genes are expressed in the brain, none is currently known to be associated with disease. CONCLUSIONS: Most human disease genes have been retained in rodent genomes. Synonymous nucleotide substitutions occur at a higher rate in disease genes, a finding that may reflect increased mutation rates in the chromosomal regions in which disease genes are found. Rodent orthologs associated with neurological function exhibit the greatest evolutionary conservation; this suggests that rodent models of human neurological disease are likely to most faithfully represent human disease processes. However, with regard to neurological triplet repeat expansion-associated human disease genes, the contraction, relative to human, of rodent trinucleotide repeats suggests that rodent loci may not achieve a 'critical repeat threshold' necessary to undergo spontaneous pathological repeat expansions. The identification of six genes in this study that have multiple characteristics associated with repeat expansion-disease genes raises the possibility that not all human loci capable of facilitating neurological disease by repeat expansion have as yet been identified

SCHEMA-Designed Variants of Human Arginase I and II Reveal Sequence Elements Important to Stability and Catalysis

Arginases catalyze the divalent cation-dependent hydrolysis of l-arginine to urea and l-ornithine. There is significant interest in using arginase as a therapeutic anti-neogenic agent against l-arginine auxotrophic tumors and in enzyme replacement therapy for treating hyperargininemia. Both therapeutic applications require enzymes with sufficient stability under physiological conditions. To explore sequence elements that contribute to arginase stability we used SCHEMA-guided recombination to design a library of chimeric enzymes composed of sequence fragments from the two human isozymes Arginase I and II. We then developed a novel active learning algorithm that selects sequences from this library that are both highly informative and functional. Using high-throughput gene synthesis and our two-step active learning algorithm, we were able to rapidly create a small but highly informative set of seven enzymatically active chimeras that had an average variant distance of 40 mutations from the closest parent arginase. Within this set of sequences, linear regression was used to identify the sequence elements that contribute to the long-term stability of human arginase under physiological conditions. This approach revealed a striking correlation between the isoelectric point and the long-term stability of the enzyme to deactivation under physiological conditions

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead