On the origins of Mendelian disease genes in man: the impact of gene duplication

Over 3,000 human diseases are known to be linked to heritable genetic variation, mapping to over 1,700 unique genes. Dating of the evolutionary age of these disease-associated genes has suggested that they have a tendency to be ancient, specifically coming into existence with early metazoa. The approach taken by past studies, however, assumes that the age of a disease is the same as the age of its common ancestor, ignoring the fundamental contribution of duplication events in the evolution of new genes and function. Here, we date both the common ancestor and the duplication history of known human disease-associated genes. We find that the majority of disease genes (80%) are genes that have been duplicated in their evolutionary history. Periods for which there are more disease-associated genes, for example, at the origins of bony vertebrates, are explained by the emergence of more genes at that time, and the majority of these are duplicates inferred to have arisen by whole-genome duplication. These relationships are similar for different disease types and the disease-associated gene's cellular function. This indicates that the emergence of duplication-associated diseases has been ongoing and approximately constant (relative to the retention of duplicate genes) throughout the evolution of life. This continued until approximately 390 Ma from which time relatively fewer novel genes came into existence on the human lineage, let alone disease genes. For single-copy genes associated with disease, we find that the numbers of disease genes decreases with recency. For the majority of duplicates, the disease-associated mutation is associated with just one of the duplicate copies. A universal explanation for heritable disease is, thus, that it is merely a by-product of the evolutionary process; the evolution of new genes (de novo or by duplication) results in the potential for new diseases to emerge

Process for bonding elastomers to metals

A process for bonding elastomeric material to a metal part includes coating a heat curable adhesive on the surfaces of the metal part to be bonded. The metal part is placed in a mold, a bottom plate and an upper transfer pot of a transfer molding machine is preheated to a predetermined cure temperature. A predetermined quantity of uncured elastomeric material is loaded into the transfer pot. The mold containing the adhesive coated metal part is clamped to the bottom plate, and almost contemporaneously, the uncured elastomeric material is pressed into the mold while maintaining heat and pressure in the mold for a time sufficient to vulcanize and thereby cure the elastomeric material simultaneously with the adhesive, whereby contacting surfaces of the metal part are strongly bonded to the vulcanized elastomeric material

The Effects of Resistance Deception on Muscular Strength, Muscular Endurance, and Perceived Exertion

Resistance deception during training is a lightly researched topic and is seen as a modification that can potentially act on central control during exercise. Studies that have observed effects of deception while training have yielded mixed results. The effects of deception on strength, muscular endurance, and perceived exertion and the mechanisms of action that may elicit changes are still unclear. Therefore, the purpose of this study is to determine the effects of resistance deception on muscular strength, muscular endurance, and perceived exertion in a trained population. Eight participants finished the study and underwent four trials, one of which was a baseline trial, that consisted of one-rep max and repetitions to failure testing, with 60% of one-rep max, on bench press. Ensuing three experimental trials consisted of the bench press tests but in deceived/masked conditions. One trial was a 5% increase in weight, one trial was a 5% decrease in weight, and the third trial consisted of a weight that was equivalent to that of baseline. Repetitions, bar speed, and perceived exertion were monitored during each trial. During the deceived equivalent weight trial, participants significantly increased the number of repetitions and mean bar speed during the repetitions to failure test and experienced significantly decreased perceived exertion during the one-rep max lift. These findings indicate deception during training can acutely enhance performance outcomes. Key words: Resistance deception, muscular strength, perceived exertion, muscular enduranc

LLV - Lunar Logistic Vehicle Final report

Evaluation of systems design training institute for engineering facult

The Canada Business Corporations Act: Some Aspects of Transnational Interest

With passage into law on March 24, 1975, of the Canada Business Corporations Act (CBCA) it is probably safe to say by way of provocative introduction that Canada has enacted the most modern corporation law in the English-speaking world. The Act is to be proclaimed in force at the end of December, 1975. Although the predecessor statute, the Canada Corporations Act, will remain in force, no new corporations may be incorporated under it

Performance of Booroola Merino and Finnsheep crossbred lambs and ewes

Booroola Merino (B, n= 18) and Finnsheep (F, n =31) rams were mated to F ewes and C3 ewes (1/2 Columbia, 1/4 Suffolk, 1/4 Hampshire). Progeny of these matings were evaluated for performance traits including ewe reproduction through 3 years of age. Averaged over dam breeds, there was no significant difference between B and F sires for conception rate (CR), litter size (LS) at birth or weaning or for lamb mortality to weaning. The difference among sire breeds was not large or significant for birth weight but F sired lambs were significantly heavier than B sired lambs at 63 and 147 days of age. Relative to F sired lambs, B sired lambs had a higher dressing percentage and less fat at the 12th rib but equal estimated percentage kidney fat. A significantly smaller percentage of B-C3 than F, F-C3 or B-F ewe lambs reached puberty by the end of their first breeding season. Ovulation rate at first mating was higher but embryo survival rate tended to be lower for B sired ewes than for F sired ewes. At 2 years of age, B sired ewes produced about 1 kg more wool than F sired ewes. With the exception of the very poor CR of B-C3 ewes at first parity, the differences between the four ewe genotypes were not large or significant for CR at first, second and third parity. The difference between B and F sired ewes in LS at birth was not significant at first parity but B sired ewes were more prolific at second and third parities. However, differences in lamb mortality reduced, and in some cases removed, the differences in LS by weaning time. Relative use of these breeds in commercial U.S. production schemes is discussed

The life-history and early stages of Corythucha parshleyi Gibson.

v. 50 (1918