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Zoo and find it. At the end of the day after 10 years of that kind of thing it became very clear that we really were stuck with rats, mice, dogs, the things we have background pathology on. To pursue that issue though of humanization, quite clearly we are somewhere between the first and second generation of approaches to that kind of thing. Of course, one of the real problems that one has in dealing with metabolism as an issue, of course, is not simply humanizing the animal but, also, de-animalizing it because you have got to stop it being an animal before you can turn it into a human. To do that with a single end point, of course, is feasible, as you know. To do it with multiple end points, multiple enzymes and so on is obviously much more demanding, but there are animal models, now of some of the human genetic polymorphisms. At the moment what we have is, a series of knockouts and knock-ins and people doing crossbreeding experiments to try to double up on them. We are not there yet, but, we heard earlier about some of the things in endocrine toxicology, for example, and I think the practitioners in that area would agree, you know, that they are, well, you, yourself, somewhere between the first and second generation of something that will come to fruition and meet these sorts of requirements about the fourth generation I don't mean F generation. You know conceptually, it is beginning to happen, but it is not going to happen just yet. Now, to do with your specific question about what do you do with human-specific metabolites, they are demanding. We have dealt with quantitative differences, metabolites that are large in humans and small in animals or vice versa, on a pretty pragmatic basis. We assume that as long as they are produced in the range of animals that you use you are covered. We need to move forward from that quite clearly, and there are some cases where it is going to be appropriate to test the metabolites themselves. Of course in a lot of ways that takes you into dangerous water because there you are testing something that is not the compound you are going to administer. It is not the compound that you want to license, and I know very many people, and I know there is one in the audience, have a healthy reluctance to do that. Nevertheless there may well be reasons to do it. The other thing just to say is it is very important to have a sound view of exactly where the differences lie, because metabolism is, as most people would be aware of, generally perceived as a series of cascades. Now, if the key difference that we are talking about is one that is close to home; if it is one of the two or three primary reactions that your drug undergoes, it is of major significance and does need to be addressed, and you have to work at the model systems that you use. On the other hand, if it is in some detail of a third or fourth step in the cascade pathway, it may well have nothing like the same significance. You have identified the issues that are clearly there. I mean right now, of course, I simply being provocative about an FDA guideline on a web site which I hope you realize, but the key issues behind it are some of those, but they won't be addressed by that guideline by itself. PROF. SOMOGYI: Thank you. Alastair, please identify yourself?.
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Champion Running Three-Year-Old, Champion Running Aged Horse four-year-old and older Champion Running TwoYear-Old Filly, Champion Running Two-Year-Old Gelding, Champion Running Two-Year-Old Colt, Champion Running Three-Year-Old Filly, Champion Running Three-Year-Old Gelding, Champion Running Three-Year-Old Colt, Champion Running Aged Mare, Champion Running Aged Gelding, Champion Running Aged Stallion. From the three age divisions, the overall World Champion Running Paint Horse will be selected. A suitable award will be presented to each of the three age and sex divisions for the annual running champion awards; and, the awards will be presented at the first directors general membership meeting of the APHA following the year which the award was won. Race results received after ten 10 ; days from December 31, will not be used in selecting the running champions. 1. The recipient of the annual racing award for the Champion Running Breeding Stock Paint will be determined by the system described in Rule RA-060. B. APHA RACING TITLES. The titles of APHA World Champion Running Paint Horse, APHA Champion Running Paint Two-Year-Old, APHA Champion Running Paint ThreeYear-Old and APHA Champion Running Aged Paint Horse, APHA National Race Futurity Champion and APHA National Race Maturity Champion are hereby, from this date and in the future, reserved by the American Paint Horse Association for its express use. The registration certificate may be revoked permanently by the APHA if the owner thereof fraudulently advertises, claims, or holds forth that this certain horse is entitled to the aforementioned titles prior to the title being officially awarded by the APHA. APHA RACING HONOR ROLL AWARD. 1. The APHA will make annual awards each year to the horse of each sex earning the most points during one calendar year in racing. The horse which earns the most points will be called the APHA Honor Roll Racing Mare, APHA Honor Roll Racing Gelding, or APHA Honor Roll Racing Stallion. The horse will receive an appropriately engraved trophy or plaque which shall be mailed to the owner of record as of December 31. Each of the remaining horses, 2nd through 10th, shall receive appropriate certificates which shall be mailed to the owners of record as of December 31. See RA-000. C. 4. ; 2. Breeding Stock Horse Honor Roll - method of tabulation same as Rule RA-060. D.1. MINIMUM RACING POINTS. To qualify for any title, running champion or Honor Roll awards, the horse must have earned a minimum of 8 racing points. See RA-010. B.1. ; APHA SUPERIOR EVENT ; HORSE. 1. See Rule SC-030. 2. See Rule RA-000. C. 4. The APHA Racing Recognition applies to all races run after January 1, 2000. For transfer of ownership in claiming races see Rule RG-155.N. 270.
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