First ASO application in sickle cell anemia[12] and ai-antitrypsin deficiency1-13-1 were subsequently expanded, since the advent of PCR, to a variety of systems.[14] It was used to analyze disease-causing mutations,[15] study the mechanism of carcinogenesis,1-16-1 or distinguish different haplotypes of the major histocompatibility locus.[17] ASO hybridization also found large application in studies of candidate susceptibility loci in complex disorders,[18,19] as well as in investigations of genetic variants predisposing individuals to adverse drug reaction.[1] ASO takes advantage of the difference in stability between the fully complementary and the mismatched DNA duplex. This difference is used to distinguish between allelic states differing as little as by a single nucleotide. Typically, two oligonucle-otide 15-mer ASO probes are designed, each complementary to one of the alleles. In a classical protocol, hybridization is carried out at a temperature favoring the formation of a fully matched duplex, whereas the binding specificity is essentially obtained through stringent post-hybridization washes. In a dynamic ASO protocol, hybrid ization starts well above the melting point and a decreasing temperature gradient is applied. The labelled probe ''finds'' its target during the cooling of the hybridization mixture. Formation of the mismatched complex is prevented by the presence of the competitor probe that is fully complementary to the opposite allele. ASO hybridization finds application in diagnostic and genetic epide-miological surveys, is reliable, and is easy to implement.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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