Historic Developments

DNA ligase was discovered in the late 1960s and the enzyme is an essential component of DNA replication, recombination, and repair systems, which catalyzes the formation of covalent phosphodiester bonds at single-stranded breaks on dsDNA. In 1972, ligation of flanking oligonucleotides while hybridized to a template was investigated,1-8-1 and soon it became apparent that DNA ligase could be used as an analytical tool for detecting the presence of two adjacent pieces of oligonucleotides hybridized to a complementary target DNA strand.[3,9] After synthetic oligonucleotides became readily available, the practical use of this concept was further exploited and Landegren et al. developed the oligonucleotide ligation assay (OLA).[5] Wu and Wallace described a technique called ligase amplification reaction (LAR), which uses two sets of complementary oligonu-cleotide probes and repeated cycles of heat denaturation, hybridization, and ligation using a mesophilic DNA ligase, leading to exponential amplification.1-10-1 Barany reported a technique called ligase detection reaction (LDR) and ligase chain reaction (LCR) that uses a thermostable ligase which dramatically improved the sensitivity of the reaction and exquisitely discriminated between single-base mismatches at the junction of the two oligonucleotide probes.[3]

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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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