Sample A: Cover Page of Thesis, Project, or Dissertation Proposal
Sample A: Cover Page of Thesis, Project, or Dissertation Proposal
Sample A: Cover Page of Thesis, Project, or Dissertation Proposal
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likelihood that no such structural regions f<strong>or</strong>m is vanishingly small. Because <strong>of</strong> the<br />
highly folded structures that result there can also be tertiary structures present,<br />
compounding the likelihood that the availability <strong>of</strong> intended sites f<strong>or</strong> probe binding<br />
will be sterically hindered, and greatly decreasing the diffusion constant <strong>of</strong> the<br />
molecule in solution (slowing the rate <strong>of</strong> duplex f<strong>or</strong>mation further) [29]. Shearing <strong>of</strong><br />
targets strands is thus recommended, with the goal <strong>of</strong> ending with target lengths that<br />
are approximately equivalent to probe lengths [5, 10, 35].<br />
3) Temperature. As noted above, the probe length and base composition affect the<br />
melting temperature (Tm) <strong>of</strong> any duplex, where the melting temperature is defined as<br />
the temperature at which 50% <strong>of</strong> the duplex structures are dissociated [22, 25, 26,<br />
36]. Experimental conditions are designed as a best fit f<strong>or</strong> the average <strong>of</strong> the<br />
hundreds <strong>of</strong> thousands <strong>of</strong> individual reactions occurring on the array. Solvent<br />
components can be altered to change the dielectric constant <strong>of</strong> the solution, altering<br />
the energetics <strong>of</strong> the product’s hydrogen bonds [34, 37].<br />
4) Equilibration Time. As noted above, the competition among highly similar targets<br />
f<strong>or</strong> the same complementary probe sequence requires that adequate hybridization<br />
time be allocated, in <strong>or</strong>der f<strong>or</strong> the reaction to achieve equilibrium. Sh<strong>or</strong>t hairpin<br />
structures are less energetically fav<strong>or</strong>able than long duplexes, but since unimolecular<br />
reactions occur in a much sh<strong>or</strong>ter period <strong>of</strong> time than bimolecular reactions,<br />
unimolecular reactions can kinetically trap probe <strong>or</strong> target in non-optimal f<strong>or</strong>ms[5,<br />
10] . The various kinetic properties <strong>of</strong> the tens <strong>of</strong> thousands <strong>of</strong> probes realistically<br />
prevent a significant prop<strong>or</strong>tion <strong>of</strong> probe-target interactions from achieving chemical<br />
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