Abstract: Provided herein are high-throughput assays for identifying quadruplex interacting molecules. These assays comprise the steps of contacting a test molecule and a signal molecule with a quadruplex nucleic acid in a system, and detecting the signal produced by the signal molecule. Also provided are high-throughput assays for identifying quadruplex forming nucleic acids. These assays comprise the steps of contacting a signal molecule with a test nucleic acid in a system, and detecting a fluorescent signal produced by the signal molecule.

Abstract: Among the different intrastrand quadruplex structures that can arise from duplex DNA, it has been discovered that a chair conformation is biologically significant. Also, it has been determined that certain mutations in quadruplex forming nucleotide sequences destabilize quadruplex structure and are associated with cancer. Thus, provided herein are quadruplex-destabilized nucleic acid acids, cancer diagnostics and prognostics, methods for using the cancer diagnostics and prognostics to prevent and/or treat cancer, nucleic acid therapeutics that target quadruplex-destabilized nucleotide sequences and methods, methods for identifying compounds that modulate the biological activity of a native quadruplex DNA in a chair conformation, and methods for modulating the biological activity of a native quadruplex DNA with a compound identified by the methods described herein.

Abstract: An improved mechanism for connecting tubular members in a subsea well in which the members are locked together in a preloaded condition. In the preferred form of the invention the loading is provided by a series of fingers mounted on the inner tubular member and flexing through a restriction in the outer tubular member during landing and then springing back from such flexed position to engage and wedge against a tapered shoulder at the lower end of the restriction to both lock the inner tubular member in its seated position and also to provide the preloading desired. In a second form, the inner member is landed on a ring which is engaged on the outer tubular member landing seat and then further lowering of the inner member moves a wedge on the inner member to cause the upper end of the ring to engage the internal profile of the outer member and the lower end to engage a lower external profile on the inner member and to be wedged therein to create the lock down and the desired preload.