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1.
Phys Rev Lett ; 90(1): 013002, 2003 Jan 10.
Article in English | MEDLINE | ID: mdl-12570606

ABSTRACT

Recording the yield of He(1snl(3)L) Rydberg states for n=11-14, we measure the photodetachment cross sections of metastable He-(1s2s2p(4)P(o)) ions in the vicinity of the two-electron escape threshold. We observe a large number of double Rydberg He- quartet state resonances and report energies and widths of intrashell states in the n=13-15 manifolds. Sharp thresholds are measured at He((3)P(o)) and He((3)D(e)) Rydberg states with preference for population of the former, whereas the He((3)S(e)) states are not populated, in agreement with qualitative theoretical arguments.

2.
Proc Natl Acad Sci U S A ; 97(10): 5633-8, 2000 May 09.
Article in English | MEDLINE | ID: mdl-10805816

ABSTRACT

Insufficient efficacy and/or specificity of antisense oligonucleotides limit their in vivo usefulness. We demonstrate here that a high-affinity DNA analog, locked nucleic acid (LNA), confers several desired properties to antisense agents. Unlike DNA, LNA/DNA copolymers were not degraded readily in blood serum and cell extracts. However, like DNA, the LNA/DNA copolymers were capable of activating RNase H, an important antisense mechanism of action. In contrast to phosphorothioate-containing oligonucleotides, isosequential LNA analogs did not cause detectable toxic reactions in rat brain. LNA/DNA copolymers exhibited potent antisense activity on assay systems as disparate as a G-protein-coupled receptor in living rat brain and an Escherichia coli reporter gene. LNA-containing oligonucleotides will likely be useful for many antisense applications.


Subject(s)
Oligodeoxyribonucleotides, Antisense/chemistry , Oligodeoxyribonucleotides, Antisense/pharmacology , Animals , Base Sequence , Biological Transport , Breast Neoplasms , Caudate Nucleus/drug effects , Cerebral Ventricles/drug effects , Cerebral Ventricles/physiology , Drug Design , Enzyme Activation , Female , Humans , Oligodeoxyribonucleotides, Antisense/pharmacokinetics , Putamen/drug effects , Rats , Receptors, Opioid, delta/genetics , Ribonuclease H/drug effects , Ribonuclease H/metabolism , Stereotaxic Techniques , Thionucleotides , Tumor Cells, Cultured
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