E26. The method of embodiment 25, wherein the mRNA is pre-mRNA or mature mRNA. E3. The method of embodiment 2, wherein the control cells are vehicle control cells. E2. The method of embodiment 1, wherein the calcium oscillations of the molecule are compared to the calcium oscillations in neuronal cells that are not exposed to the molecule ("control cells"). Not that I’m necessarily a control freak but I’d never had that sexually. E52. The method of any one of embodiments 16 to 51, wherein the polynucleotide comprises at least one nucleotide analog. E8. The method of any one of embodiments 1 to 7, wherein the molecule comprises a small molecule, a polynucleotide, a protein, a peptide, or any combination thereof. 5. The method of claim 1, wherein the molecule comprises a small molecule, a polynucleotide, a protein, a peptide, or any combination thereof. 15. The method of claim 14, wherein the behavioral test is a short term memory test, hot naked pornstars a spatial learning and chatbulate memory test, a gait analysis test, or any combination thereof. E42. The method of any one of embodiments 1 to 41, further comprising measuring a behavioral test score of the molecule.

E86. In the methods of Embodiments 81 to 85, the improvement further comprising measuring reduction of in vitro expression of a target protein of the molecule. E30. The method of any one of embodiments 23 to 29, wherein the antisense oligonucleotide modulates protein expression encoded by the target protein in the culture of the neuronal cells. E25. The method of embodiment 23, wherein the antisense oligonucleotide targets an mRNA of the target protein. E50. The method of embodiment 49, wherein the molecule treats or prevents a disease or condition. E48. The method of any one of embodiments 1 to 47, further comprising administering the molecule to a subject in need of treatment for a disease or condition. E81. In a method of testing or determining in vivo neurotoxicity of a molecule, the improvement comprising measuring calcium oscillations in vitro in neuronal cells which are in contact with the molecule. The present invention provides methods where the in vivo tolerability is graded into one of five tolerability categories.

In other embodiments, the present disclosure provides a method of selecting a molecule having tolerable in vivo acute neurotoxicity comprising measuring in vivo tolerability. E33. The method of any one of embodiments 1 to 32, further comprising measuring an in vivo tolerability of the molecule. The present disclosure provides a method of testing or determining in vivo acute neurotoxicity of a molecule comprising measuring oscillations in intracellular free calcium concentration ("calcium oscillations") in vitro in neuronal cells which are in contact with the molecule. A method of testing or determining in vivo acute neurotoxicity of a molecule comprising measuring calcium oscillations in vitro in neuronal cells which are in contact with the molecule. E1. A method of testing or determining in vivo acute neurotoxicity of a molecule comprising measuring calcium oscillations in vitro in neuronal cells which are in contact with the molecule. Thus, improved ways of determining the toxicity, such as the neurotoxicity, of a therapeutic molecule without requiring animal testing are needed.

While animal studies can be performed to determine toxicity, it is neither ethically nor economically desirable to perform animal studies where a large number of animals die due to a large number of the molecules being tested having toxic properties. They accept only limited number or banks and cards. Sequence score for each oligomer was calculated by inserting appropriate numbers in the formula: ((number of C nucleotides or the analogs-number of G nucleotides)/nucleotide length (number) in the oligomer). E43. The method of embodiment 42, wherein the behavioral test score is measured by administering the molecule to a mammal and grading the mammal's` behavioral performance. 14. The method of claim 1, further comprising measuring a behavioral test score of the molecule. 18. The method of claim 1, wherein when the molecule is administered to laboratory animals, more than 20% of the animals survive. Offering more personal interaction in the sex business can raise risks for some models — bullying is common, but some customers also can be downright scary.

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