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Terms such as "treating" or "treatment" or "to treat" or "alleviating" or "to alleviate" refer to both (1) therapeutic measures that cure, slow down, lessen symptoms of, and/or halt progression of a diagnosed pathologic condition or disorder and (2) prophylactic or preventative measures that prevent and/or slow the development of a targeted pathologic condition or disorder. Thus, those in need of treatment include those already with the disorder; those prone to have the disorder; and those in whom the disorder is to be prevented. Thus, the term "transcript" can include exons, introns, 5' UTRs, and 3' UTRs. The term "nucleotide length" as used herein means the total number of the nucleotides (monomers) in a given sequence. IC50 or EC50 can be calculated by any number of means known in the art. The percentage is calculated by counting the number of aligned bases that are identical between the two sequences, dividing by the total number of contiguous monomers in the oligomer, and multiplying by 100. In such a comparison, if gaps exist, it is preferable that such gaps are merely mismatches rather than areas where the number of monomers within the gap differs between the oligomer of the invention and the target reg


> In determining the degree of "complementarity" between oligomers of the invention (or regions thereof) and the target region of the nucleic acid which encodes the mammalian gene, such as those disclosed herein, the degree of "complementarity" (also, "homology" or "identity") is expressed as the percentage identity (or percentage homology) between the sequence of the oligomer (or region thereof) and the sequence of the target region (or the reverse complement of the target region) that best aligns therewith. FIGS. 2, 16B, and 20B lists non-limiting examples of chemical structures that can be applied to any one of the oligomers disclosed herein. Expression produces a "gene product." As used herein, a gene product can be either a nucleic acid, e.g., a messenger RNA produced by transcription of a gene, or a polypeptide which is translated from a transcript. As used herein, the design of an oligomer is shown by a combination of upper case letters and lower case letters. As used herein, "conditional expression" may refer to any type of conditional expression including, but not limited to, inducible expression; repressible expression; expression in cells or tissues having a particular physiological, biological, or disease state, etc. This definition is not intended to exclude cell type or tissue specific express


The T cell manufacturing methods contemplated herein include modifying T cells to express one or more CARs as contemplated herein. The present disclosure provides methods for testing or determining the toxicity (e.g., in vivo acute neurotoxicity) of a molecule by measuring certain characteristics of the molecule. The present disclosure also provides methods for selecting a molecule having reduced toxic side effects. By "tolerable" is meant a molecule that is well tolerated by a live subject, e.g., a molecule that, when administered, causes no harmful effects that are either visible or can be tested for using general quality of life tests or by measuring in vivo tolerability scores as described herein. A "toxic" compound can cause toxic side effects when a subject is exposed to the toxic compound, such as by injection, ingestion, inhalation or other routes, and is not suitable for administration in mammal, e.g., rodent. The term "transcript" can be interchangeably used with "pre-mRNA" and "mRNA." After DNA strands are transcribed to primary transcripts, the newly synthesized primary transcripts are modified in several ways to be converted to their mature, functional forms to produce different proteins and RNAs such as mRNA, tRNA, rRNA, lncRNA, adult group chat miRNA and others. The term "comparable to" is used herein to mean a value that is as much as 30% less than or more than the reference value to which it is being compared.
Some things people cannot control, when it comes to mental health--one such thing being the genetic link, the ageing process, and our Free sex chatroom (pornvideowebsite.Com) life.I believe any educated and sensitive massage therapist will tell you that they intend to meet individuals who are more authentic in expressing themselves than perhaps one would just meet in an office setting ideally. Not being bound by any theory, the present disclosure identifies (i) a correlation between calcium oscillations of a molecule in vitro in neuronal cells and the sequence score of the molecule (e.g., polynucleotide comprising a sequence), (ii) a correlation between calcium oscillations of a molecule and the in vivo neurotoxicity of the molecule; (iii) a correlation between the sequence score of a molecule (e.g., polynucleotide comprising a sequence) and the in vivo neurotoxicity of the molecule, or cams porn (iv) any combination thereof. In one embodiment, the disclosure shows that a molecule exhibiting calcium oscillations in neuronal cells comparable to (i.e., less than 30% or higher than) the calcium oscillations in neuronal cells not exposed to the molecule shows less in vivo neurotoxicity when administered to a mammal in vivo. Such methods are helpful to reduce unnecessary killing of animals during testing of the molecule's toxicity and/or enhance the possibilities that the molecules will be safe for in vivo administration.
The present methods can also improve efficiency (i.e., shorten) the evaluation period of candidate molecules by reducing the screening time period for selection of molecules that do not exhibit in vivo acute neurotoxicity. The present methods comprise identifying molecules that have lower or reduced toxicity. For example, molecules can be assayed to determine if they have low toxicity (e.g., in vivo acute neurotoxicity), and if they are found to have low toxicity, the molecules are selected for use in further testing or administration to a subject such as a mammal. In some embodiments, if the molecule is found to have low toxicity, it is administered to a laboratory animal for further testing of the molecule. By "subject" or "individual" or "animal" or "patient" or "mammal," is meant any subject, particularly a mammalian subject, for whom diagnosis, prognosis, or therapy is desired. Mammalian subjects include humans, domestic animals, farm animals, sports animals, and zoo animals including, e.g., humans, non-human primates, dogs, cats, guinea pigs, rabbits, rats, mice, horses, cattle, bears, and so on. The phrase "pharmaceutically acceptable" is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk r
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