Abstract: A lift mechanism of a die set apparatus includes a guide pin, a linear motion guide member, a first washer, a second washer, a first coil spring, and a second coil spring. A first positioning portion and a second positioning portion control a first end turn portion and a second end turn portion from moving in a radial direction of the guide pin in a state where a first gap is formed between the first coil spring and the guide pin. A third positioning portion and a fourth positioning portion control a third end turn portion and a fourth end turn portion from moving in the radial direction of the guide pin in a state where a second gap is formed between the second coil spring and the guide pin.

Abstract: A superconducting magnet includes a superconducting coil, a coolant container, a radiation shield, a first pipe, a second pipe, a refrigerator, and a connection pipe. The refrigerator is fixed to seal a tip end of the second pipe, and is inserted in the second pipe to define a flow path of a coolant between the refrigerator and the second pipe. The connection pipe makes the interiors of the first pipe and the second pipe communicate with each other inside a vacuum container. The connection pipe includes a first connection portion connecting to the first pipe and a second connection portion connecting to the second pipe. The second connection portion is located between the vacuum container and the radiation shield.

Abstract: Among other things, the present disclosure provides technologies for altering splicing, particularly for increasing inclusion of exons in splicing products. In some embodiments, the present disclosure provides SMN2 oligonucleotides, compositions, and methods thereof. In some embodiments, the present disclosure provides chirally controlled SMN2 oligonucleotide compositions. In some embodiments, provided oligonucleotides and compositions can increase level of an exon 7-containing SMN2 splicing product and/or a gene product thereof. In some embodiments, the present disclosure provides methods for treatment of splicing-related conditions, disorders and diseases. In some embodiments, the present disclosure provides methods for treating SMN2-related conditions, disorders and diseases such as SMA (spinal muscular atrophy) and ALS (amyotrophic lateral sclerosis).

Abstract: Among other things, the present disclosure provides designed APOC3 oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide improved single-stranded RNA interference and/or RNase H-mediated knockdown. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., RNA interference (RNAi) activity, stability, delivery, etc.

Abstract: The present disclosure pertains to the recognition that immune responses mediated by CpG oligonucleotides can be affected by the stereochemistry of modified internucleotidic linkages such as phosphorothioates. In some embodiments, the present disclosure relates to chirally controlled CpG oligonucleotide compositions comprising CpG oligonucleotides comprising multiple modified internucleotidic linkages such as phosphorothioate linkages, wherein the oligonucleotides comprise one or more CpG region motifs having defined stereochemistry patterns of chiral internucleotidic linkages. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are capable of agonizing an immune response. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are antagonistic. Methods for making and using chirally controlled CpG oligonucleotide compositions are also described.

Abstract: The present invention relates to chirally controlled oligonucleotides, chirally controlled oligonucleotide compositions, and the method of making and using the same. The invention specifically encompasses the identification of the source of certain problems with prior methodologies for preparing chiral oligonucleotides, including problems that prohibit preparation of fully chirally controlled compositions, particularly compositions comprising a plurality of oligonucleotide types. In some embodiments, the present invention provides chirally controlled oligonucleotide compositions. In some embodiments, the present invention provides methods of making chirally controlled oligonucleotides and chirally controlled oligonucleotide compositions.

Abstract: The present invention relates to chirally controlled oligonucleotides of select designs, chirally controlled oligonucleotide compositions, and methods of making and using the same. In some embodiments, a provided chirally controlled oligonucleotide composition provides different cleavage patterns of a nucleic acid polymer than a reference oligonucleotide composition. In some embodiments, a provided chirally controlled oligonucleotide composition provides single site cleavage within a complementary sequence of a nucleic acid polymer.

Abstract: A superconducting magnet apparatus includes a first superconducting coil centered around an axis extending in a direction intersecting with a vertical direction and a refrigerant circulation circuit through which refrigerant circulates. The refrigerant circulation circuit includes a first cooling pipe path in thermal contact with the first superconducting coil, an upper pipe path arranged above the first cooling pipe path, a lower pipe path arranged below the first cooling pipe path, and a connection pipe path that connects the upper pipe path and the lower pipe path to each other. The first cooling pipe path includes a first storage portion where refrigerant is stored.

Abstract: Among other things, the present disclosure provides oligonucleotides, compositions, and methods thereof. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., knockdown ability, stability, delivery, etc. In some embodiments, the oligonucleotides decrease the expression, activity and/or level of a C9orf72 gene, including but not limited to, one comprising a repeat expansion, or a gene product thereof.

Abstract: A tire includes side protectors arranged in a sidewall portion. Each of the side protectors is provided with a groove. The groove includes a first inclined groove portion inclined to a first side with respect to the tire radial direction, or a second inclined groove portion inclined to a second side opposite to the first side with respect to the tire radial direction. The side protectors include first protectors each provided with the first inclined groove portion, and second protectors each provided with the second inclined groove portion.

Abstract: Among other things, the present disclosure provides oligonucleotides, compositions, and methods thereof. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., knockdown ability, stability, delivery, etc. In some embodiments, the oligonucleotides decrease the expression, activity and/or level of a C9orf72 gene, including but not limited to, one comprising a repeat expansion, or a gene product thereof.

Abstract: The present invention relates to chirally controlled oligonucleotides of select designs, chirally controlled oligonucleotide compositions, and methods of making and using the same. In some embodiments, a provided chirally controlled oligonucleotide composition provides different cleavage patterns of a nucleic acid polymer than a reference oligonucleotide composition. In some embodiments, a provided chirally controlled oligonucleotide composition provides single site cleavage within a complementary sequence of a nucleic acid polymer.

Abstract: A heat pipe includes an insulating hollow body located inside an outer conductor. The insulating hollow body insulates a portion of the heat pipe on an outer conductor side and a portion of the heat pipe on an inner conductor side from each other. The heat pipe has a plurality of sections each connecting a corresponding one of a plurality of connection conductors to the insulating hollow body. The heat pipe further includes a communication path connecting portions of the heat pipe to each other to cause the plurality of sections to be in communication with each other. Each of the portions is connected to a corresponding one of the plurality of connection conductors.

Abstract: Among other things, the present disclosure provides designed PNPLA3 oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide improved single-stranded RNA interference and/or RNase H-mediated knockdown. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., RNA interference (RNAi) activity, stability, delivery, etc.

Abstract: Among other things, the present disclosure provides designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide improved single-stranded RNA interference and/or RNase H-mediated knockdown. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., RNA interference (RNAi) activity, stability, delivery, etc.

Abstract: A superconducting magnet device with which device breakage caused by a quench can be avoided while helium consumption is reduced. A sheet-like convection-preventing member is disposed at least either above or below a heat transfer member transferring to gaseous helium heat transferred from the outside, so as to cover a helium gas release tube for the gaseous helium, and thus heat exchange performance during transportation is improved. In the case where the quench occurs, the convection-preventing member is lifted upward in the release tube, thereby ensuring to provide a flow path for the gaseous helium and avoiding excessive increase of the internal pressure.

Abstract: The present invention relates to chirally controlled oligonucleotides, chirally controlled oligonucleotide compositions, and the method of making and using the same. The invention specifically encompasses the identification of the source of certain problems with prior methodologies for preparing chiral oligonucleotides, including problems that prohibit preparation of fully chirally controlled compositions, particularly compositions comprising a plurality of oligonucleotide types. In some embodiments, the present invention provides chirally controlled oligonucleotide compositions. In some embodiments, the present invention provides methods of making chirally controlled oligonucleotides and chirally controlled oligonucleotide compositions.

Abstract: Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.

Abstract: Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.

Abstract: In some embodiments, the present disclosure pertains to compositions and methods related to delivery of a biologically active agent, wherein the compositions comprise a biologically active agent and a lipid. In various embodiments, the lipid is selected from: lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, alpha-linolenic acid, gamma-linolenic acid, docosa-hexaenoic acid (cis-DHA), turbinaric acid and dilinoleyl. In some embodiments, a composition and method are useful for delivery of a biologically active agent to a particular cell or tissue, e.g., a muscle cell or tissue.