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: 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 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: A tire includes a tread portion 2. At least one middle lateral groove 10 includes first and second middle tie bars 16 and 17. First and second middle sipes 21 and 22 are provided on a ground-contact surface 15s of at least one middle block 15. The first middle sipe 21 includes a termination end 21a located on an inner side in a tire axial direction with respect to the first middle tie bar 16. The second middle sipe 22 includes a termination end 22a located on an outer side in the tire axial direction with respect to the second middle tie bar 17 and on the inner side in the tire axial direction with respect to the termination end 21a of the first middle sipe 21. On the ground-contact surface 15s of the middle block 15, no groove and no sipe are provided in a first region 23.

Abstract: A display device includes a display panel that includes a first hole and a device housing that is configured such that the display panel is fastened and fixed to the device housing by a screw passed through the first hole and screwed into the screw hole. The display panel includes a display-side positioning part which is configured to fit to a portion of the device housing to perform positioning of the display panel with respect to the device housing and which includes the first hole, and the device housing includes a housing-side positioning part which is configured to fit to the display-side positioning part to perform the positioning and which includes a second hole formed so as to communicate with the first hole when the housing-side positioning part is fitted to the display-side positioning part.

Abstract: Among other things, the present disclosure provides oligonucleotides and compositions thereof. In some embodiments, provided oligonucleotides and compositions are useful for adenosine modification. In some embodiments, the present disclosure provides methods for treating various conditions, disorders or diseases that can benefit from adenosine modification.

Abstract: Among other things, the present disclosure provides oligonucleotides and compositions thereof. In some embodiments, provided oligonucleotides and compositions are useful for adenosine modification. In some embodiments, the present disclosure provides methods for treating various conditions, disorders or diseases that can benefit from adenosine modification.

Abstract: A disk drive suspension of the embodiments includes a load beam, and a flexure including a mounting portion on which a slider is mounted and overlapping with the load beam. The load beam includes a tab further extending than the mounting portion longitudinal direction of the load beam. The tab is shaped in an arc such that a central portion in a lateral direction protrudes with respect to both end portions in the lateral direction, in the load beam. Each of the both end portions includes a flat surface parallel to the lateral direction.

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, docosahexaenoic 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.

Abstract: Among other things, the present disclosure provides oligonucleotides, compositions, and methods for preventing and/ or treating various conditions, disorders or diseases. In some embodiments, provided technologies comprise nucleobase modifications, sugar modifications, intemucleotidic linkage modifications and/or patterns thereof, and have improved properties, activities and/or selectivities. In some embodiments, provided technologies target MAPT. In some embodiments, the present disclosure provides MAPT oligonucleotides, compositions and methods for preventing and/or treating MAPT-associated conditions, disorders or diseases, such as Alzheimer’s Disease (AD) or Frontotemporal Dementia (FTD).

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 disclosure, among other things, provides technologies for synthesis, including reagents and methods for stereoselective synthesis. In some embodiments, the present disclosure provides compounds useful as chiral auxiliaries. In some embodiments, the present disclosure provides reagents and methods for oligonucleotide synthesis. In some embodiments, the present disclosure provides reagents and methods for chirally controlled preparation of oligonucleotides. In some embodiments, technologies of the present disclosure are particularly useful for constructing challenging internucleotidic linkages, providing high yields and stereoselectivity.

Abstract: Among other things, the present disclosure provides oligonucleotides and compositions thereof. In some embodiments, provided oligonucleotides and compositions are useful for adenosine modification. In some embodiments, the present disclosure provides methods for treating various conditions, disorders or diseases that can benefit from adenosine modification.

Abstract: The present disclosure provides double stranded oligonucleotides, compositions, and methods relating thereto. The present disclosure encompasses the recognition that structural elements of double stranded oligonucleotides, such as base sequence, chemical modifications (e.g, modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, 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. The present disclosure also provides methods for treatment of diseases using provided double stranded oligonucleotide compositions, for example, in RNA interference.

Abstract: The present disclosure provides modified oligonucleotides and compositions and methods thereof. In some embodiments, provided technologies comprise modified sugars and/or modified internucleotidic linkages. In some embodiments, the present disclosure provides technologies for preparing modified oligonucleotides. In some embodiments, the present disclosure provides chirally controlled oligonucleotide compositions and methods for their preparation and uses.

Abstract: A pneumatic tire includes a tread portion having a tread rubber and a tire inner cavity surface, and a noise damper made of a porous material fixed to the tire inner cavity surface. The tread rubber includes an outer tread rubber having a ground-contacting surface, and an inner tread rubber disposed inwardly in the tire radial direction of the outer tread rubber and outwardly in the tire radial direction of the noise damper. A loss tangent tan ? of the inner tread rubber at 30° C. is smaller than a loss tangent tan ? of the outer tread rubber at 30° C.

Abstract: Among other things, the present disclosure provides RHO oligonucleotides, compositions, and methods. In some embodiments, provided oligonucleotides comprise nucleobase modifications, sugar modifications, internucleotidic linkage modifications and/or patterns thereof, and have improved properties, activities and/or selectivities. In some embodiments, the present disclosure provides RHO oligonucleotides, compositions and methods for preventing and/or treating RHO-related conditions, disorders or diseases, such as retinopathy (e.g, retinal degeneration, retinal degenerative disease, retinal degenerative disorder, inherited retinal degenerative disorder, retinitis pigmentosa, autosomal dominant retinitis pigmentosa, etc.).

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: A spool has a cylindrical outer shape extending in an axial direction intersecting an upward/downward direction, the spool having an outer circumferential surface in which a plurality of annular groove portions extending in a circumferential direction are formed with a space being interposed between the plurality of annular groove portions in the axial direction, a superconducting coil being wound and accommodated inside each of the plurality of annular groove portions. A cover portion is attached to the spool so as to cover each of the plurality of annular groove portions, the cover portion and the plurality of annular groove portions forming a plurality of annular flow paths for refrigerant to cool the superconducting coil. One or more communication paths extend in parallel with the axial direction to communicate adjacent annular flow paths of the plurality of annular flow paths with each other.