Abstract: This disclosure relates to novel modified oligonucleotides with increased stability. The universal modified nucleotide sequences to increase the stability of an oligonucleotide are also provided.

Abstract: Chemically modified crRNAs and tracrRNAs are provided. crRNAs and tracrRNAs with 5? and/or 3? conjugated moieties are provided. crRNAs and tracrRNAs with modifications in the repeat region of the crRNA or the anti-repeat region of the tracrRNA are provided. Methods of using the crRNAs and tracrRNAs for genome editing with a CRISPR nuclease and kits for performing the same are also provided.

Abstract: A bearing cap according to one embodiment of this disclosure includes: a concave part that supports a crankshaft of an internal combustion engine; first bosses that are disposed one on each side of the concave part and each have a first bolt hole; and second bosses that are disposed one on each side of a bearing cap main body having the concave part and the first bosses so as to flank the bearing cap main body and each have a second bolt hole. The bearing cap is fixed to a first member of the internal combustion engine by first bolts inserted into the first bolt holes, and to a second member of the internal combustion engine by second bolts inserted into the second bolt holes. At least the pair of second bosses have higher rigidity than a frame.

Abstract: A vehicle-body structure comprises a pair of right-and-left crash cans provided at an end portion of a vehicle body, being spaced apart from each other in a vehicle width direction, a bumper reinforcement extending in the vehicle width direction and connecting respective tip portions of the crash cans, set plates interposed between each of the crash cans and a vehicle-body side frame, wherein each of the crash cans is fixed to the vehicle-body side frame via the set plates, and a brace extending obliquely, in a plan view, from an inward side, in the vehicle width direction, of the crash can or the set plate to the bumper reinforcement such that a space is formed, in the vehicle with direction, between the brace and the crash can. The brace is fixedly joined to a lower face of the bumper reinforcement.

Abstract: The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; Wherein R1, R3-R6, X2 and X3 are as defined herein, a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

Abstract: Provided is a rear vehicle-body structure of a vehicle, capable of reducing vibrations transmitted from a rear wheel to a floor panel, while ensuring required performance for rear side frames and a cross member. The rear vehicle-body structure comprises a symmetric pair of frame members 6 extending in a vehicle longitudinal direction along respective lateral sides of a rear of a vehicle body of the vehicle, and a rear-side rear cross member 13 bridging the symmetric pair of frame members 6 in a vehicle width direction, wherein an attachment portion between each of the frame members 6 and the rear-side rear cross member 13 is provided with rigidity difference generation means 20 to generate a rigidity difference between the frame member 6 and the rear-side rear cross member 13.

Abstract: Provided is a rear vehicle body structure that includes: a right and left pair of frame members each extending in a front-rear direction and having a damper supporting part; rear wheel wells; a rear floor panel; a rear cross member upper part connecting the right and left pair of frame members to each other on a front side of the damper supporting parts; front side reinforcements provided along a vehicle cabin inner side of each of the rear wheel wells and extending in an up-down direction on the front side of the damper supporting parts; and a reinforcing member mounted on each of the frame members and having a reinforcing member main body that reinforces the damper supporting part and a reinforcing member coupling part that couples together the rear cross member upper part and the front side reinforcement.

Abstract: A recessed portion is formed at a frame member provided at a rear portion of a vehicle body and having a closed cross section extending in a vehicle longitudinal direction such that a part of a lower face of the frame member is recessed upwardly, where a damper of a rear suspension is inserted and fixed. A front portion of the frame member is joined to a side sill extending in the vehicle longitudinal direction at a position offset outwardly in a vehicle width direction from the frame member. Branch-shaped closed cross sections branching off from the closed cross section inwardly and outwardly relative to the damper are formed at a position corresponding to the recessed portion of the frame member. A portion of the frame member located at the above-described position is wide outwardly.

Abstract: A bearing cap according to one embodiment of this disclosure includes: a concave part that supports a crankshaft of an internal combustion engine; first bosses that are disposed one on each side of the concave part and each have a first bolt hole; and second bosses that are disposed one on each side of a bearing cap main body having the concave part and the first bosses so as to flank the bearing cap main body and each have a second bolt hole. The bearing cap is fixed to a first member of the internal combustion engine by first bolts inserted into the first bolt holes, and to a second member of the internal combustion engine by second bolts inserted into the second bolt holes. At least the pair of second bosses have higher rigidity than a frame.

Abstract: Novel oligonucleotides that enhance silencing of the expression of a gene containing a single nucleotide polymorphism (SNP) relative to the expression of the corresponding wild-type gene are provided. Methods of using novel oligonucleotides that enhance silencing of the expression of a gene containing a SNP relative to the expression of the corresponding wild-type gene are provided.

Abstract: A recessed portion is formed at a frame member provided at a rear portion of a vehicle body and having a closed cross section extending in a vehicle longitudinal direction, wherein the recessed portion is configured such that a lower face of the frame member is recessed upwardly and a damper is inserted into and fixed to the recessed portion. Closed cross sections are formed inside the frame member at a position corresponding to the recessed portion. These closed cross sections are configured to branch off from the closed cross section outwardly and inwardly relative to the damper. A reinforcing member is fixed to the frame member and a wheel house inner at the position corresponding to the recessed portion such that a space is formed at a corner portion of these.

Abstract: The invention provides a conjugate comprising a biomolecule linked to a fatty acid via a linker wherein the fatty acid has the following Formulae A1, A2 or A3: wherein R1, R2, R3, R4, Ak, n, m and p are defined herein. The invention also relates to a method for manufacturing the conjugate of the invention such as GDF15 conjugate, and its therapeutic uses such as treatment or prevention of metabolic disorders or diseases, type 2 diabetes mellitus, obesity, pancreatitis, dyslipidemia, alcoholic and nonalcoholic fatty liver disease/steatohepatitis and other progressive liver diseases, insulin resistance, hyperinsulinemia, glucose intolerance, hyperglycemia, metabolic syndrome, hypertension, cardiovascular disease, atherosclerosis, peripheral arterial disease, stroke, heart failure, coronary heart disease, diabetic complications (including but not limited to chronic kidney disease), neuropathy, gastroparesis and other metabolic disorders.

Abstract: This disclosure relates to novel modified oligonucleotides. Novel modified siRNA are also provided.

Abstract: The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; Wherein R1, R3-R6, X2 and X3 are as defined herein, a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

Abstract: A recessed portion is formed at a frame member provided at a rear portion of a vehicle body and having a closed cross section extending in a vehicle longitudinal direction such that a part of a lower face of the frame member is recessed upwardly, where a damper of a rear suspension is inserted and fixed. Closed cross sections are formed at a position corresponding to the recessed portion, in a longitudinal direction, of the frame member. The closed cross sections are configured to branch off from the closed cross section inwardly and outwardly in the vehicle width direction relative to the damper. A ridgeline extending in the vehicle longitudinal direction is formed at least at a portion of the frame member which is positioned in front of the recessed portion.

Abstract: A recessed portion is formed at a lower face of a frame member provided at a vehicle rear portion and having a closed cross section extending in a vehicle longitudinal direction, where a damper of a rear suspension is inserted into and fixed. A front portion of the frame member is joined to a side sill extending in the vehicle longitudinal direction at a position offset outwardly from the frame member. Branch-shaped closed cross sections branching off from the closed cross section inwardly and outwardly relative to the damper are formed at a recessed-portion corresponding position. A front portion of the frame member located in front of the recessed-portion corresponding position extends in an oblique direction forwardly and outwardly and a front end of the frame member is joined to a rear portion of the side sill.

Abstract: Novel oligonucleotides that enhance silencing of the expression of a gene containing a single nucleotide polymorphism (SNP) relative to the expression of the corresponding wild-type gene are provided. Methods of using novel oligonucleotides that enhance silencing of the expression of a gene containing a SNP relative to the expression of the corresponding wild-type gene are provided.

Abstract: A vehicle-body structure comprises a pair of right-and-left crash cans provided at an end portion of a vehicle body, being spaced apart from each other in a vehicle width direction, a bumper reinforcement extending in the vehicle width direction and connecting respective tip portions of the crash cans, set plates interposed between each of the crash cans and a vehicle-body side frame, wherein each of the crash cans is fixed to the vehicle-body side frame via the set plates, and a brace extending obliquely, in a plan view, from an inward side, in the vehicle width direction, of the crash can or the set plate to the bumper reinforcement such that a space is formed, in the vehicle with direction, between the brace and the crash can. The brace is fixedly joined to a lower face of the bumper reinforcement.

Abstract: Provided is a rear vehicle body structure that includes: a right and left pair of frame members each extending in a front-rear direction and having a damper supporting part; rear wheel wells; a rear floor panel; a rear cross member upper part connecting the right and left pair of frame members to each other on a front side of the damper supporting parts; front side reinforcements provided along a vehicle cabin inner side of each of the rear wheel wells and extending in an up-down direction on the front side of the damper supporting parts; and a reinforcing member mounted on each of the frame members and having a reinforcing member main body that reinforces the damper supporting part and a reinforcing member coupling part that couples together the rear cross member upper part and the front side reinforcement.

Abstract: A recessed portion is formed at a frame member provided at a rear portion of a vehicle body and having a closed cross section extending in a vehicle longitudinal direction such that a part of a lower face of the frame member is recessed upwardly, where a damper of a rear suspension is inserted and fixed. Closed cross sections are formed at a position corresponding to the recessed portion, in a longitudinal direction, of the frame member. The closed cross sections are configured to branch off from the closed cross section inwardly and outwardly in the vehicle width direction relative to the damper. A ridgeline extending in the vehicle longitudinal direction is formed at least at a portion of the frame member which is positioned in front of the recessed portion.