Abstract: A compound useful as an active ingredient of a pharmaceutical composition for treatment of cancer related to activation of immune cells or cancer resistant to anti-PD-1 antibody/anti-PD-L1 antibody therapy is provided. The present inventors have conducted studies on a compound useful as an active ingredient of a pharmaceutical composition for treatment of cancer related to activation of immune cells or cancer resistant to anti-PD-1 antibody/anti-PD-L1 antibody therapy, and confirmed that a heteroaryl carboxamide compound has DGK ? (DGKzeta) inhibitory effect, leading to completion of the present invention. The heteroaryl carboxamide compound of the present invention has DGK ? inhibitory effect, and can be used as a therapeutic agent for treatment of cancer related to activation of immune cells or cancer resistant to anti-PD-1 antibody/anti-PD-L1 antibody therapy.

Abstract: A compound useful as an active ingredient of a pharmaceutical composition for treatment of cancer related to activation of immune cells or cancer resistant to anti-PD-1 antibody/anti-PD-L1 antibody therapy is provided. The present inventors have conducted studies on a compound useful as an active ingredient of a pharmaceutical composition for treatment of cancer related to activation of immune cells or cancer resistant to anti-PD-1 antibody/anti-PD-L1 antibody therapy, and confirmed that a heteroaryl carboxamide compound has DGK ? (DGKzeta) inhibitory effect, leading to completion of the present invention. The heteroaryl carboxamide compound of the present invention has DGK ? inhibitory effect, and can be used as a therapeutic agent for treatment of cancer related to activation of immune cells or cancer resistant to anti-PD-1 antibody/anti-PD-L1 antibody therapy.

Abstract: Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.

Abstract: The present invention addresses the problem of providing a pharmaceutical composition, in particular a compound suitable for prevention and/or treatment of an inflammatory disease and/or a neurodegenerative disease. The inventors of the present invention conducted extensive studies to find a compound that has suppressive action on NLRP3 inflammasome activation, and found that a substituted pyridazine compound has suppressive action on NLRP3 inflammasome activation, leading to completion of the present invention. The substituted pyridazine compound according to the present invention is expected to serve as a drug for prevention and/or treatment of an inflammatory disease and/or a neurodegenerative disease.

Abstract: Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.

Abstract: Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.

Abstract: A charged-particle beam writing apparatus includes a writing chamber to house a stage having a writing object placed thereon, a beam irradiator to irradiate a charged particle beam to the writing object placed on the stage, a stage driver to move the stage, a temperature distribution calculator to calculate temperature distribution of the writing object caused by a heat source in the writing chamber, based on movement history information of the stage, a deformed amount calculator to calculate a deformed amount of the writing object based on a constraint condition of the writing object placed on the stage and the calculated temperature distribution, and a position corrector to correct an irradiation position of the charged particle beam to the writing object based on the calculated deformed amount. The beam irradiator irradiates the charged particle beam based on the irradiation position corrected by the position corrector.

Abstract: Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.

Abstract: A charged-particle beam writing apparatus includes a writing chamber to house a stage having a writing object placed thereon, a beam irradiator to irradiate a charged particle beam to the writing object placed on the stage, a stage driver to move the stage, a temperature distribution calculator to calculate temperature distribution of the writing object caused by a heat source in the writing chamber, based on movement history information of the stage, a deformed amount calculator to calculate a deformed amount of the writing object based on a constraint condition of the writing object placed on the stage and the calculated temperature distribution, and a position corrector to correct an irradiation position of the charged particle beam to the writing object based on the calculated deformed amount. The beam irradiator irradiates the charged particle beam based on the irradiation position corrected by the position corrector.

Abstract: Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.

Abstract: Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.

Abstract: Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.

Abstract: Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.

Abstract: Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.

Abstract: In one embodiment, an aperture member producing method includes applying a charged particle beam to a plurality of chip areas on a first substrate while changing a writing condition to write a first pattern corresponding to an aperture opening, processing the first substrate based on the written first pattern to form a second pattern, cutting out a chip area provided with the second pattern having desired accuracy from the first substrate to produce a template, allowing the template to come into contact with a resist overlying a front surface of a second substrate, separating the template from the hardened resist to pattern the resist with a transfer pattern, processing the second substrate using the transfer pattern as a mask to form a first recess, and etching a rear surface of the second substrate to form a second recess communicating with the first recess.

Abstract: In one embodiment, an aperture member producing method includes applying a charged particle beam to a plurality of chip areas on a first substrate while changing a writing condition to write a first pattern corresponding to an aperture opening, processing the first substrate based on the written first pattern to form a second pattern, cutting out a chip area provided with the second pattern having desired accuracy from the first substrate to produce a template, allowing the template to come into contact with a resist overlying a front surface of a second substrate, separating the template from the hardened resist to pattern the resist with a transfer pattern, processing the second substrate using the transfer pattern as a mask to form a first recess, and etching a rear surface of the second substrate to form a second recess communicating with the first recess.

Abstract: A multi charged particle beam writing apparatus includes a beam forming member, where first openings for writing and second openings not for writing around the first openings are formed, to form multiple beams for writing and to form multiple beams for measurement, plural mark members on a blanking aperture member arranged close to the height position where crossover is formed, a measurement unit to measure positions of the multiple beams for measurement by the plural mark members, and a correction unit to correct a voltage for making a “beam on” state applied to one of the plural blankers, in order to correct a position deviation amount of a measured position.

Abstract: A multi charged particle beam writing apparatus includes a beam forming member, where first openings for writing and second openings not for writing around the first openings are formed, to form multiple beams for writing and to form multiple beams for measurement, plural mark members on a blanking aperture member arranged close to the height position where crossover is formed, a measurement unit to measure positions of the multiple beams for measurement by the plural mark members, and a correction unit to correct a voltage for making a “beam on” state applied to one of the plural blankers, in order to correct a position deviation amount of a measured position.

Abstract: A charged particle beam writing apparatus includes an unit to measure height positions of a substrate, an unit to input a position dependent height distribution obtained by converting each position error of a pattern generated depending on each corresponding writing position of the substrate into a value in a height direction, and to add the position dependent height distribution to a height distribution obtained based on the height positions in order to correct the height distribution of the substrate, an unit to calculate a deflection shift amount of a pattern to be written by using a corrected height distribution, an unit to calculate a deflection amount for deflecting a beam to a position where a calculated deflection shift amount has been corrected, and an unit to write a pattern on the substrate by deflecting the beam by a calculated deflection amount.

Abstract: A writing area of a sample is divided into a plurality of stripes having a width corresponding to an area density of a pattern to be written on the sample with a charged-particle beam. The writing is stopped when writing of at least one stripe is terminated, and a drift amount is measured. An irradiation position of the charged-particle beam is corrected with the use of the drift amount. When the average value of the area density is more than a predetermined value, a stripe has a width smaller than the reference width, and when the average value of the area density is less than the predetermined value, the stripe has a width larger than the reference width. The width of the stripe is preferably a width corresponding to the variation of a drift from the beginning of irradiation with the charged-particle beam.