Abstract: An object of the present invention is to provide methods of discovering drugs effective for tough targets, which have conventionally been discovered only with difficulty. The present invention relates to novel methods for cyclizing peptide compounds, and novel peptide compounds and libraries comprising the same, to achieve the above object.

Abstract: A DC power supply including a resonant circuit on a secondary side of a transformer suppresses a surge voltage during power recovery of diodes constituting a rectifier circuit, correctly estimates a load current from a secondary current of the transformer, and adjusts supplied power when a load is light. The DC power supply includes a DC voltage source, a converter, a transformer, a rectifier circuit, a resonant circuit composed of a resonant switch and a resonant capacitor, a filter reactor, a filter capacitor, a snubber diode, a snubber capacitor, a load, first and second voltage sensors, a current sensor, and a controller for controlling gate pulses of semiconductor devices constituting a converter and the resonant switch and a signal for adjusting operation timings of A/D converters converting the signals of these sensors.

Abstract: Semiconductor element groups constituting a unit are mounted on a cooler heat receiving part 1 on the same plane and are adapted to radiate heat by self-cooling or cooling by wind. First and fourth semiconductor elements Q1, Q4 are arranged on the lower side of the cooler heat receiving part, second and third semiconductor elements Q2, Q3 are arranged in the middle, a first diode D5 and a second diode D6 are arranged on the upper side, the first and second semiconductor elements Q1, Q2, as well as the third and fourth semiconductor elements Q3, Q4 are each arranged in positions opposite to each other in a horizontal direction with respect to a centerline of a cooler in a vertical direction.

Abstract: Various bispecific antibodies that specifically bind to both blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X and functionally substitute for the cofactor function of blood coagulation factor VIII, that is, the function to promote activation of blood coagulation factor X by activated blood coagulation factor IX, were produced. From these antibodies, multispecific antigen-binding molecules having a high activity of functionally substituting for blood coagulation factor VIII were successfully discovered.

Abstract: A body cover structure for saddle-ride type vehicles that enables enhancement of the user's comfort while increasing the rigidity of covering members constituting a center tunnel part. Step floors are configured of forward inclined parts disposed ahead of the floors in a forward rising shape, horizontal parts disposed either substantially horizontally or in a rearwardly rising shape behind these forward inclined parts, and bent parts connecting the forward inclined parts and the horizontal parts. The middle covers are provided on the lower edges thereof with downwardly extending parts extending toward the bent parts.

Abstract: In a DC power supply in which a DC power source and a transformer are connected via a power conversion circuit and a secondary winding of the transformer is connected to a load via a rectifier diode bridge and a filter circuit to supply power to the load, a resonance reactor is provided on an output side of the transformer, a resonant switch circuit including a parallel circuit of a diode and a semiconductor switch and a resonant capacitor is connected in parallel to the rectifier diode bridge and a snubber circuit including a snubber capacitor, a snubber diode and a diode for discharge is connected to a serial resonant circuit including the resonance reactor and the resonant capacitor in the resonant switch circuit to absorb a surge voltage.

Abstract: Various bispecific antibodies that specifically bind to both blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X and functionally substitute for the cofactor function of blood coagulation factor VIII, that is, the function to promote activation of blood coagulation factor X by activated blood coagulation factor IX, were produced. From these antibodies, multispecific antigen-binding molecules having a high activity of functionally substituting for blood coagulation factor VIII were successfully discovered.

Abstract: In a conventional solid-state laser device, uniformity of an excitation distribution around the axis of a solid-state laser medium is only considered, and symmetry of the excitation distribution in the optical axis direction of the solid-state laser device as a whole is not considered. Therefore, there has been a problem that it is difficult to generate a high-power and high-quality laser beam with high efficiency. In order to solve the problem, in the present invention, excitation modules 51, 52 of an even number is provided, along the optical axis of a solid-state laser beam 18, near the center of a resonator, and semiconductor lasers 21-28 serving as excitation light sources and solid-state laser media 11, 12 provided in the excitation module 51 or in the excitation module 52 are arranged to be symmetrical with respect to a virtual symmetry plane 61 located at a center gap between the excitation modules of the even number.

Abstract: Various bispecific antibodies that specifically bind to both blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X and functionally substitute for the cofactor function of blood coagulation factor VIII, that is, the function to promote activation of blood coagulation factor X by activated blood coagulation factor IX, were produced. From these antibodies, multispecific antigen-binding molecules having a high activity of functionally substituting for blood coagulation factor VIII were successfully discovered.

Abstract: A body cover structure for saddle-ride type vehicles that enables enhancement of the user's comfort while increasing the rigidity of covering members constituting a center tunnel part. Step floors are configured of forward inclined parts disposed ahead of the floors in a forward rising shape, horizontal parts disposed either substantially horizontally or in a rearwardly rising shape behind these forward inclined parts, and bent parts connecting the forward inclined parts and the horizontal parts. The middle covers are provided on the lower edges thereof with downwardly extending parts extending toward the bent parts.

Abstract: An auxiliary machine mounting structure of a saddle-ride type vehicle that ensures consistent appearance irrespective of the presence or absence of a mounting of an auxiliary machine or device such as an antenna being mounted on a meter visor to ensure the degree of freedom in layout without having to consider the possibility of the windshield creating a ghost image of the auxiliary machine or device. An opening is formed on the windshield side of the meter visor. An ETC cover is detachably mounted on the meter visor to cover the opening. An antenna is positioned beneath the ETC cover and disposed in the opening.

Abstract: Focusing on the fact that antibody molecules with one H chain are not secreted when using the “knobs-into-holes” method, the present inventors revealed that desired bispecific antibodies can be preferentially formed by first expressing the H and L chains of one arm, and then suppressing their expression, followed by expressing the H and L chains of the other arm so that first desired HL molecules (HaLa and HbLb) are constructed, and then the H chains are paired with each other (H2L2). The present invention was thus completed.

Abstract: The present inventors succeeded in discovering specific amino acid mutations in the variable region, framework region, and constant region of TOCILIZUMAB, and this enables to reduce immunogenicity risk and the heterogeneity originated from disulfide bonds in the hinge region, as well as to improve antigen binding activity, pharmacokinetics, stability under acidic conditions, and stability in high concentration preparations.

Abstract: The present invention provides pharmaceutical compositions comprising second-generation molecules that are superior than TOCILIZUMAB, by altering the amino acid sequences of the variable and constant regions of TOCILIZUMAB, which is a humanized anti-IL-6 receptor IgG1 antibody, to enhance the antigen-neutralizing ability and increase the pharmacokinetics, so that the therapeutic effect is exerted with a less frequency of administration, and the immunogenicity, safety and physicochemical properties (stability and homogeneity) are improved. The present invention also provides methods for producing these pharmaceutical compositions. The present inventors have successfully generated second-generation molecules that are superior to TOCILIZUMAB by appropriately combining amino acid sequence alterations in the CDR domains, variable regions, and constant regions.

Abstract: In order to cause the residual magnetic flux in an induction motor to decay in a short time without an excessive current flow, an induction motor control apparatus continues an operation in which an inverter apparatus is caused to output a zero voltage to the induction motor for a predetermined time before deactivating an operation of the inverter apparatus.

Abstract: The present invention relates to methods of screening for commonly shared light chains, in which the method comprises the steps of (a) generating a host secreting the heavy chain of an antibody that binds to a desired antigen; (b) introducing an antibody light chain library into the host of step (a) to generate libraries presenting antibodies composed of the heavy chain and the light chains; (c) selecting a library presenting antibodies that bind specifically to the desired antigen of step (a); (d) introducing the library selected in step (c) into a host secreting the heavy chain of an antibody that binds to a desired antigen different from the antigen of step (a) to generate libraries that display antibodies composed of the heavy chains and light chains; and (e) selecting a library that displays antibodies that bind specifically to the desired antigen of step (d).

Abstract: A DC power supply including a resonant circuit on a secondary side of a transformer suppresses a surge voltage during power recovery of diodes constituting a rectifier circuit, correctly estimates a load current from a secondary current of the transformer, and adjusts supplied power when a load is light. The DC power supply includes a DC voltage source, a converter, a transformer, a rectifier circuit, a resonant circuit composed of a resonant switch and a resonant capacitor, a filter reactor, a filter capacitor, a snubber diode, a snubber capacitor, a load, first and second voltage sensors, a current sensor, and a controller for controlling gate pulses of semiconductor devices constituting a converter and the resonant switch and a signal for adjusting operation timings of A/D converters converting the signals of these sensors.

Abstract: The present invention provides pharmaceutical compositions comprising second-generation molecules that are superior than TOCILIZUMAB, by altering the amino acid sequences of the variable and constant regions of TOCILIZUMAB, which is a humanized anti-IL-6 receptor IgG1 antibody, to enhance the antigen-neutralizing ability and increase the pharmacokinetics, so that the therapeutic effect is exerted with a less frequency of administration, and the immunogenicity, safety and physicochemical properties (stability and homogeneity) are improved. The present invention also provides methods for producing these pharmaceutical compositions. The present inventors have successfully generated second-generation molecules that are superior to TOCILIZUMAB by appropriately combining amino acid sequence alterations in the CDR domains, variable regions, and constant regions.