Farnesyl diphosphate synthases have been shown to possess seven highly conserved regions (I-VII) in their amino acid sequences [Koyama et al. (1993) J. Biochem. (Tokyo) 113, 355-363]. Site-directed mutants of farnesyl diphosphate synthase from Bacillus stearothermophilus were made to evaluate the roles of the conserved aspartic acids in region VI and lysines in regions I, V, and VI. The aspartate at position 224 was changed to alanine or glutamate (mutants designated as D224A and D224E, respectively); aspartates at positions 225 and 228 were changed to isoleucine and alanine (D225I, D228A); lysine at position 238 was changed to either alanine or arginine (K238A, K238R). The lysines at positions 47 and 183 were changed to isoleucine and alanine (K471, K183A), respectively. Kinetic analyses of the wild-type and mutant enzymes indicated that the mutagenesis of Asp-224 and Asp-225 resulted in a decrease of Kcat values of approximately 10(4)- to 10(5)-fold compared to the wild type. On the other hand, D228A showed a Kcat value approximately one-tenth of that of the wild type, and the k(m) value for isopentenyl diphosphate increased approximately 10-fold. Both K471 and K183A showed k(m) values for isopentenyl diphosphate 20-fold larger and kcat values 70-fold smaller than the wild type. These results suggest that the two conserved lysines in regions I and V contribute to the binding of isopentenyl diphosphate and that the first and the second aspartates in region VI are involved in catalytic function. Aspartate-228 is also important for the binding of isopentenyl diphosphate rather than for catalytic reaction.

Objective The novel morpholino antisense oligonucleotide viltolarsen targets exon 53 of the dystrophin gene, and could be an effective treatment for patients with Duchenne muscular dystrophy (DMD). We investigated viltolarsen’s ability to induce dystrophin expression and examined its safety in DMD patients. Methods In this open‐label, multicenter, parallel‐group, phase 1/2, exploratory study, 16 ambulant and nonambulant males aged 5–12 years with DMD received viltolarsen 40 or 80 mg/kg/week via intravenous infusion for 24 weeks. Primary endpoints were dystrophin expression and exon 53 skipping levels. Results In western blot analysis, mean changes in dystrophin expression (% normal) from baseline to Weeks 12 and 24 were − 1.21 ( P = 0.5136) and 1.46 ( P = 0.1636), respectively, in the 40 mg/kg group, and 0.76 ( P = 0.2367) and 4.81 ( P = 0.0536), respectively, in the 80 mg/kg group. The increase in mean dystrophin level at Weeks 12 and 24 was significant in the 80 mg/kg group (2.78%; P = 0.0364). Patients receiving 80 mg/kg showed a higher mean exon 53 skipping level (42.4%) than those receiving 40 mg/kg (21.8%). All adverse events were judged to be mild or moderate in intensity and none led to study discontinuation. Interpretation Treatment with viltolarsen 40 or 80 mg/kg elicited an increasing trend in dystrophin expression and exon 53 skipping levels, and was safe and well tolerated. The decline in motor function appeared less marked in patients with higher dystrophin levels; this may warrant further investigation. This study supports the potential clinical benefit of viltolarsen.

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We developed the new 32-in. , 37-in. and 42-in. PDPs (A1 series with ALIS method) with much improved moving picture qualities by the newly developed image processing LSI. Furthermore, the peak luminance of 1100cd/m2, white color temperature of 9000K, color reproduction of almost equal to NTSC is achieved.

The information of applied external forces is very important and useful in the assessment of integrity of structures. An identification method of impact force is presented in this paper. First, the relation between force histories and strain responses is formulated based on the finite element method (FEM). By applying this formulation, an error vector that indicates the force location is defined with strain responses measured at multiple points in a structure. The inverse problem can be solved with the conventional least-square method, but in an actual system, the identified force history has a large oscillation because of the influence of measurement noise and FEM modeling error. To overcome this difficulty, second, the present paper proposes a reliable force identification method that imposes the penalty on the derivative of the force history. The present method has been applied to carbon fiber reinforced plastic (CFRP) laminated plates with a SMART Layer embedded lead zirconate titanate (PZT) piezoelectric sensors. The experimental results for two kinds of plates are reported in this paper. According to the results of force location and history identification, the validity of the present method is verified, and the influence of the modeling error involved in the finite element model is discussed.

This paper proposes a reliable method identifying both a location and a history of an impact force acting on a plate using multiple sensor responses. First, a fundamental relationship between an impact force and the strain responses is formulated based on the finite element method. The impact force history is precisely identified by the least-squares method containing a penalty term on derivative of force history. The location of impact force is determined by minimizing an error vector between measured strain responses and analytically evaluated ones. An application of proposed method to aluminum plates equipped with sensors is developed to discuss the validity of the present method.

:The present paper discusses a structural health monitoring method of CFRP structures based on a impact force identification. In the first part, an experimental identification method of impact force is developed where the relation between force histories and strain responses is determined experimentally. By employing this relation, the impact force is identified for CFRP laminated plates involving impact damages under a drop-weight impact test. It is shown that the identified force history agrees well with the experimental one even when the impact damage is induced. Next, the impact damage monitoring method is proposed. When the information on the maximum impact force is obtained, the occurrence of the impact damage can be predicted easily from the shape of force history, and the damage size can also be estimated using the experimental relation between the damage size and the maximum impact force. Thus, structural health can be evaluated automatically, by monitoring the impact force from the sensor response in real time, and great improvement of the structure safety becomes possible.