Stereocontrolled Synthesis of Boranophosphate DNA by an Oxazaphospholidine Approach and Evaluation of Its Properties.

In this paper, we describe the first stereocontrolled synthesis and properties of boranophosphate DNA (PB-DNA), which contains all of the four nucleobases longer than 10mer. Synthesis was accomplished via an oxazaphospholidine approach combined with acid-labile protecting groups on nucleobases. It was demonstrated that there were significant differences between all-( Rp)- and all-( Sp)-PB-DNA in terms of the duplex-formation ability, nuclease resistance, and ribonuclease H (RNase H) activity. In particular, all-( Sp)-PB-DNA was demonstrated to show a duplex-formation ability with RNA and RNase H activity, both of which are necessary for antisense-type nucleic acid therapeutics.

Independent exercise for glottal incompetence to improve vocal problems and prevent aspiration pneumonia in the elderly: a randomized controlled trial.

OBJECTIVES: To evaluate the effect of a self-controlled vocal exercise in elderly people with glottal closure insufficiency. DESIGN: Parallel-arm, individual randomized controlled trial. METHODS: Patients who visited one of 10 medical centers under the National Hospital Organization group in Japan for the first time, aged 60 years or older, complaining of aspiration or hoarseness, and endoscopically confirmed to have glottal closure insufficiency owing to vocal cord atrophy, were enrolled in this study. They were randomly assigned to an intervention or a control group. The patients of the intervention group were given guidance and a DVD about a self-controlled vocal exercise. The maximum phonation time which is a measure of glottal closure was evaluated, and the number of patients who developed pneumonia during the six months was compared between the two groups. RESULTS: Of the 543 patients enrolled in this trial, 259 were allocated into the intervention group and 284 into the control; 60 of the intervention group and 75 of the control were not able to continue the trial. A total of 199 patients (age 73.9 ±7.25 years) in the intervention group and 209 (73.3 ±6.68 years) in the control completed the six-month trial. Intervention of the self-controlled vocal exercise extended the maximum phonation time significantly ( p < 0.001). There were two hospitalizations for pneumonia in the intervention group and 18 in the control group, representing a significant difference ( p < 0.001). CONCLUSION: The self-controlled vocal exercise allowed patients to achieve vocal cord adduction and improve glottal closure insufficiency, which reduced the rate of hospitalization for pneumonia significantly. CLINICAL TRIAL: gov Identifier-UMIN000015567.

Time and energy optimal trajectory generation for coverage motion in industrial machines.

The increase in computer numerical control machine efficiency highly contributes to environmental emission reduction and energy-savings. Path and trajectory optimizations are used to improve machine efficiency in a coverage motion such as pocket milling, polishing, inspection, gluing, and additive manufacturing. Several studies have proposed coverage motion optimization in improving machine efficiency for time and energy consumption. Ensuring the smoothness and satisfaction of the machine constraints in coverage motion is necessary. This paper proposes a multi-objective path and trajectory optimization to obtain a trade-off between time and energy consumption for coverage motion. Jerk limited acceleration profiles describe the trajectory where velocity profiles generated for each linear segment attain desirable velocities. The energy model of an industrial two-axis feed drive system is used in finding solutions to the optimization problem. The non-dominated sorting genetic algorithm II generates a Pareto front for trade-off time and energy consumption solutions. Simulation results of the proposed method are validated through experiments using the industrial two-axis feed drive system. Experimental results show the effectiveness of the proposed approach where time reduction and energy savings are 10.05% and 2.10%, respectively. In addition, the optimized path has a lower maximum error of 76.6% compared to the constantly commanded velocity optimized path.

Synthesis and properties of novel 2'-O-alkoxymethyl-modified nucleic acids.

Novel 2'-O-modified oligoribonucleotides with alkoxymethyl skeletons were synthesized, and their ability to hybridize complementary nucleic acids and their nuclease resistance were analyzed. The hybridization ability was improved by introducing electron-withdrawing groups and the increases in melting temperature (T(m) value) was particularly high for chlorine-substituted compounds. Nuclease resistance of these 2'-O-alkoxymethylated oligomers was lower than expected, but cyano substitution resulted in a higher nuclease resistance than 2'-O-methylation.

Improvement of motion accuracy and energy consumption for industrial feed drive systems using adaptive sliding mode control.

Increasing of consumed energy is the dominating challenge in many industrial fields, especially in computer numerical controlled (CNC) machines. Therefore, reducing even a small amount of the consumed energy can lead to a significant reduction in the world's energy consumption. Control techniques, which are used to manufacture industrial parts using higher controller gains can generally enhance motion accuracy of feed drive systems; however they increase the energy consumption. This paper proposes a new adaptive sliding mode control (ASMC), in which energy saving and motion accuracy of industrial machines can be effectively enhanced. The adaptation strategy allows control gains to be adaptively updated based on tracking performance. Once the resultant errors increase due to disturbance, the control gains are simultaneously modified to generate adequate control signals and achieve the precise track to the desired reference. The proposed adaptive gains can be flexibly changed during reaching and sliding phases, and therefore motion accuracy and energy reduction are improved. In order to confirm the effectiveness, the proposed adaptive law was compared with different adaptation approaches in several previous studies using a circular motion trajectory. Experimental results show a significant enhancement on the motion accuracy and energy saving for the feed drives.

Robust iterative learning contouring controller with disturbance observer for machine tool feed drives.

In feed drive systems, particularly machine tools, a contour error is more significant than the individual axial tracking errors from the view point of enhancing precision in manufacturing and production systems. The contour error must be within the permissible tolerance of given products. In machining complex or sharp-corner products, large contour errors occur mainly owing to discontinuous trajectories and the existence of nonlinear uncertainties. Therefore, it is indispensable to design robust controllers that can enhance the tracking ability of feed drive systems. In this study, an iterative learning contouring controller consisting of a classical Proportional-Derivative (PD) controller and disturbance observer is proposed. The proposed controller was evaluated experimentally by using a typical sharp-corner trajectory, and its performance was compared with that of conventional controllers. The results revealed that the maximum contour error can be reduced by about 37% on average.

Atypical Carcinoid Tumor with Anaplastic Lymphoma Kinase (ALK) Rearrangement Successfully Treated by an ALK Inhibitor.

This is the first report in which crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, reduced an atypical carcinoid tumor with ALK rearrangement. A 70-year-old man developed a tumor in the left lung and multiple metastases to the lung and brain. The pathology of transbronchial biopsied specimens demonstrated an atypical carcinoid pattern. Combined with immunohistochemical findings, we diagnosed the tumor as atypical carcinoid. ALK gene rearrangement was observed by both immunohistochemical (IHC) and fluorescence in situ hybridization. He was treated with chemotherapy as first-line therapy, however, the tumor did not respond to chemotherapy. Thereafter, he was treated with crizotinib, which successfully reduced the tumors.

Trimethylsilyl trifluoromethanesulfonate-promoted reductive 2'-O-arylmethylation of ribonucleoside derivatives.

Arylmethyl groups such as benzyl, p-methoxybenzyl, and 1-pyrenylmethyl groups were introduced to the 2'-O-position of nucleosides by reductive etherification. Combining corresponding aromatic aldehydes with 2'-O-trimethylsilylnucleoside derivatives in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) resulted in moderate to good yields of the 2'-O-arylmethyluridine derivatives, whereas the corresponding cytidine and adenosine derivatives were obtained in low yields. The reaction of ribonucleosides with aliphatic aldehydes did not proceed smoothly. Anomerization of the uridine derivatives by TMSOTf was observed in CH(2)Cl(2), toluene, and CH(3)CN, but was completely suppressed when the reactions were conducted in 1,4-dioxane.