Current Trends and Future Prospects of Molecular Targeted Therapy in Head and Neck Squamous Cell Carcinoma

In recent years, advances in drug therapy for head and neck squamous cell carcinoma (HNSCC) have progressed rapidly. In addition to cytotoxic anti-cancer agents such as platinum-based drug (cisplatin and carboplatin) and taxane-based drugs (docetaxel and paclitaxel), epidermal growth factor receptor-tyrosine kinase inhibitors (cetuximab) and immune checkpoint inhibitors such as anti-programmed cell death-1 (PD-1) antibodies (nivolumab and pembrolizumab) have come to be used. The importance of anti-cancer drug therapy is increasing year by year. Therefore, we summarize clinical trials of molecular targeted therapy and biomarkers in HNSCC from previous studies. Here we show the current trends and future prospects of molecular targeted therapy in HNSCC.     

Immunotherapy with 4-1BBL-Expressing iPS Cell‐Derived Myeloid Lines Amplifies Antigen-Specific T Cell Infiltration in Advanced Melanoma

We have established an immune cell therapy with immortalized induced pluripotent stem-cell–derived myeloid lines (iPS-ML). The benefits of using iPS-ML are the infinite proliferative capacity and ease of genetic modification. In this study, we introduced 4-1BBL gene to iPS-ML (iPS-ML-41BBL). The analysis of the cell-surface molecules showed that the expression of CD86 was upregulated in iPS-ML-41BBL more than that in control iPS-ML. Cytokine array analysis was performed using supernatants of the spleen cells that were cocultured with iPS-ML or iPS-ML-41BBL. Multiple cytokines that are beneficial to cancer immunotherapy were upregulated. Peritoneal injections of iPS-ML-41BBL inhibited tumor growth of peritoneally disseminated mouse melanoma and prolonged survival of mice compared to that of iPS-ML. Furthermore, the numbers of antigen-specific CD8⁺ T cells were significantly increased in the spleen and tumor tissues treated with epitope peptide-pulsed iPS-ML-41BBL compared to those treated with control iPS-ML. The number of CXCR6-positive T cells were increased in the tumor tissues after treatment with iPS-ML-41BBL compared to that with control iPS-ML. These results suggest that iPS-ML-41BBL could activate antigen-specific T cells and promote their infiltration into the tumor tissues. Thus, iPS-ML-41BBL may be a candidate for future immune cell therapy aiming to change immunological “cold tumor” to “hot tumor”.     

Solving large‐scale nonlinear eigenvalue problems by rational interpolation and resolvent sampling based Rayleigh–Ritz method

Numerical solution of nonlinear eigenvalue problems (NEPs) is frequently encountered in computational science and engineering. The applicability of most existing methods is limited by the matrix structures, properties of the eigen‐solutions, sizes of the problems, etc. This paper aims to remove those limitations and develop robust and universal NEP solvers for large‐scale engineering applications. The novelty lies in two aspects. First, a rational interpolation approach (RIA) is proposed based on the Keldysh theorem for holomorphic matrix functions. Comparing with the existing contour integral approach, the RIA provides the possibility to select sampling points in more general regions and has advantages in improving the accuracy and reducing the computational cost. Second, a resolvent sampling scheme using the RIA is proposed to construct reliable search spaces for the Rayleigh–Ritz procedure, based on which a robust eigen‐solver, called resolvent sampling based Rayleigh–Ritz method (RSRR), is developed for solving general NEPs. The RSRR can be easily implemented and parallelized. The advantages of the RIA and the performance of the RSRR are demonstrated by a variety of benchmark and application examples. Copyright © 2016 John Wiley & Sons, Ltd.     

Air‐Stable and High‐Performance Solution‐Processed Organic Light‐Emitting Devices Based on Hydrophobic Polymeric Ionic Liquid Carrier‐Injection Layers

A lot of research, mostly using electron‐injection layers (EILs) composed of alkali‐metal compounds has been reported with a view to increase the efficiency of solution‐processed organic light‐emitting devices (OLEDs). However, these materials have intractable properties, such as a strong affinity for moisture, which cause the degradation of OLEDs. Consequently, optimal EIL materials should exhibit high electron‐injection efficiency as well as be stable in air. In this study, polymer light‐emitting devices (PLEDs) based on the commonly used yellow‐fluorescence‐emitting polymer F8BT, which utilize poly(diallyldimethylammonium)‐based polymeric ionic liquids, are experimentally and analytically investigated. As a result, the optimized PLED employing an EIL comprising poly(diallyldimethylammonium) bis(trifluoromethanesulfonyl)imide (poly(DDA)TFSI), which is expected to display good moisture resistance because of water repellency of fluorocarbon groups, exhibits excellent storage stability in air and electroluminescence performance with a low turn‐on voltage of 2.01 V, maximum external quantum efficiency of 9.00%, current efficiency of 30.1 cd A^?1, and power efficiency of 32.4 lm W^?1. The devices with poly(DDA)TFSI show one of the highest efficiencies as compared to the reported standard PLEDs. Moreover, poly(DDA)TFSI is applied as a hole‐injection layer (HIL). The optimized PLED using poly(DDA)TFSI as the HIL exhibits performances comparable to those of a device that uses a conventional poly(3,4‐ethylenedioxy‐thiophene):poly(4‐styrenesulfonate) HIL.     

A study on effect of biarticular muscles in an antagonistically actuated robot arm through numerical simulations

Control of articulated robots by biarticular actuation has recently attracted great attention in the research field of robotics. Although many of studies concerned with this issue deal with legged robots or robot arms kinetically interacting with environment such as a floor or an object, motion control of an articulated robot arm with no kinetic interaction is also an interesting topic of biarticular actuation. In the motion control, a major issue is how it is possible for biarticular actuation to contribute to improvement of control; however, showing a clear finding for this issue seems to be considerably difficult. This paper considers a study for exploring that issue. Biarticular actuation usually constitutes a redundant actuation system; therefore, control of a robot arm to a desired posture can be achieved by many combinations of actuator forces. Based on this feature, this paper considers three typical combinations of actuator forces. Point-to-point control of the robot is performed for each of the combinations in simulation, and control performances of the combinations are compared with each other. In addition, the performances are compared with that of monoarticular actuation. In those comparisons, two of the three combinations show similar control performances, which suggests possibility of major contribution of biarticular actuators to motion control of a robot arm. On the other hand, control performance of the other combination is similar to that of monoarticular actuation, rather than those of other two combinations.     

Highly efficient fluorescent blue materials and their applications for top‐emission OLEDs

We developed new fluorescent blue dopants (BDs) for achieving high‐efficient blue organic light‐emitting diode. A new BD showed both high photoluminescent quantum yield >0.9 and highly horizontal orientation (S′ > 0.9) in doped film with keeping a chemical stability by introducing suitable substituents. We developed hole transporting materials and optimized the combination of hole transporting layers to decrease a carrier accumulation at the interface between electron blocking layer and emission layer. We found that the external quantum efficiency dependency from low to high current density was turned flat by promoting hole injection into emission layer. The top‐emission organic light‐emitting diode using the new BD and the optimized device architecture exhibited high efficiency of L/J/CIEy around 200 at CIEy = 0.043.     

Volume preserving viscoelastic fluids with large deformations using position-based velocity corrections

We propose a particle-based hybrid method for simulating volume preserving viscoelastic fluids with large deformations. Our method combines smoothed particle hydrodynamics (SPH) and position-based dynamics (PBD) to approximate the dynamics of viscoelastic fluids. While preserving their volumes using SPH, we exploit an idea of PBD and correct particle velocities for viscoelastic effects not to negatively affect volume preservation of materials. To correct particle velocities and simulate viscoelastic fluids, we use connections between particles which are adaptively generated and deleted based on the positional relations of the particles. Additionally, we weaken the effect of velocity corrections to address plastic deformations of materials. For one-way and two-way fluid-solid coupling, we incorporate solid boundary particles into our algorithm. Several examples demonstrate that our hybrid method can sufficiently preserve fluid volumes and robustly and plausibly generate a variety of viscoelastic behaviors, such as splitting and merging, large deformations, and Barus effect.     

An event-driven simulation method for motor driver in virtual machine tool system

In this paper, an event-driven simulation method is proposed for the motor driver in a virtual machine tool system (VMT), of which simulation speed is always a puzzle. This method utilizes a set of pre-defined events to trigger the execution of simulator in a non-deterministic manner and at the most efficient moment. Comparing to the conventional time domain simulation method, it dramatically reduces the CPU time consumption without losing simulation accuracy, therefore it improves the simulation efficiency. The effectiveness of this method is verified through a PMSM (Permanent Magnet Synchronous Motor) motor driver model in studying Servo/Mechanical interaction within a VMT.     

Ergonomic design of beverage can lift tabs based on numerical evaluations of fingertip discomfort

This paper introduces finite element analyses to evaluate numerically and objectively the feelings in the fingertip when opening aluminum beverage cans, in order to design the shape of the tab. Experiments of indenting vertically the fingertip pulp by a probe and by tabs of aluminum beverage can ends have allowed us to observe force responses and feelings in the fingertip. It was found that a typical force-displacement curve may be simplified as a combination of three curves with different gradients. Participants feel a touch at Curve 1 of the force-displacement curve, then feel a pressure and their pulse at Curve 2, finally feel discomfort followed by a pain in the fingertip at Curve 3. Finite element analyses have been performed to simulate indenting the tab with the fingertip vertically to confirm that the simulation results agree well with the experimental observations. Finally, numerical simulations of the finger pulling up the tab of the can end has also been performed and discomfort in the fingertip has been related to the maximum value of the contact stress of the finger model. Comparisons of three designs of tab ring shape showed that the tab with a larger contact area with finger is better.